Pre-exposure prophylaxis, or PrEP, using daily tenofovir cuts the risk of HIV infection in half for people who inject drugs, according to findings from the Bangkok Tenofovir Study published last week in the Lancet .
"This is a significant step forward for HIV prevention," said Jonathan Mermin, director of the Centers for Disease Control and Prevention's Division of HIV/AIDS Prevention. "We now know that PrEP can work for all populations at increased risk for HIV."
Based on these findings, the CDC issued updated guidelines recommending that PrEP be "considered as one of several prevention options" for people at high risk for contracting HIV through injection drug use.
The study, which enrolled more than 2,400 HIV-negative injection drug users in Thailand, randomly assigned participants to take oral tenofovir (Gilead Science's Viread) or a placebo pill once daily. They also were offered risk-reduction and adherence counseling, methadone maintenance, bleach for cleaning needles, and condoms.
The results are the first to show that PrEP can lower HIV risk among injection drug users, who have high rates of infection because the virus is easily transmitted via shared needles and other injection equipment.
A total of 50 people became infected during an average four years of follow-up: 17 in the tenofovir group and 33 in the placebo group. HIV incidence rates were 0.35 per 100 person-years in the tenofovir group compared with 0.68 in the placebo, an overall risk reduction of 49 percent.
Risk reduction rose to 70 percent among participants with detectable tenofovir in their blood, and to 74 percent among people who received directly observed drug administration and did not miss more than two consecutive days.
Previous studies have shown that PrEP using tenofovir alone or tenofovir plus emtricitabine (the drugs in the Truvada combination pill) can dramatically reduce the risk of HIV transmission through sex.
The iPrEx study showed that Truvada lowered the risk of HIV infection among gay and bisexual men by 44 percent overall, rising to 92 percent for those with measurable blood drug levels.
The Partners PrEP and TDF2 trials likewise found that daily Truvada PrEP reduced new infections among heterosexual couples by more than 60 percent. However, disappointing results from the VOICE study of heterosexual women in Africa underscored that PrEP requires good adherence, which may be difficult to achieve.
In all the studies tenofovir PrEP was generally safe and well tolerated. Nausea was more common among tenofovir compared with placebo recipients in the Bangkok study, but it usually resolved after two months. No kidney-related side effects were seen. No one who became HIV-positive showed evidence of tenofovir drug resistance.
"The full potential of antiretroviral therapy in keeping people alive and well and in preventing new HIV infections is becoming apparent," said UNAIDS Executive Director Michel Sidibe. "The results of this study are important and if used effectively in HIV programming could have a significant impact in protecting people who inject drugs from becoming infected with HIV."
The CDC last week released revised interim clinical guidance for health care professionals who wish to prescribe PrEP for people who inject drugs, published in the June 14 Morbidity and Mortality Weekly Report (available free online).
Although the Bangkok study tested tenofovir alone, the CDC recommends once-daily Truvada as the preferred PrEP regimen for injection drug users. The combo pill contains the same tenofovir dose used in the study, and it already has Food and Drug Administration approval for PrEP. Truvada is more expensive than tenofovir alone, however.
Similar to existing guidelines for preventing sexual transmission, the new guidance states that PrEP should be targeted to people at "very high risk" for HIV acquisition, should be delivered as part of a comprehensive set of prevention services, and should be accompanied by quarterly monitoring.
Tenofovir or Truvada for PrEP must not be used by people who are already HIV-positive or do not know their status, as using it alone can lead to drug resistance. It is also contraindicated for people with impaired kidney function, as tenofovir can cause kidney toxicity.
Outcomes in the real world often do not match those in clinical trials that offer participants extensive monitoring and support. The two most widely voiced concerns about PrEP are that people will not take it consistently enough, and that it could lead to increased risk behavior when people believe they are protected.
As in previous PrEP trials, so-called risk disinhibition did not appear to be a problem in the Bangkok study. Participants reported reduced risk behavior over 12 months in both the tenofovir and placebo arms, including less drug injection, needle sharing, and sex with more than one partner. In fact, less than half of participants said they injected drugs during the study and few reported sharing needles.
Some HIV prevention advocates said less expensive methods like syringe exchange should not be replaced.
"People who use drugs also have sex, and there is no way of distinguishing between infection acquired via sex versus drug use," emphasized Mitchell Warren, executive director of AVAC, a global HIV prevention advocacy organization. "This is one reason why this PrEP strategy cannot be viewed as a replacement for proven prevention such as syringe exchange and drug substitution programs that specifically reduce risk of HIV via drug use."
Local advocates also were cautious.
"We already have a more effective and dramatically cheaper way to prevent HIV transmission among people who inject drugs, that can also prevent hepatitis C and link people into treatment. It's called sterile syringe access and it works very, very well," said Laura Thomas, deputy state director of the Drug Policy Alliance. "It is always useful to have another HIV prevention tool in the toolbox, but it further highlights our failure to do what works when it comes to people who use drugs."