Sociodemographic and clinical correlates of immune activation in postpartum HIV-1/HSV-2 co-infected Kenyan women

Thesis (Master's)--University of Washington, 2016-06University of Washington Abstract Sociodemographic and clinical correlates of immune activation in postpartum HIV-1/HSV-2 co-infected Kenyan women Anton N. Quist Chair of the Supervisory Committee: Professor Carey Farquhar Department of Epidemiology Background HIV is a leading cause of death among women of reproductive age. An activated host immune system has been shown to support the pathogenesis and transmission of HIV-1 disease, with evidence suggesting that the activation state may be associated with social and environmental factors. Identifying these determinants of immune activation could help identify at-risk women for early intervention. This study examined the associations between sociodemographic indicators of poverty, household crowding, and poor nutritional status and markers of T-lymphocyte immune activation. Methods This study is nested in a recently-conducted randomized, double-blinded, placebo-controlled trial (RCT) of valacyclovir suppressive therapy among pregnant women in Nairobi, Kenya infected with both HIV-1 and HSV-2. Plasma markers of immune activation were assayed using flow cytometry at 6 and 12 months postpartum. We developed a multiple linear regression model of immune activation markers to evaluate clinical and demographic correlates. The outcome was T-cell immune activation, as demonstrated by plasma levels of CD8+ and CD4+ cells expressing both CD38+ and HLA-DR+ proteins. Results The study sample comprised 117 participants. No significant association was found between sociodemographic characteristics of the participants and immune activation. Significant associations were found between factors of immune activation and both CD4 count and HIV RNA level, measured at 12 months postpartum. In models adjusting for participant age and the use of postpartum contraception, for each additional 100 CD4+ cell per ml, the mean CD38+ HLA-DR+ percentage was lower by 10.7% (95% CI: 0.85-0.94), and for each 10% increase in plasma RNA the mean percentage of CD4+ cells demonstrating CD38 and HLA-DR was higher by 3.5% (95% CI: 1.02 – 1.05). The plasma RNA viral load was significantly positively associated with the measured percentages of activated T cells. For each 10% increase in plasma RNA concentration the geometric mean percentage of CD4+ cells expressing both CD38 and HLA-DR increased by 3.5% (95% CI: 1.02 – 1.05), and the percentage of CD8+ cells expressing these proteins increased by 3.2* (94% CI: 1.02 – 1.05). Conclusion This study results are consistent with earlier research associating immune activation with clinical measures of HIV disease progression, yet we found no association between measures of immune activation and sociodemographic factors in this population. Further research may help determine sociodemographic correlates of immune activation, and their association with the transmission and progression of HIV-1 disease