HPTN 067/ADAPT study: a comparison of daily and non-daily pre-exposure prophylaxis dosing in Thai men who have sex with men, Bangkok, Thailand
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Holtz TH и др. «HPTN 067/ADAPT study: a comparison of daily and non-daily pre-exposure prophylaxis dosing in Thai men who have sex with men, Bangkok, Thailand» 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Vancouver, 2015. MOAC0306LB.
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HPTN 067/ADAPT study: a comparison of daily and non-daily pre-exposure prophylaxis dosing in Thai men who have sex with men, Bangkok, Thailand
- 1. A Comparison of Daily and Non-daily Pre-exposure Prophylaxis Dosing in Thai Men Who Have Sex With Men, Bangkok HPTN 067 / ADAPT Study Timothy H. Holtz, Anupong Chitwarakorn, Marcel E. Curlin, James Hughes, K. Rivet Amico, Craig Hendrix, Bonnie J. Dye, Peter L. Anderson, Maoji Li, Vanessa Elharrar, Susan H. Eshleman, Michael Stirratt, Robert M. Grant and the Bangkok HPTN 067/ADAPT Study Team July 20, 2015
- 2. 249 screened 193 enrolled 56 not enrolled* HIV + rapid 11/19.6% Abnormal ALT/AST 13/23.2% Abnormal Ser Cr 7/12.5% Lab abnormality 6/10.7% HbV no immune 11/19.6% Other medical/mental 2/3.6% Not enrolled within window 5/8.9% Other 4/7.1% *not mutually exclusive 178 randomized 15 not randomized HIV + false 2/13.3% HIV + in DOT 2/13.3% Product hold 1/6.7% Withdrew 1/6.7% Lost contact 2/13.3% Other 7/46.7% 60 Daily usage 59 Time-driven usage 59 Event-driven usage Self-Administered Phase DOT Phase
- 3. Participant Demographics: Bangkok Variable % (N=178) Median age (years, IQR) Age ranges 18-20 21-25 26-30 31-35 36-40 >40 31 (27,34) 1% 21% 28% 30% 14% 6% Gender identity Male TGW 99% 1% Race Asian 100% Never married 97% Education Completed college In college, not completed 83% 6% Unemployed Student 11% 9%
- 4. Coverage (PrEP Before and After Sex): Daily vs. Time-Driven vs. Event-Driven 85% 11% 1% 3% 84% 12% 3% 1% 74% 19% 5% 3% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% % complete coverage % only pre-sex dose % only post-sex dose no coverage Daily Time-driven Event-driven D/T p = 0.79, D/E p = 0.02, T/E p = 0.04, global p = 0.19
- 5. FTC/TDF Pills by Arm 9420 4121 1928 8285 3713 2157 Daily Time-driven Event-driven Numberoftablets Required tablets Tablets reported taken Required tablets: p < 0.001 for all comparisons (D/T, D/E, and T/E) Tablets actually taken: p < 0.001 for all comparisons (D/T, D/E, and T/E)
- 6. Adherence (Total pills taken/Total pills required): Daily vs. Time-Driven vs. Event-Driven D/T p < 0.42, D/E p < 0.001, T/E p < 0.001, global p < 0.001
- 7. Neuro and GI Symptoms / Side Effects Side Effect reported Daily Time Event p value % PPTs who experienced any neurologic side effects 48% 46% 54% 0.64 % PPTs who experienced any GI side effects 45% 34% 41% 0.46
- 8. Reports of Side Effects Over Time
- 9. HIV Incidence • 2 seroconversions during the 6-week pre- randomization weekly DOT study phase – Both occurred at week 4 – Both had low levels of FTC detected and no detectable TVF in plasma – Both had low detectable levels of both FTC and TVF in PBMC – 2 of 193 participants over 22.9 person-years; incidence 8.7% (1.1%–31.5%) during DOT phase – 0 of 178 participants over 94.8 person-years; incidence 0.0% (0.0%–3.9%) during self- administered (SA) phase
- 10. Tenofovir diphosphate in PBMCs: Proportion achieving detectable concentration Time period Study Regimen Daily (D) Study Regimen Time (T) Study Regimen Event (E) Week 10 (with sex in the past 7 days) 100% (n=31/31) 97% (n=28/29) 93% (n=28/30) Week 30 (with sex in the past 7 days) 91% (N=21/23) 95% (N=18/19) 86% (N=12/14) Detectable >9.1 fmol/million PBMC D/T p = 0.90, D/T p = 0.28, T/E p = 0.35, global p = 0.48
- 11. Median tenofovir diphosphate drug concentration in PBMCs Time period Study Regimen Daily (D) Study Regimen Time (T) Study Regimen Event (E) Week 10 (with sex in past 7 days) (fmol/million cells) 81.1 (N=31) 35.3 (N=29) 26.4 (N=30) Week 30 (with sex in past 7 days) (fmol/million cells) 102.0 (N=23) 46.8 (N=19) 32.9 (N=14) D/T p < 0.001, D/T p < 0.001, T/E p = 0.0495, global p < 0.001
- 12. Qualitative Component Methods • 38 HPTN 067/ADAPT MSM participants joined a qualitative evaluation: 32 participants joined in 6 focus-group discussions (FGDs) and 6 attended key- informant interviews (KIIs). • Grounded theory and content analysis were used to analyze the data.
