iPrEx: Emtricitabine/Tenofovir Disoproxil Fumarate for HIV Prevention in Men

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00458393
• Collaborator: Bill and Melinda Gates Foundation (Other)
• Enrollment: 2,499
• Locations: 11
• Arms: 2
• Duration (Months): 80.1
• Patients Per Site: 227.2
• Patients Per Site Per Month: 2.8

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether daily use of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) can prevent HIV infection in men who also receive HIV counseling, condoms, and treatment for other sexually transmitted infections (STIs).

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: daily TDF/FTC; Drug: Placebo	Phase 3

Detailed Description

The Joint United Nations Programme on AIDS estimates that 14,000 persons are newly infected with HIV every day worldwide; one half of these infections occur in people between the ages of 15 and 24. New infections occur despite widespread awareness of the modes of HIV transmission and the protection afforded by condom use. Effective interventions for HIV prevention are urgently needed. This study will evaluate the safety and efficacy of chemoprophylaxis for HIV prevention in men who have sex with men (MSM) who are at high risk for HIV infection despite using condoms, receiving HIV counseling, and receiving treatment for STIs, particularly hepatitis B virus (HBV) infection. A daily combination dose of emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) has been selected for evaluation because it has a well-established safety record in previous studies and was demonstrated to be effective for HIV prevention in primate models. These medications have long half-lives that allow daily dosing and do not have known interactions with hormonal contraception, methadone, or tuberculosis therapies.

Once on the study drug, participants will be followed for a variable length of time, starting within 4 weeks of their screening visit and lasting up to 144 weeks. All participants will be followed for at least 8 weeks after stopping study drug. Participants who are reactive to a Hepatitis B surface antigen (HBsAg) test will be followed for hepatic flares for 16 additional weeks for a total of 24 weeks after stopping study drug. If enrolled in the optional substudy of bone mineral density, fat distribution, and fasting lipids, the participant will be asked to return for one additional visit 24 weeks after stopping study drug. Participants who HIV seroconvert during their participation will also be followed until the end of the study.

All study visits will be at 4 week intervals. At study entry, high risk, HIV uninfected MSM will be randomly assigned to receive either daily FTC/TDF or placebo, in addition to standard HIV counseling, condoms, and sexually transmitted infection (STI) management. The study will closely monitor biological and behavioral safety, including careful analysis of drug resistance, kidney and liver function, and risk behavior.

At the screening visit, participants will undergo HIV antibody and HBV testing, a medical history, a medical exam, blood and urine collection, risk behavior assessment, and STI testing. At study entry, participants will be given study medication; tested for HCV; and offered the HBV vaccine, if applicable. At all study visits, there will be HIV antibody testing, pill counts, adherence checks, study medication distribution, HIV counseling, and condom distribution. A medical history and blood will be taken on selected visits, along with STI testing and treatment if needed. Testing and treatment of STIs will be provided at no cost to the participant.

All study participants will be encouraged to join a substudy that will assess interactions between HBV infection, bone mineral density and fat distribution, and immune function. If enrolled in the substudy, the participant will be asked to return for one additional visit 24 weeks after stopping the study medication. All participants in the substudy will undergo dual energy x-ray absorptiometry (DEXA) scans, and HIV infected participants will undergo additional blood collection.

Sites will have the option of participating in the following four substudies:

The Hair Substudy: Participants who are receiving FTC/TDF will be eligible to enroll. At each 12-week follow-up study visit, hair samples will be collected and questionnaires will be completed.

The Urine Substudy: For all participants who elect to enroll in this substudy, additional testing will occur on blood and urine samples collected at each 24-week follow-up visit. An additional urine collection will occur 8 weeks after participants stop receiving FTC/TDF.

The Semen Substudy: Participants who seroconvert during the study may elect to participate in this substudy. One semen sample will be collected at participants' next study visit when plasma viral load testing is performed.

The Gonorrhea and Chlamydia Substudy: Participants in this substudy will undergo rectal and oropharyngeal swab procedures and urine collection at the 24-week study visit.

