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ING112276: A Dose Ranging Trial of GSK1349572 and 2 NRTI in HIV-1 Infected, Therapy Naive Subjects

Sponsor
ViiV Healthcare (Industry)
Overall Status
Completed
CT.gov ID
NCT00951015
Collaborator
Shionogi (Industry), GlaxoSmithKline (Industry)
208
Enrollment
35
Locations
4
Arms
88.8
Duration (Months)
5.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This Phase IIb study in HIV-infected antiretroviral naive subjects will select an optimal once daily dose of GSK1349572 from a range of doses for future evaluation.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This Phase IIb study in HIV-infected antiretroviral naive adult subjects will include a dose-ranging evaluation of GSK1349572 10mg, 25mg and 50mg once daily blinded doses and a control arm of open label efavirenz 600mg once daily. Background ART for all study subjects will be chosen by the investigators and will be either Truvada or Epzicom/Kivexa. Data from the three doses of GSK1349572 will be compared on the basis of antiviral activity, safety/tolerability and pharmacokinetics over 16-24 weeks.

Several planned interim analyses will evaluate data in real time; any doses considered inferior will be dropped and subjects on those doses of GSK1349572 will have the option to switch to either the highest dose still under investigation or the selected dose. Subjects will be able to remain in the study, unless they reach a stopping criterion, for at least 96 weeks.

ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship.

Study Design

Study Type:
Interventional
Actual Enrollment :
208 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase IIb Study to Select a Once Daily Dose of GSK1349572 Administered With Either Abacavir/Lamivudine or Tenofovir/Emtricitabine in HIV-1 Infected Antiretroviral Therapy Naive Adult Subjects
Study Start Date :
Jul 30, 2009
Actual Primary Completion Date :
Feb 26, 2010
Actual Study Completion Date :
Dec 22, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: 10 mg GSK1349572

subjects will receive GSK1349572 10mg once daily blinded to dose

Drug: GSK1349572
investigational HIV-1 integrase inhibitor
Experimental: 25mg GSK1349572

subjects will receive GSK1349572 25mg once daily blinded to dose

Drug: GSK1349572
investigational HIV-1 integrase inhibitor
Experimental: 50mg GSK1349572

subjects will receive GSK1349572 50mg once daily blinded to dose

Drug: GSK1349572
investigational HIV-1 integrase inhibitor
Other: efavirenz control

efavirenz will serve as the internal control arm

Drug: efavirenz
approved therapy for HIV-1 infection, used as an internal study control

Outcome Measures

Primary Outcome Measures

  1. Number of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 16 [Week 16]

    Plasma samples were collected for quantitative HIV-1 RNA analysis at Week 16. The analysis was performed using the time to loss of virological response (TLOVR) dataset. In the TLOVR dataset, participant responses at a specified threshold of HIV-1 RNA (<50 copies/mL) are determined by using the Food and Drug Administration's TLOVR algorithm. Using the TLOVR algorithm, participants are considered to have failed on therapy if they never achieved confirmed RNA levels below the threshold, if they had confirmed rebound of RNA above the threshold, if they made a non-permitted change in background regimen, or if they permanently discontinued investigational product for any reason. Data are reported per the Week 16 report. In later cuts of the data, the Week 16 values may have changed (because of the nature of the TLOVR algorithm).ITT-E Population included all randomized participants who received at least one dose of study medication

Secondary Outcome Measures

  1. Viral Change Over the Initial 2 Weeks of Treatment [Baseline and Week 2]

    Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline and Week 2. Viral change is defined as the change in plasma HIV-1 RNA over the initial 2 weeks of treatment, calculated as the value at Week 2 minus the value at Baseline. Only those participants available at the specified time point were analyzed.

  2. Change From Baseline in HIV-1 RNA at the Indicated Time Points [Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96]

    Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.

  3. Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points [Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96]

    Blood samples were collected for lymphocyte subset assessment by flow cytometry at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT-E Population.

  4. Number of Participants With New HIV-associated Conditions of the Indicated Class [From Baseline up to Week 96]

    HIV-associated conditions were assessed according to the Centers for Disease Control and Prevention (CDC) HIV-1 classification system. Category (CAT) A: one or more of the following conditions (CON), without any CON listed in Categories B and C: asymptomatic HIV infection, persistent generalized lymphadenopathy, acute (primary) HIV infection with accompanying illness or history of acute HIV infection. CAT B: symptomatic CON that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or that are considered by physicians to have a clinical course or to require management that is complicated by HIV infection; and not included among CON listed in clinical CAT C. CAT C: the clinical CON listed in the acquired immunodeficiency syndrome (AIDS) surveillance case definition.

  5. Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death) [From Baseline up to Week 96]

    Clinical disease progression (CDP) was assessed according to the Centers for Disease Control and Prevention (CDC) HIV-1 classification system. Category (CAT) A: one or more of the following conditions (CON), without any CON listed in Categories B and C: asymptomatic HIV infection, persistent generalized lymphadenopathy, acute (primary) HIV infection with accompanying illness or history of acute HIV infection. CAT B: symptomatic CON that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or that are considered by physicians to have a clinical course or to require management that is complicated by HIV infection; and not included among CON listed in clinical CAT C. CAT C: the clinical CON listed in the AIDS surveillance case definition. Indicators of CDP were defined as: CAT A at Baseline (BS) to CAT B event (EV), CAT A at BS to a CAT C EV; CAT B at BS to a CAT C EV; CAT C at BS to a new CAT C EV; or CAT A, B, or C at BS to death.

  6. Number of Participants With Plasma HIV-1 RNA <50 c/mL [Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96]

    Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. The analysis was performed using the time to loss of virological response (TLOVR) dataset. In the TLOVR dataset, participant responses at a specified threshold of HIV-1 RNA (<50 copies/mL) are determined by using the Food and Drug Administration's TLOVR algorithm. Using the TLOVR algorithm, participants are considered to have failed on therapy if they never achieved confirmed RNA levels below the threshold, if they had confirmed rebound of RNA above the threshold, if they made a non-permitted change in background regimen, or if they permanently discontinued investigational product for any reason.

  7. Number of Participants With Plasma HIV-1 RNA <400 c/mL [Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96]

    Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. The analysis was performed using the time to loss of virological response (TLOVR) dataset. In the TLOVR dataset, participant responses at a specified threshold of HIV-1 RNA (<400 c/mL) are determined by using the Food and Drug Administration's TLOVR algorithm. Using the TLOVR algorithm, participants are considered to have failed on therapy if they never achieved confirmed RNA levels below the threshold, if they had confirmed rebound of RNA above the threshold, if they made a non-permitted change in background regimen, or if they permanently discontinued investigational product for any reason.

  8. Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Events (SAE) [From Baseline up to Week 96/Early Withdrawal]

    An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity; or is a congenital anomaly/birth defect. All clinically suspected cases of hypersensitivity reaction to abacavir in participants receiving abacavir/lamivudine were reported as SAEs. Medical or scientific judgment was to have been exercised in other situations. Refer to the general AE/SAE module for a list of AEs (occuring at a frequency threshold >=3%) and SAEs.

  9. Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities [From Baseline up to Week 96/Early Withdrawal]

    Blood samples were collected for the measurement of clinical chemistry and hematology parameters. Toxicities were graded for severity according to the Division of AIDS (DAIDS) toxicity scales as: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (potentially life threatening).

  10. Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance [From Baseline up to Week 96/Early Withdrawal]

    For participants meeting one of the criteria for PDVF, plasma samples collected at the time point of virologic failure were tested to evaluate any potential genotypic and/or phenotypic evolution of resistance. PDVF was defined as (A) Virologic Non-response: a decrease in plasma HIV-1 RNA of <1 log10 copies/mL by Week 4, with subsequent confirmation, unless plasma HIV-1 RNA is <400 copies/mL; confirmed plasma HIV-1 RNA levels >=400 copies/mL on or after Week 24 without evidence of prior suppression to <400copies/mL or (B) Virologic Rebound: confirmed rebound in plasma HIV-1 RNA levels to >=400 copies/mL after prior confirmed suppression to <400 copies/mL; confirmed plasma HIV-1 RNA levels >0.5 log10 copies/mL above the nadir value, where nadir is the lowest HIV-1 value >=400 copies/mL.On-treatment Genotypic Resistance Population: all participants in the ITT-E Population with available on-treatment genotypic data, excluding participants who were not protocol-defined virologic failures.

  11. Number of Participants With the Indicated Treatment-emergent Major Mutations of Other Classes Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance [From Baseline up to Week 96/Early Withdrawal]

    For participants meeting one of the criteria for PDVF, plasma samples collected at the time point of virologic failure were tested to evaluate any potential genotypic and/or phenotypic evolution of resistance. PDVF was defined as (A) Virologic Non-response: a decrease in plasma HIV-1 RNA of <1 log10 copies/mL by Week 4, with subsequent confirmation, unless plasma HIV-1 RNA is <400 copies/mL; confirmed plasma HIV-1 RNA levels >=400 copies/mL on or after Week 24 without evidence of prior suppression to <400copies/mL or (B) Virologic Rebound: confirmed rebound in plasma HIV-1 RNA levels to >=400 copies/mL after prior confirmed suppression to <400 copies/mL; confirmed plasma HIV-1 RNA levels >0.5 log10 copies/mL above the nadir value, where nadir is the lowest HIV-1 value >=400 copies/mL.

  12. Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) at the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance [From Baseline up to Week 96/Early Withdrawal]

    The FC in IC50 (50% inhibitory concentration) for DTG relative to wild-type virus was determined for virus isolated at Baseline and at the time of PDVF. Fold increase in DTG FC at the time of PDVF was derived as the PDVF FC/Baseline FC ratio. PDVF was defined as (A) Virologic Non-response: a decrease in plasma HIV-1 RNA of <1 log10 copies/mL by Week 4, with subsequent confirmation, unless plasma HIV-1 RNA is <400 copies/mL; confirmed plasma HIV-1 RNA levels >=400 copies/mL on or after Week 24 without evidence of prior suppression to <400copies/mL or (B) Virologic Rebound: confirmed rebound in plasma HIV-1 RNA levels to >=400 copies/mL after prior confirmed suppression to <400 copies/mL; confirmed plasma HIV-1 RNA levels >0.5 log10 copies/mL above the nadir value, where nadir is the lowest HIV-1 value >=400 copies/mL.On-treatment Phenotypic Resistance Population: all participants in the ITT-E Population with available on-treatment phenotypic data

  13. Plasma DTG Concentration [Week 2, Week 12, and Week 24]

    Blood samples for the determination of plasma DTG concentration were collected from the participants randomized to receive DTG, at the following time points: pre-dose and 2-4 hours post-dose at Weeks 2, Week 12, and Week 24. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. The Pharmacokinetic (PK) Summary Population is comprised of all participants who received DTG and underwent intensive PK sampling or limited PK sampling during the study and provided evaluable DTG PK parameters. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles).Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the PK Summary Population.

  14. AUC(0-tau) of DTG [Pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2]

    The area under the time concentration curve over the dosing interval (AUC[0-tau]) of DTG was determined using non-compartmental analysis based on intensive PK sampling at the following time points: pre-dose; 2, 3, 4, 8, and 24 hours post-dose at Week 2. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. Only those participants available at the specified time points were analyzed.

