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HIV Treatment Dramatically Reduces Sexual Transmission

Early antiretroviral therapy (ART) decreased the likelihood of HIV transmission between heterosexual partners by 96% in the large international HPTN 052 trial.

Effective combination antiretroviral treatment usually reduces HIV RNA to a low or undetectable level, and people with a low viral load are much less likely to transmit the virus. This has been conclusively demonstrated for mother-to-child HIV transmission, and new findings confirm that it applies to sexual transmission as well.

HIV Prevention Trials Network (HPTN) Study 052 is a large Phase 3 clinical study, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), looking at the effects of early ART on HIV transmission risk.

Myron Cohen from the University of North Carolina at Chapel Hill and colleagues enrolled 1763 serodiscordant couples -- almost all of them heterosexual -- in 9 countries (Botswana, Brazil, India, Kenya, Malawi, South Africa, Thailand, U.S., and Zimbabwe) starting in 2005. Couples were about evenly divided between those with an HIV positive woman and those with an HIV positive man; past research has shown that HIV is more easily transmitted sexually from male to female than vice versa.

At the time of enrollment the HIV positive partners had CD4 T-cells counts between 350 and 550 cells/mm3 -- above the recommended threshold for treatment initiation at the start of the trial. (U.S. treatment guidelines now recommend starting when the CD4 count falls to 500 cells/mm3.)

HIV positive participants were randomly assigned to either start a 3-drug antiretroviral regimen immediately or defer treatment until their CD4 count fell below 250 cells/mm3 or they developed an AIDS-related illness. Participants used various combinations made up of 11 different drugs. In addition, people in both groups received safer sex counseling, free condoms, regular HIV testing, and screening and treatment for other sexually transmitted infections.

Results

• HIV positive men and women who started ART early were significantly less likely to transmit the virus to their sexual partner.
• An interim analysis found 39 cases of HIV infection among previously negative participants, 28 of which were genetically linked to their regular HIV positive partner.
• Of these 28 linked infections, only 1 occurred among couples in the immediate ART arm, compared with 27 in the deferred treatment group.
• Based on these numbers, immediate ART reduced the risk of HIV transmission by 96.3%.
• Furthermore, 17 cases of extrapulmonary tuberculosis occurred among HIV positive partners in the deferred treatment arm compared with just 3 cases in the immediate ART arm, a statistically significant difference.
• The number of deaths was similar, however, with 10 in the immediate ART arm and 13 in the deferred treatment group.

HPTN 052 was originally designed to end in 2015, but an independent Data and Safety Monitoring Board recommended that the study should be halted and results released ahead of schedule after an interim review showed that immediate ART substantially reduced HIV transmission risk. HIV positive partners in the deferred treatment arm will now be offered ART and participants will be followed for at least a year.

"The results are the first from a major randomized clinical trial to indicate that treating an HIV-infected individual can reduce the risk of sexual transmission of HIV to an uninfected partner," according to a NIAID press release.

Previous observational studies and mathematical models have indicated that early ART could reduce transmission, but these new findings from a "gold standard" randomized trial provide stronger evidence.

"This new finding convincingly demonstrates that treating the infected individual -- and doing so sooner rather than later -- can have a major impact on reducing HIV transmission, said NIAID Director Anthony Fauci. He added in a media briefing that HPTN 052 "nails the concept down."

In 2008 the Swiss Federal Commission for HIV/AIDS sparked controversy when it issued a statement saying, "An HIV-infected person on antiretroviral therapy with completely suppressed viremia...is not sexually infectious." The commission emphasized that the statement only applied to vaginal intercourse between heterosexual partners in which neither had other sexually transmitted infections and the HIV positive person had a stable undetectable viral load on ART for at least 6 months.

A number of researchers have reported rare cases of HIV transmission from individuals on ART with undetectable viral load, however, and many clinicians and advocates have argued that it is irresponsible to suggest that people on treatment can safely engage in unprotected sex.

Since HPTN 052 almost exclusively enrolled heterosexual couples, its results cannot be applied to men who have sex with men. There is good reason to expect that lowering viral load will reduce transmission in this population as well, but similar controlled studies are needed to show the magnitude of risk reduction.

The latest findings will further inform the ongoing debate about treatment as prevention. These data lend support to "test and treat" proponents who believe everyone who tests HIV positive should begin treatment right away, both for their own health and for the public health benefit of reducing transmission. In early 2010 the San Francisco Department of Public Health and San Francisco General Hospital were the first to adopt a policy of offering immediate ART to everyone diagnosed with HIV.

Others, however, feel that the long-term effects of antiretroviral agents are not yet fully understood, and argue that concerns about drug resistance, lifelong adherence, and cost weigh in favor of a more cautious approach.

"With these results we should redouble our efforts to diagnose individuals with HIV earlier," said HIV Medicine Association Chair Kathleen Squires in a press release issued by HIVMA and the Center for Global Health Policy. "We now have further evidence that effective treatment not only benefits the individual but also will help reduce the spread of this disease."

"This rigorously conducted clinical trial demonstrates that ART dramatically reduces HIV transmission from an infected partner to an uninfected spouse or partner," concurred HPTN investigator Sten Vermund from Vanderbilt University in a Family Health International press release. "Earlier therapy is a superior option that benefits both an infected individual and his or her uninfected partner and we support global efforts to offer ART to everyone who needs it."

A NIAID press release describing HPTN 052 is available online at www.niaid.nih.gov/news/newsreleases/2011/Pages/HPTN052.aspx.

Questions and Answers about the study are available at www.niaid.nih.gov/news/QA/Pages/HPTN052qa.aspx.

5/13/11

Sources

NIAID. Treating HIV-infected People with Antiretrovirals Protects Partners from Infection. Press release. May 12, 2011.

Family Health International. Initiation of Antiretroviral Treatment Protects Uninfected Sexual Partners from HIV Infection (HPTN Study 052). Press release. May 12, 2011.

HIV Medicine Association and Center for Global Health Policy. Study Shows Early HIV Treatment Prevents New Infections and Preserves Health. Press release. May 12, 2011.