RANIA: Evaluation of Renal Function, Efficacy, and Safety When Switching From Tenofovir/Emtricitabine Plus a Protease Inhibitor/Ritonavir, to a Combination of Raltegravir (MK-0518) Plus Nevirapine Plus Lamivudine in HIV-1 Participants With Suppressed Viremia and Impaired Renal Function (MK-0518-284)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02116660
• Collaborator: (none)
• Enrollment: 11
• Arms: 2
• Actual Duration (Months): 34.2

Study Details

Study Description

Brief Summary

To evaluate changes in renal function, efficacy, and safety when switching from a combination of tenofovir/emtricitabine (TDF/FTC) plus a protease inhibitor/ritonavir (PI/r) to a combination of raltegravir (MK-0518) plus nevirapine plus lamivudine in human immunodeficiency virus (HIV)-1 infected participants with suppressed viremia and impaired renal function.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Raltegravir (MK-0518); Drug: Nevirapine; Drug: Lamivudine; Drug: Tenofovir; Drug: Emtricitabine; Drug: Lopinavir; Drug: Ritonavir; Drug: Atazanavir; Drug: Darunavir	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Switching From Regimens Consisting of a RTV-Boosted Protease Inhibitor Plus TDF/FTC to a Combination of Raltegravir Plus Nevirapine and Lamivudine in HIV Patients With Suppressed Viremia and Impaired Renal Function (RANIA Study) (Pilot Study) Protocol MK-0518-284-03
• Actual Study Start Date: Sep 3, 2014
• Actual Primary Completion Date: Jul 10, 2017
• Actual Study Completion Date: Jul 10, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Raltegravir plus Nevirapine plus Lamivudine Raltegravir 400 mg oral twice daily for 96 weeks; plus nevirapine 200 mg oral once daily for 14 days followed by nevirapine 200 mg oral twice daily, plus lamivudine 150 mg oral twice daily for 96 weeks	Drug: Raltegravir (MK-0518); Raltegravir (MK-0518) 400 mg tablets; Drug: Nevirapine; Nevirapine (NVP) 200 mg tablets; Drug: Lamivudine; Lamivudine (3TC) 150 mg tablets
Active Comparator: Protease Inhibitor/Ritonavir plus tenofovir/emtricitabine Tenofovir/emtricitabine 300/200 mg oral once daily plus 1) lopinavir/ritonavir 400/100 mg oral twice daily or 800/200 mg oral once daily, or 2) atazanavir/ritonavir 300/100 mg oral once daily, or 3) darunavir/ritonavir 800/100 mg oral once daily or 600/100 mg oral twice daily	Drug: Tenofovir; Tenofovir disoproxil fumarate (TDF) 300 mg tablets; Drug: Emtricitabine; Emtricitabine (FTC) 200 mg tablets; Drug: Lopinavir; Lopinavir (LPV) 200 mg tablets; Drug: Ritonavir; Ritonavir (r) 100 mg tablets; Drug: Atazanavir; Atazanavir (ATV) 300 mg tablets; Drug: Darunavir; Darunavir (DAR) 400 mg tablets

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) [Baseline and Week 48]

   Glomerular Filtration Rate (eGFR) was estimated from the Modification of Diet in Renal Disease (MDRD)-6 equation. The MDRD-6 equation = 198 × [serum creatinine(mg/dL)]^-0.858 × [age]-0.167 × [0.822 if patient is female] × [1.178 if patient is black] × [serum urea nitrogen concentration (mg/dL)]^-0.293 × [urine urea nitrogen excretion (g/d)]^0.249.

Secondary Outcome Measures

1. Percentage of Participants With Suppressed Viremia (<50 Copies/mL HIV-1 Ribonucleic Acid [RNA]) at Week 48 [Week 48]

   Plasma was to be collected at Week 48 in order to quantify HIV-1 RNA. and identify the percentage of participants with <50 copies/mL HIV-1 RNA.

2. Percentage of Participants With Suppressed Viremia (<50 Copies/mL HIV-1 RNA) at Week 96 [Week 96]

   Plasma was to be collected at Week 96 in order to quantify HIV-1 RNA. and identify the percentage of participants with <50 copies/mL HIV-1 RNA.

3. Percentage of Participants With Decline in Renal Function at Week 48 [Week 48]

   Decline in renal function was to be assessed by evaluating MDRD-6, creatinine clearance and serum phosphate.

