In individuals with HIV-1 infection, depletion of CD4(+) T-cells is often accompanied by a malfunction of CD8(+) T-cells that are persistently activated and/or exhausted. While the dynamics and correlates of CD4 counts have been well-documented, the same does not apply to CD8 counts. Here, we examined CD8 counts in a cohort of 497 Africans with primary HIV-1 infection and monthly to quarterly follow-up visits for up to three years in the absence of antiretroviral therapy. Statistical models revealed that i) CD8 counts were relatively steady in the 3-36 months period of infection and similar between men and women; ii) neither geography nor heterogeneity in HIV-1 set-point viral load could account for the roughly 10-fold range of CD8 counts in the cohort (P >0.25 in all tests); and iii) factors independently associated with relatively high CD8 counts included demographics (age ≤40 years, adjusted P = 0.010) and several human leukocyte antigen class I (HLA-I) alleles, including HLA-A*03:01 (P = 0.013), B*15:10 (P = 0.007), and B*58:02 (P <0.001). Several sensitivity analyses provided supporting evidence for these novel relationships. Overall, these findings suggest that factors associated with CD8 count have little overlap with those previously reported for other HIV-1-related outcome measures, including viral load, CD4 count, and CD4:CD8 ratio. IMPORTANCE
Longitudinal data from 497 HIV-1 seroconverters have allowed us to systematically evaluate the dynamics and correlates of CD8(+) T-cell counts during untreated primary HIV-1 infection in eastern and southern Africans. Our findings suggest that individuals with certain HLA-I alleles, including A*03 (exclusively A*03:01), persistently maintain a relatively high CD8 counts following HIV-1 infection, which may offer an intriguing explanation for the recently reported, negative association of A*03 with HIV-1-specific, broadly neutralizing antibody responses. In future studies, attention to HLA-I genotyping data may benefit in-depth understanding of both cellular and humoral immunity, as well as their intrinsic balances, especially in settings where there is emerging evidence of antagonism between the two arms of adaptive immunity.
Dynamics and Correlates of CD8 T-cell Counts in Africans with Primary Human Immunodeficient Virus Type I (HIV-1) Infection.