After the randomized phase ends, if the daily oral FTC/TDF arm is shown to be beneficial and safe, participants will be given the option of participating in an open label extension phase. During this extension phase, study participants will receive daily oral open-label FTC/TDF, in addition to standard counseling, condoms, and STI management.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2499 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Chemoprophylaxis for HIV Prevention in Men
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Feb 1, 2014
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TDF/FTC Drug. Daily oral tablet of co-formulated 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate (TDF/FTC).	Drug: daily TDF/FTC; daily oral medication; Other Names: truvada
Placebo Comparator: Placebo Drug. Daily oral placebo	Drug: Placebo; daily oral medication

Outcome Measures

Primary Outcome Measures

1. HIV Seroconversion [Monthly follow-up through a median of 1.2 years]

   Confirmed HIV infection

2. Grade 1 or Higher Creatinine Toxicity [Duration of follow-up, median 1.2 years]

   Creatinine which reach grade 1 (mild, 1.1 to 1.3 local upper limit of normal) or higher by the US Division of AIDS grading table (version 1) or a 50% increase in creatinine from the baseline value. The DAIDS table can be found at https://rsc.tech-res.com/docs/default-source/safety/table_for_grading_severity_of_adult_pediatric_adverse_events.pdf

3. Grade 3 or Higher Phosphorous Toxicity [The entire follow-up period, median 1.2 years]

   Grade 3 or higher phosphorous toxicity (hypophosphatemia) by the Division of AIDS Grading Table (severe, level at or below 1.9 mg/dL)

4. Grade 2, 3, or 4 Laboratory Adverse Events [Entire follow-up, median 1.2 years]

   Number of participants with at least one Grade 2, 3, or 4 laboratory adverse events (moderate, severe of life threatening based one the US Division of AIDS Grading of adverse events, version 1.0). The table can be found at https://rsc.tech-res.com/docs/default-source/safety/table_for_grading_severity_of_adult_pediatric_adverse_events.pdf

5. Grade 2, 3, or 4 Clinical Adverse Events [Entire follow-up, median 1.2 years]

   Number of participants with at least 1 Grade 2, 3, or 4 clinical adverse events (moderate, severe of life threatening based one the US Division of AIDS Grading of adverse events, version 1.0). The table can be found at https://rsc.tech-res.com/docs/default-source/safety/table_for_grading_severity_of_adult_pediatric_adverse_events.pdf

Secondary Outcome Measures

1. Hepatitis Flares Among Hepatitis B Virus (HBV) Infected Persons During and After Chemoprophylaxis [Quarterly lab tests through a median follow-up of 1.2 years]

   A hepatic flare is defined as an increase in alanine transaminase or aspartate transaminase to >5 fold upper limit of normal at any visit, or an increase to >2.5 fold upper limit of normal for 3 months, within 24 weeks of permanently stopping study drug. More details in https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752387/

2. Percentage Change in Bone Mineral Density [baseline and week 24.]

   % Change from baseline in bone mineral density (100 * [(value at 24 weeks- value at baseline)/ (value at baseline)]) in in hip and L1-L4 spine by dual-energy x-ray absorptiometry

3. Percentage Change in Body Fat [Baseline and Week 24]

   Percentage Change (100 * [(value at 24 weeks- value at baseline)/ (value at baseline)]) in Body Fat from Baseline by dual-energy x-ray absorptiometry

4. Percentage Change in Fasting Triglycerides [Baseline and Week 24]

   Percentage Change (Percentage Change (100 * [(value at 24 weeks- value at baseline)/ (value at baseline)]) in Triglycerides from Baseline from a fasting sample.

5. Percent Change in Total Cholesterol [Baseline and Week 24]

   Percent change (100 * [(value at 24 weeks- value at baseline)/ (value at baseline)]) in fasting total cholesterol from baseline

6. Viral Load Among HIV Infected Participants [At the time closest to HIV detection]

   HIV-RNA in log10 units among HIV infected participants at the time closest to HIV detection

7. Among HIV Infected Participants Drug Resistance [at the time of HIV acquisition]

   Genotypic resistance by clinical assays among the seroconverters from baseline to the end of the study treatment period

8. CD4 Count Among HIV Infected Participants [at the time infection was detected]

   CD4 cell count for HIV infected participants during the trial

9. Proportion of Missed Doses by Pill Count [At 24 weeks]

   Estimated proportion of missed doses by pill count (assuming pills taken in unreturned bottles)

10. Percentage of Missed Doses by Estimate During CASI Interview [Week 24]

    Percentage of missed doses by estimate during computer assisted structured interview

11. Number of Condomless Sexual Partners With HIV Positive or Unknown Status [At 24 weeks]

    Participants self-report of the number of sexual partners with HIV positive or unknown status in the previous 12 weeks with whom they had condomless anal sex

12. Total Number of Sexual Partners [24 weeks]

    Self-reported total number of sexual partners in the previous 12 weeks.