4. Percentage of Participants With Virologic Failure (HIV-1 RNA > 50 Copies/mL) [Up to Week 96]

   Plasma was to be collected up to Week 96 in order to quantify HIV-1 RNA, and identify the percentage of participants with >50 copies/mL HIV-1 RNA.

5. Change From Baseline of HIV-RNA Absolute Values [Baseline and Week 96]

   Plasma was to be collected at baseline and Week 96 in order to determine the change from baseline in HIV-1 RNA.

6. Percentage of Participants With Mutations Associated With Resistance to NRTIs, NNRTIs, INI, at Virological Failure. [Up to Week 96]

   Participants were to be identified with mutations associated with Nucleoside/ Nucleotide Reverse Transcriptase Inhibitors (NRTIs), Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs), and Integrase Inhibitor (INI). Virological failure is defined as 2 consecutive plasma HIV-1 RNA >200 copies/mL at least two weeks apart while on previous or current ARV therapy.

7. Change From Baseline in Absolute CD4+ T-lymphocyte Count [Baseline and Week 96]

   Cluster of Differentiation 4 + (CD4+) T-lymphocyte cell counts were to be determined at baseline and Week 96, in order to determine the change from baseline.

8. Percentage of Participants With Altered Liver Enzymes and Lipid Profile [Up to Week 96]

   Values of liver enzymes and lipids were to be determined from laboratory tests, in order to identify the percentage of participants classified with altered values.

9. Percentage of Participants With Altered Values of Tubular Kidney Injury Markers. [Up to Week 96]

   Values of tubular kidney injury markers. were to be determined, in order to identify the percentage of participants classified with altered values.

10. Percentage of Participants Having Changes From Baseline in Metabolic Bone Markers [Baseline and up to Week 96]

    Changes from baseline in metabolic bone markers, serum Bone Specific Alkaline Phosphatase (s-BSAP) and C-telopeptides of type 1 Collagen (s-CTx), were to be determined, in order to classify the percentage of participants with changes.

11. Area Under the Concentration Time Curve From Time 0 the Last Measurement Time t (AUC0-t) for Raltegravir and Nevirapine [Week 12: Fasted state (0 h) and 1, 2, 3, 6 and 12 h post-dose]

    Blood samples were to be collected in Week 12 in order to use the trapezoidal method to determine the AUC0-t of Raltegravir and Nevirapine

12. Trough Concentration (Ctrough) for Raltegravir and Nevirapine [Weeks 12 and 48: at the end of dosing interval at 12 h]

    Blood samples were to be collected in Weeks 12 and 48 in order to use the trapezoidal method to determine the Ctrough, the lowest concentration reached by the drug before the next dose is administered, of Raltegravir and Nevirapine.

13. Percentage of Participants With Genotypic Resistance at Virologic Failure. [Up to Week 96]

    Genotypic resistance measures the presence of particular HIV-1 mutations that give rise to drug resistance. Virological failure is defined as 2 consecutive plasma HIV-1 RNA >200 copies/mL at least two weeks apart while on previous or current ARV therapy.

14. Percentage of Participants With Adherence to Study Therapy [Up to Week 96]

    An Adherence Questionnaire was to be given in order to determine the percentage of participants who adhered to study therapy.

15. Change From Baseline in Bone Disease Risk Assessment [Baseline and week 96]

    Bone disease risk assessment was to be based on a Fracture Risk Assessment Tool (FRAX®) score in participants > 40 years old, and the change from baseline determined.

16. Change From Baseline in the VACS Index [Baseline and week 96]

    The Veterans Aging Cohort Risk Index (VACS Index) combines various clinical biomarkers into a cumulative index weighted according to the risk of all-cause mortality.

17. Percentage of Participants Experiencing a Decline of Renal Function [Up to Week 96]

    Decline in renal function was to be assessed by evaluating MDRD-6, creatinine clearance and serum phosphate.