  15. Maximal Concentration (Cmax), Minimal Concentration (Cmin), and Concentration at the End of Dosing Interval (Ctau) of DTG [Pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2]

    The Cmax, Cmax, and Ctau of DTG were determined using non-compartmental analysis based on intensive PK sampling at the following time points: pre-dose; 2, 3, 4, 8, and 24 hours post-dose at Week 2. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed.

  16. Pre-dose Concentration (C0) and C0 Avg of DTG [Week 2, Week 12, and Week 24]

    The plasma DTG C0 of DTG was determined using limited/sparse PK sampling at Week 2, Week 12, and Week 24. C0 avg was calculated at Week 24 as the mean of the C0 of DTG at Week 2, Week 12, and Week 24. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the PK Summary Population.

  17. Time to Maximal Drug Concentration (Tmax) of DTG [Pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2]

    Tmax of DTG was determined using non-compartmental analysis based on intensive PK sampling at the following time points: pre-dose; 2, 3, 4, 8, and 24 hours post-dose at Week 2. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed.

  18. Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters [Week 2]

    Relationships between Week 2 plasma DTG PK parameters (AUC[0-tau] [area under the time concentration curve over the dosing interval], Cmax [maximal concentration], and Ctau [concentration at the end of the dosing interval]) and the change from Baseline in plasma HIV-1 RNA at Week 2 (calculated as the post-Baseline value minus the value at Baseline) was assessed using Pearson's correlation analyses. The Pearson's correlation coefficient is a measure of the correlation between plasma HIV-1 RNA and plasma DTG PK parameters and ranges from -1 to 1. A value of 0 indicates no statistical association; a value close to -1 or 1 indicates a higher association. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. PK/Pharmacodynamic (PD) Analysis Population: all participants with available PD measures (e.g., safety and/or efficacy data) and with evaluable DTG plasma concentration data considered suitable for investigation of relationship with the PD measures

  19. Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters [Week 96]

    Relationships between plasma DTG PK parameters (AUC[0-tau] [area under the time concentration curve over the dosing interval], Cmax [maximal concentration], C0avg [average pre-dose concentration], and Ctau [concentration at the end of the dosing interval]) and the change from Baseline in CD4+ cell counts at Week 96 (calculated as the post-Baseline value minus the value at Baseline) was assessed using Pearson's correlation analyses. The Pearson's correlation coefficient is a measure of the correlation between CD4+ cell counts and plasma DTG PK parameters and ranges from -1 to 1. A value of 0 indicates no statistical association; a value close to -1 or 1 indicates a higher association.Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed.Only those participants available at the specified time points were analyzed (represented by n=X in the category titles)

  20. Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters [Week 96]

    Relationships between log-transformed plasma DTG PK parameters (AUC[0-tau], Cmax, C0, C0avg, Ctau, and Cmin) and safety parameters (AE occurrence, maximum AE intensity, alanine aminotransferase [ALT], change from Baseline [CFB] in ALT, total bilirubin, CFB in total bilirubin, creatine kinase, CFB in creatine kinase, triglycerides, CFB in triglycerides, lipase, CFB in lipase, total cholesterol [TC], CFB in TC) was assessed using Pearson's correlation analyses. The Pearson's correlation coefficient is a measure of the correlation between safety parameters and plasma DTG PK parameters and ranges from -1 to 1. A value of 0 indicates no statistical association; a value close to -1 or 1 indicates a higher association. The presence of >=1 AE was used for AE occurrence. The most severe AE grade/intensity was used for maximum AE intensity. Maximum laboratory values per participant were used for safety parameters. CFB was calculated as the post-Baseline value minus the value at Baseline.

  21. Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters [Week 96]

    Logistic regressions were performed to examine the correlation between plasma DTG PK parameters (AUC[0-tau] [area under the time concentration curve over the dosing interval], Cmax [maximal concentration], Ctau [concentration at the end of the dosing interval], and C0avg [average pre-dose concentration]) on log scales and the presence of gastrointestinal system organ class AEs (abdominal pain, diarrhea, nausea, and vomiting) at Week 96. Data are presented as estimates from logistic regression, which is a measure of the association between AEs of special interest and plasma DTG PK parameters. A value of 0 indicates no statistical association; a large absolute value of the estimate indicates higher association. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. Results are presented for participants in any DTG group (overall DTG).Only those participants available at the specified time points were analyzed represented by n=X in the category titles

Other Outcome Measures

  1. Change From Baseline in Cluster of Differentiation 8+ (CD8+) Cell Counts at the Indicated Time Points [Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96]

    Change from Baseline in CD8+ cell count data are not available; CD8+ data are only listed on a per-participant basis and were not summarized.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • HIV-1 infected male or female adults at least 18 years of age. Women capable of becoming pregnant must use appropriate contraception during the study (as defined by the protocol);

  • HIV-1 infection with a screening plasma HIV-1 RNA greater than or equal to 1000copies/mL;

  • CD4+ cell count greater than or equal to 200cells/mm3 (or higher as local guidelines dictate);

  • ART-naive (less than or equal to 10 days of prior therapy with any antiretroviral agent). Any previous exposure to an HIV integrase inhibitor other than GSK1349572 will be exclusionary.

  • No evidence of viral resistance to any antiretroviral drug indicative of primary transmitted resistance at screening;

  • Able to understand and comply with protocol requirements;

  • Able to provide written informed consent prior to screening;

  • French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Note: Subjects starting abacavir as part of the NRTI backbone must have been screened and be negative for the HLA-B*5701 allele.

Exclusion Criteria:

  • Any pre-existing or serious mental or physical disorder which could compromise ability to comply with the protocol or compromise subject safety;

  • Women who are pregnant or breastfeeding;

  • An active AIDS-defining condition at the screening visit;

  • Previous participation in an experimental drug and/or vaccine trial(s) within 30 days or 5 half-lives;

  • History of clinically relevant pancreatitis or hepatitis within the previous 6 months, including HBsAg positive result. Asymptomatic HCV infection will not be exclusionary, however subject who will require HCV therapy during the trial should be excluded. Any subject with a history of liver cirrhosis with or without hepatitis viral co-infection will be excluded.

  • Any condition which could interfere with the absorption, distribution, metabolism or excretion of the drug;

  • Any acute or Grade 4 laboratory abnormality at screening;

  • History of upper gastrointestinal bleed and/or subjects with active peptic ulcer disease;

  • Estimated creatinine clearance <50 mL/min;

  • Alanine aminotransferase (ALT) greater than or equal to 5 times ULN;

  • Alanine aminotransferase (ALT) greater than or equal to 3xULN and bilirubin greater than or equal to 1.5xULN (with >35% direct bilirubin);

  • Lipase greater than or equal to 3xULN;

  • Hemoglobin < 100 g/L(10 g/dL);

  • History of allergy to the study drugs or their components or drugs of their class;

  • Treatment with radiation therapy, cytotoxic chemotherapeutic agents, any agents with activity against HIV-1 or immunomodulators within 28 days prior to screening;

  • Treatment with an HIV-1 immunotherapeutic vaccine within 90 days prior to screening;

  • History of protocol-defined cardiac diseases;

  • Personal or family history of prolonged QT syndrome;

  • Any clinically significant finding, as specified in the protocol, on electrocardiograph (ECG);

  • Significant blood loss in excess of 500 mL within a 56 day period prior to screening visit;

  • Immunization within 30 days prior to first dose of investigational product;

  • French subjects: The subject has participated in any study using an investigational drug during the previous 60 days or 5 half-lives, or twice the duration of the biological effect of the experimental drug or vaccine - whichever is longer, prior to screening for the study or the subject will participate simultaneously in another clinical study.

Contacts and Locations

Locations

Site City State Country Postal Code
1 GSK Investigational Site Phoenix Arizona United States 85012
2 GSK Investigational Site Bakersfield California United States 93301
3 GSK Investigational Site Long Beach California United States 90813
4 GSK Investigational Site San Francisco California United States 94115
5 GSK Investigational Site Denver Colorado United States 80209
6 GSK Investigational Site Washington District of Columbia United States 20037
7 GSK Investigational Site Fort Lauderdale Florida United States 33306
8 GSK Investigational Site Fort Lauderdale Florida United States 33308
9 GSK Investigational Site Fort Lauderdale Florida United States 33316
10 GSK Investigational Site Orlando Florida United States 32804
11 GSK Investigational Site Santa Fe New Mexico United States 87505
12 GSK Investigational Site Charlotte North Carolina United States 28209
13 GSK Investigational Site Dallas Texas United States 75246
14 GSK Investigational Site Lyon cedex 04 France 69317
15 GSK Investigational Site Montpellier Cedex 5 France 34295
16 GSK Investigational Site Nantes France 44093
17 GSK Investigational Site Paris Cedex 10 France 75475
18 GSK Investigational Site Paris Cedex 13 France 75651
19 GSK Investigational Site Paris France 75018
20 GSK Investigational Site Frankfurt Hessen Germany 60311
21 GSK Investigational Site Hannover Niedersachsen Germany 30625
22 GSK Investigational Site Hamburg Germany 20146
23 GSK Investigational Site Hamburg Germany 20246
24 GSK Investigational Site Bergamo Lombardia Italy 24127
25 GSK Investigational Site Brescia Lombardia Italy 25123
26 GSK Investigational Site Milano Lombardia Italy 20127
27 GSK Investigational Site Milano Lombardia Italy 20157
28 GSK Investigational Site Smolensk Russian Federation 214006
29 GSK Investigational Site St. Petersburg Russian Federation 190103
30 GSK Investigational Site St. Petersburg Russian Federation 196645
31 GSK Investigational Site Badalona Spain 08916
32 GSK Investigational Site Barcelona Spain 08036
33 GSK Investigational Site Madrid Spain 28034
34 GSK Investigational Site Madrid Spain 28041
35 GSK Investigational Site Madrid Spain 28046

Sponsors and Collaborators

  • ViiV Healthcare
  • Shionogi
  • GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, ViiV Healthcare

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT00951015
Other Study ID Numbers:
  • 112276
First Posted:
Aug 3, 2009
Last Update Posted:
Jan 16, 2018
Last Verified:
Apr 1, 2017
Keywords provided by ViiV Healthcare
GSK1349572
emtricitabine
tenofovir
efavirenz
abacavir
antiretroviral therapy naive
dose selection
HIV-1 Infection
integrase inhibitor
HIV infection
once daily
lamivudine
Additional relevant MeSH terms:
Infections
Acquired Immunodeficiency Syndrome
HIV Infections
Efavirenz
Dolutegravir

Study Results

Participant Flow

Recruitment Details Randomization Phase participants received Dolutegravir (DTG 10, 25 or 50 milligrams[mg]) with Placebo/Efavirenz (EFV) for 96 Weeks . DTG participants who completed 96 Weeks continued or were switched to receive DTG 50 mg in Open label phase until DTG was locally available.
Pre-assignment Detail A total of 278 par were screened of which 70 were screen failures and 208 were randomized; 205 received at least one dose of study medication and comprised the Intent-To-Treat exposed (ITT-E) population. 17 participants out of 155 from DTG arm withdrew during Randomization phase and total 138 participants were enrolled in an Open-label phase.
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD Open-label DTG 50 mg QD
Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and Abacavir/lamivudine (ABC/3TC) 600 mg/300 mg or tenofovir/emtricitabine (TDF/FTC) 300 mg/200 mg orally once daily (QD) for 96 weeks. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 50 mg matching placebo and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. All DTG participants were switched to or continued DTG 50 mg with either ABC/3TC orally at 600 mg/300 mg (1 tablet) or TDF/FTC orally QD during the Open label phase
Period Title: Randomization Phase 96 Week
STARTED 53 51 51 50 0
COMPLETED 48 44 46 40 0
NOT COMPLETED 5 7 5 10 0
Period Title: Randomization Phase 96 Week
STARTED 0 0 0 0 138
COMPLETED 0 0 0 0 88
NOT COMPLETED 0 0 0 0 50

