OBJECTIVE: To study transmission dynamics during acute infection, during the aviremic phase over the period of early antiretroviral therapy (ART) and during the phase of viral rebound after early treatment was stopped. METHODS: Transmission dynamics was assessed within 111 patients, enrolled in the Zurich primary HIV infection study, by molecular epidemiological methods using pol sequences from genotypic resistance tests and clonal env C2-V3-C3 sequences. Coclustering of Zurich primary HIV infection sequences with 12,303 sequences from 8837 HIV-positive patients enrolled in the multisite Swiss HIV Cohort Study was identified. Furthermore, we investigated transmission patterns within phylogenetic clusters by using longitudinal clinical data and analyzed HIV transmission by stage of infection and attempted to localize transmission events to periods before or after early ART. RESULTS: Six transmission clusters comprising 20 men having sex with men were identified. Furthermore, linkage to eight men having sex with men from the Swiss HIV Cohort Study could be established. Strikingly, we detected at least five new primary infection events originating from Zurich primary HIV infection patients within 16-61 weeks after stopping early ART. Viral loads of likely index patients varied from 314 up to 1,690,000 HIV-1 RNA copies/ml of plasma at the estimated time of infection. CONCLUSION: The large number of new infections originating from men having sex with men who stopped early ART indicates that current preventive efforts are insufficient. In contrast, these patients showed no adherence problems. These findings argue for early, continuous ART in sexually active HIV-1-infected persons not only for individual patient benefits but also specifically to reduce the spread of HIV-1.
OBJECTIVE: To study transmission dynamics during acute infection, during the aviremic phase over the period of early antiretroviral therapy (ART) and during the phase of viral rebound after early treatment was stopped. METHODS: Transmission dynamics was assessed within 111 patients, enrolled in the Zurich primary HIV infection study, by molecular epidemiological methods using pol sequences from genotypic resistance tests and clonal env C2-V3-C3 sequences. Coclustering of Zurich primary HIV infection sequences with 12,303 sequences from 8837 HIV-positivepatients enrolled in the multisite Swiss HIV Cohort Study was identified. Furthermore, we investigated transmission patterns within phylogenetic clusters by using longitudinal clinical data and analyzed HIV transmission by stage of infection and attempted to localize transmission events to periods before or after early ART. RESULTS: Six transmission clusters comprising 20 men having sex with men were identified. Furthermore, linkage to eight men having sex with men from the Swiss HIV Cohort Study could be established. Strikingly, we detected at least five new primary infection events originating from Zurich primary HIV infectionpatients within 16-61 weeks after stopping early ART. Viral loads of likely index patients varied from 314 up to 1,690,000 HIV-1 RNA copies/ml of plasma at the estimated time of infection. CONCLUSION: The large number of new infections originating from men having sex with men who stopped early ART indicates that current preventive efforts are insufficient. In contrast, these patients showed no adherence problems. These findings argue for early, continuous ART in sexually active HIV-1-infectedpersons not only for individual patient benefits but also specifically to reduce the spread of HIV-1.
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