18. Change From Baseline in eGFR at Week 96 [Baseline and Week 96]

    Glomerular Filtration Rate (eGFR) was estimated from the Modification of Diet in Renal Disease (MDRD)-6 equation. The MDRD-6 equation = 198 × [serum creatinine(mg/dL)]^-0.858 × [age]-0.167 × [0.822 if patient is female] × [1.178 if patient is black] × [serum urea nitrogen concentration (mg/dL)]^-0.293 × [urine urea nitrogen excretion (g/d)]^0.249.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male, or non-pregnant, non-breastfeeding female

• No previous history of virological failure

• No previous exposure to non-nucleoside reverse transcriptase inhibitors or integrase inhibitors

• No previous history of intolerance to lamivudine

• At least 2 documented plasma HIV-1 RNA <50 copies/mL and no HIV-1 >50 copies/mL in the 12 months before screening

• Receiving the same protease inhibitor/ritonavir plus tenofovir/emtricitabine combination for at least the 6 months before screening

• Has no major International Antiviral Society (IAS)-USA mutations on genotype testing performed before starting antiretroviral treatment

• Sexually-active participants and their partners of child-bearing potential agree to use a medically acceptable method of contraception from 2 weeks before Day 1 and for at least 6 months after the last dose of study drug (postmenopausal women are not required to use contraception; sexually-active male participants with a female partner of child-bearing potential must provide written informed consent to information regarding any pregnancy)

Exclusion Criteria:

• Positive for hepatitis B surface antigen (HBsAg+) or anticipated need for hepatitis C virus treatment

• Liver cirrhosis

• Has a history of diabetes mellitus, defined as initiation of antidiabetic treatment or verification of diabetes in a case report form

• Has any cancer, excluding stable Kaposi Sarcoma

• Allergy or sensitivity to the investigational product or excipients

• Female participant who is nursing

• Female participant who is pregnant or intends to become pregnant

• Has an active Acquired Immunodeficiency Syndrome (AIDS)-defining event except stable Kaposi Sarcoma or HIV Wasting Syndrome

• Received any investigational drug within 30 days before screening

• Participated in any other clinical trial within 30 days before signing informed consent for the current trial

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 16, 2015

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT02116660
• Other Study ID Numbers: 0518-284; 2013-001637-40; MK-0518-284
• First Posted: Apr 17, 2014
• Last Update Posted: Apr 8, 2019
• Last Verified: Apr 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Viremia; Renal Insufficiency; Ritonavir; Lopinavir; Atazanavir Sulfate; Darunavir; Tenofovir; Lamivudine; Emtricitabine; Raltegravir Potassium; Nevirapine

Study Results

Participant Flow

Recruitment Details	Human immunodeficiency virus (HIV) infected adults with stable suppressed HIV-1 ribonucleic acid (RNA) from at least 12 months prior to the screening visit, and with a current stable anti-retroviral (ARV) regimen were enrolled in this trial.

Arm/Group Title	Raltegravir Plus Nevirapine Plus Lamivudine	Protease Inhibitor/Ritonavir Plus Tenofovir/Emtricitabine
Arm/Group Description	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks	Tenofovir/emtricitabine 300/200 mg orally once daily plus 1) lopinavir/ritonavir 400/100 mg orally twice daily or 800/200 mg orally once daily, or 2) atazanavir/ritonavir 300/100 mg orally once daily, or 3) darunavir/ritonavir 800/100 mg orally once daily or 600/100 mg orally twice daily
Period Title: Overall Study
STARTED	6	5
COMPLETED	4	1
NOT COMPLETED	2	4

Baseline Characteristics

Arm/Group Title	Raltegravir Plus Nevirapine Plus Lamivudine	Protease Inhibitor/Ritonavir Plus Tenofovir/Emtricitabine	Total
Arm/Group Description	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks	Tenofovir/emtricitabine 300/200 mg orally once daily plus 1) lopinavir/ritonavir 400/100 mg orally twice daily or 800/200 mg orally once daily, or 2) atazanavir/ritonavir 300/100 mg orally once daily, or 3) darunavir/ritonavir 800/100 mg orally once daily or 600/100 mg orally twice daily	Total of all reporting groups
Overall Participants	6	5	11
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	49.83 (6.21)	54.00 (5.92)	51.7 (6.2)
Sex: Female, Male (Count of Participants)
Female	2 33.3%	2 40%	4 36.4%
Male	4 66.7%	3 60%	7 63.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	6 100%	5 100%	11 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 20%	1 9.1%
White	6 100%	4 80%	10 90.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Estimated Glomerular Filtration Rate (eGFR) (mL/min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL/min]	87.5 (7.32)	87.7 (6.52)	87.62 (6.54)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Description	Glomerular Filtration Rate (eGFR) was estimated from the Modification of Diet in Renal Disease (MDRD)-6 equation. The MDRD-6 equation = 198 × [serum creatinine(mg/dL)]^-0.858 × [age]-0.167 × [0.822 if patient is female] × [1.178 if patient is black] × [serum urea nitrogen concentration (mg/dL)]^-0.293 × [urine urea nitrogen excretion (g/d)]^0.249.
Time Frame	Baseline and Week 48

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study medications and who had both a baseline assessment, and at least one post-baseline assessment.