Baseline Characteristics

Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD Total
Arm/Group Description Participants received Dolutegravir (DTG) 10 milligrams (mg), DTG matching placebo, and Abacavir (ABC)/Lamivudine (3TC) 600 mg/300 mg or Tenofovir (TDF)/Emtricitabine (FTC) 300 mg/200 mg orally once daily (QD) for 96 weeks. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Total of all reporting groups
Overall Participants 53 51 51 50 205
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
34.2
(9.25)
37.0
(9.79)
37.0
(8.89)
40.7
(11.19)
37.2
(10.00)
Sex: Female, Male (Count of Participants)
Female
11
20.8%
5
9.8%
6
11.8%
6
12%
28
13.7%
Male
42
79.2%
46
90.2%
45
88.2%
44
88%
177
86.3%
Race/Ethnicity, Customized (participants) [Number]
African American/African Heritage (HER)
7
13.2%
6
11.8%
8
15.7%
4
8%
25
12.2%
American Indian or Alaska Native
1
1.9%
3
5.9%
4
7.8%
2
4%
10
4.9%
Japanese/East Asian HER/South East Asian HER
0
0%
0
0%
0
0%
1
2%
1
0.5%
Native Hawaiian or other Pacific Islander
3
5.7%
0
0%
0
0%
0
0%
3
1.5%
White
41
77.4%
42
82.4%
38
74.5%
43
86%
164
80%
African American/African HER & White
0
0%
0
0%
1
2%
0
0%
1
0.5%
Asian & White
1
1.9%
0
0%
0
0%
0
0%
1
0.5%

Outcome Measures

1. Primary Outcome
Title Number of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 16
Description Plasma samples were collected for quantitative HIV-1 RNA analysis at Week 16. The analysis was performed using the time to loss of virological response (TLOVR) dataset. In the TLOVR dataset, participant responses at a specified threshold of HIV-1 RNA (<50 copies/mL) are determined by using the Food and Drug Administration's TLOVR algorithm. Using the TLOVR algorithm, participants are considered to have failed on therapy if they never achieved confirmed RNA levels below the threshold, if they had confirmed rebound of RNA above the threshold, if they made a non-permitted change in background regimen, or if they permanently discontinued investigational product for any reason. Data are reported per the Week 16 report. In later cuts of the data, the Week 16 values may have changed (because of the nature of the TLOVR algorithm).ITT-E Population included all randomized participants who received at least one dose of study medication
Time Frame Week 16

Outcome Measure Data

Analysis Population Description
ITT-E Population
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Arm/Group Description Participants received Dolutegravir (DTG) 10 milligrams (mg), DTG matching placebo, and Abacavir (ABC)/Lamivudine (3TC) 600 mg/300 mg or Tenofovir (TDF)/Emtricitabine (FTC) 300 mg/200 mg orally once daily (QD) for 96 weeks. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Measure Participants 53 51 51 50
Number [participants]
51
96.2%
47
92.2%
46
90.2%
29
58%
2. Secondary Outcome
Title Viral Change Over the Initial 2 Weeks of Treatment
Description Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline and Week 2. Viral change is defined as the change in plasma HIV-1 RNA over the initial 2 weeks of treatment, calculated as the value at Week 2 minus the value at Baseline. Only those participants available at the specified time point were analyzed.
Time Frame Baseline and Week 2

Outcome Measure Data

Analysis Population Description
ITT-E Population.
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Measure Participants 53 50 50 48
Mean (Standard Deviation) [Log10 c/mL]
-2.387
(0.4595)
-2.365
(0.5458)
-2.392
(0.4241)
-1.930
(0.4312)
3. Secondary Outcome
Title Change From Baseline in HIV-1 RNA at the Indicated Time Points
Description Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.
Time Frame Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96

Outcome Measure Data

Analysis Population Description
ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT-E Population.
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Measure Participants 53 51 51 50
Week 1, n=53, 50, 48, 50
-1.815
(0.3999)
-1.773
(0.4650)
-1.738
(0.3840)
-1.562
(0.4158)
Week 2, n=53, 50, 50, 48
-2.387
(0.4595)
-2.365
(0.5458)
-2.392
(0.4241)
-1.930
(0.4312)
Week 4, n=53, 50, 50, 45
-2.629
(0.5863)
-2.583
(0.6337)
-2.713
(0.5471)
-2.162
(0.5400)
Week 8, n=52, 50, 49, 45
-2.657
(0.6980)
-2.666
(0.6667)
-2.848
(0.6556)
-2.450
(0.5989)
Week 12, n=53, 49, 49, 45
-2.685
(0.6831)
-2.671
(0.6850)
-2.860
(0.6772)
-2.603
(0.5869)
Week 16, n=52, 49, 49, 45
-2.718
(0.6593)
-2.668
(0.6826)
-2.859
(0.6876)
-2.698
(0.6715)
Week 20, n=52, 48, 49, 44
-2.701
(0.6423)
-2.662
(0.6908)
-2.869
(0.6896)
-2.745
(0.6602)
Week 24, n=52, 49, 48, 45
-2.700
(0.6261)
-2.657
(0.6969)
-2.853
(0.6889)
-2.773
(0.7026)
Week 32, n=52, 49, 47, 45
-2.717
(0.6588)
-2.658
(0.6991)
-2.855
(0.6963)
-2.772
(0.7021)
Week 40, n=51, 48, 47, 44
-2.647
(0.7039)
-2.665
(0.7051)
-2.855
(0.6934)
-2.795
(0.7169)
Week 48, n=51, 48, 48, 45
-2.723
(0.6519)
-2.667
(0.6934)
-2.850
(0.6849)
-2.711
(0.7765)
Week 60, n=50, 48, 48, 44
-2.741
(0.6444)
-2.675
(0.7012)
-2.825
(0.7458)
-2.765
(0.7035)
Week 72, n=51, 47, 48, 44
-2.742
(0.6453)
-2.622
(0.8052)
-2.860
(0.6930)
-2.757
(0.7094)
Week 84, n=51, 47, 47, 43
-2.725
(0.6506)
-2.670
(0.7064)
-2.855
(0.6923)
-2.743
(0.7321)
Week 96, n=48, 44, 46, 39
-2.728
(0.6494)
-2.680
(0.7116)
-2.854
(0.7061)
-2.807
(0.7238)
4. Secondary Outcome
Title Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points
Description Blood samples were collected for lymphocyte subset assessment by flow cytometry at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT-E Population.
Time Frame Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96

Outcome Measure Data

Analysis Population Description
ITT-E Population.
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Measure Participants 53 51 51 50
Week 1, n=53, 50, 48, 50
85.0
94.5
75.5
42.5
Week 2, n=53, 50, 50, 47
75.0
79.0
99.5
55.0
Week 4, n=53, 50, 50, 45
75.0
89.0
110.0
89.0
Week 8, n=52, 50, 49, 44
118.5
156.5
129.0
104.5
Week 12, n=53, 48, 48, 45
139.0
137.5
171.5
127.0
Week 16, n=52, 49, 49, 44
153.0
176.0
160.0
115.5
Week 20, n=52, 48, 49, 44
163.5
200.0
139.0
136.0
Week 24, n=51, 49, 47, 44
159.0
206.0
167.0
109.5
Week 32, n=50, 48, 47, 44
221.5
195.5
203.0
146.5
Week 40, n=50, 48, 47, 44
205.0
204.5
224.0
171.5
Week 48, n=51, 47, 47, 45
204.0
249.0
223.0
174.0
Week 60, n=51, 48, 47, 43
265.0
278.0
229.0
221.0
Week 72, n=51, 47, 48, 44
236.0
285.0
220.0
195.0
Week 84, n=51, 47, 46, 42
292.0
313.0
280.0
296.5
Week 96, n=48, 44, 46, 39
335.0
391.5
326.0
301.0
5. Secondary Outcome
Title Number of Participants With New HIV-associated Conditions of the Indicated Class
Description HIV-associated conditions were assessed according to the Centers for Disease Control and Prevention (CDC) HIV-1 classification system. Category (CAT) A: one or more of the following conditions (CON), without any CON listed in Categories B and C: asymptomatic HIV infection, persistent generalized lymphadenopathy, acute (primary) HIV infection with accompanying illness or history of acute HIV infection. CAT B: symptomatic CON that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or that are considered by physicians to have a clinical course or to require management that is complicated by HIV infection; and not included among CON listed in clinical CAT C. CAT C: the clinical CON listed in the acquired immunodeficiency syndrome (AIDS) surveillance case definition.
Time Frame From Baseline up to Week 96

Outcome Measure Data

Analysis Population Description
ITT-E Population
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Measure Participants 53 51 51 50
Category B
2
3.8%
0
0%
1
2%
1
2%
Category C
0
0%
0
0%
1
2%
0
0%
Death
1
1.9%
0
0%
0
0%
0
0%
6. Secondary Outcome
Title Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death)
Description Clinical disease progression (CDP) was assessed according to the Centers for Disease Control and Prevention (CDC) HIV-1 classification system. Category (CAT) A: one or more of the following conditions (CON), without any CON listed in Categories B and C: asymptomatic HIV infection, persistent generalized lymphadenopathy, acute (primary) HIV infection with accompanying illness or history of acute HIV infection. CAT B: symptomatic CON that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or that are considered by physicians to have a clinical course or to require management that is complicated by HIV infection; and not included among CON listed in clinical CAT C. CAT C: the clinical CON listed in the AIDS surveillance case definition. Indicators of CDP were defined as: CAT A at Baseline (BS) to CAT B event (EV), CAT A at BS to a CAT C EV; CAT B at BS to a CAT C EV; CAT C at BS to a new CAT C EV; or CAT A, B, or C at BS to death.
Time Frame From Baseline up to Week 96

Outcome Measure Data

Analysis Population Description
ITT-E Population
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Measure Participants 53 51 51 50
CAT A at Baseline to a CAT C event
0
0%
0
0%
0
0%
0
0%
CAT B at Baseline to a CAT C event
0
0%
0
0%
1
2%
0
0%
CAT C at Baseline to a new CAT C event
0
0%
0
0%
0
0%
0
0%
CAT A, B, or C at Baseline to death
1
1.9%
0
0%
0
0%
0
0%
7. Secondary Outcome
Title Number of Participants With Plasma HIV-1 RNA <50 c/mL
Description Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. The analysis was performed using the time to loss of virological response (TLOVR) dataset. In the TLOVR dataset, participant responses at a specified threshold of HIV-1 RNA (<50 copies/mL) are determined by using the Food and Drug Administration's TLOVR algorithm. Using the TLOVR algorithm, participants are considered to have failed on therapy if they never achieved confirmed RNA levels below the threshold, if they had confirmed rebound of RNA above the threshold, if they made a non-permitted change in background regimen, or if they permanently discontinued investigational product for any reason.
Time Frame Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96

