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

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Summary

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.

Introduction

Pre-exposure prophylaxis (PrEP) with oral emtricitabine and tenofovir disoproxil fumarate prevents the acquisition of HIV among men and transgender women who have sex with men,1 heterosexual couples,2 and heterosexual men and women.3 The effectiveness of PrEP depends greatly on both the efficacy of the drugs4, 5 and multiple social interactions and behaviours related to uptake and adherence.

In randomised placebo-controlled trials,1, 2 adherence to PrEP (assessed by detection of drugs in blood) was a strong correlate of efficacy. HIV risk was reduced by 90% or more among people using PrEP who had detectable drug in two trials,4, 5 whereas two trials of African women showed no evidence of efficacy on an intention-to-treat basis; despite high reported adherence, less than a third of participants receiving active drug had detectable concentrations in their blood.6, 7

The theory of risk compensation predicts that people are more likely to participate in risky sexual practices with the advent of biomedical disease-prevention strategies, including medical circumcision, antiretroviral treatment for HIV infection, and PrEP.8 By contrast, self-reported sexual practices became safer in trials of PrEP,2, 9, 10 including among people who thought that they were receiving the active treatment and that it would be effective.9 Self-reported increases in safe behaviour were corroborated by decreases in the incidence of syphilis and prevalence of acute HIV infection.9

Patterns in PrEP use11 and sexual practices12 could differ in clinical practice from those reported in clinical trials. Participants in masked and placebo-controlled efficacy trials are informed that they might be receiving a placebo or a drug with no benefit and that product safety requires further confirmation. Such messages could undermine adherence and limit risk compensation. As information from trials about PrEP safety and efficacy becomes available, adherence could increase and condom use could decrease. Open-label treatment could also alter uptake of PrEP; as people focus more on their personal goals rather than research goals, intentions to use PrEP might be greater when HIV exposure is greatest or PrEP might be taken up in clinical practice primarily by the so-called worried well, who are already protecting themselves in other ways. The overall effect of PrEP in practice depends on these behaviours.

Our aim was to investigate PrEP uptake, adherence, and sexual practices in a way that more closely resembles clinical practice. Because social desirability can bias self-reported adherence, we use tenofovir diphosphate measured in dried blood spots as a novel biomarker of long-term PrEP use.

Section snippets

Participants

In this cohort study we sought to identify demographic and behavioural characteristics associated with PrEP uptake and adherence and the effect of PrEP uptake and adherence on HIV incidence and sexual practices. We enrolled participants from three previous randomised controlled trials: ATN 082,13 iPrEx,1 and US Safety Study.14 All participants in the iPrEx open-label extension were designated male at birth, reported having had anal intercourse with men, were older than age 18 years, and had

Results

We enrolled participants between June 13, 2011, and June 26, 2012. Most patients came from the randomised phase of the iPrEx study, which had the last treatment visits in November, 2010 (figure 1). Former participants of ATN 082 completed treatment visits in November, 2010, and were enrolled in Chicago and were all non-white men aged 18–25 years. Former participants of US Safety Study ended treatment visits in 2009 and enrolled in San Francisco and Boston. 265 (17%) of 1603 who enrolled and

Discussion

Uptake of PrEP was high across a range of demographic subgroups of men and transgender women who have sex with men who were previously enrolled in masked placebo-controlled trials, and had access to PrEP at no charge from experienced health-care providers. Such high uptake has also been reported among heterosexual couples finishing the placebo-controlled phase of the Partner's PrEP trial.21 These findings contrast with population surveys of men who have sex with men suggesting that use of PrEP

References (32)

  • MM Cassell et al.

    Risk compensation: the Achilles' heel of innovations in HIV prevention?

    BMJ

    (2006)
  • JL Marcus et al.

    No evidence of sexual risk compensation in the iPrEx trial of daily oral HIV preexposure prophylaxis

    PLoS One

    (2013)
  • AY Liu et al.

    Sexual risk behavior among HIV-uninfected men who have sex with men participating in a tenofovir preexposure prophylaxis randomized trial in the United States

    J Acquir Immune Defic Syndr

    (2013)
  • KR Amico et al.

    Adherence to preexposure prophylaxis: current, emerging, and anticipated bases of evidence

    Clin Infect Dis

    (2014)
  • SG Hosek et al.

    The acceptability and feasibility of an HIV preexposure prophylaxis (PrEP) trial with young men who have sex with men

    J Acquir Immune Defic Syndr

    (2013)
  • LA Grohskopf et al.

    randomized trial of clinical safety of daily oral tenofovir disoproxil fumarate (tdf) among HIV-uninfected men who have sex with men (MSM) in the United States

    J Acquir Immune Defic Syndr

    (2013)
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