Elevated stress-responsive biomarkers are associated with HIV acquisition in young women in rural South Africa.

ABSTRACT

OBJECTIVE: Biological markers of stress have been associated with HIV progression and pathogenesis but not with HIV incidence. We sought to determine if elevated stress-responsive biomarkers would be associated with incident HIV among adolescent girls and young women (AGYW). DESIGN: We conducted a case-cohort study within the HIV Prevention Trials Network (HPTN) 068 study among 949 AGYW in South Africa. Cases were AGYW who tested HIV-positive during the eight-year follow-up. Unmatched controls were randomly selected from the HIV-negative population at enrollment. METHODS: Dried blood spots from cases and controls were tested from enrollment (2011-2012) for C-reactive protein (CRP), herpes simplex virus type-1 (HSV-1) antibody titers, and cytomegalovirus (CMV) antibody titers. Cox proportional hazards models estimated the association between each biomarker and time to incident HIV. RESULTS: Compared to AGYW with the lowest CRP levels, those with medium and high CRP levels had a higher hazard ratio (HR) of incident HIV [HR 1.45, 95% confidence interval (CI) 0.95, 2.21; HR 1.50, 95% CI 0.98, 2.30, respectively], although not statistically significant. The relative hazard of incident HIV was also higher among AGYW who were CMV seropositive vs. seronegative (low antibodies HR 2.18, 95% CI 1.2, 3.87; medium HR 2.25, 95% CI 1.28, 3.95; high HR 1.78, 95% CI 0.99, 3.21). Those with the highest HSV-1 antibody levels experienced an increased hazard of HIV compared to those who were HSV-1 seronegative (HR 1.58, 95% CI 1.03, 2.44). CONCLUSIONS: Biological stress may increase AGYW's susceptibility to HIV acquisition through changes in immune function, viral infection, and increased biological vulnerability to disease.