학술논문

The Impact of Different CD4 Cell-Count Monitoring and Switching Strategies on Mortality in HIV-Infected African Adults on Antiretroviral Therapy: An Application of Dynamic Marginal Structural Models
Document Type
article
Source
American Journal of Epidemiology. 182(7)
Subject
Clinical Research
Clinical Trials and Supportive Activities
HIV/AIDS
Evaluation of treatments and therapeutic interventions
6.1 Pharmaceuticals
Infection
Good Health and Well Being
Adult
Anti-Retroviral Agents
CD4 Lymphocyte Count
Female
HIV Infections
Humans
Male
Models
Statistical
Uganda
Zimbabwe
Africa
antiretroviral therapy
drug switching
dynamic marginal structural models
HIV
monitoring
DART Trial Team
Mathematical Sciences
Medical and Health Sciences
Epidemiology
Language
Abstract
In Africa, antiretroviral therapy (ART) is delivered with limited laboratory monitoring, often none. In 2003-2004, investigators in the Development of Antiretroviral Therapy in Africa (DART) Trial randomized persons initiating ART in Uganda and Zimbabwe to either laboratory and clinical monitoring (LCM) or clinically driven monitoring (CDM). CD4 cell counts were measured every 12 weeks in both groups but were only returned to treating clinicians for management in the LCM group. Follow-up continued through 2008. In observational analyses, dynamic marginal structural models on pooled randomized groups were used to estimate survival under different monitoring-frequency and clinical/immunological switching strategies. Assumptions included no direct effect of randomized group on mortality or confounders and no unmeasured confounders which influenced treatment switch and mortality or treatment switch and time-dependent covariates. After 48 weeks of first-line ART, 2,946 individuals contributed 11,351 person-years of follow-up, 625 switches, and 179 deaths. The estimated survival probability after a further 240 weeks for post-48-week switch at the first CD4 cell count less than 100 cells/mm(3) or non-Candida World Health Organization stage 4 event (with CD4 count