Outcome Measure Data

Analysis Population Description
ITT-E Population
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Measure Participants 53 51 51 50
Baseline
0
0%
0
0%
0
0%
0
0%
Week 1
6
11.3%
4
7.8%
4
7.8%
3
6%
Week 2
22
41.5%
19
37.3%
11
21.6%
6
12%
Week 4
37
69.8%
35
68.6%
31
60.8%
9
18%
Week 8
46
86.8%
45
88.2%
43
84.3%
18
36%
Week 12
50
94.3%
46
90.2%
45
88.2%
25
50%
Week 16
51
96.2%
46
90.2%
47
92.2%
29
58%
Week 20
51
96.2%
47
92.2%
47
92.2%
38
76%
Week 24
51
96.2%
46
90.2%
47
92.2%
41
82%
Week 32
50
94.3%
45
88.2%
46
90.2%
43
86%
Week 40
49
92.5%
45
88.2%
46
90.2%
42
84%
Week 48
48
90.6%
45
88.2%
46
90.2%
40
80%
Week 60
48
90.6%
44
86.3%
46
90.2%
41
82%
Week 72
48
90.6%
44
86.3%
45
88.2%
40
80%
Week 84
47
88.7%
43
84.3%
46
90.2%
38
76%
Week 96
42
79.2%
40
78.4%
45
88.2%
36
72%
8. Secondary Outcome
Title Number of Participants With Plasma HIV-1 RNA <400 c/mL
Description Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. The analysis was performed using the time to loss of virological response (TLOVR) dataset. In the TLOVR dataset, participant responses at a specified threshold of HIV-1 RNA (<400 c/mL) are determined by using the Food and Drug Administration's TLOVR algorithm. Using the TLOVR algorithm, participants are considered to have failed on therapy if they never achieved confirmed RNA levels below the threshold, if they had confirmed rebound of RNA above the threshold, if they made a non-permitted change in background regimen, or if they permanently discontinued investigational product for any reason.
Time Frame Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96

Outcome Measure Data

Analysis Population Description
ITT-E Population
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Measure Participants 53 51 51 50
Baseline
0
0%
0
0%
0
0%
0
0%
Week 1
25
47.2%
20
39.2%
16
31.4%
15
30%
Week 2
45
84.9%
45
88.2%
41
80.4%
23
46%
Week 4
52
98.1%
49
96.1%
48
94.1%
32
64%
Week 8
52
98.1%
49
96.1%
49
96.1%
41
82%
Week 12
52
98.1%
49
96.1%
49
96.1%
45
90%
Week 16
52
98.1%
48
94.1%
49
96.1%
45
90%
Week 20
52
98.1%
48
94.1%
49
96.1%
45
90%
Week 24
52
98.1%
47
92.2%
48
94.1%
45
90%
Week 32
52
98.1%
47
92.2%
48
94.1%
45
90%
Week 40
50
94.3%
47
92.2%
48
94.1%
45
90%
Week 48
50
94.3%
47
92.2%
48
94.1%
44
88%
Week 60
50
94.3%
46
90.2%
48
94.1%
44
88%
Week 72
50
94.3%
46
90.2%
47
92.2%
43
86%
Week 84
50
94.3%
45
88.2%
47
92.2%
42
84%
Week 96
46
86.8%
43
84.3%
46
90.2%
39
78%
9. Secondary Outcome
Title Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Events (SAE)
Description An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity; or is a congenital anomaly/birth defect. All clinically suspected cases of hypersensitivity reaction to abacavir in participants receiving abacavir/lamivudine were reported as SAEs. Medical or scientific judgment was to have been exercised in other situations. Refer to the general AE/SAE module for a list of AEs (occuring at a frequency threshold >=3%) and SAEs.
Time Frame From Baseline up to Week 96/Early Withdrawal

Outcome Measure Data

Analysis Population Description
Safety Population:All participants who received at least one dose of the study medication
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Measure Participants 53 51 51 50
Any AE
50
94.3%
46
90.2%
46
90.2%
46
92%
Any SAE
5
9.4%
5
9.8%
7
13.7%
7
14%
10. Secondary Outcome
Title Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities
Description Blood samples were collected for the measurement of clinical chemistry and hematology parameters. Toxicities were graded for severity according to the Division of AIDS (DAIDS) toxicity scales as: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (potentially life threatening).
Time Frame From Baseline up to Week 96/Early Withdrawal

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Measure Participants 53 51 51 50
Alanine amino transferase
7
13.2%
11
21.6%
3
5.9%
19
38%
Cholesterol
18
34%
16
31.4%
13
25.5%
24
48%
Creatinine kinase
17
32.1%
6
11.8%
7
13.7%
5
10%
Lipase
11
20.8%
13
25.5%
11
21.6%
9
18%
Triglycerides
0
0%
1
2%
2
3.9%
1
2%
Alkaline phosphatase
1
1.9%
0
0%
1
2%
10
20%
Amylase
2
3.8%
3
5.9%
1
2%
4
8%
Aspartate amino transferase
12
22.6%
8
15.7%
6
11.8%
9
18%
Carbon dioxide content/bicarbonate
28
52.8%
24
47.1%
23
45.1%
30
60%
Creatinine
0
0%
4
7.8%
0
0%
0
0%
Hypercalcemia
0
0%
0
0%
0
0%
1
2%
Hyperglycaemia
16
30.2%
15
29.4%
17
33.3%
17
34%
Hyperkalemia
0
0%
0
0%
1
2%
1
2%
Hypernatremia
1
1.9%
1
2%
1
2%
0
0%
Hypocalcemia
4
7.5%
5
9.8%
5
9.8%
8
16%
Hypoglycaemia
3
5.7%
3
5.9%
5
9.8%
4
8%
Hypokalemia
4
7.5%
1
2%
3
5.9%
3
6%
Hyponatremia
6
11.3%
12
23.5%
7
13.7%
13
26%
Low-density lipoprotein cholesterol
14
26.4%
15
29.4%
11
21.6%
20
40%
Magnesium
7
13.2%
6
11.8%
5
9.8%
4
8%
Phosphate, inorganic
9
17%
15
29.4%
14
27.5%
11
22%
Total bilirubin
3
5.7%
4
7.8%
3
5.9%
0
0%
Activated partial thromboplastin time
7
13.2%
12
23.5%
6
11.8%
5
10%
Hemoglobin
0
0%
1
2%
0
0%
1
2%
International normalized ratio
6
11.3%
9
17.6%
6
11.8%
5
10%
Platelet count
1
1.9%
4
7.8%
1
2%
1
2%
Prothrombin time
7
13.2%
8
15.7%
7
13.7%
4
8%
Total neutrophils
9
17%
7
13.7%
6
11.8%
10
20%
White blood cell count
1
1.9%
1
2%
1
2%
1
2%
11. Secondary Outcome
Title Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance
Description For participants meeting one of the criteria for PDVF, plasma samples collected at the time point of virologic failure were tested to evaluate any potential genotypic and/or phenotypic evolution of resistance. PDVF was defined as (A) Virologic Non-response: a decrease in plasma HIV-1 RNA of <1 log10 copies/mL by Week 4, with subsequent confirmation, unless plasma HIV-1 RNA is <400 copies/mL; confirmed plasma HIV-1 RNA levels >=400 copies/mL on or after Week 24 without evidence of prior suppression to <400copies/mL or (B) Virologic Rebound: confirmed rebound in plasma HIV-1 RNA levels to >=400 copies/mL after prior confirmed suppression to <400 copies/mL; confirmed plasma HIV-1 RNA levels >0.5 log10 copies/mL above the nadir value, where nadir is the lowest HIV-1 value >=400 copies/mL.On-treatment Genotypic Resistance Population: all participants in the ITT-E Population with available on-treatment genotypic data, excluding participants who were not protocol-defined virologic failures.
Time Frame From Baseline up to Week 96/Early Withdrawal

Outcome Measure Data

Analysis Population Description
On-treatment Genotypic Resistance Population.
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Measure Participants 2 1 0 1
A23A/V
1
1.9%
0
0%
0
0%
S255N
1
1.9%
0
0%
0
0%
12. Secondary Outcome
Title Number of Participants With the Indicated Treatment-emergent Major Mutations of Other Classes Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance
Description For participants meeting one of the criteria for PDVF, plasma samples collected at the time point of virologic failure were tested to evaluate any potential genotypic and/or phenotypic evolution of resistance. PDVF was defined as (A) Virologic Non-response: a decrease in plasma HIV-1 RNA of <1 log10 copies/mL by Week 4, with subsequent confirmation, unless plasma HIV-1 RNA is <400 copies/mL; confirmed plasma HIV-1 RNA levels >=400 copies/mL on or after Week 24 without evidence of prior suppression to <400copies/mL or (B) Virologic Rebound: confirmed rebound in plasma HIV-1 RNA levels to >=400 copies/mL after prior confirmed suppression to <400 copies/mL; confirmed plasma HIV-1 RNA levels >0.5 log10 copies/mL above the nadir value, where nadir is the lowest HIV-1 value >=400 copies/mL.
Time Frame From Baseline up to Week 96/Early Withdrawal

Outcome Measure Data

Analysis Population Description
On-treatment Genotypic Resistance Population
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg QD. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg QD. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg QD. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Measure Participants 2 1 0 1
Number [Participants]
1
1.9%
0
0%
0
0%
13. Secondary Outcome
Title Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) at the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance
Description The FC in IC50 (50% inhibitory concentration) for DTG relative to wild-type virus was determined for virus isolated at Baseline and at the time of PDVF. Fold increase in DTG FC at the time of PDVF was derived as the PDVF FC/Baseline FC ratio. PDVF was defined as (A) Virologic Non-response: a decrease in plasma HIV-1 RNA of <1 log10 copies/mL by Week 4, with subsequent confirmation, unless plasma HIV-1 RNA is <400 copies/mL; confirmed plasma HIV-1 RNA levels >=400 copies/mL on or after Week 24 without evidence of prior suppression to <400copies/mL or (B) Virologic Rebound: confirmed rebound in plasma HIV-1 RNA levels to >=400 copies/mL after prior confirmed suppression to <400 copies/mL; confirmed plasma HIV-1 RNA levels >0.5 log10 copies/mL above the nadir value, where nadir is the lowest HIV-1 value >=400 copies/mL.On-treatment Phenotypic Resistance Population: all participants in the ITT-E Population with available on-treatment phenotypic data
Time Frame From Baseline up to Week 96/Early Withdrawal

Outcome Measure Data

Analysis Population Description
On-treatment Phenotypic Resistance Population
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Measure Participants 2 1 0 0
<1 fold
0
0%
1
2%
1-<2 fold
2
3.8%
0
0%
2-<4 fold
0
0%
0
0%
4-<8 fold
0
0%
0
0%
>=8 fold
0
0%
0
0%
14. Secondary Outcome
Title Plasma DTG Concentration
Description Blood samples for the determination of plasma DTG concentration were collected from the participants randomized to receive DTG, at the following time points: pre-dose and 2-4 hours post-dose at Weeks 2, Week 12, and Week 24. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. The Pharmacokinetic (PK) Summary Population is comprised of all participants who received DTG and underwent intensive PK sampling or limited PK sampling during the study and provided evaluable DTG PK parameters. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles).Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the PK Summary Population.
Time Frame Week 2, Week 12, and Week 24

