HIV Infections
Conditions
Keywords
HIV, Chemoprophylaxis, Hepatitis, Viral human hepatitis, HIV Seronegativity
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).
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.
Interventions
DRUGdaily TDF/FTC
daily oral medication
DRUGPlacebo
daily oral medication
Sponsors
Bill and Melinda Gates Foundation
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HIV Seroconversion | Monthly follow-up through a median of 1.2 years | Confirmed HIV infection |
| 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 |
| 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) |
| 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 |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| CD4 Count Among HIV Infected Participants | at the time infection was detected | CD4 cell count for HIV infected participants during the trial |
| Proportion of Missed Doses by Pill Count | At 24 weeks | Estimated proportion of missed doses by pill count (assuming pills taken in unreturned bottles) |
| Percentage of Missed Doses by Estimate During CASI Interview | Week 24 | Percentage of missed doses by estimate during computer assisted structured interview |
| 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/ |
| Total Number of Sexual Partners | 24 weeks | Self-reported total number of sexual partners in the previous 12 weeks. |
| 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. |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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. |
| 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 |
Countries
Brazil, Ecuador, Peru, South Africa, Thailand, United States
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.
Participants by arm
| Arm | Count |
|---|---|
| TDF/FTC Daily oral emtricitabine/tenofovir disoproxil fumarate
Emtricitabine/tenofovir disoproxil fumarate: Fixed-dose coformulation of 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate | 1,251 |
| Placebo Daily oral placebo
Placebo: Placebo for emtricitabine/tenofovir disoproxil fumarate | 1,248 |
| Total | 2,499 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 115 | 92 |
| Overall Study | Physician Decision | 31 | 22 |
| Overall Study | Relocated | 77 | 81 |
| Overall Study | Sites marked other on the form. | 19 | 20 |
| Overall Study | Withdrawal by Subject | 67 | 80 |
Baseline characteristics
| Characteristic | TDF/FTC | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 92 Participants | 101 Participants | 193 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1158 Participants | 1147 Participants | 2305 Participants |
| Age, Continuous | 25 years | 24 years | 24 years |
| Region of Enrollment Brazil | 186 participants | 184 participants | 370 participants |
| Region of Enrollment Ecuador | 150 participants | 150 participants | 300 participants |
| Region of Enrollment Peru | 700 participants | 700 participants | 1400 participants |
| Region of Enrollment South Africa | 45 participants | 43 participants | 88 participants |
| Region of Enrollment Thailand | 57 participants | 57 participants | 114 participants |
| Region of Enrollment United States | 113 participants | 114 participants | 227 participants |
| Sex/Gender, Customized Male Sex at Birth. Identify Female | 15 Participants | 14 Participants | 29 Participants |
| Sex/Gender, Customized Male Sex at Birth. Identify Male | 1081 Participants | 1079 Participants | 2160 Participants |
| Sex/Gender, Customized Male Sex at Birth. Identify Trans | 155 Participants | 155 Participants | 310 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 906 / 1,226 | 937 / 1,230 |
| serious Total, serious adverse events | 92 / 1,226 | 94 / 1,230 |
Outcome results
Primary
Grade 1 or Higher Creatinine Toxicity
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
Population: All randomized participants which at least 1 follow-up creatinine value
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TDF/FTC | Grade 1 or Higher Creatinine Toxicity | 32 Participants |
| Placebo | Grade 1 or Higher Creatinine Toxicity | 24 Participants |
p-value: 0.2895% CI: [0.79, 2.25]Fisher Exact
Primary
Grade 2, 3, or 4 Clinical Adverse Events
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
Population: At participants with at least one follow-up visit
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TDF/FTC | Grade 2, 3, or 4 Clinical Adverse Events | 157 Participants |
| Placebo | Grade 2, 3, or 4 Clinical Adverse Events | 162 Participants |
p-value: 0.9295% CI: [0.79, 1.23]Log Rank
Primary
Grade 2, 3, or 4 Laboratory Adverse Events
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
Population: At participants with at least one visit with laboratory values post-baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TDF/FTC | Grade 2, 3, or 4 Laboratory Adverse Events | 70 Participants |
| Placebo | Grade 2, 3, or 4 Laboratory Adverse Events | 79 Participants |
p-value: 0.595% CI: [0.65, 1.23]Log Rank
