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. 2017 May 15;31(8):1073-1082.
doi: 10.1097/QAD.0000000000001437.

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

Tara D Mangal  1 ; UNAIDS Working Group on CD4 Progression and Mortality Amongst HIV Seroconverters including the CASCADE Collaboration in EuroCoord
Collaborators, Affiliations

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

Tara D Mangal et al. AIDS. .

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.

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Figures

Fig. 1
Fig. 1
The staged Markov model of HIV disease progression.
Fig. 2
Fig. 2
Geographic distribution of 16 373 HIV-1-infected individuals enrolled throughout 1979–2014, in 25 countries∗.
Fig. 3
Fig. 3
Initial state probabilities at seroconversion for HIV-1-infected individuals stratified by region and age for 12 567 men (a–c) and 3806 women (d–f).
See this image and copyright information in PMC

References

    1. Stover J, Andreev K, Slaymaker E, Gopalappa C, Sabin K, Velasquez C, et al. Updates to the Spectrum model to estimate key HIV indicators for adults and children. AIDS 2014; 28:S427–S434. - PMC - PubMed
    1. Cori A, Ayles H, Beyers N, Schaap A, Floyd S, Sabapathy K, et al. HPTN 071 (PopART): a cluster-randomized trial of the population impact of an HIV combination prevention intervention including universal testing and treatment: mathematical model. PLoS One 2014; 9:e84511. - PMC - PubMed
    1. Birrell PJ, Gill ON, Delpech VC, Brown AE, Desai S, Chadborn TR, et al. HIV incidence in men who have sex with men in England and Wales 2001–10: a nationwide population study. Lancet Infect Dis 2013; 13:313–318. - PMC - PubMed
    1. Lodi S, Phillips A, Touloumi G, Geskus R, Meyer L, Thiébaut R, et al. Time from human immunodeficiency virus seroconversion to reaching CD4+ cell count thresholds <200, <350, and <500 cells/mm3: assessment of need following changes in treatment guidelines. Clin Infect Dis 2011; 53:817–825. - PubMed
    1. Touloumi G, Pantazis N, Pillay D, Paraskevis D, Chaix M-L, Bucher HC, et al. Impact of HIV-1 subtype on CD4 count at HIV seroconversion, rate of decline, and viral load set point in European seroconverter cohorts. Clin Infect Dis 2013; 56:888–897. - PubMed