Outcome Measure Data

Analysis Population Description
PK Summary Population.
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Measure Participants 48 46 46 0
Week 2, Pre-dose, n=46, 44, 43, 0
0.3580
(0.18321)
0.6779
(0.44085)
1.4044
(0.88041)
Week 2, 2-4 hours post-dose, n=31, 29, 29, 0
1.0121
(0.28125)
1.9716
(0.71890)
3.8414
(1.87405)
Week 12, Pre-dose, n= 46, 45, 44, 0
0.3648
(0.16791)
0.5759
(0.32645)
1.4169
(1.00152)
Week 12, 2-4 hours post-dose, n=48, 45, 45, 0
1.0374
(0.27517)
1.7907
(0.70953)
3.6056
(1.33862)
Week 24, Pre-dose, n=45, 44, 44, 0
0.3766
(0.23399)
0.6636
(0.50767)
1.4534
(0.94283)
Week 24, 2-4 hours post-dose, n=45, 45, 45, 0
1.0113
(0.34083)
1.9021
(0.79430)
3.5397
(1.36538)
15. Secondary Outcome
Title AUC(0-tau) of DTG
Description The area under the time concentration curve over the dosing interval (AUC[0-tau]) of DTG was determined using non-compartmental analysis based on intensive PK sampling at the following time points: pre-dose; 2, 3, 4, 8, and 24 hours post-dose at Week 2. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. Only those participants available at the specified time points were analyzed.
Time Frame Pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2

Outcome Measure Data

Analysis Population Description
PK Summary Population.
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg QD. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg QD. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Measure Participants 15 15 15 0
Geometric Mean (Geometric Coefficient of Variation) [Hours*µg/mL]
16.0
(40)
23.1
(48)
48.1
(40)
16. Secondary Outcome
Title Maximal Concentration (Cmax), Minimal Concentration (Cmin), and Concentration at the End of Dosing Interval (Ctau) of DTG
Description The Cmax, Cmax, and Ctau of DTG were determined using non-compartmental analysis based on intensive PK sampling at the following time points: pre-dose; 2, 3, 4, 8, and 24 hours post-dose at Week 2. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed.
Time Frame Pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2

Outcome Measure Data

Analysis Population Description
PK Summary Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title DTG 10 mg OD DTG 25 mg OD DTG 50 mg OD EFV 600 mg OD
Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.
Measure Participants 15 15 15 0
Cmax
1.10
(37)
1.71
(43)
3.40
(27)
Cmin
0.33
(64)
0.44
(68)
0.94
(74)
Ctau
0.37
(55)
0.45
(71)
1.05
(72)
17. Secondary Outcome
Title Pre-dose Concentration (C0) and C0 Avg of DTG
Description The plasma DTG C0 of DTG was determined using limited/sparse PK sampling at Week 2, Week 12, and Week 24. C0 avg was calculated at Week 24 as the mean of the C0 of DTG at Week 2, Week 12, and Week 24. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the PK Summary Population.
Time Frame Week 2, Week 12, and Week 24

Outcome Measure Data

Analysis Population Description
PK Summary Population.
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg QD. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg QD. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg QD. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Measure Participants 49 46 46 0
C0, Week 2, n=46, 44, 43, 0
0.31
(58)
0.57
(62)
1.20
(61)
C0, Week 12, n=46, 45, 44, 0
0.33
(49)
0.47
(77)
1.13
(95)
C0, Week 24, n=45, 44, 44, 0
0.33
(67)
0.57
(74)
1.20
(74)
C0 avg, n=48, 46, 46, 0
0.34
(49)
0.56
(61)
1.25
(55)
18. Secondary Outcome
Title Time to Maximal Drug Concentration (Tmax) of DTG
Description Tmax of DTG was determined using non-compartmental analysis based on intensive PK sampling at the following time points: pre-dose; 2, 3, 4, 8, and 24 hours post-dose at Week 2. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed.
Time Frame Pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2

Outcome Measure Data

Analysis Population Description
PK Summary Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Measure Participants 15 15 15 0
Median (Full Range) [Hours]
2.0
2.0
2.0
19. Secondary Outcome
Title Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters
Description Relationships between Week 2 plasma DTG PK parameters (AUC[0-tau] [area under the time concentration curve over the dosing interval], Cmax [maximal concentration], and Ctau [concentration at the end of the dosing interval]) and the change from Baseline in plasma HIV-1 RNA at Week 2 (calculated as the post-Baseline value minus the value at Baseline) was assessed using Pearson's correlation analyses. The Pearson's correlation coefficient is a measure of the correlation between plasma HIV-1 RNA and plasma DTG PK parameters and ranges from -1 to 1. A value of 0 indicates no statistical association; a value close to -1 or 1 indicates a higher association. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. PK/Pharmacodynamic (PD) Analysis Population: all participants with available PD measures (e.g., safety and/or efficacy data) and with evaluable DTG plasma concentration data considered suitable for investigation of relationship with the PD measures
Time Frame Week 2

Outcome Measure Data

Analysis Population Description
PK/PD Analysis Population.Only those participants available at the specified time points were analyzed.
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD Overall DTG
Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. All participants who received DTG in any DTG treatment group (DTG 10 mg QD, DTG 25 mg QD, and DTG 50 mg QD)
Measure Participants 15 15 15 0 45
AUC(0-tau)
0.426
-0.018
-0.258
-0.086
Cmax
0.452
-0.051
-0.150
-0.055
Ctau
0.273
-0.100
-0.263
-0.129
20. Secondary Outcome
Title Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters
Description Relationships between plasma DTG PK parameters (AUC[0-tau] [area under the time concentration curve over the dosing interval], Cmax [maximal concentration], C0avg [average pre-dose concentration], and Ctau [concentration at the end of the dosing interval]) and the change from Baseline in CD4+ cell counts at Week 96 (calculated as the post-Baseline value minus the value at Baseline) was assessed using Pearson's correlation analyses. The Pearson's correlation coefficient is a measure of the correlation between CD4+ cell counts and plasma DTG PK parameters and ranges from -1 to 1. A value of 0 indicates no statistical association; a value close to -1 or 1 indicates a higher association.Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed.Only those participants available at the specified time points were analyzed (represented by n=X in the category titles)
Time Frame Week 96

Outcome Measure Data

Analysis Population Description
PK/PD Analysis Population.
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD Overall DTG
Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. All participants who received DTG in any DTG treatment group (DTG 10 mg QD, DTG 25 mg QD, and DTG 50 mg QD)
Measure Participants 50 46 46 0 142
AUC(0-tau), n=13, 14, 15, 0
-0.100
0.379
0.008
-0.005
Cmax, n=13, 14, 15, 0
-0.047
0.332
0.234
0.037
C0avg, n=43, 40, 42, 0
-0.009
-0.013
0.206
-0.011
Ctau, n=13, 14, 15, 0
-0.289
0.299
-0.074
-0.055
21. Secondary Outcome
Title Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters
Description Relationships between log-transformed plasma DTG PK parameters (AUC[0-tau], Cmax, C0, C0avg, Ctau, and Cmin) and safety parameters (AE occurrence, maximum AE intensity, alanine aminotransferase [ALT], change from Baseline [CFB] in ALT, total bilirubin, CFB in total bilirubin, creatine kinase, CFB in creatine kinase, triglycerides, CFB in triglycerides, lipase, CFB in lipase, total cholesterol [TC], CFB in TC) was assessed using Pearson's correlation analyses. The Pearson's correlation coefficient is a measure of the correlation between safety parameters and plasma DTG PK parameters and ranges from -1 to 1. A value of 0 indicates no statistical association; a value close to -1 or 1 indicates a higher association. The presence of >=1 AE was used for AE occurrence. The most severe AE grade/intensity was used for maximum AE intensity. Maximum laboratory values per participant were used for safety parameters. CFB was calculated as the post-Baseline value minus the value at Baseline.
Time Frame Week 96

Outcome Measure Data

Analysis Population Description
PK/PD Analysis Population.Only those participants available at the specified time points were analyzed
Arm/Group Title Overall DTG
Arm/Group Description All participants who received DTG in any DTG treatment group (DTG 10 mg QD, DTG 25 mg QD, and DTG 50 mg QD)
Measure Participants 142
AUC(0-tau) versus AE occurrence, n=45
0.114
AUC(0-tau) versus maximum AE intensity, n=45
0.171
AUC(0-tau) versus ALT, n=45
-0.196
AUC(0-tau) versus CFB in ALT, n=45
-0.201
AUC(0-tau) versus total bilirubin, n=45
0.364
AUC(0-tau) versus CFB in total bilirubin, n=45
0.147
AUC(0-tau) versus creatine kinase, n=45
-0.168
AUC(0-tau) versus CFB in creatine kinase, n=45
-0.145
AUC(0-tau) vs Triglycerides, n=45
0.104
AUC(0-tau) versus CFB in triglycerides, n=45
0.216
AUC(0-tau) versus lipase, n=45
-0.066
AUC(0-tau) versus CFB in lipase, n=45
0.092
AUC(0-tau) versus total cholesterol, n=45
-0.097
AUC(0-tau) versus CFB in total cholesterol, n=45
-0.153
Cmax versus AE occurrence, n=45
0.061
Cmax versus maximum AE intensity, n=45
0.110
Cmax versus ALT, n=45
-0.135
Cmax versus CFB in ALT, n=45
-0.135
Cmax versus total bilirubin, n=45
0.265
Cmax versus CFB in total bilirubin, n=45
0.033
Cmax versus creatine kinase, n=45
-0.188
Cmax versus CFB in creatine kinase, n=45
-0.161
Cmax versus triglycerides, n=45
0.134
Cmax versus CFB in triglycerides, n=45
0.244
Cmax versus lipase, n=45
-0.034
Cmax versus CFB in lipase, n=45
0.115
Cmax versus total cholesterol, n=45
-0.101
Cmax versus CFB in total cholesterol, n=45
-0.192
C0 versus AE occurrence, n=133
-0.080
C0 versus maximum AE intensity, n=133
-0.003
C0 versus ALT, n=133
-0.196
C0 versus CFB in ALT, n=133
-0.237
C0 versus total bilirubin, n=133
0.298
C0 versus CFB in total bilirubin, n=133
0.120
C0 versus creatine kinase, n=133
-0.094
C0 versus CFB in creatine kinase, n=133
-0.093
C0 versus triglycerides, n=133
-0.058
C0 versus CFB in triglycerides, n=133
-0.012
C0 versus lipase, n=133
-0.187
C0 versus CFB in lipase, n=133
-0.137
C0 versus total cholesterol, n=133
-0.179
C0 versus CFB in total cholesterol, n=133
-0.125
C0avg versus AE occurrence, n=140
-0.028
C0avg versus maximum AE intensity, n=140
0.036
C0avg versus ALT, n=140
-0.166
C0avg versus CFB in ALT, n=140
-0.177
C0avg versus total bilirubin, n=140
0.319
C0avg versus CFB in total bilirubin, n=140
0.109
C0avg versus creatine kinase, n=140
-0.114
C0avg versus CFB in creatine kinase, n=140
-0.110
C0avg versus triglycerides, n=140
0.057
C0avg versus CFB in triglycerides, n=140
0.092
C0avg versus lipase, n=140
-0.164
C0avg versus CFB in lipase, n=140
-0.120
C0avg versus total cholesterol, n=140
-0.170
C0avg versus CFB in total cholesterol, n=140
-0.083
Ctau versus AE occurrence, n=45
0.190
Ctau versus maximum AE intensity, n=45
0.205
Ctau versus ALT, n=45
-0.281
Ctau versus CFB in ALT, n=45
-0.285
Ctau versus total bilirubin, n=45
0.446
Ctau versus CFB in total bilirubin, n=45
0.237
Ctau versus creatine kinase, n=45
-0.143
Ctau versus CFB in creatine kinase, n=45
-0.125
Ctau versus triglycerides, n=45
0.061
Ctau versus CFB in triglycerides, n=45
0.172
Ctau versus lipase, n=45
-0.131
Ctau versus CFB in lipase, n=45
0.056
Ctau versus total cholesterol, n=45
-0.039
Ctau versus CFB in total cholesterol, n=45
-0.108
Cmin versus AE occurrence, n=45
0.156
Cmin versus maximum AE intensity, n=45
0.193
Cmin versus ALT, n=45
-0.236
Cmin versus CFB in ALT, n=45
-0.253
Cmin versus total bilirubin, n=45
0.430
Cmin versus CFB in total bilirubin, n=45
0.171
Cmin versus creatine kinase, n=45
-0.132
Cmin versus CFB in creatine kinase, n=45
-0.124
Cmin versus triglycerides, n=45
-0.042
Cmin versus CFB in triglycerides, n=45
0.057
Cmin versus lipase, n=45
-0.135
Cmin versus CFB in lipase, n=45
0.032
Cmin versus total cholesterol, n=45
-0.194
Cmin versus CFB in total cholesterol, n=45
-0.208
22. Secondary Outcome
Title Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters
Description Logistic regressions were performed to examine the correlation between plasma DTG PK parameters (AUC[0-tau] [area under the time concentration curve over the dosing interval], Cmax [maximal concentration], Ctau [concentration at the end of the dosing interval], and C0avg [average pre-dose concentration]) on log scales and the presence of gastrointestinal system organ class AEs (abdominal pain, diarrhea, nausea, and vomiting) at Week 96. Data are presented as estimates from logistic regression, which is a measure of the association between AEs of special interest and plasma DTG PK parameters. A value of 0 indicates no statistical association; a large absolute value of the estimate indicates higher association. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. Results are presented for participants in any DTG group (overall DTG).Only those participants available at the specified time points were analyzed represented by n=X in the category titles
Time Frame Week 96

