HIV spread rapidly among injecting drug users (IDUs) in Bangkok in the late 1980s 
and HIV prevalence has remained high, 30% to 50% 
. Safe and effective tools to prevent HIV infection among IDUs are urgently needed. Use of antiretroviral drugs before HIV exposure (pre-exposure prophylaxis) may protect people at high risk of HIV from infection and provide a new tool to reduce HIV transmission.
The Bangkok Tenofovir Study is an ongoing phase-3, randomized, double-blind, placebo-controlled, endpoint-driven HIV prevention trial that aims to determine if daily oral Tenofovir Disoproxil Fumarate (tenofovir) will reduce HIV transmission among IDUs. Tenofovir, a nucleotide reverse transcriptase inhibitor, is a potent antiretroviral with a long half-life allowing once-daily dosing 
. Data from clinical trials among people infected with HIV have shown that tenofovir has a good safety profile 
, a low potential to select for tenofovir resistance 
, and co-administration of tenofovir with methadone and/or oral contraceptives does not alter the pharmacokinetics or pharmacodynamics of these drugs 
. Tenofovir was licensed for the treatment of HIV infection by the US Food and Drug Administration in 2001 and the Thailand Food and Drug Administration in 2006.
Several lines of evidence suggest that pre-exposure prophylaxis with tenofovir will reduce HIV transmission among IDUs. Studies of macaques have shown that tenofovir can prevent or delay infection with simian immunodeficiency virus and humanized derivatives called SHIV 
and the use of antiretroviral drugs reduces the risk that HIV-infected pregnant women will transmit HIV to their newborns 
and that health care workers will become infected following occupational exposures to HIV 
Following consultations with IDUs and representatives of organizations working with communities at risk for HIV infection, we began preparations for an HIV pre-exposure prophylaxis trial in 2004 
. The findings of two longitudinal studies conducted among IDUs in Bangkok informed the design of the study. The first was a preparatory cohort study 
that enrolled 1209 IDUs at drug-treatment clinics managed by the Bangkok Metropolitan Administration (BMA), the city government of Bangkok, during 1995–1996 and followed them for 3 years. The second study was the 1999–2003 AIDSVAX B/E Vaccine Trial 
conducted among 2546 IDUs in the same BMA drug-treatment clinics. The vaccine did not prevent HIV infection, but IDUs showed a continued willingness to participate in research and 90% completed the study. HIV incidence remained stable during follow-up at 3.4 per 100 person-years.
Based on community interest in promising HIV prevention interventions, ongoing high HIV incidence among IDUs 
, and evidence suggesting pre-exposure prophylaxis with tenofovir would prevent HIV infection 
, a protocol to evaluate tenofovir among IDUs was developed and submitted for regulatory review. Regulatory approvals were obtained in May 2005 and the Bangkok Tenofovir Study was launched in June 2005.
Since the study began several other pre-exposure prophylaxis trials have provided results that support the rationale for the Bangkok Tenofovir Study. A trial among women in South Africa found use of tenofovir vaginal gel reduced HIV acquisition by 39% 
and a trial among men who have sex with men found use of daily oral truvada (tenofovir+emtricitabine) reduced HIV incidence by 44% 
. Although a trial comparing daily oral truvada to placebo among women in several African countries was stopped in 2010 because interim data showed that it was unlikely the study would demonstrate lower HIV infection rates among women receiving truvada 
, a trial among heterosexual men and women in Botswana found that participants randomized to receive daily truvada were 63% less likely to become HIV infected than participants receiving placebo 
and a trial among heterosexual HIV serodiscordant couples in Kenya and Uganda found that daily tenofovir reduced HIV acquisition 62% and daily truvada 73% compared to placebo 
Overall, these studies provide evidence that pre-exposure prophylaxis with tenofovir or truvada is safe and can reduce the risk of sexual transmission of HIV among heterosexual couples and men who have sex with men. The results do not provide information about the efficacy of tenofovir or truvada to prevent parenteral transmission of HIV among IDUs. In order to determine if daily oral tenofovir can reduce the risk of HIV infection among IDUs, we are moving forward to complete the Bangkok Tenofovir Study.
The research team became aware during the first year of the study that participant risk behavior differed from Vaccine Trial participants, suggesting HIV incidence would be lower than expected. Here, we describe Bangkok Tenofovir Study recruitment, screening, and enrollment, and contrast risk behavior of Tenofovir Study participants with Vaccine Trial participants. These findings led the research team to increase Bangkok Tenofovir Study enrollment and change to an endpoint-driven study design.