Gonorrhea (GC) and chlamydia (CT) at the pharynx and the rectum comprise the majority of GC and CT infections in men who have sex with men (MSM). However, as primarily asymptomatic infections, they often go undiagnosed and untreated. As such, GC/CT infections at these extra-genital sites may constitute an important reservoir of sustained transmission in the MSM population. Gonococcal infections at the pharynx may also play an important role in fostering the development of antimicrobial resistance due to the unique constellation of Neisseria gonorrhoeae's ability to scavenge DNA and the oropharynx as important environment for commensal Neisseria species. Rectal GC/CT infections have been shown to increase the risk for HIV acquisition. However, little is known about the natural history of extra-genital GC and CT, nor the extent to which rectal GC/CT increase the risk of HIV acquisition through a biologically-mediated process or sexual behavior. This K23 proposal aims to 1) determine the natural history extra-genital gonorrhea and chlamydia infection among MSM & associated sociobehavioral determinants, and 2) quantify variations in HIV shedding at the rectum during rectal GC/CT infection by conducting a prospective cohort study of MSM, half of which are HIV-infected, who will self-collect pharyngeal and rectal swabs and document sexual activity on a weekly basis for one year. We will document incidence, duration of infection, and associated sociobehavioral factors with extra-genital GC/CT; and we will evaluate differences in HIV RNA log copies between baseline and incident rectal infections as well as describe temporal variations in HIV RNA shedding over the course of rectal GC/CT infections. We will also 3) test whether the risk of HIV acquisition is associated with rectal GC or CT infection controlling for seroadaptive behaviors using more than 10 years of clinical data collected at an urban STD Clinic; and 4) estimate the potential impact of enhanced extra-genital testing and treating on the incidence of GC, CT and HIV using deterministic mathematical modeling. Not only will these studies answer key clinical and epidemiologic question about extra-genital GC, CT and HIV, but these studies will provide experiential learning to complement a structured career development plan for the PI to develop skills in longitudinal data analysis, sociobehavioral research and mathematical modeling. The ultimate goal of this K23 award is to provide the time, experience, training and mentorship necessary to allow the PI to become an independent investigator dedicated to the prevention and control of STD and HIV in vulnerable populations.

Public Health Relevance

The proposed research will determine the natural history of extra-genital gonorrhea (GC) and chlamydia (CT) infections and their relationship with HIV among men who have sex with men (MSM). By understanding the basic epidemiologic determinants, incidence and duration of infection, of extra-genital GC/CT, and attempting to resolve the question of a biologic or behavioral relationship between rectal GC/CT and HIV, this proposal will add to the body of knowledge on STD/HIV epidemiology and provide crucial information for effective strategies to prevent and control of gonorrhea, chlamydia and HIV among MSM.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AI113185-02
Application #
8900941
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Sharp, Gerald B
Project Start
2014-08-01
Project End
2019-07-31
Budget Start
2015-08-01
Budget End
2016-07-31
Support Year
2
Fiscal Year
2015
Total Cost
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Barbee, Lindley A; Khosropour, Christine M; Dombrowksi, Julia C et al. (2017) New Human Immunodeficiency Virus Diagnosis Independently Associated With Rectal Gonorrhea and Chlamydia in Men Who Have Sex With Men. Sex Transm Dis 44:385-389
Myers, Julie E; Xia, Qiang; Torian, Lucia V et al. (2016) Implementation and Operational Research: CD4 Count Monitoring Frequency and Risk of CD4 Count Dropping Below 200 Cells Per Cubic Millimeter Among Stable HIV-Infected Patients in New York City, 2007-2013. J Acquir Immune Defic Syndr 71:e73-8
Khosropour, Christine M; Dombrowski, Julia C; Swanson, Fred et al. (2016) Trends in Serosorting and the Association With HIV/STI Risk Over Time Among Men Who Have Sex With Men. J Acquir Immune Defic Syndr 72:189-97
Barbee, Lindley A; Khosropour, Christine M; Dombrowski, Julia C et al. (2016) An estimate of the proportion of symptomatic gonococcal, chlamydial and non-gonococcal non-chlamydial urethritis attributable to oral sex among men who have sex with men: a case-control study. Sex Transm Infect 92:155-60
Barbee, Lindley A; Tat, Susana; Dhanireddy, Shireesha et al. (2016) Implementation and Operational Research: Effectiveness and Patient Acceptability of a Sexually Transmitted Infection Self-Testing Program in an HIV Care Setting. J Acquir Immune Defic Syndr 72:e26-31
Barbee, Lindley A; Dhanireddy, Shireesha; Tat, Susana A et al. (2015) Barriers to Bacterial Sexually Transmitted Infection Testing of HIV-Infected Men Who Have Sex With Men Engaged in HIV Primary Care. Sex Transm Dis 42:590-4