Outcome Measure Data

Analysis Population Description
PK/PD Analysis Population.
Arm/Group Title Overall DTG
Arm/Group Description All participants who received DTG in any DTG treatment group (DTG 10 mg OD, DTG 25 mg OD, and DTG 50 mg OD).
Measure Participants 142
Abdominal pain versus AUC(0-tau), n=45
-2.49
Abdominal pain versus Cmax, n=45
-2.98
Abdominal pain versus Ctau, n=45
-1.72
Abdominal pain versus C0avg, n=140
-0.41
Diarrhoea versus AUC(0-tau), n=45
-0.62
Diarrhoea versus Cmax, n=45
-0.98
Diarrhoea versus Ctau, n=45
-0.29
Diarrhoea versus C0avg, n=140
0.13
Nausea versus AUC(0-tau), n=45
-0.31
Nausea versus Cmax, n=45
-0.72
Nausea versus Ctau, n=45
0.03
Nausea versus C0avg, n=140
-0.32
Vomiting versus AUC(0-tau), n=45
-1.29
Vomiting versus Cmax, n=45
-1.61
Vomiting versus Ctau, n=45
-1.15
Vomiting versus C0avg, n=140
-0.89
23. Other Pre-specified Outcome
Title Change From Baseline in Cluster of Differentiation 8+ (CD8+) Cell Counts at the Indicated Time Points
Description Change from Baseline in CD8+ cell count data are not available; CD8+ data are only listed on a per-participant basis and were not summarized.
Time Frame Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96

Outcome Measure Data

Analysis Population Description
ITT-E Population
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Measure Participants 0 0 0 0