13. Condomless Receptive Anal Intercourse in the Previous 12 Weeks With Any Partners Regardless of Status. [At 24 weeks]

    Self-reported condomless receptive anal intercourse in the previous 12 weeks with any partners regardless of status.

14. Incidence of Confirmed Syphilis During Follow-Up [All Follow-Up median of 1.2 years of follow-up]

    Number of participants who have at least 1 confirmed syphilis infection during the study

15. Incidence of HSV-2 During the Follow-up Period [Total study follow-up, a median of 1.2 years]

    Incidence of HSV-2 during the follow-up period among those HIV-2 negative at baseline

16. Diagnosis of Gonorrhea During the Follow-up Period [All of follow-up period, median of 1.2 years]

    Diagnosis of gonorrhea during the follow-up period by PCR

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Male sex (at birth)

• HIV uninfected

• Age having reached the local age of consent

• High risk for HIV infection including any of the following: 1) No condom use during anal intercourse with a male HIV-positive partner or a male partner of unknown HIV status during the last 6 months; (2) anal intercourse with more than 3 male sex partners during the last 6 months; (3) exchange of money, gifts, shelter, or drugs for anal sex with a male partner during the last 6 months; (4) sex with a male partner and STI diagnosis during the last 6 months or at screening, or (5) sexual partner of an HIV-infected man with whom condoms are not consistently used in the last 6 months.

• Able to provide a street address of residence for themselves and one personal contact who would know their whereabouts during the study period

• Healthy enough to work, as indicated by score of 80 or greater on the Karnofsky scale

• Certain laboratory values

• A urine dipstick with a negative or trace result for both glucose and protein within 28 days of enrollment.

• Ability to understand and local language for which an informed consent form has been approved by a local IRB and registered with the study sponsor.

Inclusion Criteria for Open-Label Extension:

• Participated in a randomized, placebo-controlled, PrEP trail

• Has been unblinded

• Has provided informed consent

Exclusion Criteria:

• Previously diagnosed active and serious infections, including tuberculosis infection, osteomyelitis, or infections requiring parenteral antibiotic therapy

• Active clinically significant medical problems including heart disease (e.g., symptoms of ischemia, congestive heart failure, arrhythmia), lung disease (steroid-dependent chronic obstructive pulmonary disease), diabetes requiring hypoglycemic medication, or previously diagnosed cancer expected to require further treatment

• Acute HBV infection at the screening visit or presence of treatment indications for hepatitis B based on local practice standards; or clinical signs of hepatic cirrhosis

• History of pathological bone fractures not related to trauma

• Receiving ongoing therapy with certain HIV/AIDS-related medications or other medications as determined by the investigator

• Definitely or possibly received an anti-HIV vaccine while participating in a blinded clinical trial

• Current alcohol or drug use that, in the opinion of the investigator, may interfere with the study

• Current participation in a clinical trial or cohort study other than sub-studies of this protocol

• Any condition at enrollment that, in the opinion of the investigator, would make participation in the study unsafe or would interfere with the study

• Sites may utilize additional criteria that restrict enrollment to a subset of people who meet the protocol-defined enrollment criteria.

Exclusion Criteria for Open-Label Extension:

• Site leadership believes participant will have difficulty completing requirements

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	San Francisco Dept. of Public Health iPrEx CRS	San Francisco	California	United States	94102
2	Stroger Hospital of Cook County/Core Center IPREX CRS	Chicago	Illinois	United States	60612
3	Fenway Community Health iPrEx CRS	Boston	Massachusetts	United States	02215
4	IPEC/FIOCRUZ iPrEx CRS	Rio de Janeiro		Brazil	21040-900
5	Projeto Praca Onze, Universidade Federal do Rio de Janeiro iPrEx CRS	Rio de Janeiro		Brazil	21941.590
6	Universidade de Sao Paulo iPrEx CRS	Sao Paulo		Brazil	05403
7	Fundación Ecuatoriana Equidad, Guayaquil, iPrEx CRS	Guayaquil	Guayas	Ecuador
8	Asociación Civil Selva Amazónica, Iquitos, iPrEx CRS	Iquitos	Maynas	Peru
9	Investigaciones Médicas en Salud (INMENSA), Lince, iPrEx CRS	Lima		Peru
10	Desmond Tutu HIV Ctr. iPrEx CRS	Cape Town		South Africa	7925
11	Research Institute for Health Sciences iPrEx CRS	Chiang Mai		Thailand	50200

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• Bill and Melinda Gates Foundation