- 13. Patterns of sex • Have sex frequently • Prefer not to plan for sex • Do not have control over planning for sex with sexual partners • Self-perceived of having high HIV risk Pros • Easily taken, can take with daily vitamins • Able to set tablet-taking time regardless of sex • No need to carry tablets • No need to disclose about PrEP use Cons • Concerns about long-term impacts and side effects • Fear of being seen as being HIV-infected • Difficult to use if sex were infrequent • Difficulty to take daily for long period of time • Routine change • Tablet fatigue • Affordability Daily regimen
- 14. Patterns of sex • Have infrequent sex event • Inability to plan sex / have no control over planning for sex with sexual partners Pros • Fewer doses (less concerns about side effects) • Able to choose the day to take tablets (2 doses/week) • No need to plan for sex (keep few tablets in pocket for post-sex dose after unexpected sex event) Cons • Difficulty in linking routine activity with 2 tablet-taking days • Complicated regimen (No more than 1 dose in a 2 hour window) • Need to carry few tablets at all times • Difficult to hide tablets from sexual partners • Planning for sex made sex no longer enjoyable Time- driven regimen
- 15. Patterns of sex • Have infrequent sex event • Ability of sex planning / have control over planning for sex with sexual partners Pros • Fewer doses (less concerns about side effects) Cons • Need sex planning • Need to carry tablets at all times (pre/post-sex dose) • Difficult to hide tablets from sexual partners • Regimen confusion (need to count by hours) • Complicated regimen (No more than 1 dose in a 2 hour window) Event- driven regimen
- 16. • Compared with the daily regimen, the time-driven dosing regimens offered comparably high PrEP coverage for sex acts with – slightly less adherence – fewer tablets required • Among Thai MSM, adherence and drug concentrations were highest in the daily arm • TFV drug detection in PBMCs was high (>85%) in all 3 arms at weeks 10 and 30 in this population in Bangkok – Indicates feasibility of non-daily regimens in this population Summary of Study Results
- 17. • Daily dose was the easiest regimen without the ability to plan for sex, but there were concerns about long-term impact and affordability • Non-daily PrEP would be another choice for those MSM who have infrequent sex events, capacity to plan for sex, and ability to take a post-sex dose Summary cont’d – Qualitative Poster presentation # WELBPE23
- 18. • Among those with few exposures, non-daily dosing of PrEP could result in fewer tablets required to achieve comparable coverage – Importantly: coverage as defined in this study (1 or more pills before & after sex) is not yet known to be effective – If proven effective in future research, non-daily regimens could provide an alternative for those who can adhere • Study results offer additional support for current CDC guidelines for daily dosing Conclusion
- 19. The HIV Prevention Trials Network is sponsored by the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, and the National Institute on Drug Abuse, all components of the U.S. National Institutes of Health. ACKNOWLEDGEMENTS The HPTN 067 Bangkok Study Team acknowledges: Our HPTN 067 participants Study staff at Silom Community Clinic @TropMed DAIDS and NIMH Thailand Ministry of Public Health Epidemiology Branch, Division of HIV/AIDS Prevention, CDC MSM Community Advisory Board FHI 360 SCHARP HPTN Laboratory Center
- 20. HPTN 067: Bangkok Site Staff Supaporn Chaikummao 11/3/1954 – 31/5/2015
- 21. Pill-taking from Weekly Interview Log vs Pill Count Form
- 22. Number of Sex Acts Over Study Follow-up by Study Arm, Weekly Interview
- 23. Average number of sex acts per week (excluding oral) reported at weekly interviews by study arm
- 24. • Over the span of each previous 3 months, MSM in our study had sex on average about once per week (13 at week 6, and 12 at week 30) • Rarely if ever without a condom Period D T E Number of times had sex in past 3 months at week 6 Mean Median Without a condom 13 10 0 17 10 0 10 6 0 Number of times had sex in past 3 months at week 30 Mean Median Without a condom 14 10 0 13 10 0 9 6 0 Kruskall-Wallis p for difference between three groups at week 30 = 0.023
- 25. • Over the span of each previous 3 months, MSM had on average 7 different sex partners Period D T E Number of sex partners in past 3 months at week 6 Mean Median 5.9 3 10.8 3 4.5 3 Number of sex partners in past 3 months at week 30 Mean Median 6.2 3 9.3 4 4.5 3 Kruskall-Wallis p for difference between three groups at week 30 = 0.099