Arm/Group Title	Raltegravir Plus Nevirapine Plus Lamivudine	Protease Inhibitor/Ritonavir Plus Tenofovir/Emtricitabine
Arm/Group Description	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks	Tenofovir/emtricitabine 300/200 mg orally once daily plus 1) lopinavir/ritonavir 400/100 mg orally twice daily or 800/200 mg orally once daily, or 2) atazanavir/ritonavir 300/100 mg orally once daily, or 3) darunavir/ritonavir 800/100 mg orally once daily or 600/100 mg orally twice daily
Measure Participants	5	4
Mean (Standard Deviation) [mL/min]	-1.1 (4.65)	-5.5 (11.78)

2. Secondary Outcome

Title	Percentage of Participants With Suppressed Viremia (<50 Copies/mL HIV-1 Ribonucleic Acid [RNA]) at Week 48
Description	Plasma was to be collected at Week 48 in order to quantify HIV-1 RNA. and identify the percentage of participants with <50 copies/mL HIV-1 RNA.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Due to poor enrollment the study was terminated early; therefore data for secondary outcome measures were not collected, and were not analyzed.

Arm/Group Title	Raltegravir Plus Nevirapine Plus Lamivudine	Protease Inhibitor/Ritonavir Plus Tenofovir/Emtricitabine
Arm/Group Description	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks	Tenofovir/emtricitabine 300/200 mg orally once daily plus 1) lopinavir/ritonavir 400/100 mg orally twice daily or 800/200 mg orally once daily, or 2) atazanavir/ritonavir 300/100 mg orally once daily, or 3) darunavir/ritonavir 800/100 mg orally once daily or 600/100 mg orally twice daily
Measure Participants	0	0

3. Secondary Outcome

Title	Percentage of Participants With Suppressed Viremia (<50 Copies/mL HIV-1 RNA) at Week 96
Description	Plasma was to be collected at Week 96 in order to quantify HIV-1 RNA. and identify the percentage of participants with <50 copies/mL HIV-1 RNA.
Time Frame	Week 96

Outcome Measure Data

Analysis Population Description

Due to poor enrollment the study was terminated early; therefore data for secondary outcome measures were not collected, and were not analyzed.

Arm/Group Title	Raltegravir Plus Nevirapine Plus Lamivudine	Protease Inhibitor/Ritonavir Plus Tenofovir/Emtricitabine
Arm/Group Description	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks	Tenofovir/emtricitabine 300/200 mg orally once daily plus 1) lopinavir/ritonavir 400/100 mg orally twice daily or 800/200 mg orally once daily, or 2) atazanavir/ritonavir 300/100 mg orally once daily, or 3) darunavir/ritonavir 800/100 mg orally once daily or 600/100 mg orally twice daily
Measure Participants	0	0

4. Secondary Outcome

Title	Percentage of Participants With Decline in Renal Function at Week 48
Description	Decline in renal function was to be assessed by evaluating MDRD-6, creatinine clearance and serum phosphate.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Due to poor enrollment the study was terminated early; therefore data for secondary outcome measures were not collected, and were not analyzed.

Arm/Group Title	Raltegravir Plus Nevirapine Plus Lamivudine	Protease Inhibitor/Ritonavir Plus Tenofovir/Emtricitabine
Arm/Group Description	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks	Tenofovir/emtricitabine 300/200 mg orally once daily plus 1) lopinavir/ritonavir 400/100 mg orally twice daily or 800/200 mg orally once daily, or 2) atazanavir/ritonavir 300/100 mg orally once daily, or 3) darunavir/ritonavir 800/100 mg orally once daily or 600/100 mg orally twice daily
Measure Participants	0	0

5. Secondary Outcome

Title	Percentage of Participants With Virologic Failure (HIV-1 RNA > 50 Copies/mL)
Description	Plasma was to be collected up to Week 96 in order to quantify HIV-1 RNA, and identify the percentage of participants with >50 copies/mL HIV-1 RNA.
Time Frame	Up to Week 96

Outcome Measure Data

Analysis Population Description

Due to poor enrollment the study was terminated early; therefore data for secondary outcome measures were not collected, and were not analyzed.

