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Does Partner Selection Mediate the Relationship Between School Attendance and HIV/Herpes Simplex Virus-2 Among Adolescent Girls and Young Women in South Africa: An Analysis of HIV Prevention Trials Network 068 Data

Stoner, Marie C. D., PhD*; Edwards, Jessie K., PhD*; Miller, William C., PhD; Aiello, Allison E., PhD*; Halpern, Carolyn T., PhD; Julien, Aimée, MPH*,§; Rucinski, Katherine B., MPH*; Selin, Amanda, MHS*; Twine, Rhian, MPH§; Hughes, James P., PhD║,¶; Wang, Jing, MS; Agyei, Yaw, MPH#; Gómez-Olivé, Francesc Xavier, PhD§,**; Wagner, Ryan G., PhD§,††; Laeyendecker, Oliver, PhD‡‡; Macphail, Catherine, PhD§,§§,‖‖; Kahn, Kathleen, PhD§,**,††; Pettifor, Audrey, PhD*,§

JAIDS Journal of Acquired Immune Deficiency Syndromes: September 1, 2018 - Volume 79 - Issue 1 - p 20–27
doi: 10.1097/QAI.0000000000001766

Objective: School attendance prevents HIV and herpes simplex virus-2 (HSV-2) in adolescent girls and young women, but the mechanisms to explain this relationship remain unclear. Our study assesses the extent to which characteristics of sex partners, partner age, and number mediate the relationship between attendance and risk of infection in adolescent girls and young women in South Africa.

Design: We use longitudinal data from the HIV Prevention Trials Network 068 randomized controlled trial in rural South Africa, where girls were enrolled in early adolescence and followed in the main trial for more than 3 years. We examined older partners and the number of partners as possible mediators.

Methods: We used the parametric g-formula to estimate 4-year risk differences for the effect of school attendance on the cumulative incidence of HIV/HSV-2 overall and the controlled direct effect (CDE) for mediation. We examined mediation separately and jointly for the mediators of interest.

Results: We found that young women with high attendance in school had a lower cumulative incidence of HIV compared with those with low attendance (risk difference = −1.6%). Partner age difference (CDE = −1.2%) and the number of partners (CDE = −0.4%) mediated a large portion of this effect. In fact, when we accounted for the mediators jointly, the effect of schooling on HIV was almost removed, showing full mediation (CDE = −0.3%). The same patterns were observed for the relationship between school attendance and cumulative incidence of HSV-2 infection.

Conclusion: Increasing school attendance reduces the risk of acquiring HIV and HSV-2. Our results indicate the importance of school attendance in reducing partner number and partner age difference in this relationship.

*Department of Epidemiology, University of North Carolina, Chapel Hill, NC;

Division of Epidemiology, The Ohio State University, Columbus, OH;

Department of Maternal and Child Health, University of North Carolina, Chapel Hill, NC;

§MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;

Department of Biostatistics, University of Washington, Seattle, WA;

Fred Hutchinson Cancer Research Center, Seattle, WA;

#School of Medicine, Johns Hopkins University, Baltimore, MD;

**INDEPTH Network, Accra, Ghana;

††Department of Public Health and Clinical Medicine, Epidemiology and Global Health Unit, Umeå University, Umeå, Sweden;

‡‡Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Baltimore, MD;

§§School of Health and Society, University of Wollongong, Wollongong, New South Wales, Australia; and

‖‖Wits Reproductive Health and HIV Research Institute, University of the Witwatersrand, Johannesburg, South Africa.

Correspondence to: Marie C. D. Stoner, PhD, Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599 (e-mail:

Supported by T32 5T32AI007001, R01 MH110186 from the National Institutes of Health (NIH) and by Award Numbers UM1 AI068619 (HPTN Leadership and Operations Center), UM1AI068617 (HPTN Statistical and Data Management Center), and UM1AI068613 (HPTN Laboratory Center) from the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, and the National Institute on Drug Abuse of the National Institutes of Health. This work was also supported by NIMH R01 (R01MH087118) and the Carolina Population Center and its NIH Center grant (P2C HD050924). The MRC/Wits Rural Public Health and Health Transitions Research Unit and Agincourt Health and Socio-Demographic Surveillance System have been supported by the University of the Witwatersrand, the Medical Research Council, South Africa, and the Wellcome Trust, UK (grants 058893/Z/99/A; 069683/Z/02/Z; 085477/Z/08/Z; 085477/B/08/Z). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Planning to submit to AIDS 2018 Conference; Amsterdam, the Netherlands; July 23–27.

The authors have no funding or conflicts of interest to disclose.

Similar prior publications by the first author using the same data source include the following: (1) M.C.D.S., J.K.E., W.C.M., A.E.A, C.T.H., A.S., J.P.H., J.W., O.L., Y.A., McPhail C, K.K., A.P. (2017). The effect of schooling on incident HIV and HSV-2 infection in young South African women enrolled in HPTN 068. AIDS. 24; 31:2127–2213. PMCID: PMC5599334. (2) M.C.D.S., J.K.E., W.C.M., A.E.A, C.T.H., Julien Suarez, A.S., J.P.H., J.W., McPhail C, K.K., A.P. (2017). The effect of schooling on age-disparate relationships and number of sexual partners among young women in rural South Africa enrolled in HPTN 068. J Acquir Immune Defic Syndr. 76:e107–e114. PMCID: PMC56801112.

A.P., J.K.E., A.E.A., K.B.R., W.C.M. and C.T.H. contributed to the conception, design of the analysis, and review of the writing. The remaining authors were involved in data acquisition, data collection, study management, and design of the original parent study. Additionally, J.K.E. and J.P.H. contributed to the analysis of data.

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Received March 02, 2018

Accepted May 09, 2018

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