- 26. Number of Sex Acts over Last 3 Months from CASI vs Weekly Interview Log
- 27. Plasma Tenofovir Level by Number of Pills Reported Taken in Prior Week
- 28. A Phase II, Randomized, Open-label, Pharmacokinetic And Behavioral Study Of The Use Of Intermittent Oral Emtricitabine/Tenofovir Disoproxil Fumarate Pre-exposure Prophylaxis (PrEP) Alternative Dosing to Augment PrEP Pill Taking
- 29. • Oral FTC/TDF PrEP is effective for preventing sexual HIV infection when used daily • Concerns about cost and side effects can limit uptake • Daily and non-daily regimens have not been compared directly with respect to prophylactic coverage for sexual exposure • Less frequent oral dosing regimens might reduce side effects and might favorably or unfavorably affect adherence • Daily FTC/TDF (Truvada) is currently FDA-approved in U.S. for pre-exposure prophylaxis (PrEP) for HIV prevention for populations at risk including men who have sex with men (MSM) Introduction
- 30. • The HPTN 067 ADAPT trial Bangkok site, a phase 2, randomized, open-label clinical trial of oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) PrEP was conducted among men who have sex with men (MSM), and transgender women (TGW) • To assess whether recommending non-daily usage of oral FTC/TDF PrEP, compared with recommending daily usage, will be associated with: • Equivalent coverage of sex events with pre- and post- exposure dosing • Lower number of pills needed for coverage and fewer pills used • Decreased self-reported symptoms/side effects during 24 weeks of self-administered use ADAPT Study Primary Objective
- 31. • Assess safety of PrEP users • Assess adherence by study arm • Assess PrEP acceptability by arm • Evaluate potential influence of PrEP on sexual risk behavior • Assess drug levels of tenofovir, emtricitabine, and their metabolites in plasma and peripheral blood mononuclear cells (PBMCs) ADAPT Study Secondary Objectives
- 32. Methods: Eligibility • MSM and TGW were eligible if: – Male at birth, and – Reported anal intercourse with another male in the past 6 months, and – Reported >1 other HIV risk factor in the past 6 months – Normal renal function (CrCl > 70 ml/min) • Exclusion criteria included: – HIV infection – Hepatitis B infection – Symptoms of acute HIV – Use of nephrotoxic drugs – Proteinuria or glucosuria or low serum phosphate – Recent PEP or PrEP use
- 33. Final Study Visit 6 week DOT phase 24 weeks self-administered dosing 4 weeks off drug RandomizedD T E HPTN 067 Design: Bangkok Site From 07/12-08/13 Screened: 249 Enrolled: 193 Randomized: 178 Screen/Enrollment ratio of 1.29 FTC/TDF Sex coverage (D) Daily- 1 tab daily (T) Time driven- 1 tab twice a week plus 1 tab post-sex (E) Event driven- 1 tab before and 1 tab after sex No more than 2 dose daily and 7 doses/week Wk 0 Wk 34 Qualitative: 32 FGD and 6 KII: Participants, Staff MSM & TGW
- 34. Methods cont’d • We contacted participants weekly to collect dates/times of PrEP use (monitored electronically by the Wisepill™ dispensing device) and sex events • Participants filled out a computer-assisted self interview (CASI) about sexual behavior and frequency at screening, 6, 10, and 30 weeks • We collected plasma and PBMCs and analyzed for tenofovir (TFV) and FTC and their active metabolites at 10 and 30 weeks • Participants who acquired HIV infection during the study discontinued dosing and were followed until study closure and referred for post-trial care
- 35. • Coverage for all arms was defined as >1 pill taken in the 4 days before and >1 pill taken in the 24 hours after sexual intercourse • Adherence was defined as the proportion of recommended pills taken for each regimen Methods: Definitions
- 36. Definition: Covered event Coverage for all arms: >1 pill taken in the 4 days before sex >1 pill taken in the 24 hours after sex >1 tablet >1 tablet
Editor's Notes
- Good afternoon, and nice to see such a large, full room! My name is Timothy Holtz, a medical officer from the US CDC, and the director of the HIV/STD Research Program at the Thailand Ministry of Public Health – US CDC Collaboration in Bangkok. I will be presenting results of the HPTN 067 ADAPT study in Bangkok on behalf of my coauthors listed on the title slide. Given that Sharon my co-investigator has presented the background and methods of this study, I will launch into presenting the results from our site. The only difference in methods is that we tested PBMCs for tenofovir drug levels, which I will discuss in my talk.