Investigators

• Principal Investigator: Robert M. Grant, MD, MPH, J. David Gladstone Institutes, University of California San Francisco

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Primary Manuscript

Publications

None provided.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00458393
• Other Study ID Numbers: CO-US-104-0288; 10445; 1U01AI064002; iPrEx; NCT00350324
• First Posted: Apr 10, 2007
• Last Update Posted: Nov 2, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): HIV; Chemoprophylaxis; Hepatitis; Viral human hepatitis; HIV Seronegativity
• Additional relevant MeSH terms: HIV Infections; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Study Results

Participant Flow

Recruitment Details	The study recruited HIV uninfected participants whose sexual practices put them at risk for HIV infection. They were recruited from community clinics.

Arm/Group Title	TDF/FTC	Placebo
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate Emtricitabine/tenofovir disoproxil fumarate: Fixed-dose coformulation of 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate	Daily oral placebo Placebo: Placebo for emtricitabine/tenofovir disoproxil fumarate
Period Title: Overall Study
STARTED	1251	1248
COMPLETED	942	953
NOT COMPLETED	309	295

Baseline Characteristics

Arm/Group Title	TDF/FTC	Placebo	Total
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate Emtricitabine/tenofovir disoproxil fumarate: Fixed-dose coformulation of 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate	Daily oral placebo Placebo: Placebo for emtricitabine/tenofovir disoproxil fumarate	Total of all reporting groups
Overall Participants	1251	1248	2499
Age (Count of Participants)
<=18 years	92 7.4%	101 8.1%	193 7.7%
Between 18 and 65 years	1158 92.6%	1147 91.9%	2305 92.2%
>=65 years	1 0.1%	0 0%	1 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	25	24	24
Sex/Gender, Customized (Count of Participants)
Male Sex at Birth. Identify Trans	155 12.4%	155 12.4%	310 12.4%
Male Sex at Birth. Identify Female	15 1.2%	14 1.1%	29 1.2%
Male Sex at Birth. Identify Male	1081 86.4%	1079 86.5%	2160 86.4%
Region of Enrollment (participants) [Number]
Ecuador	150 12%	150 12%	300 12%
United States	113 9%	114 9.1%	227 9.1%
Brazil	186 14.9%	184 14.7%	370 14.8%
South Africa	45 3.6%	43 3.4%	88 3.5%
Thailand	57 4.6%	57 4.6%	114 4.6%
Peru	700 56%	700 56.1%	1400 56%

Outcome Measures

1. Primary Outcome

Title	HIV Seroconversion
Description	Confirmed HIV infection
Time Frame	Monthly follow-up through a median of 1.2 years

Outcome Measure Data

Analysis Population Description

Excludes participants who were HIV+ at enrollment (2 TDF/FTC, 8 Placebo) and those with no follow-up HIV test (25 TDF/FTC and 22 Placebo).

Arm/Group Title	TDF/FTC	Placebo
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate Emtricitabine/tenofovir disoproxil fumarate: Fixed-dose coformulation of 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate	Daily oral placebo Placebo: Placebo for emtricitabine/tenofovir disoproxil fumarate
Measure Participants	1224	1218
Count of Participants [Participants]	48 3.8%	83 6.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TDF/FTC, Placebo
	Comments	Primary null hypothesis: Relative hazard of 0.7 or less. Secondary null hypothesis: Relative hazard of 1.0 or less.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	secondary p-value given.
	Method	Log Rank
	Comments	stratified by site
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.577
	Confidence Interval	(2-Sided) 95%; .404 to .824
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.105
	Estimation Comments	Efron correction for ties. Placebo is reference. Results typically quoted as efficacy = 100*(1-HR)

2. Primary Outcome

Title	Grade 1 or Higher Creatinine Toxicity
Description	Creatinine which reach grade 1 (mild, 1.1 to 1.3 local upper limit of normal) or higher by the US Division of AIDS grading table (version 1) or a 50% increase in creatinine from the baseline value. The DAIDS table can be found at https://rsc.tech-res.com/docs/default-source/safety/table_for_grading_severity_of_adult_pediatric_adverse_events.pdf
Time Frame	Duration of follow-up, median 1.2 years

Outcome Measure Data

Analysis Population Description

All randomized participants which at least 1 follow-up creatinine value

Arm/Group Title	TDF/FTC	Placebo
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate	Daily oral placebo
Measure Participants	1216	1217
Count of Participants [Participants]	32 2.6%	24 1.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TDF/FTC, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments	p-value is not adjusted for multiple comparisons, a priori threshold for statistical significance was p < 0.05
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.33
	Confidence Interval	(2-Sided) 95%; 0.79 to 2.25
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Extensive analysis and methods published in https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3966916/

