Chronic immune activation and accelerated immune aging among HIV-infected adults receiving suppressive antiretroviral therapy for at least 12 years in an African cohort
Damalie Nakanjako, Rose Nabatanzi, Isaac Ssinabulya, Lois Bayigga, Agnes Kiragga, Grace Banturaki, Barbara Castelnuovo
Abstract
Background HIV-associated alterations innate and adaptive immune cell compartments are reminiscent of the process of immune aging. Objectives We described immune aging phenotypes among ART-treated HIV-infected adults relative to age-matched HIV-negative counterparts. Methods In a cross-sectional comparative study of HIV-infected adults with CD4≥500 cells/μl after at least 12 years of suppressive ART and age-and-gender-matched HIV-negative individuals, immune activation and immune aging phenotypes were measured, using multi-color flowcytometry. Results ART-treated HIV-infected individuals had higher body mass index (P = 0.004), waist-hip circumference (P = 0.041), hip circumference (P < 0.001), and diastolic blood pressure (P = 0.012) and immune activation (CD4 + CD38+HLADR+; median 4.15,IQR(1.030,14.6)] relative to the HIV-negative age-matched individuals [median 3.14,IQR(1.030, 6.68)]; P=0.0034. Immune aging markers [CD4 + CD57+T-cells; median 13.00 IQR (0.45,64.1)] were higher among HIV-infected ART-treated adults<50 years relative to HIV-negative<50 years[median 8.020,IQR(0.004,21.2)]; P=0.0010 . Naïve CD4 T-cells, Central memory CD4 T-cells, Terminal Effector Memory T cells (TEMRA: CD27 − CD45RA + CCR7-) and immune senescence CD4/CD8+CD28-/CD57+ T-cells were similar among ART-treated HIV-infected individuals<45 years relative to 60 years-and-older HIV-negative counterparts≥; p = 0.0932, p = 0.05357, p = 0.0950 and p = 0.5714 respectively . Conclusion ART-treated adults are immunologically two decades older than their HIV-negative counterparts. Accelerated immune aging among individuals aging with HIV underscores the need for an HIV cure to avert the unprecedented complications of accelerated immune senescence and the associated NCD risk in African settings with protracted exposure to endemic co-infections.