- In total, we screened 249 men and transgender women for enrollment into 067. 56 persons were not enrolled, most commonly for abnormal liver enzymes. Among these were 11 persons who tested positive for HIV, reflecting the fact that this was a very high risk population with previously undiagnosed HIV infection After enrolling 193 MSM and TGW, 15 were not randomized, including 2 persons who seroconverted in the DOT Phase, which I will discuss shortly. We randomized 178 participants that were evenly distributed between the three arms in the self administered phase of the study.
- Among the 178 Thai participants, the median age was 31 years, with a min/max of 20 to 58 and an IQR of 27 and 34. Thus, the majority of participants were in their early 30s, and nearly 90% had completed or were still in college. There were 2 TGW participants, with the rest self identifying as male. Only 11% were unemployed. Participants also included some students. There were no statistically significant differences between the 3 arms for any of the participant demographic characteristics collected.
- As Sharon described, the primary outcomes in this trial were coverage of sex events, number of tablets required and taken, and self-reported side effects. At our site, PrEP coverages were similar in arms D and T, at 85% and 84%, with no statistically significant difference between these arms [[with a p=0.79]] . Both coverages were statistically significantly greater than in arm E at 74%, which is still quite high for a non-daily regimen. Among people randomized to non-daily dosing in all cohorts, the missed dose required for full coverage was usually the post-sex dose. NOT SPOKEN The global p value for the 3 arms was 0.19, reflecting the nearly identical coverage of sex events between the daily arm, and the time-driven arm.
- As in the other sites, the number of tablets required, shown in blue, was calculated by the number required by each dosing regimen over study follow-up based on the number of reported sex acts, or daily for the D arm. The number of required tablets differed significantly by arms - daily required the most, E required the fewest tablets. The number of tablets actually taken (shown in red) were significantly lower in the T and E arms compared to daily. Sometimes participants took more tablets than required. The E arm participants were told to take a tablet if they thought they might have sex.
- We computed a single adherence number over follow-up for each participant and used a t-test (effectively) to compare mean adherence between the arms. Adherence was greater in D (at 85%) compared with T (at 79%) or E (at 65%), although there was no statistically significant difference between arms D and T in adherence. Compared with D, the number of doses required for full adherence was reduced by 57% in T and by 80% in E (p<0.001) NOT SPOKEN The “effect sizes” are the differences in mean adherence between arms. T vs D effect size -0.02; E vs D effect size -0.20; T vs E effect size 0.17 Middle line of box is the median, and edges of the box at the quartiles (so the difference is the IQR). Lines are standard for boxplot, namely length 1.5*IQR or the furthest data point, whichever is closer. The global p [< 0.001] refers to differences in adherence among all three arms These coverage and adherence findings indicate that MANY MSM and TGW can adhere to non-daily PrEP regimens.
- The neurologic and GI side effect proportions shown here are EVER occurring during the follow up period. Reported side effects were not uncommon, but were generally mild, and not substantially different in the daily and non-daily arms. CHANGE: Self reported GI: (such as nausea, vomiting, diarrhea, gas, bloating and abdominal pain) Self reported Neuro (such as headache, dizziness, lightheadedness) Jim – which p value?