3. Primary Outcome

Title	Grade 3 or Higher Phosphorous Toxicity
Description	Grade 3 or higher phosphorous toxicity (hypophosphatemia) by the Division of AIDS Grading Table (severe, level at or below 1.9 mg/dL)
Time Frame	The entire follow-up period, median 1.2 years

Outcome Measure Data

Analysis Population Description

All participants with at least 1 follow-up phosphorus value

Arm/Group Title	TDF/FTC	Placebo
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate	Daily oral placebo
Measure Participants	1225	1226
Count of Participants [Participants]	13 1%	10 0.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TDF/FTC, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.54
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; .57 to 2.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Grade 2, 3, or 4 Laboratory Adverse Events
Description	Number of participants with at least one Grade 2, 3, or 4 laboratory adverse events (moderate, severe of life threatening based one the US Division of AIDS Grading of adverse events, version 1.0). The table can be found at https://rsc.tech-res.com/docs/default-source/safety/table_for_grading_severity_of_adult_pediatric_adverse_events.pdf
Time Frame	Entire follow-up, median 1.2 years

Outcome Measure Data

Analysis Population Description

At participants with at least one visit with laboratory values post-baseline

Arm/Group Title	TDF/FTC	Placebo
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate	Daily oral placebo
Measure Participants	1229	1226
Count of Participants [Participants]	70 5.6%	79 6.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TDF/FTC, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.50
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.65 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	Grade 2, 3, or 4 Clinical Adverse Events
Description	Number of participants with at least 1 Grade 2, 3, or 4 clinical adverse events (moderate, severe of life threatening based one the US Division of AIDS Grading of adverse events, version 1.0). The table can be found at https://rsc.tech-res.com/docs/default-source/safety/table_for_grading_severity_of_adult_pediatric_adverse_events.pdf
Time Frame	Entire follow-up, median 1.2 years

Outcome Measure Data

Analysis Population Description

At participants with at least one follow-up visit

Arm/Group Title	TDF/FTC	Placebo
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate	Daily oral placebo
Measure Participants	1226	1230
Count of Participants [Participants]	157 12.5%	162 13%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TDF/FTC, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.92
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.79 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Hepatitis Flares Among Hepatitis B Virus (HBV) Infected Persons During and After Chemoprophylaxis
Description	A hepatic flare is defined as an increase in alanine transaminase or aspartate transaminase to >5 fold upper limit of normal at any visit, or an increase to >2.5 fold upper limit of normal for 3 months, within 24 weeks of permanently stopping study drug. More details in https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752387/
Time Frame	Quarterly lab tests through a median follow-up of 1.2 years

Outcome Measure Data

Analysis Population Description

Those with chronic active hepatitis B at enrollment.

Arm/Group Title	TDF/FTC	Placebo
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate Emtricitabine/tenofovir disoproxil fumarate: Fixed-dose coformulation of 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate	Daily oral placebo Placebo: Placebo for emtricitabine/tenofovir disoproxil fumarate
Measure Participants	6	6
Count of Participants [Participants]	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TDF/FTC, Placebo
	Comments	Null hypothesis of no difference
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TDF/FTC, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	Desc
Statistical Test of Hypothesis	p-Value	1.00
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.00
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percentage Change in Bone Mineral Density
Description	% Change from baseline in bone mineral density (100 * [(value at 24 weeks- value at baseline)/ (value at baseline)]) in in hip and L1-L4 spine by dual-energy x-ray absorptiometry
Time Frame	baseline and week 24.

Outcome Measure Data

Analysis Population Description

Participants confirmed to be HIV negative at enrollment who consented to participate in the metabolic substudy. Full details in https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25908682/

Arm/Group Title	TDF/FTC	Placebo
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate Emtricitabine/tenofovir disoproxil fumarate: Fixed-dose coformulation of 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate	Daily oral placebo Placebo: Placebo for emtricitabine/tenofovir disoproxil fumarate
Measure Participants	210	211
L1-L4 Spine bone mineral density	-0.59 (0.21)	0.32 (0.21)
Hip bone mineral density	-0.34 (0.16)	0.29 (0.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TDF/FTC, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	< 0.05 for statistical significance. no adjustment for multiple comparisons
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-.91
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Percentage Change in Body Fat
Description	Percentage Change (100 * [(value at 24 weeks- value at baseline)/ (value at baseline)]) in Body Fat from Baseline by dual-energy x-ray absorptiometry
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

