Dataset Information

Joint estimation of CD4+ cell progression and survival in untreated individuals with HIV-1 infection.

ABSTRACT:

Objective

We compiled the largest dataset of seroconverter cohorts to date from 25 countries across Africa, North America, Europe, and Southeast/East (SE/E) Asia to simultaneously estimate transition rates between CD4 cell stages and death, in antiretroviral therapy (ART)-naive HIV-1-infected individuals.

Design

A hidden Markov model incorporating a misclassification matrix was used to represent natural short-term fluctuations and measurement errors in CD4 cell counts. Covariates were included to estimate the transition rates and survival probabilities for each subgroup.

Results

The median follow-up time for 16?373 eligible individuals was 4.1 years (interquartile range 1.7-7.1), and the mean age at seroconversion was 31.1 years (SD 8.8). A total of 14?525 individuals had recorded CD4 cell counts pre-ART, 1885 died, and 6947 initiated ART. Median (interquartile range) survival for men aged 20 years at seroconversion was 13.0 (12.4-13.4), 11.6 (10.9-12.3), and 8.3 years (7.9-8.9) in Europe/North America, Africa, and SE/E Asia, respectively. Mortality rates increase with age (hazard ratio 2.22, 95% confidence interval 1.84-2.67 for >45 years compared with <25 years) and vary by region (hazard ratio 2.68, 1.75-4.12 for Africa and 1.88, 1.50-2.35 for Asia compared with Europe/North America). CD4 cell decline was significantly faster in Asian cohorts compared with Europe/North America (hazard ratio 1.45, 1.36-1.54).

Conclusion

Mortality and CD4 cell progression rates exhibited regional and age-specific differences, with decreased survival in African and SE/E Asian cohorts compared with Europe/North America and in older age groups. This extensive dataset reveals heterogeneities between regions and ages, which should be incorporated into future HIV models.

SUBMITTER: Mangal TD

PROVIDER: S-EPMC5414573 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Publications

Joint estimation of CD4+ cell progression and survival in untreated individuals with HIV-1 infection.

Mangal Tara D TD

AIDS (London, England) 20170501 8

<h4>Objective</h4>We compiled the largest dataset of seroconverter cohorts to date from 25 countries across Africa, North America, Europe, and Southeast/East (SE/E) Asia to simultaneously estimate transition rates between CD4 cell stages and death, in antiretroviral therapy (ART)-naive HIV-1-infected individuals.<h4>Design</h4>A hidden Markov model incorporating a misclassification matrix was used to represent natural short-term fluctuations and measurement errors in CD4 cell counts. Covariates ...[more]

PMID: 28301424

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Project description:BackgroundHIV-1 infects a wide range of CD4+ T cells with different phenotypic properties and differing expression levels of entry coreceptors. We sought to determine the viral tropism of subtype C (C-HIV) Envelope (Env) clones for different CD4+ T cell subsets and whether tropism changes during acute to chronic disease progression. HIV-1 envs were amplified from the plasma of five C-HIV infected women from three untreated time points; less than 2 months, 1-year and 3-years post-infection. Pseudoviruses were generated from Env clones, phenotyped for coreceptor usage and CD4+ T cell subset tropism was measured by flow cytometry.ResultsA total of 50 C-HIV envs were cloned and screened for functionality in pseudovirus infection assays. Phylogenetic and variable region characteristic analysis demonstrated evolution in envs between time points. We found 45 pseudoviruses were functional and all used CCR5 to mediate entry into NP2/CD4/CCR5 cells. In vitro infection assays showed transitional memory (TM) and effector memory (EM) CD4+ T cells were more frequently infected (median: 46% and 25% of total infected CD4+ T cells respectively) than naïve, stem cell memory, central memory and terminally differentiated cells. This was not due to these subsets contributing a higher proportion of the CD4+ T cell pool, rather these subsets were more susceptible to infection (median: 5.38% EM and 2.15% TM cells infected), consistent with heightened CCR5 expression on EM and TM cells. No inter- or intra-participant changes in CD4+ T cell subset tropism were observed across the three-time points.ConclusionsCD4+ T cell subsets that express more CCR5 were more susceptible to infection with C-HIV Envs, suggesting that these may be the major cellular targets during the first 3 years of infection. Moreover, we found that viral tropism for different CD4+ T cell subsets in vitro did not change between Envs cloned from acute to chronic disease stages. Finally, central memory, naïve and stem cell memory CD4+ T cell subsets were susceptible to infection, albeit inefficiently by Envs from all time-points, suggesting that direct infection of these cells may help establish the latent reservoir early in infection.

Dataset Information

Joint estimation of CD4+ cell progression and survival in untreated individuals with HIV-1 infection.

Objective

Design

Results

Conclusion

Publications

Joint estimation of CD4+ cell progression and survival in untreated individuals with HIV-1 infection.

Similar Datasets

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