Immunologic Determinants of CD4+ T Cell Recovery in Treated HIV+ Africans

Investigator: Peter Hunt, MD
Sponsor: Doris Duke Charitable Foundation

Location(s): Uganda


Dr. Peter Hunt and Dr. Martin, manages the UARTO (Uganda AIDS Rural Treatment Outcomes) Data Coordinating Center, which is based in San Francisco. Along with Dr. David Bangsberg of Harvard, it plays a substantial role in field work supervision. Patterned after SCOPE, and supported by the UCSF CFAR, UARTO is an infrastructural resource for pathogenesis-oriented clinical and translational researchers who are given access to the cohort's diverse array of biological specimens from subjects who are well-characterized in terms of clinical, behavioral, and epidemiologic parameters.

While prevalent co-infections and host differences might affect immunologic recovery in sub-Saharan Africa, few studies have assessed the efficacy of ART on immunologic outcomes in HIV-infected Africans during confirmed treatment-mediated viral suppression. To address this, Dr. Hunt and colleagues longitudinally examined 174 subjects in UARTO who achieved a plasma HIV RNA level <400 copies/ml by month 6 of ART (Hunt et al. 2008). Subsequent observation was censored when plasma HIV RNA levels went above 1,000 copies/ml, resulting in mean follow-up of 9 months. Dr. Hunt found that compared to resource-rich settings, the rate of early CD4+ T cell recovery from baseline to month 3 appeared high (mean +33 cells/month), while the rate of CD4+ T cell recovery after month 3 appeared low (mean +4 cells/month, p<0.001 for rate between intervals). CD8+ T cell activation also declined biphasically with a mean 3% fewer activated CD8+ T cells/month before month 6, and 0.4% fewer activated CD8+ T cells/month after month 6 (p<0.001 for rate between intervals). Compared to resource-rich settings, CD8+ T cell activation levels remained high at month 12 (mean 46% activated CD8+ T cells). The authors concluded that African patients maintaining ART-mediated viral suppression experience significant CD4 recovery and declines in T cell activation, but the rate of CD4 recovery after month 3 is relatively low and high T cell activation levels persist, potentially limiting long-term immune recovery.