Arm/Group Title	Raltegravir Plus Nevirapine Plus Lamivudine	Protease Inhibitor/Ritonavir Plus Tenofovir/Emtricitabine
Arm/Group Description	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks	Tenofovir/emtricitabine 300/200 mg orally once daily plus 1) lopinavir/ritonavir 400/100 mg orally twice daily or 800/200 mg orally once daily, or 2) atazanavir/ritonavir 300/100 mg orally once daily, or 3) darunavir/ritonavir 800/100 mg orally once daily or 600/100 mg orally twice daily
Measure Participants	0	0

6. Secondary Outcome

Title	Change From Baseline of HIV-RNA Absolute Values
Description	Plasma was to be collected at baseline and Week 96 in order to determine the change from baseline in HIV-1 RNA.
Time Frame	Baseline and Week 96

Outcome Measure Data

Analysis Population Description

Due to poor enrollment the study was terminated early; therefore data for secondary outcome measures were not collected, and were not analyzed.

Arm/Group Title	Raltegravir Plus Nevirapine Plus Lamivudine	Protease Inhibitor/Ritonavir Plus Tenofovir/Emtricitabine
Arm/Group Description	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks	Tenofovir/emtricitabine 300/200 mg orally once daily plus 1) lopinavir/ritonavir 400/100 mg orally twice daily or 800/200 mg orally once daily, or 2) atazanavir/ritonavir 300/100 mg orally once daily, or 3) darunavir/ritonavir 800/100 mg orally once daily or 600/100 mg orally twice daily
Measure Participants	0	0

7. Secondary Outcome

Title	Percentage of Participants With Mutations Associated With Resistance to NRTIs, NNRTIs, INI, at Virological Failure.
Description	Participants were to be identified with mutations associated with Nucleoside/ Nucleotide Reverse Transcriptase Inhibitors (NRTIs), Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs), and Integrase Inhibitor (INI). Virological failure is defined as 2 consecutive plasma HIV-1 RNA >200 copies/mL at least two weeks apart while on previous or current ARV therapy.
Time Frame	Up to Week 96

Outcome Measure Data

Analysis Population Description

Due to poor enrollment the study was terminated early; therefore data for secondary outcome measures were not collected, and were not analyzed.

Arm/Group Title	Raltegravir Plus Nevirapine Plus Lamivudine	Protease Inhibitor/Ritonavir Plus Tenofovir/Emtricitabine
Arm/Group Description	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks	Tenofovir/emtricitabine 300/200 mg orally once daily plus 1) lopinavir/ritonavir 400/100 mg orally twice daily or 800/200 mg orally once daily, or 2) atazanavir/ritonavir 300/100 mg orally once daily, or 3) darunavir/ritonavir 800/100 mg orally once daily or 600/100 mg orally twice daily
Measure Participants	0	0

8. Secondary Outcome

Title	Change From Baseline in Absolute CD4+ T-lymphocyte Count
Description	Cluster of Differentiation 4 + (CD4+) T-lymphocyte cell counts were to be determined at baseline and Week 96, in order to determine the change from baseline.
Time Frame	Baseline and Week 96

Outcome Measure Data

Analysis Population Description

Due to poor enrollment the study was terminated early; therefore data for secondary outcome measures were not collected, and were not analyzed.

Arm/Group Title	Raltegravir Plus Nevirapine Plus Lamivudine	Protease Inhibitor/Ritonavir Plus Tenofovir/Emtricitabine
Arm/Group Description	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks	Tenofovir/emtricitabine 300/200 mg orally once daily plus 1) lopinavir/ritonavir 400/100 mg orally twice daily or 800/200 mg orally once daily, or 2) atazanavir/ritonavir 300/100 mg orally once daily, or 3) darunavir/ritonavir 800/100 mg orally once daily or 600/100 mg orally twice daily
Measure Participants	0	0

9. Secondary Outcome

Title	Percentage of Participants With Altered Liver Enzymes and Lipid Profile
Description	Values of liver enzymes and lipids were to be determined from laboratory tests, in order to identify the percentage of participants classified with altered values.
Time Frame	Up to Week 96

Outcome Measure Data

Analysis Population Description

Due to poor enrollment the study was terminated early; therefore data for secondary outcome measures were not collected, and were not analyzed.

