Elsevier

The Lancet

Volume 381, Issue 9883, 15–21 June 2013, Pages 2083-2090
The Lancet

Articles
Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial

https://doi.org/10.1016/S0140-6736(13)61127-7Get rights and content

Summary

Background

Antiretroviral pre-exposure prophylaxis reduces sexual transmission of HIV. We assessed whether daily oral use of tenofovir disoproxil fumarate (tenofovir), an antiretroviral, can reduce HIV transmission in injecting drug users.

Methods

In this randomised, double-blind, placebo-controlled trial, we enrolled volunteers from 17 drug-treatment clinics in Bangkok, Thailand. Participants were eligible if they were aged 20–60 years, were HIV-negative, and reported injecting drugs during the previous year. We randomly assigned participants (1:1; blocks of four) to either tenofovir or placebo using a computer-generated randomisation sequence. Participants chose either daily directly observed treatment or monthly visits and could switch at monthly visits. Participants received monthly HIV testing and individualised risk-reduction and adherence counselling, blood safety assessments every 3 months, and were offered condoms and methadone treatment. The primary efficacy endpoint was HIV infection, analysed by modified intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, number NCT00119106.

Findings

Between June 9, 2005, and July 22, 2010, we enrolled 2413 participants, assigning 1204 to tenofovir and 1209 to placebo. Two participants had HIV at enrolment and 50 became infected during follow-up: 17 in the tenofovir group (an incidence of 0·35 per 100 person-years) and 33 in the placebo group (0·68 per 100 person-years), indicating a 48·9% reduction in HIV incidence (95% CI 9·6–72·2; p=0·01). The occurrence of serious adverse events was much the same between the two groups (p=0·35). Nausea was more common in participants in the tenofovir group than in the placebo group (p=0·002).

Interpretation

In this study, daily oral tenofovir reduced the risk of HIV infection in people who inject drugs. Pre-exposure prophylaxis with tenofovir can now be considered for use as part of an HIV prevention package for people who inject drugs.

Funding

US Centers for Disease Control and Prevention and the Bangkok Metropolitan Administration.

Introduction

The Joint UN Programme on HIV/AIDS reports that 2·5 million people contracted HIV in 2011.1 One in ten of these new HIV infections was probably caused by injecting drug use; in some countries in eastern Europe and central Asia, more than 80% of all HIV infections are related to drug use.2 In Thailand, HIV spread rapidly in people who inject drugs in the late 1980s3 and HIV prevalence has remained high in this group, ranging from 30% to 50%, through 2009.4 Safe and effective interventions to prevent HIV infection in this population are needed.

The use of antiretrovirals to prevent HIV infection is a promising new strategy to end the HIV/AIDS epidemic. Several lines of evidence suggest that pre-exposure prophylaxis with tenofovir disoproxil fumarate (tenofovir) can reduce HIV transmission in people who inject drugs. Findings from studies in macaque monkeys show that tenofovir can prevent or delay mucosal and parenteral infection with HIV-like viruses.5, 6, 7 Antiretrovirals are also used to reduce mother-to-child transmission8 and the risk that health-care workers will become infected after occupational HIV exposure.9 Additionally, tenofovir is an attractive candidate for use in injecting-drug users because it does not alter the pharmacokinetics or pharmacodynamics of methadone.10 In this context, we did the Bangkok Tenofovir Study, a phase 3, randomised, double-blind, placebo-controlled trial to establish whether pre-exposure prophylaxis with daily oral tenofovir would reduce the risk of HIV infection in people who inject drugs.

Since the study started in 2005, findings from other trials have shown that daily use of the combination antiretroviral tenofovir-emtricitabine can reduce HIV incidence by 44% (95% CI 15–63) in men who have sex with men,11 by 62% (22–83) in heterosexual men and women,12 and by 75% (55–87) in HIV-serodiscordant heterosexual couples,13 and that tenofovir alone can reduce transmission by 67% (44–81) in HIV-serodiscordant heterosexual couples.13 On the basis of these findings, the US Centers for Disease Control and Prevention (CDC) issued guidance on the use of pre-exposure prophylaxis to limit sexual HIV transmission in 2012.14, 15 To our knowledge, this is the first trial to assess HIV pre-exposure prophylaxis in people who inject drugs.

Section snippets

Participants and trial design

We recruited participants at 17 drug-treatment clinics in densely populated urban communities of Bangkok, Thailand. The clinics offer HIV counselling and testing, risk-reduction counselling, social services, primary medical care, methadone treatment, condoms, and bleach to clean injection equipment, all free of charge. Thailand's narcotics law prohibits the distribution of needles to inject illegal drugs, so needles are not provided in the clinics. However, sterile needles are available without

Results

Enrolment and baseline characteristics are described elsewhere.16 Briefly, from June 9, 2005, to July 22, 2010, we screened 4094 volunteers, randomly assigning 2413 to either tenofovir or placebo (figure 1). Baseline characteristics were much the same between groups (except for sexual intercourse with a casual partner in the past 12 weeks and men having sex with men in the past 12 weeks, which both seemed more common in the placebo group): the median age of participants was 31 years (mean 32·4

Discussion

Once-daily oral tenofovir decreased the risk of HIV infection by 48·9% in injecting drug users when provided with other HIV prevention services at drug-treatment clinics in Bangkok. Findings from other pre-exposure prophylaxis trials showed that adherence had an important effect on efficacy.11, 12 In this study, efficacy increased from 46% to 56% in the per-protocol analysis based on observed adherence and to 74% when limited to participants with detectable tenofovir concentrations. Although

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