Early retroviral therapy reduces HIV-1 transmission [Classics Series]

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1. HIV-1 transmission rates were significantly lower in the early-therapy group compared to the delayed-therapy group

2. Patients in the early-therapy group had lower incidence of HIV-related clinical events with a lower viral load and higher CD4 cell count than those whose therapy was delayed

Original Date of Publication: August 11, 2011

Study Rundown: This study showed that treatment of HIV with antiretroviral therapy (ART) reduces HIV-1 transmission between serodiscordant couples. The participants who started ART early also showed a reduction in the viral load and an increase in CD4 count while those in the delayed-therapy group on average had a modest decline in CD4 counts over the course of the study. ART also proved beneficial to reducing the incidence of HIV-related clinical events. The participants in the two groups did not differ with regards to gender, location, marital status, education level, self-reported sexual activity, condom use, and baseline CD4 count and viral load. The partners of HIV-infected individuals who eventually tested positive for the HIV virus were tested to ascertain whether the patient was infected by their partner. In summary, the delayed-therapy group had a significantly higher incidence of linked transmission between couples than those in the early-therapy group (HR 0.04; 95%CI 0.01-0.27).

Click to read the study in NEJM

Click to read an accompanying editorial in NEJM

In-Depth [randomized, controlled study]: This 2011 study published in NEJM was a multicenter, randomized controlled trial that randomized 1,763 serodiscordant couples to either early or delayed retroviral therapy for the HIV-infected partner and looked at the rate of seroconversion in the non-infected partner over a five-year period. Participants all had CD4 cell counts between 350-550 cells per cubic millimeter and had not received antiretroviral therapy in the past. The delayed therapy group was started on antiretroviral medication once their cell counts dropped below 250 or they developed an AIDS-defining infection. Antiretroviral medications varied between the sites. All participants had sexual intercourse with one monogamous partner, as per self-reported measures. The primary outcome was the seroconversion of the non-infected partner. Secondary outcomes included incidence of HIV-1 related clinical events and adverse events from ART.

The study demonstrated that the rate of seroconversion in the early-therapy group was significantly lower than in the delayed-therapy group (HR 0.11; 95%CI 0.04-0.32). Moreover, there were significantly lower incidence of linked transmission between couples in the early-therapy group, as compared to the delayed-therapy group (HR 0.04; 95%CI 0.01-0.27). The early therapy group also had a lower incidence of HIV-related clinical events (HR 0.59; 95%CI 0.4-0.88). Most of the difference in HIV-related clinical events was driven by the higher incidence of extrapulmonary tuberculosis in the delayed-therapy group.

By Milana Bogorodskaya and Andrew Cheung, M.D.

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