PROJECT SUMMARY/ABSTRACT
Adolescent girls and young women (AGYW) remain at very high risk of HIV acquisition in sub-Saharan Africa
and this increased risk is tied to social and interpersonal factors. Few studies in low- and middle-income
countries have collected stress-responsive biomarkers to understand biological processes, such as the
physiological stress response, that may underlie the increased risk of HIV infection observed among AGYW.
Evidence is mounting for the association between social determinants of health and the physiological effects
of stress in the United States and Europe, but it is lacking in sub-Saharan Africa. Stress has been associated
with social determinants of health and with adverse outcomes in individuals with HIV; however, these studies
are among adults and with small sample sizes and evidence is limited regarding incident HIV infection. The
overarching objective of the proposed project is to generate preliminary evidence examining the
relationships between psychosocial stressors; biological stress; and HIV prevention, care, and treatment in
AGYW in South Africa. The project objective will be met through three Specific Aims: Using an existing and
unique data source (HIV Prevention Trials Network 068 study) with information on psychosocial stressors,
stress responsive biomarkers, and HIV incidence among a cohort of 2,533 AGYW that have been followed
for 9 years in South Africa, in Aim 1 we will assess associations between acute (physical and sexual intimate
partner violence, traumatic events) and chronic (food insecurity, depression, and low parental support)
psychosocial stressors with stress-responsive immune biomarkers (C-reactive protein [CRP] titers, herpes
simplex virus type 1 (HSV-1) titers, and cytomegalovirus (CMV)) among AGYW. We will use data from 1,517
AGYW with biomarker information available at the 2018/19 visit and will explore effect modification by HIV
status and correlations with perceived stress. In Aim 2 we will conduct a case-cohort study of 849 AGYW to
estimate the association between stress-responsive biomarkers during adolescence with sexual behavior
and incident HIV infection at later time points. We will retrospectively test existing, stored biospecimens for
cases and controls to assess these relationships. In Aim 3 we will estimate associations between stress-
responsive biomarkers and antiretroviral therapy (ART) adherence and viral load among AGYW with HIV.
We will use data from 164 AGYW with HIV along with information available about stress-responsive
biomarkers, viral load, and ART from the 2018/19 visit. This study will provide preliminary data for an R34
application to develop and pilot an intervention mitigating the effects of physiological stress among AGYW to
prevent HIV and improve access to care and treatment. The research aligns with the NIH HIV/AIDS research
priority to advance cross-cutting areas of research and the Maternal and Pediatric Infectious Disease Branch
(MPIDB) priority of preventing HIV in adolescents.