Adverse Events

Time Frame Serious adverse events (SAEs) and non-serious AEs were collected in the time period from Baseline up to end of study.
Adverse Event Reporting Description SAEs and AEs were collected in members of Safety Population, comprised of all participants who received at least one dose of study medication.
Arm/Group Title DTG 10mg QD DTG 25mg QD DTG 50mg QD EFV 600mg Open-label DTG 50 mg QD
Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. All DTG participants were switched to or continued DTG 50 mg with either ABC/3TC orally at 600 mg/300 mg (1 tablet) or TDF/FTC orally QD during the Open label phase
All Cause Mortality
DTG 10mg QD DTG 25mg QD DTG 50mg QD EFV 600mg Open-label DTG 50 mg QD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 2/53 (3.8%) 0/51 (0%) 0/51 (0%) 0/50 (0%) 2/138 (1.4%)
Serious Adverse Events
DTG 10mg QD DTG 25mg QD DTG 50mg QD EFV 600mg Open-label DTG 50 mg QD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 6/53 (11.3%) 4/51 (7.8%) 7/51 (13.7%) 7/50 (14%) 16/138 (11.6%)
Cardiac disorders
Acute myocardial infarction 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Myocardial infarction 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Gastrointestinal disorders
Constipation 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Flatulence 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Inguinal hernia 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Mallory-Weiss syndrome 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Nausea 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Upper gastrointestinal haemorrhage 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
General disorders
Pyrexia 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Systemic inflammatory response syndrome 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Hepatobiliary disorders
Cholelithiasis 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Infections and infestations
Pneumonia 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 1/138 (0.7%) 1
Abscess 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Appendicitis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Bronchitis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Diverticulitis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Epididymitis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Gastroenteritis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Herpes zoster 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Meningitis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Neurosyphilis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Pneumococcal sepsis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Pneumonia pneumococcal 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Primary syphilis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Pyelonephritis acute 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Injury, poisoning and procedural complications
Wrist fracture 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 1/138 (0.7%) 1
Foot fracture 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 2 0/50 (0%) 0 0/138 (0%) 0
Humerus fracture 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Injury 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Joint dislocation 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Multiple injuries 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Road traffic accident 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Spinal compression fracture 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Metabolism and nutrition disorders
Lipomatosis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Obesity 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Musculoskeletal and connective tissue disorders
Back pain 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 3
Osteoarthritis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 3
Tendonitis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Burkitt's lymphoma 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Nervous system disorders
Headache 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Hydrocephalus 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Seizure 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Product Issues
Device malfunction 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 1/138 (0.7%) 1
Psychiatric disorders
Anxiety 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Depression 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Suicide attempt 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Reproductive system and breast disorders
Dysmenorrhoea 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Vascular disorders
Phlebitis 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Other (Not Including Serious) Adverse Events
DTG 10mg QD DTG 25mg QD DTG 50mg QD EFV 600mg Open-label DTG 50 mg QD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 49/53 (92.5%) 46/51 (90.2%) 45/51 (88.2%) 46/50 (92%) 112/138 (81.2%)
Blood and lymphatic system disorders
Lymphadenopathy 2/53 (3.8%) 2 3/51 (5.9%) 3 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Neutropenia 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 1/138 (0.7%) 1
Iron deficiency anaemia 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Lymphadenitis 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Cardiac disorders
Sinus tachycardia 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 1/50 (2%) 1 0/138 (0%) 0
Tachycardia 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Aortic valve incompetence 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Arrhythmia 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Bradycardia 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Cardiomegaly 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Palpitations 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Ear and labyrinth disorders
Vertigo 2/53 (3.8%) 2 1/51 (2%) 1 2/51 (3.9%) 2 2/50 (4%) 2 0/138 (0%) 0
Tinnitus 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 2/138 (1.4%) 2
Ear pain 0/53 (0%) 0 2/51 (3.9%) 2 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Hypoacusis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 2/50 (4%) 2 0/138 (0%) 0
Cerumen impaction 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Ear congestion 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Ear pruritus 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Presbyacusis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Endocrine disorders
Hypogonadism 2/53 (3.8%) 2 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Hypothyroidism 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Goitre 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Eye disorders
Astigmatism 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Chalazion 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Dark circles under eyes 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Myopia 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Vision blurred 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Visual acuity reduced 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Vitreous floaters 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Gastrointestinal disorders
Diarrhoea 6/53 (11.3%) 6 9/51 (17.6%) 10 7/51 (13.7%) 8 5/50 (10%) 7 12/138 (8.7%) 14
Nausea 10/53 (18.9%) 10 8/51 (15.7%) 9 6/51 (11.8%) 6 7/50 (14%) 7 2/138 (1.4%) 2
Haemorrhoids 0/53 (0%) 0 0/51 (0%) 0 2/51 (3.9%) 2 2/50 (4%) 2 8/138 (5.8%) 10
Abdominal pain 3/53 (5.7%) 3 1/51 (2%) 1 2/51 (3.9%) 2 1/50 (2%) 1 3/138 (2.2%) 3
Dyspepsia 1/53 (1.9%) 1 2/51 (3.9%) 3 2/51 (3.9%) 2 2/50 (4%) 2 3/138 (2.2%) 3
Abdominal pain upper 4/53 (7.5%) 5 3/51 (5.9%) 3 1/51 (2%) 1 1/50 (2%) 1 0/138 (0%) 0
Gastrooesophageal reflux disease 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 2/50 (4%) 2 5/138 (3.6%) 5
Vomiting 3/53 (5.7%) 3 3/51 (5.9%) 3 0/51 (0%) 0 1/50 (2%) 1 1/138 (0.7%) 1
Toothache 2/53 (3.8%) 2 2/51 (3.9%) 2 1/51 (2%) 2 1/50 (2%) 1 1/138 (0.7%) 2
Gastritis 1/53 (1.9%) 1 1/51 (2%) 1 0/51 (0%) 0 1/50 (2%) 1 3/138 (2.2%) 3
Abdominal discomfort 2/53 (3.8%) 2 1/51 (2%) 1 1/51 (2%) 1 1/50 (2%) 1 0/138 (0%) 0
Constipation 2/53 (3.8%) 3 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 2/138 (1.4%) 2
Proctitis 1/53 (1.9%) 1 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 3/138 (2.2%) 4
Faeces soft 1/53 (1.9%) 1 0/51 (0%) 0 1/51 (2%) 1 2/50 (4%) 2 0/138 (0%) 0
Haematochezia 1/53 (1.9%) 1 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Anal fissure 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 2/138 (1.4%) 2
Anal fistula 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 2/138 (1.4%) 2
Anogenital dysplasia 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Aphthous ulcer 1/53 (1.9%) 4 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Epigastric discomfort 1/53 (1.9%) 1 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Flatulence 1/53 (1.9%) 1 1/51 (2%) 3 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Inguinal hernia 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Rectal haemorrhage 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 1/50 (2%) 1 0/138 (0%) 0
Abdominal distension 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Abdominal pain lower 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Anal pruritus 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Anal skin tags 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Anal sphincter hypertonia 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Anal ulcer 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Anorectal disorder 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Anorectal ulcer 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Change of bowel habit 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Chronic gastritis 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Dental caries 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Enteritis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 3
Enterocolitis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Food poisoning 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 2 0/138 (0%) 0
Gastrointestinal disorder 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Hiatus hernia 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Hypoaesthesia oral 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Intestinal polyp 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Leukoplakia oral 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Odynophagia 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Pancreatic atrophy 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Perianal erythema 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Rectal polyp 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Stomatitis 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Tongue discolouration 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Tongue disorder 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Umbilical hernia 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
General disorders
Pyrexia 5/53 (9.4%) 5 4/51 (7.8%) 4 1/51 (2%) 1 4/50 (8%) 5 6/138 (4.3%) 9
Fatigue 2/53 (3.8%) 2 4/51 (7.8%) 7 2/51 (3.9%) 2 6/50 (12%) 6 3/138 (2.2%) 4
Asthenia 4/53 (7.5%) 4 2/51 (3.9%) 3 1/51 (2%) 1 0/50 (0%) 0 3/138 (2.2%) 3
Influenza like illness 1/53 (1.9%) 1 0/51 (0%) 0 2/51 (3.9%) 2 1/50 (2%) 1 3/138 (2.2%) 3
Chest pain 1/53 (1.9%) 1 1/51 (2%) 1 0/51 (0%) 0 2/50 (4%) 2 2/138 (1.4%) 2
Malaise 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 1/50 (2%) 1 2/138 (1.4%) 2
Oedema peripheral 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 2/138 (1.4%) 2
Pain 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 1/138 (0.7%) 1
Adverse drug reaction 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Chest discomfort 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Drug intolerance 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Feeling drunk 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Feeling hot 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
General physical health deterioration 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Injection site pain 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Nodule 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Oedema 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Hepatobiliary disorders
Hypertransaminasaemia 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 1/50 (2%) 1 1/138 (0.7%) 1
Hepatic steatosis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 2/138 (1.4%) 2
Cholestasis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Immune system disorders
Seasonal allergy 1/53 (1.9%) 1 2/51 (3.9%) 2 1/51 (2%) 1 0/50 (0%) 0 2/138 (1.4%) 2
Allergy to arthropod sting 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Drug hypersensitivity 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 2 0/138 (0%) 0
Food allergy 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Hypersensitivity 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Multiple allergies 1/53 (1.9%) 2 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Infections and infestations
Viral upper respiratory tract infection 7/53 (13.2%) 10 7/51 (13.7%) 10 6/51 (11.8%) 10 5/50 (10%) 7 20/138 (14.5%) 27
Bronchitis 5/53 (9.4%) 7 2/51 (3.9%) 3 2/51 (3.9%) 3 5/50 (10%) 6 10/138 (7.2%) 14
Influenza 5/53 (9.4%) 5 5/51 (9.8%) 6 4/51 (7.8%) 4 3/50 (6%) 3 6/138 (4.3%) 9
Syphilis 1/53 (1.9%) 1 3/51 (5.9%) 3 1/51 (2%) 1 4/50 (8%) 4 12/138 (8.7%) 15
Respiratory tract infection 4/53 (7.5%) 6 1/51 (2%) 2 2/51 (3.9%) 3 3/50 (6%) 4 9/138 (6.5%) 13
Upper respiratory tract infection 2/53 (3.8%) 2 3/51 (5.9%) 4 6/51 (11.8%) 8 1/50 (2%) 1 7/138 (5.1%) 10
Sinusitis 2/53 (3.8%) 3 2/51 (3.9%) 3 3/51 (5.9%) 4 4/50 (8%) 6 6/138 (4.3%) 6
Pharyngitis 3/53 (5.7%) 3 3/51 (5.9%) 3 1/51 (2%) 1 2/50 (4%) 2 3/138 (2.2%) 3
Gastroenteritis 0/53 (0%) 0 1/51 (2%) 1 2/51 (3.9%) 2 1/50 (2%) 1 5/138 (3.6%) 5
Rhinitis 1/53 (1.9%) 1 0/51 (0%) 0 2/51 (3.9%) 2 0/50 (0%) 0 5/138 (3.6%) 7
Tonsillitis 3/53 (5.7%) 10 1/51 (2%) 1 0/51 (0%) 0 1/50 (2%) 2 3/138 (2.2%) 5
Oral herpes 4/53 (7.5%) 4 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 2/138 (1.4%) 2
Respiratory tract infection viral 3/53 (5.7%) 4 1/51 (2%) 4 0/51 (0%) 0 1/50 (2%) 1 2/138 (1.4%) 2
Folliculitis 0/53 (0%) 0 1/51 (2%) 1 1/51 (2%) 1 0/50 (0%) 0 4/138 (2.9%) 4
Herpes simplex 1/53 (1.9%) 1 0/51 (0%) 0 1/51 (2%) 1 1/50 (2%) 1 3/138 (2.2%) 3
Tooth abscess 2/53 (3.8%) 2 1/51 (2%) 1 1/51 (2%) 1 0/50 (0%) 0 2/138 (1.4%) 2
Tooth infection 0/53 (0%) 0 2/51 (3.9%) 3 1/51 (2%) 1 0/50 (0%) 0 3/138 (2.2%) 3
Urinary tract infection 1/53 (1.9%) 1 0/51 (0%) 0 2/51 (3.9%) 2 0/50 (0%) 0 3/138 (2.2%) 3
Viral infection 1/53 (1.9%) 1 3/51 (5.9%) 3 0/51 (0%) 0 1/50 (2%) 1 1/138 (0.7%) 3
Cellulitis 0/53 (0%) 0 1/51 (2%) 1 1/51 (2%) 1 2/50 (4%) 2 1/138 (0.7%) 1
Fungal skin infection 1/53 (1.9%) 1 1/51 (2%) 1 1/51 (2%) 2 1/50 (2%) 1 1/138 (0.7%) 1
Herpes zoster 1/53 (1.9%) 1 1/51 (2%) 1 1/51 (2%) 1 0/50 (0%) 0 2/138 (1.4%) 2
Acarodermatitis 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 3/138 (2.2%) 5
Chlamydial infection 1/53 (1.9%) 1 1/51 (2%) 1 0/51 (0%) 0 1/50 (2%) 1 1/138 (0.7%) 1
Conjunctivitis 0/53 (0%) 0 2/51 (3.9%) 2 1/51 (2%) 1 0/50 (0%) 0 1/138 (0.7%) 1
Ear infection 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 2/138 (1.4%) 2
Furuncle 1/53 (1.9%) 1 0/51 (0%) 0 2/51 (3.9%) 3 0/50 (0%) 0 1/138 (0.7%) 1
Gonorrhoea 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 1/50 (2%) 1 2/138 (1.4%) 2
Onychomycosis 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 1/50 (2%) 1 2/138 (1.4%) 2
Otitis media 3/53 (5.7%) 4 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Urethritis 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 2/138 (1.4%) 2
Gastroenteritis viral 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 1/50 (2%) 1 1/138 (0.7%) 1
Herpes virus infection 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 1/138 (0.7%) 1
Nasopharyngitis 1/53 (1.9%) 1 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 2
Pharyngitis streptococcal 0/53 (0%) 0 1/51 (2%) 1 1/51 (2%) 1 0/50 (0%) 0 1/138 (0.7%) 1
Tinea pedis 1/53 (1.9%) 1 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 1/138 (0.7%) 1
Amoebic dysentery 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 1/50 (2%) 1 0/138 (0%) 0
Angular cheilitis 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Bacteriuria 1/53 (1.9%) 1 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Body tinea 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Cystitis 1/53 (1.9%) 1 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Dermatophytosis 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Diverticulitis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 2/138 (1.4%) 3
Fungal infection 1/53 (1.9%) 1 1/51 (2%) 2 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Genital herpes 0/53 (0%) 0 0/51 (0%) 0 2/51 (3.9%) 2 0/50 (0%) 0 0/138 (0%) 0
Giardiasis 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 1/138 (0.7%) 1
Hepatitis C 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 1/138 (0.7%) 1
Laryngitis 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 1/138 (0.7%) 1
Molluscum contagiosum 0/53 (0%) 0 0/51 (0%) 0 2/51 (3.9%) 2 0/50 (0%) 0 0/138 (0%) 0
Otitis externa 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 2/138 (1.4%) 2
Papilloma viral infection 1/53 (1.9%) 1 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Shigella infection 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 2/138 (1.4%) 2
Staphylococcal infection 0/53 (0%) 0 1/51 (2%) 2 0/51 (0%) 0 1/50 (2%) 3 0/138 (0%) 0
Subcutaneous abscess 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 2/138 (1.4%) 2
Superinfection bacterial 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 1/138 (0.7%) 1
Vulvovaginal mycotic infection 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 2 0/138 (0%) 0
Acute hepatitis C 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Acute sinusitis 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Anal abscess 0/53 (0%) 0 1/51 (2%) 2 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Anal infection 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Anorectal infection 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Candida infection 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Endometritis 1/53 (1.9%) 2 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Enterocolitis viral 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Epididymitis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