Arm/Group Title	Raltegravir Plus Nevirapine Plus Lamivudine	Protease Inhibitor/Ritonavir Plus Tenofovir/Emtricitabine
Arm/Group Description	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks	Tenofovir/emtricitabine 300/200 mg orally once daily plus 1) lopinavir/ritonavir 400/100 mg orally twice daily or 800/200 mg orally once daily, or 2) atazanavir/ritonavir 300/100 mg orally once daily, or 3) darunavir/ritonavir 800/100 mg orally once daily or 600/100 mg orally twice daily
Measure Participants	0	0

10. Secondary Outcome

Title	Percentage of Participants With Altered Values of Tubular Kidney Injury Markers.
Description	Values of tubular kidney injury markers. were to be determined, in order to identify the percentage of participants classified with altered values.
Time Frame	Up to Week 96

Outcome Measure Data

Analysis Population Description

Due to poor enrollment the study was terminated early; therefore data for secondary outcome measures were not collected, and were not analyzed.

Arm/Group Title	Raltegravir Plus Nevirapine Plus Lamivudine	Protease Inhibitor/Ritonavir Plus Tenofovir/Emtricitabine
Arm/Group Description	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks	Tenofovir/emtricitabine 300/200 mg orally once daily plus 1) lopinavir/ritonavir 400/100 mg orally twice daily or 800/200 mg orally once daily, or 2) atazanavir/ritonavir 300/100 mg orally once daily, or 3) darunavir/ritonavir 800/100 mg orally once daily or 600/100 mg orally twice daily
Measure Participants	0	0

11. Secondary Outcome

Title	Percentage of Participants Having Changes From Baseline in Metabolic Bone Markers
Description	Changes from baseline in metabolic bone markers, serum Bone Specific Alkaline Phosphatase (s-BSAP) and C-telopeptides of type 1 Collagen (s-CTx), were to be determined, in order to classify the percentage of participants with changes.
Time Frame	Baseline and up to Week 96

Outcome Measure Data

Analysis Population Description

Due to poor enrollment the study was terminated early; therefore data for secondary outcome measures were not collected, and were not analyzed.

Arm/Group Title	Raltegravir Plus Nevirapine Plus Lamivudine	Protease Inhibitor/Ritonavir Plus Tenofovir/Emtricitabine
Arm/Group Description	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks	Tenofovir/emtricitabine 300/200 mg orally once daily plus 1) lopinavir/ritonavir 400/100 mg orally twice daily or 800/200 mg orally once daily, or 2) atazanavir/ritonavir 300/100 mg orally once daily, or 3) darunavir/ritonavir 800/100 mg orally once daily or 600/100 mg orally twice daily
Measure Participants	0	0

12. Secondary Outcome

Title	Area Under the Concentration Time Curve From Time 0 the Last Measurement Time t (AUC0-t) for Raltegravir and Nevirapine
Description	Blood samples were to be collected in Week 12 in order to use the trapezoidal method to determine the AUC0-t of Raltegravir and Nevirapine
Time Frame	Week 12: Fasted state (0 h) and 1, 2, 3, 6 and 12 h post-dose

Outcome Measure Data

Analysis Population Description

Due to poor enrollment the study was terminated early; therefore data for secondary outcome measures were not collected, and were not analyzed.

Arm/Group Title	Raltegravir	Nevirapine
Arm/Group Description	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks
Measure Participants	0	0

13. Secondary Outcome

Title	Trough Concentration (Ctrough) for Raltegravir and Nevirapine
Description	Blood samples were to be collected in Weeks 12 and 48 in order to use the trapezoidal method to determine the Ctrough, the lowest concentration reached by the drug before the next dose is administered, of Raltegravir and Nevirapine.
Time Frame	Weeks 12 and 48: at the end of dosing interval at 12 h

Outcome Measure Data

Analysis Population Description

Due to poor enrollment the study was terminated early; therefore data for secondary outcome measures were not collected, and were not analyzed.

Arm/Group Title	Raltegravir	Nevirapine
Arm/Group Description	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks
Measure Participants	0	0

14. Secondary Outcome

Title	Percentage of Participants With Genotypic Resistance at Virologic Failure.
Description	Genotypic resistance measures the presence of particular HIV-1 mutations that give rise to drug resistance. Virological failure is defined as 2 consecutive plasma HIV-1 RNA >200 copies/mL at least two weeks apart while on previous or current ARV therapy.
Time Frame	Up to Week 96

Outcome Measure Data

Analysis Population Description

Due to poor enrollment the study was terminated early; therefore data for secondary outcome measures were not collected, and were not analyzed.

