Electronic Thesis and Dissertation Repository

Thesis Format

Alternative Format

Degree

Master of Science

Program

Microbiology and Immunology

Supervisor

Prodger, Jessica

Abstract

Despite global reductions in HIV, adolescents represent a population where HIV acquisition is still high. While high-risk taking behavior may contribute to the increased incidence seen in adolescents, the effects of physical maturation and sexual debut are not well characterized in males. We enrolled n=200 uncircumcised adolescent males aged 15-17 with no history of sexual experience and assessed them as they matured reproductively and/or engaged in penile-vaginal sex over 3 years. For adolescents who underwent circumcision, we characterized their foreskin immune cells to assess HIV risk. We found that cryopreserved foreskin tissue is equally suitable for immunological analysis as fresh tissue. We also found that in participants who remained sexually naïve at circumcision, HIV risk did not correlate with puberty. Lastly, we noted that sexual debut may be associated with changes in the abundance of HIV-susceptible cells. These results suggest that sexual debut may modify adolescents’ risk for HIV acquisition.

Summary for Lay Audience

Despite global reductions in HIV, adolescents represent a population where HIV risk remains high. Although high-risk taking behavior may contribute to the increased risk we see in adolescents, it is possible that biological changes that occur throughout puberty and with the initiation of sexual behavior modify their HIV risk. Previous studies suggest that certain types of cells are associated with increased chances of acquiring HIV. We enrolled n=200 uncircumcised adolescent males aged 15-17 with no history of sexual experience, and we followed them every three months for three years as they went through puberty and/or had sex for the first time. During the study, some adolescents elected to get circumcised. In participants who elected to undergo circumcision, foreskin tissue (an important site of HIV transmission) was used to assess how puberty or sex would change the types of immune cells present. We hypothesized that sex and puberty might increase adolescents’ risk for acquiring HIV by increasing the proportion of cells that HIV can infect in the foreskin. From our work, we learned that storing foreskin for prolong periods at cold temperatures, then assessing cell proportions, is similar to using fresh tissues. We also found that puberty was not associated with changes in the proportions of cells that are related to HIV. Lastly, we found that engaging in sexual activity modifies the types of cells in foreskin, and this may modify HIV risk in adolescents. The results from this study provide a foundation for understanding how puberty and sex might alter cell populations in adolescent males. They also provide valuable insights into HIV risk in adolescents, and how that risk is modified by sex and puberty, and independently of high-risk taking behavior.

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