The burden of HIV is ~60% higher in women than men in sub-Saharan Africa, and this gender inequity is a key challenge to HIV control. Identifying women at greatest risk for HIV and their infecting male partners is critical for effective, targeted control of the African HIV epidemic. It is also vital to identify those HIV-infected women most likely to contribute to ongoing viral spread. However, African women vastly underreport sexual contacts and high risk occupations such as sex work in interview-based surveys and clinical settings making their identification challenging. Here, we propose to use phylogenetic, epidemiological, and qualitative methods to study network drivers of female risk of HIV acquisition and onward transmission to men in the rural Rakai District, Uganda. We will use existing data from the Rakai Community Cohort Study (RCCS), a population- based study of HIV incidence and behaviors in 50 communities (n~17,000).
In Aim 1 we will identify HIV- infected women who have central roles in transmission networks using viral phylogenetics and then characterize them with RCCS epidemiological data. We will also conduct in-depth interviews with these women to gain deeper insight into their HIV-related risks and to understand the barriers to reporting these risks.
In Aim 2 we will use viral phylogenetics in conjunction with probabilistic statistical models to identify the pool of infecting male partners tat sustain the excess HIV burden among Rakai women. Lastly, in Aim 3 we will use microsimulation models to estimate the potential effectiveness of various combination HIV prevention strategies targeted to high risk subgroups to reduce HIV incidence. The proposed research is part of a K01 award and will provide the applicant with the advanced training in HIV modelling, behavioral science, and phylogenetics necessary to transition to an independent investigator with expertise in the application of interdisciplinary methods to HIV epidemiology and prevention. Results will improve female HIV risk assessment and identify candidate targeted strategies to prevent HIV in African women. It also will provide critical formative data fr a future R01 to implement and empirically assess the effectiveness of targeted interventions to high risk women and their partners in Rakai.

Public Health Relevance

The success of interventions to reduce female HIV risk depends upon an understanding of the drivers of excess HIV infection in women. This project studies network drivers of female HIV risk and onward transmission to men in rural Uganda using interdisciplinary methods. We also explore barriers to HIV risk assessment in a setting where women vastly underreport sex work and risky sexual partnerships. This study will inform targeted PEPFAR initiatives to prevent HIV in high risk African women such as DREAMS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01AI125086-03
Application #
9442677
Study Section
Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
Program Officer
Bacon, Melanie C
Project Start
2016-03-15
Project End
2021-02-28
Budget Start
2018-03-01
Budget End
2019-02-28
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Pathology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Grabowski, Mary K; Reynolds, Steven J; Kagaayi, Joseph et al. (2018) The validity of self-reported antiretroviral use in persons living with HIV: a population-based study. AIDS 32:363-369
Olawore, Oluwasolape; Tobian, Aaron A R; Kagaayi, Joseph et al. (2018) Migration and risk of HIV acquisition in Rakai, Uganda: a population-based cohort study. Lancet HIV 5:e181-e189
Mwinnyaa, George; Gray, Ronald H; Grabowski, Mary K et al. (2018) Brief Report: Age-Disparate Relationships and HIV Prevalence Among Never Married Women in Rakai, Uganda. J Acquir Immune Defic Syndr 79:430-434
Sivay, Mariya V; Hudelson, Sarah E; Wang, Jing et al. (2018) HIV-1 diversity among young women in rural South Africa: HPTN 068. PLoS One 13:e0198999
Grabowski, M Kate; Serwadda, David M; Gray, Ronald H et al. (2017) HIV Prevention Efforts and Incidence of HIV in Uganda. N Engl J Med 377:2154-2166
Grabowski, Mary K; Gravitt, Patti E; Gray, Ronald H et al. (2017) Trends and Determinants of Human Papillomavirus Concordance Among Human Immunodeficiency Virus-Positive and -Negative Heterosexual Couples in Rakai, Uganda. J Infect Dis 215:772-780
Rose, Rebecca; Lamers, Susanna L; Dollar, James J et al. (2017) Identifying Transmission Clusters with Cluster Picker and HIV-TRACE. AIDS Res Hum Retroviruses 33:211-218
Blanquart, François; Wymant, Chris; Cornelissen, Marion et al. (2017) Viral genetic variation accounts for a third of variability in HIV-1 set-point viral load in Europe. PLoS Biol 15:e2001855
Patel, Eshan U; Kirkpatrick, Allison R; Grabowski, Mary Kate et al. (2017) Penile Immune Activation and Risk of HIV Shedding: A Prospective Cohort Study. Clin Infect Dis 64:776-784
German, Danielle; Grabowski, Mary Kate; Beyrer, Chris (2017) Enhanced use of phylogenetic data to inform public health approaches to HIV among men who have sex with men. Sex Health 14:89-96

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