ArticleAIDS (London, England)2015
CD4+ cell dynamics in untreated HIV-1 infection: overall rates, and effects of age, viral load, sex and calendar time.
Article in AIDS (London, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A Review of Network Models for HIV Spread.Journal of acquired immune deficiency syndromes (1999) · 2025Pooled it
- Projected outcomes of universal testing and treatment in a generalised HIV epidemic in Zambia and South Africa (the HPTN 071 [PopART] trial): a modelling study.The lancet. HIV · 2022Trial
- The age and sex dynamics of heterosexual HIV transmission in Zambia: an HPTN 071 (PopART) phylogenetic and modelling study.medRxiv : the preprint server for health sciences · 2026Article
- Robust phylodynamic inference and model specification for HIV transmission dynamics.Epidemics · 2025Article
- Evolution of HIV virulence in response to disease-modifying vaccines: A modeling study.Vaccine · 2023Article
- Public health interventions, priority populations, and the impact of COVID-19 disruptions on hepatitis C elimination among people who have injected drugs in Montreal (Canada): A modeling study.The International journal on drug policy · 2023Article
- Key Factors and Parameter Ranges for Immune Control of Equine Infectious Anemia Virus Infection.Viruses · 2023Article
- Probabilistic HIV recency classification-a logistic regression without labeled individual level training data.The annals of applied statistics · 2023Article
- Measuring progress towards reaching zero new HIV acquisitions among key populations in Québec (Canada) using routine surveillance data: a mathematical modelling study.Journal of the International AIDS Society · 2022Article
- Past dynamics of HIV transmission among men who have sex with men in Montréal, Canada: a mathematical modeling study.BMC infectious diseases · 2022Article
- PopART-IBM, a highly efficient stochastic individual-based simulation model of generalised HIV epidemics developed in the context of the HPTN 071 (PopART) trial.PLoS computational biology · 2021Article
- Cost and cost-effectiveness of a universal HIV testing and treatment intervention in Zambia and South Africa: evidence and projections from the HPTN 071 (PopART) trial.The Lancet. Global health · 2021Article
- Asymptomatic Adolescent HIV: Identifying a Role for Universal HIV Screening in the Pediatric Emergency Department.AIDS patient care and STDs · 2020Article
- Understanding the HIV Epidemic Among MSM in Baltimore: A Modeling Study Estimating the Impact of Past HIV Interventions and Who Acquired and Contributed to Infections.Journal of acquired immune deficiency syndromes (1999) · 2020Article
- The impact of bone marrow stromal antigen-2 (BST2) gene variants on HIV-1 control in black South African individuals.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2020Article
- Modelling of viral load dynamics and CD4 cell count progression in an antiretroviral naive cohort: using a joint linear mixed and multistate Markov model.BMC infectious diseases · 2020Article
- Natural selection favoring more transmissible HIV detected in United States molecular transmission network.Nature communications · 2019Article
- Getting more from heterogeneous HIV-1 surveillance data in a high immigration country: estimation of incidence and undiagnosed population size using multiple biomarkers.International journal of epidemiology · 2019Article
- Large benefits to youth-focused HIV treatment-as-prevention efforts in generalized heterosexual populations: An agent-based simulation model.PLoS computational biology · 2019Article
- HIV-1 Transmission Patterns in Men Who Have Sex with Men: Insights from Genetic Source Attribution Analysis.AIDS research and human retroviruses · 2019Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
backgroundCD4 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.
methodsWe 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.
resultsAmong 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.
conclusionMany 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.
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