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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., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Many developing countries have not implemented the AIDS Clinical Trials Group 076 zidovudine regimen for prevention of perinatal HIV-1 transmission because of its complexity and cost. We investigated the safety and efficacy of short-course oral zidovudine administered during late pregnancy and labour., Methods: In a randomised, double-blind, placebo-controlled trial, HIV-1-infected pregnant women at two Bangkok hospitals were randomly assigned placebo or one zidovudine 300 mg tablet twice daily from 36 weeks' gestation and every 3 h from onset of labour until delivery. Mothers were given infant formula and asked not to breastfeed. The main endpoint was babies' HIV-1-infection status, tested with HIV-1-DNA PCR at birth, 2 months, and 6 months. We measured maternal plasma viral concentrations by RNA PCR., Findings: Between May, 1996, and December, 1997, 397 women were randomised; 393 gave birth to 395 live-born babies. Median duration of antenatal treatment was 25 days, and median number of doses during labour was three. 99% of women took at least 90% of scheduled antenatal doses. Adverse events were similar in the study groups. Of 392 babies with at least one PCR test, 55 tested positive: 18 in the zidovudine group and 37 in the placebo group. The estimated transmission risks were 9.4% (95% CI 5.2-13.5) on zidovudine and 18.9% (13.2-24.2) on placebo (p=0.006; efficacy 50.1% [15.4-70.6]). Between enrolment and delivery, women in the zidovudine group had a mean decrease in viral load of 0.56 log. About 80% of the treatment effect was explained by lowered maternal viral concentrations at delivery., Interpretation: A short course of twice-daily oral zidovudine was safe and well tolerated and, in the absence of breastfeeding, can lessen the risk for mother-to-child HIV-1 transmission by half. This regimen could prevent many HIV-1 infections during late pregnancy and labour in less-developed countries unable to implement the full 076 regimen.