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Joint estimation of CD4 progression and survival in untreated individuals with HIV-1 infection: A pooled analysis of data from 25 countries.

Joint estimation of CD4 progression and survival in untreated individuals with HIV-1 infection: A pooled analysis of data from 25 countries.
Author Information (click to view)

Mangal TD,


Mangal TD, (click to view)

Mangal TD,

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AIDS (London, England) 2017 03 15() doi 10.1097/QAD.0000000000001437

Abstract
OBJECTIVE
We compiled the largest dataset of seroconverter cohorts to date from 25 countries across Africa, North America, Europe, and SE/E. Asia to simultaneously estimate transition rates between CD4 stages and death, in 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 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 (IQR 1·7-7·1) years and the mean age at seroconversion was 31·1 (standard deviation 8·8) years. 14,525 individuals had recorded CD4 counts pre-ART, 1,885 died, and 6,947 initiated ART. Median (IQR) survival for males aged 20 years at seroconversion was 13·0 (12 4 – 13·4), 11·6 (10 9 – 12·3) and 8·3 (7 9 – 8·9) years in, Europe/North America, Africa and South-East/East Asia, respectively. Mortality rates increase with age (hazard ratio [HR] 2·22, 95% CI 1·84 – 2·67 for >45 years compared with <25 years) and vary by region (HR 2·68, 1·75 - 4·12 for Africa and 1·88, 1·50 - 2·35 for Asia compared with Europe/North America). CD4 decline was significantly faster in Asian cohorts compared with Europe/North America (HR 1·45, 1·36 - 1·54). CONCLUSIONS
Mortality and CD4 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.

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