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

Mangal, T. D. and UNAIDS Working Group, (2017) Joint estimation of CD4+ cell progression and survival in untreated individuals with HIV-1 infection. AIDS, 31(8), pp. 1073-1082. (doi: 10.1097/QAD.0000000000001437) (PMID:28301424) (PMCID:PMC5414573)

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.

• Item Type: Articles
• Additional Information: Author: UNAIDS Working Group on CD4 Progression and Mortality Amongst HIV Seroconverters including the CASCADE Collaboration in EuroCoord
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Crampin, Professor Mia
• Authors: Mangal, T. D., and UNAIDS Working Group,
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health
• Journal Name: AIDS
• Publisher: Lippincott, Williams and Wilkins
• ISSN: 0269-9370
• ISSN (Online): 1473-5571
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in AIDS 31(8):1073-1082
• Publisher Policy: Reproduced under a Creative Commons License