The small scale spatial dynamics of HIV-1 transmission in Rakai, Uganda

The highest prevalence of viral sexually transmitted infections is found in sub-Saharan Africa where very little is known about the dynamics of viral transmission within local sexual networks. An understanding of these dynamics is essential for the control of sexually transmitted infections within and between communities. Here we analyzed the small scale spatial dynamics of HIV transmission in rural Rakai District, Uganda using data from a cohort of 14,594 individuals residing within 46 communities.We applied spatial clustering statistics, molecular phylogenetics, and egocentric transmission models to quantify the relative contribution of viral introductions into communities versus community and household-based transmission to HIV incidence. We found that the majority of HIV transmissions acquired outside of households are acquired from non-stable sexual partners who reside outside of an individual’s community of residence.Our results have critical implications for the design of community randomized trials which assume that the preponderance of HIV transmissions occur within local sexual networks by design. They also suggest that HIV prevention efforts should be implemented at spatial scales broader than the community and target key populations responsible for introductions into communities.We next examined household-based HIV transmission in Rakai, Uganda, focusing on the dynamics of HIV introduction into stable concordant HIV-negative couples. Using data from more than ten thousand couples, we found men introduced HIV into initially uninfected couples more often than did females, though female partners accounted for a substantial proportion of HIV introductions. HIV was introduced into household-based partnerships most frequently by young men and women, the latter of whom were at especially high risk from extra-marital sexual partners. This study was conducted before and after the introduction of antiretroviral therapies and rapid scale up of medical male circumcision in Rakai. We found that incidence of HIV introduction into stable partnerships declined significantly with the scale up of HIV prevention services, though the protective benefits were only observed in males. Lastly, this dissertation examined the dynamics of high risk human papilloma virus (HR_HPV) viral load and persistent HR-HPV detection among HIV-infected and uninfected men in Rakai, Uganda. Using data from a randomized clinical trial, we found HR-HPV genotypes with high viral load are more likely to persist among both HIV-negative and HIV-positive men, though persistence is more common among HIV-positive men overall. These results may explain the association between high HR-HPV viral load and HR-HPV transmission and increased levels of HR-HPV detection among individuals co-infected with HIV