All participants in the body composition substudy who made a week 24 body scan

Arm/Group Title	TDF/FTC	Placebo
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate	Daily oral placebo
Measure Participants	210	211
Median (Standard Error) [percent change from baseline]	0.0 (1.0)	3.8 (1.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TDF/FTC, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	median regression
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-3.8
	Confidence Interval	(2-Sided) 95%; -6.6 to -0.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Percentage Change in Fasting Triglycerides
Description	Percentage Change (Percentage Change (100 * [(value at 24 weeks- value at baseline)/ (value at baseline)]) in Triglycerides from Baseline from a fasting sample.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

All participants in the metabolic substudy with a week 24 fast triglyceride value

Arm/Group Title	TDF/FTC	Placebo
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate	Daily oral placebo
Measure Participants	199	194
Median (Standard Error) [percent change from baseline]	0.0 (3.3)	0.0 (3.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TDF/FTC, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments
	Method	median regression
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -9.3 to 9.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Percent Change in Total Cholesterol
Description	Percent change (100 * [(value at 24 weeks- value at baseline)/ (value at baseline)]) in fasting total cholesterol from baseline
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

All participants in the metabolic substudy with a week 24 fasting cholesterol

Arm/Group Title	TDF/FTC	Placebo
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate	Daily oral placebo
Measure Participants	199	194
Median (Standard Error) [percent change from baseline]	-3.2 (1.2)	-1.1 (1.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TDF/FTC, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.19
	Comments
	Method	median regression
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-2.2
	Confidence Interval	(2-Sided) 95%; -5.5 to 1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Viral Load Among HIV Infected Participants
Description	HIV-RNA in log10 units among HIV infected participants at the time closest to HIV detection
Time Frame	At the time closest to HIV detection

Outcome Measure Data

Analysis Population Description

All HIV infections detected during the study including prior to, during and after study treatment

Arm/Group Title	TDF/FTC	Placebo
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate	Daily oral placebo
Measure Participants	54	93
Mean (Standard Error) [log RNA copies per ml]	5.2 (0.11)	5.1 (0.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TDF/FTC, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.56
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 95%; -.18 to 0.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Among HIV Infected Participants Drug Resistance
Description	Genotypic resistance by clinical assays among the seroconverters from baseline to the end of the study treatment period
Time Frame	at the time of HIV acquisition

Outcome Measure Data

Analysis Population Description

There were 2 TDF/FTC seroconversions at enrollment and 48 during follow-up. There were 8 Placebo seroconversions at enrollment and 83 during follow-up.

Arm/Group Title	TDF/FTC	Placebo
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate Emtricitabine/tenofovir disoproxil fumarate: Fixed-dose coformulation of 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate	Daily oral placebo Placebo: Placebo for emtricitabine/tenofovir disoproxil fumarate
Measure Participants	50	91
Infected at Enrollment (prior to randomization)	2 0.2%	1 0.1%
Infected after Randomization	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TDF/FTC, Placebo
	Comments	Null hypothesis is the proportion of mutations is identical.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Detailed resistance data is found at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176446/

13. Secondary Outcome

Title	CD4 Count Among HIV Infected Participants
Description	CD4 cell count for HIV infected participants during the trial
Time Frame	at the time infection was detected

Outcome Measure Data

Analysis Population Description

HIV infected participants during the trial including those HIV+ at baseline

Arm/Group Title	TDF/FTC	Placebo
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate	Daily oral placebo
Measure Participants	51	87
Mean (95% Confidence Interval) [cells per cubic mm]	495	502

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TDF/FTC, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.32
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-7
	Confidence Interval	(2-Sided) 95%; -69 to 54
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Proportion of Missed Doses by Pill Count
Description	Estimated proportion of missed doses by pill count (assuming pills taken in unreturned bottles)
Time Frame	At 24 weeks

Outcome Measure Data

Analysis Population Description

Those who bottles returned at the week 24 visit.

