Impact of CD8+ T-cell activation on CD4+ T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy
Year: 2011
Type: article
Study design: Observational Study
Abstract: OBJECTIVES: To assess whether T-cell activation independently predicts the extent of CD4(+) T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy (ART). DESIGN: Prospective cohort study. METHODS: HIV-infected adults starting ART and achieving a plasma HIV RNA level (VL) less than 400 copies/ml by month 6 were sampled from the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort in Mbarara, Uganda. CD4 count, VL, and the percentage-activated (CD38(+)HLA-DR(+)) T cells were measured every 3 months. RESULTS: Of 451 HIV-infected Ugandans starting ART, most were women (70%) with median pre-ART values: age, 34 years; CD4 count, 135 cells/μl; and VL, 5.1 log(10) copies/ml. Of these, 93% achieved a VL less than 400 copies/ml by month 6 and were followed for a median of 24 months, with 8% lost to follow-up at 3 years. Higher pre-ART CD8(+) T-cell activation was associated with diminished CD4 recovery after year 1, after adjustment for pre-ART CD4 count, VL, and sex (P = 0.017). Thirty-four participants died, 15 after month 6. Each 10% point increase in activated CD8(+) T cells at month 6 of suppressive ART was associated with a 1.6-fold increased hazard of subsequent death after adjusting for pretherapy CD4 count (P = 0.048). CONCLUSIONS: Higher pre-ART CD8(+) T-cell activation independently predicts slower CD4(+) T-cell recovery and higher persistent CD8(+) T-cell activation during ART-mediated viral suppression independently predicts increased mortality among HIV-infected Ugandans. Novel therapeutic strategies aimed at preventing or reversing immune activation during ART are needed in this setting.
Source: AIDS
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: (CHAVI) Center for HIV/AIDS Vaccine Immunology, G1572886882, G1647758084, Impact of HIV-associated inflammation on disease, UCSF-GIVI CENTER FOR AIDS RESEARCH, G200995756, The Determinants of T Cell Activation in HIV Infection, G2026096560, G2256131462, G2586943461, DYNAMICS OF HIV1 SPECIFIC CTL IN HIV1 INFECTION, G446944062, G5418282550, Mentoring Patient Oriented Adherence Research in Uganda, G688529966, Basic and Comparative Studies of CCR5 Inhibition to Prevent HIV Transmission, (CHAVI) Center for HIV/AIDS Vaccine Immunology, G81379742, Center for AIDS Prevention Studies (CAPS), G97119092
OpenAlex ID: W2087092404