Dataset Information

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

ABSTRACT: High levels of HIV-1 viremia 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.Prospective cohort of 188 African women with primary HIV-1 infection.HIV-uninfected and infected women were followed quarterly; we tested serial plasma specimens by HIV PCR to estimate infection dates. We used the Loess procedure to estimate the magnitude and timing of viral setpoints in plasma and cervical secretions and generalized estimating equations (GEE) to identify predictors of plasma and cervical viral setpoints.We 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.

SUBMITTER: Morrison CS

PROVIDER: S-EPMC3148071 | biostudies-other | 2010 Feb

REPOSITORIES: biostudies-other

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

Morrison Charles S CS Demers Korey K Kwok Cynthia C Bulime Stanley S Rinaldi Anne A Munjoma Marshall M Dunbar Megan M Chipato Tsungai T Byamugisha Josaphat J Van Der Pol Barbara B Arts Eric E Salata Robert A RA

AIDS (London, England) 20100201 4

<h4>Objectives</h4>High levels of HIV-1 viremia 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.<h4>Design</h4>Prospective cohort of 188 African women with primary HIV-1 infection.<h4>Methods</h4>HIV-uninfected and infected women were followed quarterly; we tested serial plasma specimens by HIV PCR to estimate infection dates. We used the Loess procedure to estimate the magnitude and timing ...[more]

PMID: 20154581

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Project description:BackgroundThe use of in vitro models to unravel the phenotypic characteristics of circulating viral variants is key to understanding HIV-1 pathogenesis but limited by the availability of primary viral isolates from biological samples. However, overall in vivo genetic variability of HIV-1 within a subject may not be reflected in the viable viral population obtained after isolation. Although several studies have tried to determine whether viral populations expanded in vitro are representative of in vivo findings, the answer remains unclear due to the reduced number of clonal sequences analyzed or samples compared. In order to overcome previous experimental limitations, here we applied Deep Pyrosequencing (DPS) technology in combination with phenotypic experiments to analyze and compare with unprecedented detail the composition of viral isolates and in vivo quasispecies.Methodology/principal findingsWe amplified by DPS HIV-1 genomic regions covering gag, protease, integrase and env-V3 to characterize paired isolates from plasma and peripheral blood mononuclear cells and compare them with total plasma viral RNA in four recently HIV-1 infected subjects. Our study demonstrated the presence of unique haplotypes scattered between sample types with conservation of major variants. In addition, no differences in intra- and inter-population encoded protein variability were found between the different types of isolates or when these were compared to plasma viral RNA within subjects. Additionally, in vitro experiments demonstrated phenotypic similarities in terms of replicative capacity and co-receptor usage between viral isolates and plasma viral RNA.ConclusionThis study is the first in-depth comparison and characterization of viral isolates from different sources and plasma circulating quasispecies using DPS in recently HIV-1 infected subjects. Our data supports the use of primary isolates regardless of their plasma or cellular origin to define genetic variability and biological traits of circulating HIV-1 quasispecies.

Dataset Information

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

Publications

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

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