Primary
Grade 3 or Higher Phosphorous Toxicity
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
Population: All participants with at least 1 follow-up phosphorus value
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TDF/FTC | Grade 3 or Higher Phosphorous Toxicity | 13 Participants |
| Placebo | Grade 3 or Higher Phosphorous Toxicity | 10 Participants |
p-value: 0.5495% CI: [0.57, 2.96]Fisher Exact
Primary
HIV Seroconversion
Confirmed HIV infection
Time frame: Monthly follow-up through a median of 1.2 years
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TDF/FTC | HIV Seroconversion | 48 Participants |
| Placebo | HIV Seroconversion | 83 Participants |
Comparison: Primary null hypothesis: Relative hazard of 0.7 or less. Secondary null hypothesis: Relative hazard of 1.0 or less.p-value: 0.00295% CI: [0.404, 0.824]Log Rank
Secondary
Among HIV Infected Participants Drug Resistance
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
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TDF/FTC | Among HIV Infected Participants Drug Resistance | Infected at Enrollment (prior to randomization) | 2 Participants |
| TDF/FTC | Among HIV Infected Participants Drug Resistance | Infected after Randomization | 0 Participants |
| Placebo | Among HIV Infected Participants Drug Resistance | Infected at Enrollment (prior to randomization) | 1 Participants |
| Placebo | Among HIV Infected Participants Drug Resistance | Infected after Randomization | 0 Participants |
Comparison: Null hypothesis is the proportion of mutations is identical.p-value: 1Fisher Exact
Secondary
CD4 Count Among HIV Infected Participants
CD4 cell count for HIV infected participants during the trial
Time frame: at the time infection was detected
Population: HIV infected participants during the trial including those HIV+ at baseline
| Arm | Measure | Value (MEAN) |
|---|---|---|
| TDF/FTC | CD4 Count Among HIV Infected Participants | 495 cells per cubic mm |
| Placebo | CD4 Count Among HIV Infected Participants | 502 cells per cubic mm |
p-value: 0.3295% CI: [-69, 54]Mixed Models Analysis
Secondary
Condomless Receptive Anal Intercourse in the Previous 12 Weeks With Any Partners Regardless of Status.
Self-reported condomless receptive anal intercourse in the previous 12 weeks with any partners regardless of status.
Time frame: At 24 weeks
Population: Participants interviewed about sexual practices at week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TDF/FTC | Condomless Receptive Anal Intercourse in the Previous 12 Weeks With Any Partners Regardless of Status. | 332 Participants |
| Placebo | Condomless Receptive Anal Intercourse in the Previous 12 Weeks With Any Partners Regardless of Status. | 348 Participants |
Comparison: Null is no difference between armsp-value: 0.6895% CI: [-0.047, 0.03]Chi-squared
Secondary
Diagnosis of Gonorrhea During the Follow-up Period
Diagnosis of gonorrhea during the follow-up period by PCR
Time frame: All of follow-up period, median of 1.2 years
Population: All participants with at least one follow-up test for gonorrhea
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TDF/FTC | Diagnosis of Gonorrhea During the Follow-up Period | 18 Participants |
| Placebo | Diagnosis of Gonorrhea During the Follow-up Period | 30 Participants |
p-value: 0.0995% CI: [0.34, 1.09]Log Rank
Secondary
Hepatitis Flares Among Hepatitis B Virus (HBV) Infected Persons During and After Chemoprophylaxis
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
Population: Those with chronic active hepatitis B at enrollment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TDF/FTC | Hepatitis Flares Among Hepatitis B Virus (HBV) Infected Persons During and After Chemoprophylaxis | 0 Participants |
| Placebo | Hepatitis Flares Among Hepatitis B Virus (HBV) Infected Persons During and After Chemoprophylaxis | 0 Participants |
Comparison: Null hypothesis of no differencep-value: 1Fisher Exact
p-value: 1Fisher Exact
Secondary
Incidence of Confirmed Syphilis During Follow-Up
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
Population: Participants without active syphilis at baseline with a follow-up syphilis test.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TDF/FTC | Incidence of Confirmed Syphilis During Follow-Up | 147 Participants |
| Placebo | Incidence of Confirmed Syphilis During Follow-Up | 132 Participants |
Comparison: Null hypothesis of no difference between the armsp-value: 0.395% CI: [0.89, 1.43]Log Rank
Secondary
Incidence of HSV-2 During the Follow-up Period
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
Population: All HSV-2 negative participants with a follow-up HSV-2 test.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TDF/FTC | Incidence of HSV-2 During the Follow-up Period | 65 Participants |
| Placebo | Incidence of HSV-2 During the Follow-up Period | 60 Participants |
p-value: 0.4195% CI: [0.8, 1.7]Log Rank
Secondary