Arm/Group Title	TDF/FTC	Placebo
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate Emtricitabine/tenofovir disoproxil fumarate: Fixed-dose coformulation of 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate	Daily oral placebo Placebo: Placebo for emtricitabine/tenofovir disoproxil fumarate
Measure Participants	983	999
Mean (95% Confidence Interval) [proportion of pills not returned]	0.92	0.93

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TDF/FTC, Placebo
	Comments	Null hypothesis is equal proportion of pills returned
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.53
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.005
	Confidence Interval	(2-Sided) 95%; -0.02 to 0.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Percentage of Missed Doses by Estimate During CASI Interview
Description	Percentage of missed doses by estimate during computer assisted structured interview
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

All participants who answered the adherence question with an estimated adherence on the week 24 computer assisted structured interview

Arm/Group Title	TDF/FTC	Placebo
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate	Daily oral placebo
Measure Participants	884	902
Mean (Standard Error) [percentage of doses taken]	91.0 (0.5)	91.2 (0.50)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TDF/FTC, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.70
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.25
	Confidence Interval	(2-Sided) 95%; -1.1 to 1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Detailed methods and results are available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110718/

16. Secondary Outcome

Title	Number of Condomless Sexual Partners With HIV Positive or Unknown Status
Description	Participants self-report of the number of sexual partners with HIV positive or unknown status in the previous 12 weeks with whom they had condomless anal sex
Time Frame	At 24 weeks

Outcome Measure Data

Analysis Population Description

Participants interviewed about sexual practices at week 24

Arm/Group Title	TDF/FTC	Placebo
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate	Daily oral placebo
Measure Participants	1091	1114
Median (Inter-Quartile Range) [count]	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TDF/FTC, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.99
	Comments	Not adjusted for multiple comparisons and the a priori threshold for statistical significance was p < 0.05
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Total Number of Sexual Partners
Description	Self-reported total number of sexual partners in the previous 12 weeks.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Participants interviewed about sexual practices at week 24

Arm/Group Title	TDF/FTC	Placebo
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate	Daily oral placebo
Measure Participants	1091	1114
Median (Inter-Quartile Range) [Count]	3	3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TDF/FTC, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.76
	Comments	Not adjusted for multiple comparisons, a priori threshold for statistical significance, p < 0.05
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0
	Confidence Interval	(2-Sided) 95%; -.42 to .42
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Full details available in the methods section of https://www.ncbi.nlm.nih.gov/pubmed/24367497

18. Secondary Outcome

Title	Condomless Receptive Anal Intercourse in the Previous 12 Weeks With Any Partners Regardless of Status.
Description	Self-reported condomless receptive anal intercourse in the previous 12 weeks with any partners regardless of status.
Time Frame	At 24 weeks

Outcome Measure Data

Analysis Population Description

Participants interviewed about sexual practices at week 24

Arm/Group Title	TDF/FTC	Placebo
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate Emtricitabine/tenofovir disoproxil fumarate: Fixed-dose coformulation of 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate	Daily oral placebo Placebo: Placebo for emtricitabine/tenofovir disoproxil fumarate
Measure Participants	1091	1114
Count of Participants [Participants]	332 26.5%	348 27.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TDF/FTC, Placebo
	Comments	Null is no difference between arms
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.68
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.008
	Confidence Interval	(2-Sided) 95%; -0.047 to 0.030
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Incidence of Confirmed Syphilis During Follow-Up
Description	Number of participants who have at least 1 confirmed syphilis infection during the study
Time Frame	All Follow-Up median of 1.2 years of follow-up

Outcome Measure Data

Analysis Population Description

Participants without active syphilis at baseline with a follow-up syphilis test.

Arm/Group Title	TDF/FTC	Placebo
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate Emtricitabine/tenofovir disoproxil fumarate: Fixed-dose coformulation of 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate	Daily oral placebo Placebo: Placebo for emtricitabine/tenofovir disoproxil fumarate
Measure Participants	1155	1171
Count of Participants [Participants]	147 11.8%	132 10.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TDF/FTC, Placebo
	Comments	Null hypothesis of no difference between the arms
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Incidence of HSV-2 During the Follow-up Period
Description	Incidence of HSV-2 during the follow-up period among those HIV-2 negative at baseline
Time Frame	Total study follow-up, a median of 1.2 years

Outcome Measure Data

Analysis Population Description

All HSV-2 negative participants with a follow-up HSV-2 test.