Arm/Group Title	Raltegravir Plus Nevirapine Plus Lamivudine	Protease Inhibitor/Ritonavir Plus Tenofovir/Emtricitabine
Arm/Group Description	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks	Tenofovir/emtricitabine 300/200 mg orally once daily plus 1) lopinavir/ritonavir 400/100 mg orally twice daily or 800/200 mg orally once daily, or 2) atazanavir/ritonavir 300/100 mg orally once daily, or 3) darunavir/ritonavir 800/100 mg orally once daily or 600/100 mg orally twice daily
Measure Participants	0	0

15. Secondary Outcome

Title	Percentage of Participants With Adherence to Study Therapy
Description	An Adherence Questionnaire was to be given in order to determine the percentage of participants who adhered to study therapy.
Time Frame	Up to Week 96

Outcome Measure Data

Analysis Population Description

Due to poor enrollment the study was terminated early; therefore data for secondary outcome measures were not collected, and were not analyzed.

Arm/Group Title	Raltegravir Plus Nevirapine Plus Lamivudine	Protease Inhibitor/Ritonavir Plus Tenofovir/Emtricitabine
Arm/Group Description	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks	Tenofovir/emtricitabine 300/200 mg orally once daily plus 1) lopinavir/ritonavir 400/100 mg orally twice daily or 800/200 mg orally once daily, or 2) atazanavir/ritonavir 300/100 mg orally once daily, or 3) darunavir/ritonavir 800/100 mg orally once daily or 600/100 mg orally twice daily
Measure Participants	0	0

16. Secondary Outcome

Title	Change From Baseline in Bone Disease Risk Assessment
Description	Bone disease risk assessment was to be based on a Fracture Risk Assessment Tool (FRAX®) score in participants > 40 years old, and the change from baseline determined.
Time Frame	Baseline and week 96

Outcome Measure Data

Analysis Population Description

Due to poor enrollment the study was terminated early; therefore data for secondary outcome measures were not collected, and were not analyzed.

Arm/Group Title	Raltegravir Plus Nevirapine Plus Lamivudine	Protease Inhibitor/Ritonavir Plus Tenofovir/Emtricitabine
Arm/Group Description	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks	Tenofovir/emtricitabine 300/200 mg orally once daily plus 1) lopinavir/ritonavir 400/100 mg orally twice daily or 800/200 mg orally once daily, or 2) atazanavir/ritonavir 300/100 mg orally once daily, or 3) darunavir/ritonavir 800/100 mg orally once daily or 600/100 mg orally twice daily
Measure Participants	0	0

17. Secondary Outcome

Title	Change From Baseline in the VACS Index
Description	The Veterans Aging Cohort Risk Index (VACS Index) combines various clinical biomarkers into a cumulative index weighted according to the risk of all-cause mortality.
Time Frame	Baseline and week 96

Outcome Measure Data

Analysis Population Description

Due to poor enrollment the study was terminated early; therefore data for secondary outcome measures were not collected, and were not analyzed.

Arm/Group Title	Raltegravir Plus Nevirapine Plus Lamivudine	Protease Inhibitor/Ritonavir Plus Tenofovir/Emtricitabine
Arm/Group Description	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks	Tenofovir/emtricitabine 300/200 mg orally once daily plus 1) lopinavir/ritonavir 400/100 mg orally twice daily or 800/200 mg orally once daily, or 2) atazanavir/ritonavir 300/100 mg orally once daily, or 3) darunavir/ritonavir 800/100 mg orally once daily or 600/100 mg orally twice daily
Measure Participants	0	0

18. Secondary Outcome

Title	Percentage of Participants Experiencing a Decline of Renal Function
Description	Decline in renal function was to be assessed by evaluating MDRD-6, creatinine clearance and serum phosphate.
Time Frame	Up to Week 96

Outcome Measure Data

Analysis Population Description

Due to poor enrollment the study was terminated early; therefore data for secondary outcome measures were not collected, and were not analyzed.

