Early antiretroviral treatment dramatically decreases the risk of HIV transmission to sexual partners, according to study findings released last week.
HIV Prevention Trials Network Study 052, which included more than 1,700 serodiscordant couples (one HIV-positive and one -negative partner) in nine countries, found that positive partners who started treatment right away were 96 percent less likely to pass on the virus than those who delayed therapy.
These findings lend support to test and treat proponents who believe expanded HIV screening and early treatment offer both individual and public health benefits.
"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 Dr. Anthony Fauci of the National Institute of Allergy and Infectious Diseases, which sponsored the trial.
Combination antiretroviral therapy typically reduces HIV viral load to a low or undetectable level, and people with low viral load have been shown to be less likely to transmit the virus.
Current U.S. guidelines recommend starting treatment when a person's CD4 T-cell count falls to 500. World Health Organization guidelines for resource-limited countries call for starting at a threshold of 350.
A growing body of evidence suggests that earlier treatment may be beneficial for individual health, for example by controlling HIV-related inflammation. Skeptics argue that concerns about long-term side effects, drug resistance, and cost favor a more cautious approach.
The San Francisco Department of Public Health and San Francisco General Hospital sparked controversy in early 2010 when they adopted a policy of offering immediate treatment to everyone diagnosed with HIV, regardless of CD4 cell count.
HPTN 052 is the first randomized study to show that early treatment started when a person's CD4 count is still high reduces the risk of sexual transmission of HIV. This strategy is already routinely used for HIV-positive pregnant women to prevent mother-to-child transmission.
"In San Francisco, we already recommend that everyone with HIV, regardless of their CD4 count, consider starting treatment to benefit their own health," said Dr. Bradley Hare, medical director of SFGH's Positive Health Program. "This study shows an additional benefit in terms of dramatically reducing new HIV infections among sexual partners."
Starting in 2005, trial investigators enrolled 1,763 serodiscordant couples – almost all of them heterosexual – in Brazil, Thailand, several African countries, and a few in the U.S. Couples were about evenly divided between those with an HIV-positive woman and those with an HIV-positive man.
At the time of enrollment, HIV-positive partners had CD4 counts between 350 and 550, above the treatment initiation threshold in effect at the time. Positive participants were randomly assigned to either start a three-drug antiretroviral regimen immediately or to defer treatment until their T-cell count fell below 250 or they developed an AIDS-related illness.
Participants in both groups also received safer sex counseling, free condoms, regular HIV testing, and screening and treatment for other sexually transmitted diseases.
A planned interim analysis found that HIV-positive men and women who started treatment right away were significantly less likely to transmit the virus. Among the 28 people who were newly infected with an HIV strain genetically linked to that of their regular partner, 27 were in the delayed therapy group compared with just one assigned to the immediate treatment group.
In addition, 17 HIV-positive people in the delayed treatment group developed extrapulmonary tuberculosis compared with three in the immediate treatment arm, demonstrating an individual benefit for partners with HIV as well.
The researchers originally planned to end the trial in 2015, but based on these findings an independent data and safety monitoring board recommended that it should end ahead of schedule and HIV-positive partners in the delayed treatment group should now be offered therapy.
"With these results we should redouble our efforts to diagnose individuals with HIV earlier," said HIV Medicine Association Chair Kathleen Squires. "We now have further evidence that effective treatment not only benefits the individual but also will help reduce the spread of this disease."
HPTN 052 lead investigator Myron Cohen emphasized that the risk-reduction counseling offered to all participants was itself a "powerful intervention," as shown by the overall low likelihood of HIV transmission in the study.
"Counseling as background in both groups really drastically reduced transmission by itself, and antiretroviral therapy provided a profound additional reduction," Cohen told the Bay Area Reporter . "These results prove beyond a doubt that early therapy benefits personal health as well as public health."
While this study provides further strong evidence that early treatment reduces HIV transmission risk, a number of researchers have reported occasional cases of transmission from individuals on combination therapy with undetectable viral load. Many clinicians and advocates have therefore argued that it is irresponsible to suggest that people on treatment can safely engage in unprotected sex.
Rather, early antiretroviral therapy can play a role as one of several interventions in a comprehensive risk reduction approach that also includes counseling, condoms, and perhaps microbicides and pre-exposure prophylaxis, or PrEP.
Since HPTN 052 almost exclusively enrolled heterosexual couples, its results cannot be assumed to apply to men who have sex with men. There is good reason to expect that lowering viral load would decrease transmission risk among gay and bisexual men as well, but similar controlled studies are needed to demonstrate the magnitude of risk reduction.