Arm/Group Title	TDF/FTC	Placebo
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate	Daily oral placebo
Measure Participants	671	676
Count of Participants [Participants]	65 5.2%	60 4.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TDF/FTC, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.41
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; 0.8 to 1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Details in the manuscript https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3956614/

21. Secondary Outcome

Title	Diagnosis of Gonorrhea During the Follow-up Period
Description	Diagnosis of gonorrhea during the follow-up period by PCR
Time Frame	All of follow-up period, median of 1.2 years

Outcome Measure Data

Analysis Population Description

All participants with at least one follow-up test for gonorrhea

Arm/Group Title	TDF/FTC	Placebo
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate	Daily oral placebo
Measure Participants	1226	1229
Count of Participants [Participants]	18 1.4%	30 2.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TDF/FTC, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.09
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.61
	Confidence Interval	(2-Sided) 95%; 0.34 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Monthly follow-up with quarterly lab assessments though a median of 1.2 years of follow-up
Adverse Event Reporting Description	Adverse events graded by the NIH Division of AIDS grading tables, version 1.0
Arm/Group Title	TDF/FTC		Placebo
Arm/Group Description	Daily oral emtricitabine/tenofovir disoproxil fumarate Emtricitabine/tenofovir disoproxil fumarate: Fixed-dose coformulation of 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate		Daily oral placebo Placebo: Placebo for emtricitabine/tenofovir disoproxil fumarate
All Cause Mortality
	TDF/FTC		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	TDF/FTC		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	92/1226 (7.5%)		94/1230 (7.6%)
Blood and lymphatic system disorders
CREATININE INCREASE	9/1226 (0.7%)	9	7/1230 (0.6%)	7
ALT INCREASE	1/1226 (0.1%)	1	4/1230 (0.3%)	4
AST	4/1226 (0.3%)	4	5/1230 (0.4%)	5
General disorders
OTHER EVENTS	28/1226 (2.3%)	28	29/1230 (2.4%)	29
Hepatobiliary disorders
APPENDICITIS	3/1226 (0.2%)	3	3/1230 (0.2%)	3
Musculoskeletal and connective tissue disorders
Bone Fracture	8/1226 (0.7%)	8	9/1230 (0.7%)	9
Psychiatric disorders
SUICIDE ATTEMPT	17/1226 (1.4%)	17	14/1230 (1.1%)	14
SUICIDAL IDEATION	5/1226 (0.4%)	5	6/1230 (0.5%)	6
DEPRESSION	7/1226 (0.6%)	7	11/1230 (0.9%)	11
SUICIDAL DEPRESSION	5/1226 (0.4%)	5	6/1230 (0.5%)	6
MAJOR DEPRESSION	5/1226 (0.4%)	5	0/1230 (0%)	0
Other (Not Including Serious) Adverse Events
	TDF/FTC		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	906/1226 (73.9%)		937/1230 (76.2%)
Gastrointestinal disorders
PARASITIC INFECTION INTESTINAL	231/1226 (18.8%)	231	216/1230 (17.6%)	216
DIARRHOEA	109/1226 (8.9%)	109	123/1230 (10%)	123
Infections and infestations
SYPHILIS	82/1226 (6.7%)	82	71/1230 (5.8%)	71
UPPER RESPIRATORY TRACT INFECTION	73/1226 (6%)	73	76/1230 (6.2%)	76
SECONDARY SYPHILIS	81/1226 (6.6%)	81	64/1230 (5.2%)	64
BLOOD AMYLASE INCREASED	62/1226 (5.1%)	62	57/1230 (4.6%)	57
Investigations
ALANINE AMINOTRANSFERASE INCREASED	151/1226 (12.3%)	151	155/1230 (12.6%)	155
BILIRUBIN INCREASE	127/1226 (10.4%)	127	132/1230 (10.7%)	132
BLOOD GLUCOSE INCREASED	109/1226 (8.9%)	109	123/1230 (10%)	123
BLOOD PHOSPHORUS DECREASED	122/1226 (10%)	122	100/1230 (8.1%)	100
ASPARTATE AMINOTRANSFERASE INCREASED	76/1226 (6.2%)	76	93/1230 (7.6%)	93
Musculoskeletal and connective tissue disorders
BACK PAIN	84/1226 (6.9%)	84	87/1230 (7.1%)	87
Nervous system disorders
HEADACHE	102/1226 (8.3%)	102	107/1230 (8.7%)	107
DEPRESSION	81/1226 (6.6%)	81	84/1230 (6.8%)	84
Renal and urinary disorders
URETHRITIS	84/1226 (6.9%)	84	102/1230 (8.3%)	102
Respiratory, thoracic and mediastinal disorders
PHARYNGITIS	248/1226 (20.2%)	248	282/1230 (22.9%)	282
NASOPHARYNGITIS	98/1226 (8%)	98	92/1230 (7.5%)	92

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.