Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis
High plasma HIV-1 RNA concentrations are associated with increased risk of HIV-1 transmission. Initiation of antiretroviral therapy reduces plasma HIV-1 concentrations. The authors aimed to assess the effect of antiretroviral therapy use by patients infected with HIV-1 on risk of transmission to their uninfected partners. Participants in their prospective cohort analysis were from a randomised placebo-controlled trial that enrolled heterosexual African adults who were seropositive for both HIV-1 and herpes simplex virus type 2, and their HIV-1 seronegative partners. At enrolment, HIV-1 infected participants had CD4 counts of 250 cells per microlitre or greater and did not meet national guidelines for antiretroviral therapy initiation; during 24 months of follow-up, CD4 counts were measured every 6 months and antiretroviral therapy was initiated in accordance with national guidelines. Uninfected partners were tested for HIV-1 every 3 months. The primary outcome was genetically-linked HIV-1 transmission within the study partnership. The research team assessed rates of HIV-1 transmission by antiretroviral therapy status of infected participants. 3381 couples were eligible for analysis. 349 (10%) participants with HIV-1 initiated antiretroviral therapy during the study, at a median CD4 cell count of 198 (IQR 161-265) cells per microlitre. Only one of 103 genetically-linked HIV-1 transmissions was from an infected participant who had started antiretroviral therapy, corresponding to transmission rates of 0.37 (95% CI 0.09-2.04) per 100 person-years in those who had initiated treatment and 2.24 (1.84-2.72) per 100 person-years in those who had not-a 92% reduction (adjusted incidence rate ratio 0.08, 95% CI 0.00-0.57, p=0.004). In participants not on antiretroviral therapy, the highest HIV-1 transmission rate (8.79 per 100 person-years) was from those with CD4 cell counts lower than 200 cells per microlitre. In couples in whom the untreated HIV-1 infected partner had a CD4 cell count greater than 200 cells per microlitre, 66 (70%) of 94 transmissions occurred when plasma HIV-1 concentrations exceeded 50 000 copies per millilitre. Low CD4 cell counts and high plasma HIV-1 concentrations might guide use of antiretroviral therapy to achieve an HIV-1 prevention benefit. Provision of antiretroviral therapy to HIV-1 infected patients could be an effective strategy to achieve population-level reductions in HIV-1 transmission.
The results of this study, first reported at the Retrovirus Conference in San Francisco in February, were the silver lining for a trial team that had seen their acyclovir suppression trial produce flat results. They had enrolled 3400 HIV serodiscordant couples in 5 countries, couples in which one partner had HIV and herpes simplex virus-2 infection while the other was not infected. HIV-positive participants who met national guidelines for antiretroviral therapy (at the time, clinical AIDS or CD4 cell count less than 200-250 cells per ul) were referred to local HIV care clinics to start treatment. Overall, there were 103 genetically-linked transmissions (within couples) and 39 unlinked transmissions (from someone else). Of the partners of the 349 people who started antiretroviral treatment, only one person transmitted HIV to her partner and this happened within 4 months of her starting on treatment. Overall, antiretroviral treatment was associated with a 92% reduction in risk of transmission. The study also confirmed that viral load greater than 50,000 copies per ml predicted risk of transmission in participants with CD4 cell counts above 200. This suggests that from an HIV prevention perspective, prioritising people with high viral loads, regardless of CD4 cell count, would have the greatest epidemic impact. From an HIV treatment perspective, however, those who have CD4 cell counts below 350 cells/ul or with clinical AIDS are the top priority
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