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Antiretroviral PrEP Prevents HIV Transmission among Injection Drug Users

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Pre-exposure prophylaxis (PrEP) using daily oral tenofovir (Viread) reduced the risk of HIV acquisition among injection drug users in Thailand by half, according to findings from the Bangkok Tenofovir Study, published in the June 13, 2013, advance online edition of The Lancet. These findings led the CDC to recommend that PrEP be "considered as one of several prevention options for persons at very high risk for HIV acquisition" through injection drug use.

PrEP refers to taking antiretroviral medication in advance of exposure to HIV. The iPrEx study showed that daily PrEP using tenofovir plus emtricitabine (the drugs in Truvada) prevents sexual transmission of HIV among gay and bisexual men. Likewise, the Partners PrEP and TDF2 trials found that daily Truvada PrEP reduced the incidence of new infections among heterosexual couples.However, the disappointing results from the VOICE study of women in Africa indicate that PrEP requires good adherence, which may be difficult to achieve.

The new data are the first to show that PrEP reduces HIV risk among injection drug users (IDUs), who have high rates of infection because the virus is efficiently transmitted via blood left on shared needles and other injection equipment.

Kachit Choopanya and fellow investigators with the Bangkok Tenofovir Study enrolled 2413 HIV negative injection drug users from 17 drug treatment clinics in Bangkok, who were paid for their participation. The Phase 3 study -- which ran from 2005 through 2012 -- was conducted by the U.S. Centers for Disease Control and Prevention (CDC), the Bangkok Metropolitan Administration, and the Thailand Ministry of Public Health.

Most study participants (about 80%) were men and the median age was 31 years. People already infected with HIV, those with hepatitis B, and women who were pregnant or breast-feeding were excluded. All participants reported injecting heroin or other drugs within the past year. The mean follow-up period was 4 years, with a maximum of about 7 years.

Participants were randomly assigned (1:1) to receive 300 mg oral tenofovir or placebo once-daily, and could choose either directly observed therapy (DOT) during daily visits or self-administration with monthly visits. They also received risk-reduction and adherence counseling, and were offered methadone maintenance, bleach for cleaning needles, and condoms. They underwent HIV testing every month and blood tests to monitor safety every 3 months.

Results

  • 2 participants were found to have been HIV-infected at enrollment and were excluded from further analysis.
  • 50 people became infected during follow-up: 17 in the tenofovir group and 33 in the placebo group.
  • The HIV incidence rate was 0.35 per 100 person-years in the tenofovir group compared with 0.68 per 100 person-years in the placebo group in a modified intent-to-treat analysis, a statistically significant difference.
  • This represents an overall 49% reduction in the risk of HIV infection.
  • Risk reduction rose to 70% amongparticipants with detectable blood plasma tenofovir levels.
  • Risk reduction was 74% among people in the DOT arm who took tenofovir consistently and did not miss more than 2 consecutive days.
  • Adherence was good overall, with participants who chose DOT receiving tenofovir 87% of the time, and participant diaries (DOT and self-administration combined) reporting 84% adherence.
  • Daily tenofovir was generally safe and well-tolerated.
  • Serious adverse events were uncommon and occurred with similar frequency in the tenofovir and placebo groups.
  • Nausea was reported significantly more often in the tenofovir group (8% vs 5%), but typically resolved after 2 months on the drug.
  • No one who became infected during the trial developed tenofovir drug resistance.
  • Reported risk behavior decreased over 12 months in both study arms, including drug injection (63% down to 23%), needle sharing (18% to 2%), and sex with more than 1 partner (22% to 11%). 
  • About 24% of participants were lost to follow-up or voluntary withdrew from the study, with similar drop-out rates in the tenofovir and placebo groups.

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

It is important to note that less than half of participants said they injected drugs during the study (45%, rising to 70% among those who became infected), and few reported sharing needles, so it is unclear how high their risk was for HIV infection via this route, as opposed to through sex.

"Although findings from this study provide the evidence to show that PrEP is effective in preventing HIV infection in people who inject drugs, it is less clear as to whether the findings show that PrEP prevents parenteral transmission of HIV," Salim Abdool Karim from University of KwaZulu-Natal wrote in an accompanying editorial. Nevertheless, "the overall result is that daily tenofovir does reduce HIV transmission in injecting drug users."

Trial participants will now be offered tenofovir for HIV prevention for 1 more year as part of a follow-on study to provide additional data on PrEP use and effectiveness outside a clinical trial setting.

Updated CDC Guidance

"Since daily PrEP has already been proven to reduce sexual transmission of HIV among both heterosexuals and gay/bisexual men, the new findings complete the picture of PrEP efficacy -- PrEP is now proven to prevent HIV transmission among all populations at high risk," the CDC stated in a press release.