Arm/Group Title	Raltegravir Plus Nevirapine Plus Lamivudine	Protease Inhibitor/Ritonavir Plus Tenofovir/Emtricitabine
Arm/Group Description	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks	Tenofovir/emtricitabine 300/200 mg orally once daily plus 1) lopinavir/ritonavir 400/100 mg orally twice daily or 800/200 mg orally once daily, or 2) atazanavir/ritonavir 300/100 mg orally once daily, or 3) darunavir/ritonavir 800/100 mg orally once daily or 600/100 mg orally twice daily
Measure Participants	0	0

19. Secondary Outcome

Title	Change From Baseline in eGFR at Week 96
Description	Glomerular Filtration Rate (eGFR) was estimated from the Modification of Diet in Renal Disease (MDRD)-6 equation. The MDRD-6 equation = 198 × [serum creatinine(mg/dL)]^-0.858 × [age]-0.167 × [0.822 if patient is female] × [1.178 if patient is black] × [serum urea nitrogen concentration (mg/dL)]^-0.293 × [urine urea nitrogen excretion (g/d)]^0.249.
Time Frame	Baseline and Week 96

Outcome Measure Data

Analysis Population Description

Due to poor enrollment the study was terminated early; therefore data for secondary outcome measures were not collected, and were not analyzed.

Arm/Group Title	Raltegravir Plus Nevirapine Plus Lamivudine	Protease Inhibitor/Ritonavir Plus Tenofovir/Emtricitabine
Arm/Group Description	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks	Tenofovir/emtricitabine 300/200 mg orally once daily plus 1) lopinavir/ritonavir 400/100 mg orally twice daily or 800/200 mg orally once daily, or 2) atazanavir/ritonavir 300/100 mg orally once daily, or 3) darunavir/ritonavir 800/100 mg orally once daily or 600/100 mg orally twice daily
Measure Participants	0	0

Adverse Events

Time Frame	Up to Week 98
Adverse Event Reporting Description	All randomized participants who received at least one dose of study treatment.
Arm/Group Title	Raltegravir Plus Nevirapine Plus Lamivudine		Protease Inhibitor/Ritonavir Plus Tenofovir/Emtricitabine
Arm/Group Description	Raltegravir 400 mg orally twice daily for 96 weeks; plus nevirapine 200 mg orally once daily for 14 days followed by nevirapine 200 mg orally twice daily, plus lamivudine 150 mg orally twice daily for 96 weeks		Tenofovir/emtricitabine 300/200 mg orally once daily plus 1) lopinavir/ritonavir 400/100 mg orally twice daily or 800/200 mg orally once daily, or 2) atazanavir/ritonavir 300/100 mg orally once daily, or 3) darunavir/ritonavir 800/100 mg orally once daily or 600/100 mg orally twice daily
All Cause Mortality
	Raltegravir Plus Nevirapine Plus Lamivudine		Protease Inhibitor/Ritonavir Plus Tenofovir/Emtricitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/5 (0%)
Serious Adverse Events
	Raltegravir Plus Nevirapine Plus Lamivudine		Protease Inhibitor/Ritonavir Plus Tenofovir/Emtricitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		1/5 (20%)
Cardiac disorders
Myocardial infarction	0/6 (0%)	0	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	Raltegravir Plus Nevirapine Plus Lamivudine		Protease Inhibitor/Ritonavir Plus Tenofovir/Emtricitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/6 (50%)		2/5 (40%)
General disorders
Pyrexia	1/6 (16.7%)	1	0/5 (0%)	0
Infections and infestations
Gonorrhoea	1/6 (16.7%)	1	0/5 (0%)	0
Herpes zoster	1/6 (16.7%)	1	0/5 (0%)	0
Influenza	1/6 (16.7%)	1	0/5 (0%)	0
Pharyngitis	1/6 (16.7%)	1	0/5 (0%)	0
Investigations
Alanine aminotransferase increased	1/6 (16.7%)	1	0/5 (0%)	0
Aspartate aminotransferase increased	1/6 (16.7%)	1	0/5 (0%)	0
Metabolism and nutrition disorders
Hypophosphataemia	0/6 (0%)	0	2/5 (40%)	2
Renal and urinary disorders
Renal impairment	0/6 (0%)	0	1/5 (20%)	1
Skin and subcutaneous tissue disorders
Lichen planus	1/6 (16.7%)	1	0/5 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The investigator agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the trial. The sponsor shall have the right to review and comment with respect to publications, abstracts, slides, and manuscripts and the right to review and comment on the data analysis and presentation.