Number of Condomless Sexual Partners With HIV Positive or Unknown Status
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
Population: Participants interviewed about sexual practices at week 24
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TDF/FTC | Number of Condomless Sexual Partners With HIV Positive or Unknown Status | 0 count |
| Placebo | Number of Condomless Sexual Partners With HIV Positive or Unknown Status | 0 count |
p-value: 0.99Wilcoxon (Mann-Whitney)
Secondary
Percentage Change in Body Fat
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
Population: All participants in the body composition substudy who made a week 24 body scan
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| TDF/FTC | Percentage Change in Body Fat | 0.0 percent change from baseline | Standard Error 1 |
| Placebo | Percentage Change in Body Fat | 3.8 percent change from baseline | Standard Error 1 |
p-value: 0.00995% CI: [-6.6, -0.95]median regression
Secondary
Percentage Change in Bone Mineral Density
% 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.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TDF/FTC | Percentage Change in Bone Mineral Density | L1-L4 Spine bone mineral density | -0.59 percent change from baseline | Standard Error 0.21 |
| TDF/FTC | Percentage Change in Bone Mineral Density | Hip bone mineral density | -0.34 percent change from baseline | Standard Error 0.16 |
| Placebo | Percentage Change in Bone Mineral Density | L1-L4 Spine bone mineral density | 0.32 percent change from baseline | Standard Error 0.21 |
| Placebo | Percentage Change in Bone Mineral Density | Hip bone mineral density | 0.29 percent change from baseline | Standard Error 0.16 |
p-value: 0.001Mixed Models Analysis
Secondary
Percentage Change in Fasting Triglycerides
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
Population: All participants in the metabolic substudy with a week 24 fast triglyceride value
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| TDF/FTC | Percentage Change in Fasting Triglycerides | 0.0 percent change from baseline | Standard Error 3.3 |
| Placebo | Percentage Change in Fasting Triglycerides | 0.0 percent change from baseline | Standard Error 3.4 |
p-value: 195% CI: [-9.3, 9.3]median regression
Secondary
Percentage of Missed Doses by Estimate During CASI Interview
Percentage of missed doses by estimate during computer assisted structured interview
Time frame: Week 24
Population: All participants who answered the adherence question with an estimated adherence on the week 24 computer assisted structured interview
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TDF/FTC | Percentage of Missed Doses by Estimate During CASI Interview | 91.0 percentage of doses taken | Standard Error 0.5 |
| Placebo | Percentage of Missed Doses by Estimate During CASI Interview | 91.2 percentage of doses taken | Standard Error 0.5 |
p-value: 0.795% CI: [-1.1, 1.6]t-test, 2 sided
Secondary
Percent Change in Total Cholesterol
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
Population: All participants in the metabolic substudy with a week 24 fasting cholesterol
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| TDF/FTC | Percent Change in Total Cholesterol | -3.2 percent change from baseline | Standard Error 1.2 |
| Placebo | Percent Change in Total Cholesterol | -1.1 percent change from baseline | Standard Error 1.2 |
p-value: 0.1995% CI: [-5.5, 1.1]median regression
Secondary
Proportion of Missed Doses by Pill Count
Estimated proportion of missed doses by pill count (assuming pills taken in unreturned bottles)
Time frame: At 24 weeks
Population: Those who bottles returned at the week 24 visit.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| TDF/FTC | Proportion of Missed Doses by Pill Count | 0.92 proportion of pills not returned |
| Placebo | Proportion of Missed Doses by Pill Count | 0.93 proportion of pills not returned |
Comparison: Null hypothesis is equal proportion of pills returnedp-value: 0.5395% CI: [-0.02, 0.01]Mixed Models Analysis
Secondary
Total Number of Sexual Partners
Self-reported total number of sexual partners in the previous 12 weeks.
Time frame: 24 weeks
Population: Participants interviewed about sexual practices at week 24
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TDF/FTC | Total Number of Sexual Partners | 3 Count |
| Placebo | Total Number of Sexual Partners | 3 Count |
p-value: 0.7695% CI: [-0.42, 0.42]Wilcoxon (Mann-Whitney)
Secondary
Viral Load Among HIV Infected Participants
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
Population: All HIV infections detected during the study including prior to, during and after study treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TDF/FTC | Viral Load Among HIV Infected Participants | 5.2 log RNA copies per ml | Standard Error 0.11 |
| Placebo | Viral Load Among HIV Infected Participants | 5.1 log RNA copies per ml | Standard Error 0.08 |
p-value: 0.5695% CI: [-0.18, 0.33]t-test, 2 sided