- Side effects over time demonstrated a clear start up effect. Over time, all side effect reports gradually diminished with each visit, and most participants did not believe that these side effects were related to the tablets. These were data from symptom side effect CRFs.
- As stated, we had 2 seroconversions during the 6-week pre-randomization weekly DOT study phase. Both occurred at week 4. Both had low levels of FTC detected and no detectable TVF in plasma. Both had low detectable levels of FTC and TVF in PBMCs. These 2/193 participants contributed 22.9 person-years; with an incidence of 8.7% (1.1%–31.5%) during DOT phase. This is comparable to the published incidence data from our MSM cohort and VCT services, and reflects the high risk population we enrolled. Not Spoken 0 of 178 participants over 94.8 person-years; incidence 0.0% (0.0%–3.9%) during self-administered (SA) phase Resistant virus?
- Among those reporting sex in the past 7 days, the proportion of MSM and TGW in BKK who had detectable drug levels in PBMCs associated with pre- and post sex dosing was equivalent in all three arms. There was no statistically significant difference between any of the three daily or non-daily arms in our study, at either 10 or 30 weeks. With one exception, in each arm at both time periods, we found over 90% of participants had detectable concentration of tenofovir. Not Spoken All participants in daily and time-driven arm were expected to have ≥9.1fmol/106 per regimen recommendations; Only sexually active in past 7 days event-driven arm participants expected to have ≥9.1fmol/106 per regimen recommendations. Commensurate with taking 2 tablets per week in any of the arms, which was the minimum if there was full adherence.
- When we looked at TFV drug Concentrations in PBMCs at Weeks 10 and 30, participants in the daily arm had the highest concentration of drug. Higher concentrations of drug provide greater forgiveness for occasional missed doses, which is therefore greater in the D arm. The T and E arms had statistically significantly lower drug levels in PBMCs than did the D arm, and the T arm was significantly higher than E. NOT SPOKEN The median value for 4 doses per week is 18.8 (14.5-20.4) fmol/million cells, based on HPTN 066 (Anderson) Femtomole = 10-15 However, at the rate of one sex event per week on average, the only arm which would reach 4 tablets/week if they were 100% adherent is the daily arm.
- We collected qualitative data from 38 THAI participants who joined the ADAPT study IN BANGKOK. We conducted 6 focus group discussions with 32 participants and 6 key-informant interviews. Grounded theory and content analysis were used in this study COMPONENT.
- We assessed patterns of sex in 3 different arms with pros and cons of each regimen. For THE D arm, participants reported THAT this regimen worked well if they had: frequent sex eventS, A preference not to plan for sex, having no control over planning for sex with sexual partners, and self-perceived high risk for HIV. There WERE pros and cons about THE daily regimen, such as being easy-to-take as it can be taken with daily vitamins, no need to plan for sex, no need to carry the TABLETS, and no need to disclose about PrEP use. But there were concerns about long-term impact and side effects and fears about being seen as an HIV-infected PERSON. Some reported it was difficult to use if they DIDN’T have sex that much. Long-term TABLET-taking, routine change, TABLET fatigue, and affordability were also reported.
- Participants in THE T ARM reported THAT this regimen was optimal for: participants with infrequent sex eventS, an inability to plan sex or having no control over planning for sex with sexual partners. The PROs about this regimen WERE: fewer doses which meant less concerns about side effects; ABILITY TO choose the day to take 2 TABLETS a week, NO need to plan for sex, AND just keepING a few TABLETS with them for THE POST sex dose. On the other hand, the participants reported difficulty in linking routine activity with 2 TABLET-taking days, confusion about THE regimen because it is quite complicated, the need to carry TABLETS and hide them from others, and they noted that planning for sex made sex no longer enjoyable.
- Participants in THE E ARM reported THAT this regimen worked well if participants had: infrequent sex events, AND an ability to plan sex or having control over planning for sex with sexual partners. The PRO about this regimen was fewer doses REQUIRED. On the other hand, it WAS difficult for PARTICIPANTS to plan for sex, to carry TABLETS, and to hide them from others. It WAS confusing to count THE TABLET-taking time by the hour, and the regimen WAS complicated or difficult for them to follow.
