Genital HIV shedding among women can be affected

Plasma and cervical viral loads among Ugandan and Zimbabwean women during acute and early HIV-1 infection.

Morrison CS, Demers K, Kwok C, Bulime S, Rinaldi A, Munjoma M, Dunbar M, Chipato T, Byamugisha J, Van Der Pol B, Arts E, Salata RA. AIDS. 2010 Feb. [Epub ahead of print]

High levels of HIV-1 viraemia exist in peripheral blood during acute and early infection; however, data on HIV-1 viral loads in female genital secretions during this period are sparse. The study was a prospective cohort of 188 African women with primary HIV-1 infection. HIV-uninfected and infected women were followed quarterly and the authors tested serial plasma specimens by HIV PCR to estimate infection dates. They used the Loess procedure to estimate the magnitude and timing of viral setpoints in plasma and cervical secretions and generalized estimating equations to identify predictors of plasma and cervical viral setpoints. Morrison and colleagues estimated the mean HIV-1 plasma setpoint to be 4.20 log10 HIV-1 RNA copies/ml [95% confidence interval (CI) 4.04-4.35] at 121 days (95% CI 91-137) from infection; an analogous mean cervical viral setpoint was 1.64 log10 HIV-1 RNA copies/swab (95% CI 1.46-1.82) at 174 days (95% CI 145-194) from infection. Cervical loads were significantly higher (0.7-1.1 log10 copies/swab) during acute infection than subsequently. Subtype D infection, pregnancy, breastfeeding, and older age at the time of infection were associated with higher plasma viral setpoint. Subtype C infection, nonviral sexually transmitted infections, having a partner spending nights away from home, recent unprotected sex, and shorter time since infection were associated with higher cervical HIV-1 loads. Hormonal contraception was not associated with either the HIV-1 plasma setpoint or cervical loads during early infection. Cervical HIV-1 viral loads were highest during acute infection and then declined up to 6 months following infection, when a 'setpoint' was attained. The prognostic value of a cervical 'setpoint' on future transmission risk remains unclear.

Genital HIV shedding among women can be affected by both local factors (menstruation, cervical and vaginal infections, abnormal vaginal flora, and genital inflammation) and systemic factors (plasma viral load, CD4 counts, HIV-1 subtype, pregnancy, hormonal contraceptive use, and antiretroviral therapy). This study documented a strong correlation between plasma viral load and genital viral load in early infection. Higher cervical viral loads during early infection were associated with nonviral sexually transmitted infections (i.e. Chlamydia, gonorrhoea, trichomonas), recent unprotected sex, subtype C infection, having a partner more than 1 night away from home in the past 30 days, and shorter duration since infection. Further, this is the first study to describe a genital viral setpoint. The fact that it was achieved later in the genital compartment, being reached at 174 days from the estimated date of seroconversion compared to the plasma viral setpoint reached at 121 days, suggests further avenues of research to determine whether both the time to achieving setpoint as well as the actual setpoint level predict potential infectivity. Importantly, would addressing the factors associated with higher cervical viral loads in early infection bring down viral load and lead to a lower genital viral setpoint?