Uptake of pre-exposure prophylaxis, sexual practices, and HIV incidence in men and transgender women who have sex with men: a cohort study

Abstract

Background: The effect of HIV pre-exposure prophylaxis (PrEP) depends on uptake, adherence, and sexual practices. We aimed to assess these factors in a cohort of HIV-negative people at risk of infection.

Methods: In our cohort study, men and transgender women who have sex with men previously enrolled in PrEP trials (ATN 082, iPrEx, and US Safety Study) were enrolled in a 72 week open-label extension. We measured drug concentrations in plasma and dried blood spots in seroconverters and a random sample of seronegative participants. We assessed PrEP uptake, adherence, sexual practices, and HIV incidence. Statistical methods included Poisson models, comparison of proportions, and generalised estimating equations.

Findings: We enrolled 1603 HIV-negative people, of whom 1225 (76%) received PrEP. Uptake was higher among those reporting condomless receptive anal intercourse (416/519 [81%] vs 809/1084 [75%], p=0·003) and having serological evidence of herpes (612/791 [77%] vs 613/812 [75%] p=0·03). Of those receiving PrEP, HIV incidence was 1·8 infections per 100 person-years, compared with 2·6 infections per 100 person-years in those who concurrently did not choose PrEP (HR 0·51, 95% CI 0·26-1·01, adjusted for sexual behaviours), and 3·9 infections per 100 person-years in the placebo group of the previous randomised phase (HR 0·49, 95% CI 0·31-0·77). Among those receiving PrEP, HIV incidence was 4·7 infections per 100 person-years if drug was not detected in dried blood spots, 2·3 infections per 100 person-years if drug concentrations suggested use of fewer than two tablets per week, 0·6 per 100 person-years for use of two to three tablets per week, and 0·0 per 100 person-years for use of four or more tablets per week (p<0·0001). PrEP drug concentrations were higher among people of older age, with more schooling, who reported non-condom receptive anal intercourse, who had more sexual partners, and who had a history of syphilis or herpes.

Interpretation: PrEP uptake was high when made available free of charge by experienced providers. The effect of PrEP is increased by greater uptake and adherence during periods of higher risk. Drug concentrations in dried blood spots are strongly correlated with protective benefit.

Funding: US National Institutes of Health.

Figure 1

Consort Diagram of the HIV Uninfected iPrEx OLE Cohort. The sources of participants, HIV status, PrEP eligibility, and PrEP use is tracked. All HIV infected persons were offered participation in the study. Numbers of visits and seroconversions at week 72 are higher due to participants who had been out of follow up who returned for a final visit.

Figure 2

HIV-1 Incidence and TFV-DP in DBS. For those visits on PrEP, the incidence of HIV is estimated by exponential regression by TFV-DP in DBS. The incidence for the prior placebo group is depicted as a constant for reference. The dotted lines represent the estimate bounded by one standard error. Dosing for each interval is estimated by pharmacokinetic modeling. The hazard ratios were adjusted for study site, age, ncRAI at entry and syphilis. TFV-DP measurements were not available for 5% of visits in the cohort.

Figure 3

PrEP Drug Detection Over Time. Panel A is the proportion of study participants who had TFV-DP detected in DBS over the course of the study, stratified by the level of detection in DBS at week 4. Week 4 concentrations greater than 350 fmol/punch were associated with sustained PrEP use over time. PrEP discontinuation occurs mainly in the first 24 weeks. Panel B depicts patterns of drug concentrations in DBS for each seronegative participant who received PrEP at enrollment. Each line reflects one participant. Panel C depicts the proportion of seronegative controls and seronconverters having drug concentrations that were detectable or clinically significant (>350/punch) over time. The x axis plots time from the first laboratory evidence of HIV-1 infection, which could have been seroconversion, or detection of HIV RNA, or both in seroconverters. Seronegatives were frequency matched to cases by site on this time scale. Panel D depicts a cascade of PrEP uptake and treatment as a percentage of people with indications for PrEP at enrollment. Indications for PrEP use included more than one anal intercourse partner in the past 6 months, ncRAI, syphilis, GC, or CT infection at enrollment. DBS levels of TFV-DP of >350 fmol/punch are associated with substantial reductions in HIV incidence.

Figure 3

PrEP Drug Detection Over Time. Panel A is the proportion of study participants who had TFV-DP detected in DBS over the course of the study, stratified by the level of detection in DBS at week 4. Week 4 concentrations greater than 350 fmol/punch were associated with sustained PrEP use over time. PrEP discontinuation occurs mainly in the first 24 weeks. Panel B depicts patterns of drug concentrations in DBS for each seronegative participant who received PrEP at enrollment. Each line reflects one participant. Panel C depicts the proportion of seronegative controls and seronconverters having drug concentrations that were detectable or clinically significant (>350/punch) over time. The x axis plots time from the first laboratory evidence of HIV-1 infection, which could have been seroconversion, or detection of HIV RNA, or both in seroconverters. Seronegatives were frequency matched to cases by site on this time scale. Panel D depicts a cascade of PrEP uptake and treatment as a percentage of people with indications for PrEP at enrollment. Indications for PrEP use included more than one anal intercourse partner in the past 6 months, ncRAI, syphilis, GC, or CT infection at enrollment. DBS levels of TFV-DP of >350 fmol/punch are associated with substantial reductions in HIV incidence.

Figure 3

PrEP Drug Detection Over Time. Panel A is the proportion of study participants who had TFV-DP detected in DBS over the course of the study, stratified by the level of detection in DBS at week 4. Week 4 concentrations greater than 350 fmol/punch were associated with sustained PrEP use over time. PrEP discontinuation occurs mainly in the first 24 weeks. Panel B depicts patterns of drug concentrations in DBS for each seronegative participant who received PrEP at enrollment. Each line reflects one participant. Panel C depicts the proportion of seronegative controls and seronconverters having drug concentrations that were detectable or clinically significant (>350/punch) over time. The x axis plots time from the first laboratory evidence of HIV-1 infection, which could have been seroconversion, or detection of HIV RNA, or both in seroconverters. Seronegatives were frequency matched to cases by site on this time scale. Panel D depicts a cascade of PrEP uptake and treatment as a percentage of people with indications for PrEP at enrollment. Indications for PrEP use included more than one anal intercourse partner in the past 6 months, ncRAI, syphilis, GC, or CT infection at enrollment. DBS levels of TFV-DP of >350 fmol/punch are associated with substantial reductions in HIV incidence.

Figure 3

PrEP Drug Detection Over Time. Panel A is the proportion of study participants who had TFV-DP detected in DBS over the course of the study, stratified by the level of detection in DBS at week 4. Week 4 concentrations greater than 350 fmol/punch were associated with sustained PrEP use over time. PrEP discontinuation occurs mainly in the first 24 weeks. Panel B depicts patterns of drug concentrations in DBS for each seronegative participant who received PrEP at enrollment. Each line reflects one participant. Panel C depicts the proportion of seronegative controls and seronconverters having drug concentrations that were detectable or clinically significant (>350/punch) over time. The x axis plots time from the first laboratory evidence of HIV-1 infection, which could have been seroconversion, or detection of HIV RNA, or both in seroconverters. Seronegatives were frequency matched to cases by site on this time scale. Panel D depicts a cascade of PrEP uptake and treatment as a percentage of people with indications for PrEP at enrollment. Indications for PrEP use included more than one anal intercourse partner in the past 6 months, ncRAI, syphilis, GC, or CT infection at enrollment. DBS levels of TFV-DP of >350 fmol/punch are associated with substantial reductions in HIV incidence.