- In summary, large proportions of Thai MSM and TGW took PrEP consistently when given access in a clinical setting, with coverage and adherence highest in the daily arm. However, at our site, time-driven dosing among MSM and TGW provided coverage of sexual exposures and adherence that was comparable to daily dosing, and spared a considerable number of tablets required. In our indicator of long term drug coverage, namely PBMCs, tenofovir drug detection was high in all three arms at weeks 10 and 30, indicating the feasibility of non-daily regimens in this population. Not SPOKEN And for those of you with Ipergay in mind, and trying to compare the populations, in data that was not shown, I can tell you that non-oral sex events in this population occurred on average of once per week.
- Participants reported that the daily dose was the easiest regimen without THE ability of planning for sex, but there WERE concerns about long-term impacts and affordability. We found that NON-DAILY PrEP would be another choice for those MSM who have infrequent sex events. Candidates for non-daily dosing could include MSM having relatively infrequent sexual intercourse (less than once a week), capacity for planning for sex, and ability to take a post sex dose. For more information, please visit OUR poster presentation TOMORROW.
- In Conclusion, per CDC Clinical Practice Guidelines, and US Public Health Service Guidelines, daily dosing has proven effective at reducing the risk of HIV infection in multiple clinical trials, and is the FDA-approved regimen. It provides the highest level of protection, the most forgiveness for missed doses, and fosters daily habit formation. Among those with few exposures, non-daily dosing of PrEP could result in fewer tablets required to achieve comparable coverage. However, one would lose that margin of forgiveness for missed doses [[as we found that drug concentrations were lower]] We note that coverage as defined in this study is not yet known to be effective. We have shown non-daily regimens to be feasible, and if proven effective in future research, could provide an alternative for those who are able to adhere.
- I would like to dedicate this talk to our former site coordinator for 067 at the Silom Community Clinic, who passed away before the release of these results.
- Page 52
- Data from weekly interview CRFs, page 96 Bangkok
- Page 109
- Screening, 6, 18, 30 There is a significant difference between arms in the number of times they had sex in the three months prior to week 30 as reported in the CASI? Difference is only between E and T/D Hypothesis being tested is for a difference in the outcome (number of times had sex in past 3 months) between arms at week 30. The test used was a Kruskall-Wallis test (nonparametric test)
- There is no significant difference between the arms in the number of partners in the three months prior to week 30 as reported in the CASI Hypothesis being tested is for a difference in the outcome (number of partners in the past 3 months) between arms at week 30. The test used was a Kruskall-Wallis test (nonparametric test)
- Page 92
- From page 101
- PBMC Indicator of long term drug coverage
- After 6 weeks of DOT [DOT weeks 1,2,3,4, rest 5, randomize at 6] to estimate steady state drug levels, participants were randomly assigned to one of three unblinded PrEP dosing regimens for 24 weeks of self-administered dosing as follows: Daily (D) Time Driven: Twice weekly with a post-intercourse boost (T) Event-driven: Before and after intercourse (E) Pills were dispensed from an electronic dispensing Wisepill device that recorded each opening Participants were contacted weekly by phone or in person to review Wisepill data and sex events The study included a six week lead-in period which included directly observed therapy (DOT) at Enrollment and Weeks 1 through 4, followed by one week without dosing to determine individual steady state pharmacokinetics (PK). This provided the opportunity to create a pharmacokinetic analysis of drug levels to be expected at given rates of intake (adherence). After randomization, participants completed a 24-week period of self-administered dosing (Weeks 6 through 30), with one visit four weeks after the completion of dosing (34 weeks total). Final study visit at 34 weeks, 4 weeks after ending self-administered dosing
- The regimens used in this trial and the definition of PrEP coverage was based on information that was available when the trial was designed in 2010. More current information suggests that higher concentrations of PrEP medications are required for protection from vaginal exposure to HIV, as would be afforded by daily oral dosing or any topical dosing.
- Coverage Definition is the same for all 3 arms. Only vaginal and anal sex acts will be considered; oral sex acts will not be included. Periods of product hold (prior to acquisition of HIV) are included The date and time of the sex act will be compared to the data and time of pill use as reported on item 2 of the Weekly Interview Log. A sex act will be considered “covered” if the following two conditions are met: i) At least one pill is taken during the 96 hours before the act ii) A pill is taken within 24 hours after the act Note that the same pill can cover a post-exposure dose for one event and a pre-exposure dose for a different event.