In response to the findings, CDC released revised interim clinical guidance for healthcare professionals who wish to prescribe PrEP for HIV prevention to people who inject drugs, published in the June 14, 2013, issue of Morbidity and Mortality Weekly Report.

"CDC recommends that pre-exposure prophylaxis (PrEP) be considered as one of several prevention options for persons at very high risk for HIV acquisition through the injection of illicit drugs," the guidance states.

The agency recommends daily Truvada as the preferred PrEP regimen for IDUs because the combo pill contains the same 300 mg tenofovir dose used in the Bangkok trial and it shows no additional toxicities compared with tenofovir alone. Tenofovir/emtricitabine is recommended as PrEP for sexual transmission -- for which IDUs are also at risk -- and has U.S. Food and Drug Administration (FDA) approval for this indication. However, the 2-in-1 pill is more expensive than tenofovir alone.

In accordance with existing guidelines for PrEP to prevent sexual transmission, the IDU guidance also 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 PrEP must not be used by people who are already HIV positive or do not know their status (as using 1 or 2 NRTIs alone can lead to drug resistance), and is contraindicated for people with impaired kidney function (as tenofovir can cause kidney toxicity).

"[I]f PrEP delivery is integrated with prevention and clinical care for the additional health concerns faced by IDUs (e.g., hepatitis B and C infection, abscesses, and overdose), substance abuse treatment and behavioral health care, and social services, PrEP will contribute additional benefits to a population with multiple life-threatening physical, mental, and social health challenges," the guidance concludes.

Positive Response

Public health officials, researchers, and advocates lauded the Bangkok PrEP findings.

"This is a significant step forward for HIV prevention. We now know that PrEP can work for all populations at increased risk for HIV," said Jonathan Mermin, director of CDC’s Division of HIV/AIDS Prevention. "Injection drug use accounts for a substantial portion of the HIV epidemic around the world, and we are hopeful that PrEP can play a role in reducing the continued toll of HIV infection in this population."

"Today’s news, that PrEP prevents HIV among people whose primary infection risk is injection drug use, adds to clear evidence from earlier studies that PrEP is safe and effective at preventing the sexual transmission of HIV in gay and bisexual men and in heterosexual women and men," the iPrEX team stated in a press release. "With 2.5 million new HIV infections occurring last year alone, there is no reason to delay efforts to make PrEP available to the millions of people worldwide who [need] new, safe and effective HIV prevention tools."

"Piece by piece scientific advances are paving the way to the end of the AIDS epidemic," concurred UNAIDS executive director Michel Sidibé. "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."

"These results underscore what we’ve learned in a range of studies -- daily tenofovir-based PrEP works when you take it," concluded AVAC executive director Mitchell Warren.

"We need to continue to roll out proven prevention and find out more about how this oral PrEP strategy might work in a group that is at very high risk for HIV infection and has too often been ignored," he added. "PrEP using tenofovir-based drugs is a niche product that cannot and will not replace other options that are part of combination prevention. Yet it is an intervention with the real possibility of preventing infections, especially where other prevention options aren’t enough."

6/13/13

References

K Choopanya, M Martin, P Suntharasamai, et al (Bangkok Tenofovir Study Group). 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. The Lancet. June 13, 2013 (Epub ahead of print).

SS Abdool Karim. HIV pre-exposure prophylaxis in injection drug users. The Lancet. June 13, 2013 (Epub ahead of print).

CDC. Update to Interim Guidance for Preexposure Prophylaxis (PrEP) for the Prevention of HIV Infection: PrEP for Injecting Drug Users. Morbidity and Mortality Weekly Report 62(23):463-465. June 14, 2013.

Other Sources

CDC. Study Finds First Evidence that PrEP Can Reduce HIV Risk among People Who Inject Drugs. Press release. June 12, 2013.

CDC. Bangkok Tenofovir Study: PrEP for HIV prevention among people who inject drugs. CDC Fact Sheet. June 2013.

iPrEx Study. iPrEx Welcomes CDC’s Bangkok Tenofovir Study Showing Pre-Exposure Prophylaxis (PrEP) is Safe and Effective for HIV Prevention in Injection Drug Users. iPrEx New press release. June 12, 2013.

AVAC. New PrEP Trial Results Among Injecting Drug Users Underscore that PrEP Works When Taken Consistently; AVAC Calls for Accelerated Action to Get PrEP to Those Who Can Benefit From It. Press release. June 12, 2013.

UNAIDS. UNAIDS welcomes new findings that provide an additional tool for HIV prevention for people who inject drugs. Press release. June 12, 2013.