Primary HIV Infection Patients Research Articles

HIV-1 transmission after cessation of early antiretroviral therapy among men having sex with men

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. 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. 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. 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.

HIV-1 viral rebound dynamics after a single treatment interruption depends on time of initiation of highly active antiretroviral therapy

An important pending question is whether temporary highly active antiretroviral therapy during primary HIV infection can influence viral rebound dynamics and the subsequently established viral setpoint, through preservation and enhancement of HIV-1-specific immune responses, or through other mechanisms. We included all patients from two prospective studies who underwent a single treatment interruption while being well suppressed on highly active antiretroviral therapy. One group started highly active antiretroviral therapy during primary HIV infection, and the other group started it during chronic HIV infection with CD4 cell counts above 350 cells/microl. Data were collected up to 48 weeks from treatment interruption. The median time to viral rebound was analysed for three levels of viraemia: 50, 500 and 5000 copies HIV-RNA/ml plasma. The median time to viral rebound was significantly longer in primary HIV infection patients (n = 24) than in chronic HIV infection patients (n = 46): 8 versus 4 weeks (P < 0.001 for all three endpoints). In two primary HIV infection patients, no rebound of plasma HIV-1 RNA over 50 copies/ml occurred. In the first 4 weeks after treatment interruption, CD4+ T-cell counts declined with a median of -5.0 cells/microl blood per week in the primary HIV infection group and -45 cells/microl blood per week in the chronic HIV infection group (P < 0.05). From week 4 to 48, the decline in CD4+ T-cell count was similar in both groups. Plasma viral load and CD4 dynamics after a single interruption of highly active antiretroviral therapy were different for primary HIV infection and chronic HIV infection patients. Viral rebound is delayed or absent and early CD4 cell count decline after treatment interruption is less pronounced in primary HIV infection patients.