External ear cellulitis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Febrile infection 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Gastritis viral 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Gastroenteritis shigella 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Genital herpes simplex 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Genital infection fungal 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Genitourinary chlamydia infection 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Gingivitis 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Helicobacter infection 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Impetigo 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Infection 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Joint abscess 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Lower respiratory tract infection 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Lymphogranuloma venereum 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Neurosyphilis 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Paronychia 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Periodontitis 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Pilonidal cyst 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Pneumonia 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Primary syphilis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Proctitis gonococcal 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Pulpitis dental 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Pyelonephritis acute 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Rash pustular 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Rubella 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Secondary syphilis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Sialoadenitis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Skin candida 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Staphylococcal skin infection 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Tinea cruris 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Tinea infection 1/53 (1.9%) 2 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Toxocariasis 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Urethritis gonococcal 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Urinary tract infection bacterial 1/53 (1.9%) 2 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Vaginal infection 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Viral pharyngitis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Vulvovaginal candidiasis 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Injury, poisoning and procedural complications
Ligament sprain 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 3/138 (2.2%) 5
Concussion 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 2/138 (1.4%) 2
Contusion 2/53 (3.8%) 2 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Laceration 0/53 (0%) 0 2/51 (3.9%) 2 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Limb injury 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Muscle strain 1/53 (1.9%) 1 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Procedural pain 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Anal injury 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Cervical vertebral fracture 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Clavicle fracture 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Epicondylitis 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Face injury 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Fall 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Foot fracture 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Joint dislocation 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Rib fracture 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Scrotal haematoma 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Stress fracture 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Tendon rupture 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Vaccination complication 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Wrist fracture 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Investigations
Blood creatine phosphokinase increased 0/53 (0%) 0 3/51 (5.9%) 3 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Blood cholesterol increased 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 1/50 (2%) 1 1/138 (0.7%) 1
Alanine aminotransferase increased 0/53 (0%) 0 1/51 (2%) 1 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Blood glucose increased 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Lipase increased 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 2/138 (1.4%) 2
Amylase increased 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Anal pap smear abnormal 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Bacterial test positive 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Blood creatinine increased 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Cardiac murmur 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Electrocardiogram repolarisation abnormality 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Liver function test increased 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Neutrophil count decreased 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Transaminases increased 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Urinary sediment present 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Weight decreased 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Weight increased 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Metabolism and nutrition disorders
Vitamin D deficiency 2/53 (3.8%) 2 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 4/138 (2.9%) 4
Hyperglycaemia 2/53 (3.8%) 2 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 3/138 (2.2%) 3
Hyperlipidaemia 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 2 1/50 (2%) 1 1/138 (0.7%) 1
Decreased appetite 0/53 (0%) 0 1/51 (2%) 1 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Gout 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 2/138 (1.4%) 2
Hypercholesterolaemia 0/53 (0%) 0 2/51 (3.9%) 4 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Hyperinsulinaemia 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 2/138 (1.4%) 2
Diabetes mellitus 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Fat redistribution 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Fluid retention 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Hypertriglyceridaemia 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Hyponatraemia 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Type 2 diabetes mellitus 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Musculoskeletal and connective tissue disorders
Back pain 3/53 (5.7%) 4 2/51 (3.9%) 2 2/51 (3.9%) 2 4/50 (8%) 5 10/138 (7.2%) 10
Arthralgia 1/53 (1.9%) 1 3/51 (5.9%) 3 2/51 (3.9%) 2 1/50 (2%) 1 5/138 (3.6%) 5
Musculoskeletal pain 1/53 (1.9%) 1 2/51 (3.9%) 2 3/51 (5.9%) 3 0/50 (0%) 0 1/138 (0.7%) 1
Myalgia 2/53 (3.8%) 2 0/51 (0%) 0 2/51 (3.9%) 2 1/50 (2%) 1 2/138 (1.4%) 2
Muscle spasms 0/53 (0%) 0 4/51 (7.8%) 5 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Exostosis 1/53 (1.9%) 1 0/51 (0%) 0 2/51 (3.9%) 2 0/50 (0%) 0 1/138 (0.7%) 1
Pain in extremity 0/53 (0%) 0 2/51 (3.9%) 2 1/51 (2%) 1 0/50 (0%) 0 1/138 (0.7%) 1
Tendonitis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 4/138 (2.9%) 6
Arthritis 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 1/138 (0.7%) 1
Facet joint syndrome 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Osteopenia 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 1/138 (0.7%) 1
Plantar fasciitis 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 1/138 (0.7%) 1
Ankle impingement 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Chondropathy 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Fistula 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 3 0/138 (0%) 0
Joint stiffness 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Muscle contracture 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Muscle haemorrhage 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Muscular weakness 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Musculoskeletal chest pain 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Musculoskeletal discomfort 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Musculoskeletal stiffness 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Myosclerosis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Neck pain 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Osteoarthritis 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Patellofemoral pain syndrome 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Rheumatoid arthritis 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Rotator cuff syndrome 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Synovitis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Temporomandibular joint syndrome 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts 2/53 (3.8%) 4 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 2/138 (1.4%) 2
Melanocytic naevus 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 2/138 (1.4%) 2
Infected naevus 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Papilloma 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Prostatic adenoma 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Skin papilloma 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Nervous system disorders
Headache 7/53 (13.2%) 9 6/51 (11.8%) 10 8/51 (15.7%) 12 3/50 (6%) 5 8/138 (5.8%) 10
Dizziness 2/53 (3.8%) 2 3/51 (5.9%) 4 3/51 (5.9%) 3 11/50 (22%) 13 2/138 (1.4%) 2
Paraesthesia 3/53 (5.7%) 3 0/51 (0%) 0 0/51 (0%) 0 2/50 (4%) 2 3/138 (2.2%) 3
Somnolence 2/53 (3.8%) 2 1/51 (2%) 1 1/51 (2%) 1 2/50 (4%) 2 0/138 (0%) 0
Dysgeusia 2/53 (3.8%) 2 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Memory impairment 1/53 (1.9%) 1 0/51 (0%) 0 1/51 (2%) 2 1/50 (2%) 1 0/138 (0%) 0
Sciatica 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 2/138 (1.4%) 3
Hypoaesthesia 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Poor quality sleep 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Restless legs syndrome 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 2/50 (4%) 2 0/138 (0%) 0
Syncope 1/53 (1.9%) 1 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Ageusia 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Anosmia 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Cervical radiculopathy 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Cluster headache 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Cognitive disorder 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Hyperaesthesia 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Hypertonia 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Migraine 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Neuropathy peripheral 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Post herpetic neuralgia 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Presyncope 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Sinus headache 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Tongue biting 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Tremor 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Trigeminal neuralgia 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Visual field defect 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Psychiatric disorders
Insomnia 0/53 (0%) 0 7/51 (13.7%) 7 6/51 (11.8%) 6 6/50 (12%) 6 5/138 (3.6%) 5
Depression 3/53 (5.7%) 3 6/51 (11.8%) 6 2/51 (3.9%) 3 5/50 (10%) 5 6/138 (4.3%) 6
Anxiety 1/53 (1.9%) 2 2/51 (3.9%) 2 2/51 (3.9%) 2 3/50 (6%) 3 4/138 (2.9%) 4
Abnormal dreams 1/53 (1.9%) 1 2/51 (3.9%) 2 0/51 (0%) 0 3/50 (6%) 3 0/138 (0%) 0
Nightmare 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 4/50 (8%) 4 0/138 (0%) 0
Stress 0/53 (0%) 0 1/51 (2%) 1 2/51 (3.9%) 2 0/50 (0%) 0 1/138 (0.7%) 1
Acute stress disorder 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Loss of libido 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Sleep disorder 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Affect lability 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Anxiety disorder 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Bulimia nervosa 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Disorientation 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Hallucination 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Libido increased 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Listless 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Mental disorder 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Panic attack 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 2 0/138 (0%) 0
Post-traumatic stress disorder 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Substance use disorder 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Renal and urinary disorders
Dysuria 1/53 (1.9%) 1 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 3/138 (2.2%) 4
Proteinuria 0/53 (0%) 0 2/51 (3.9%) 2 1/51 (2%) 1 0/50 (0%) 0 2/138 (1.4%) 2
Nephrolithiasis 2/53 (3.8%) 2 1/51 (2%) 1 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Haematuria 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 1/50 (2%) 1 1/138 (0.7%) 1
Pollakiuria 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 2/138 (1.4%) 2
Leukocyturia 1/53 (1.9%) 1 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Acute kidney injury 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Chronic kidney disease 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Micturition urgency 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Urethral discharge 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Urethritis noninfective 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Urinary hesitation 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Reproductive system and breast disorders
Erectile dysfunction 1/53 (1.9%) 1 0/51 (0%) 0 2/51 (3.9%) 2 1/50 (2%) 1 3/138 (2.2%) 3
Genital lesion 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 1/138 (0.7%) 1
Ovarian cyst 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 1/138 (0.7%) 1
Prostatitis 1/53 (1.9%) 1 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Breast discomfort 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Breast mass 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Cervical dysplasia 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Gynaecomastia 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Penile discharge 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Peyronie's disease 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Respiratory, thoracic and mediastinal disorders
Cough 5/53 (9.4%) 5 4/51 (7.8%) 4 6/51 (11.8%) 8 2/50 (4%) 2 10/138 (7.2%) 12
Oropharyngeal pain 3/53 (5.7%) 3 0/51 (0%) 0 3/51 (5.9%) 3 1/50 (2%) 1 5/138 (3.6%) 5
Asthma 1/53 (1.9%) 1 2/51 (3.9%) 3 1/51 (2%) 1 0/50 (0%) 0 3/138 (2.2%) 3
Sinus congestion 0/53 (0%) 0 1/51 (2%) 1 2/51 (3.9%) 2 2/50 (4%) 2 1/138 (0.7%) 1
Dyspnoea 0/53 (0%) 0 2/51 (3.9%) 2 1/51 (2%) 1 0/50 (0%) 0 2/138 (1.4%) 5
Rhinitis allergic 0/53 (0%) 0 1/51 (2%) 2 1/51 (2%) 1 1/50 (2%) 2 1/138 (0.7%) 1
Lung disorder 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 2/138 (1.4%) 3
Respiratory disorder 0/53 (0%) 0 1/51 (2%) 1 1/51 (2%) 1 1/50 (2%) 1 0/138 (0%) 0
Rhinorrhoea 0/53 (0%) 0 0/51 (0%) 0 2/51 (3.9%) 2 0/50 (0%) 0 0/138 (0%) 0
Asthmatic crisis 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Bronchitis chronic 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Bronchopneumopathy 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Dysphonia 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Hyperventilation 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Lower respiratory tract congestion 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Nasal congestion 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Pharyngeal disorder 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Respiratory tract congestion 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Sleep apnoea syndrome 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Snoring 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Upper respiratory tract congestion 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Upper-airway cough syndrome 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Skin and subcutaneous tissue disorders
Rash 5/53 (9.4%) 6 3/51 (5.9%) 3 2/51 (3.9%) 2 6/50 (12%) 6 2/138 (1.4%) 2
Pruritus 2/53 (3.8%) 3 0/51 (0%) 0 1/51 (2%) 1 3/50 (6%) 3 3/138 (2.2%) 3
Dermatitis 0/53 (0%) 0 3/51 (5.9%) 3 1/51 (2%) 1 1/50 (2%) 1 1/138 (0.7%) 1
Alopecia 2/53 (3.8%) 2 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 1/138 (0.7%) 1
Eczema 1/53 (1.9%) 1 1/51 (2%) 1 1/51 (2%) 1 1/50 (2%) 1 0/138 (0%) 0
Night sweats 1/53 (1.9%) 1 1/51 (2%) 1 2/51 (3.9%) 2 0/50 (0%) 0 0/138 (0%) 0
Urticaria 1/53 (1.9%) 1 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 2/138 (1.4%) 2
Erythema 0/53 (0%) 0 1/51 (2%) 1 1/51 (2%) 2 0/50 (0%) 0 1/138 (0.7%) 1
Hyperhidrosis 1/53 (1.9%) 1 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 4
Photosensitivity reaction 0/53 (0%) 0 0/51 (0%) 0 2/51 (3.9%) 2 1/50 (2%) 1 0/138 (0%) 0
Dry skin 1/53 (1.9%) 1 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Hyperkeratosis 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 1/138 (0.7%) 1
Prurigo 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 2
Seborrhoeic dermatitis 1/53 (1.9%) 2 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Skin hyperpigmentation 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Actinic keratosis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Blister 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Dermal cyst 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Hand dermatitis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Intertrigo 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Lipoatrophy 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Miliaria 1/53 (1.9%) 1 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Palmar erythema 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Pigmentation disorder 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Pruritus generalised 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Psoriasis 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Rash macular 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Rash maculo-papular 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Rash papular 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Rash pruritic 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Skin erosion 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Skin lesion 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Solar dermatitis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Toxic skin eruption 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Vascular disorders
Hypertension 0/53 (0%) 0 2/51 (3.9%) 2 0/51 (0%) 0 2/50 (4%) 2 2/138 (1.4%) 2
Aortic arteriosclerosis 0/53 (0%) 0 0/51 (0%) 0 1/51 (2%) 1 0/50 (0%) 0 0/138 (0%) 0
Arterial fibrosis 0/53 (0%) 0 1/51 (2%) 1 0/51 (0%) 0 0/50 (0%) 0 0/138 (0%) 0
Hot flush 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Peripheral coldness 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 1/50 (2%) 1 0/138 (0%) 0
Peripheral venous disease 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1
Phlebitis 0/53 (0%) 0 0/51 (0%) 0 0/51 (0%) 0 0/50 (0%) 0 1/138 (0.7%) 1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

Name/Title GSK Response Center
Organization ViiV Healthcare
Phone 866-435-7343
Email
Responsible Party:
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT00951015
Other Study ID Numbers:
  • 112276
First Posted:
Aug 3, 2009
Last Update Posted:
Jan 16, 2018
Last Verified:
Apr 1, 2017