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