CD4+ cell dynamics in untreated HIV-1 infection: overall rates, and effects of age, viral load, sex and calendar time. (28th November 2015)

• Record Type: Journal Article
• Authors: Cori, Anne; Pickles, Michael; van Sighem, Ard; Gras, Luuk; Bezemer, Daniela; Reiss, Peter; Fraser, Christophe
• Is Part Of: AIDS. Volume 29:Number 18(2015)
• Publication Date: 2015-11-28
• Subjects: CD4+ cell count -- HIV -- mathematical model -- set-point viral load -- viral load; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000000854
• Languages: English
• ISSNs: 0269-9370

Abstract

Abstract : Background: CD4 + cell count is a key measure of HIV disease progression, and the basis of successive international guidelines for treatment initiation. CD4 + cell dynamics are used in mathematical and econometric models for evaluating public health need and interventions. Here, we estimate rates of CD4 + decline, stratified by relevant covariates, in a form that is clinically transparent and can be directly used in such models. Methods: We analyse the AIDS Therapy Evaluation in the Netherlands cohort, including individuals with date of seroconversion estimated to be within 1 year and with intensive clinical follow-up prior to treatment initiation. Owing to the fact that CD4 + cell counts are intrinsically noisy, we separate the analysis into long-term trends of smoothed CD4 + cell counts and an observation model relating actual CD4 + measurements to the underlying smoothed counts. We use a monotonic spline smoothing model to describe the decline of smoothed CD4 + cell counts through categories CD4 + above 500, 350–500, 200–350 and 200 cells/μl or less. We estimate the proportion of individuals starting in each category after seroconversion and the average time spent in each category. We examine individual-level cofactors which influence these parameters. Results: Among untreated individuals, the time spent in each compartment was 3.32, 2.70, 5.50 and 5.06 years. Only 76% started in the CD4 + cell count above 500 cells/μl compartment after seroconversion. Set-point viral load (SPVL) was an important factor: individuals with at least 5 log10 copies/ml took 5.37 years to reach CD4 + cell count less than 200 cells/μl compared with 15.76 years for SPVL less than 4 log10 copies/ml. Conclusion: Many individuals already have CD4 + cell count below 500 cells/μl after seroconversion. SPVL strongly influences the rate of CD4 + decline. Treatment guidelines should consider measuring SPVL, whereas mathematical models should incorporate SPVL stratification. Abstract : Supplemental Digital Content is available in the text