Protocol for a longitudinal study to evaluate the use of tenofovir-based PrEP for safer conception and pregnancy among women in South Africa

Lynn T Matthews, Manjeetha Jaggernath, Yolandie Kriel, Patricia M Smith, Kasey O'Neil, Jessica E Haberer, Craig Hendrix, Jared M Baeten, Norma C Ware, Kathleen Wirth, Christina Psaros, David R Bangsberg, Jennifer A Smit, Lynn T Matthews, Manjeetha Jaggernath, Yolandie Kriel, Patricia M Smith, Kasey O'Neil, Jessica E Haberer, Craig Hendrix, Jared M Baeten, Norma C Ware, Kathleen Wirth, Christina Psaros, David R Bangsberg, Jennifer A Smit

Abstract

Introduction: Women who choose to conceive a baby with a partner living with HIV or a partner whose HIV serostatus is unknown in HIV-endemic settings need prevention strategies to mitigate HIV acquisition during conception and pregnancy.

Methods and analysis: We are conducting a single-arm longitudinal study offering oral tenofovirdisoproxil fumarate/emtricitabine (TDF/FTC) as pre-exposure prophylaxis (PrEP) for periconception use to 350 HIV-uninfected women in KwaZulu-Natal, South Africa. PrEP is offered as part of woman-centred safer conception programme that promotes couples-based HIV counselling and testing, antiretroviral therapy for partners who are HIV-infected, treatment for sexually transmitted infections and safer conception strategies, such as limiting condomless sex to peak fertility. We enrol HIV-uninfected women who are not currently pregnant, in a stable relationship (≥6 months) with a partner living with HIV or of unknown serostatus, and personal or partner plans for pregnancy in the next 12 months. We follow enrolled women for 12 months. Women who become pregnant are followed through pregnancy outcome, independent of their decisions regarding PrEP use. The primary objective of the study is to evaluate the uptake of and adherence to PrEP during the periconception period and pregnancy. Secondary outcomes include the uptake of other safer conception strategies. We also measure clinical outcomes including HIV seroconversion rates and pregnancy and infant outcomes. Finally, we will explore conduct and evaluate qualitative interviews in 25 participants to further inform our conceptual framework for periconception PrEP uptake and adherence among HIV-exposed women in South Africa.

Ethics and dissemination: The protocol has been approved by the Human Research Ethics Committee at the University of the Witwatersrand (Johannesburg, South Africa) and the Institutional Review Board of Partners Healthcare (Boston, Massachusetts, USA). Study findings will be made available to interested participants. Results will be presented to local health officials and stakeholders at meetings. Investigators will share the results at meetings and in manuscripts. De-identified quantitative data will be made available.

Trial registration number: The protocol is registered with the South African Health Products Regulatory Agency (SAHPRA, formerly known as the Medicine Controls Council, MCC#20170131) and ClinicalTrials.gov (NCT03194308); Pre-results.

Keywords: HIV prevention; Pmtct/emtct; adherence; pregnancy; prep; safer conception.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Locally-relevant images developed to convey key safer conception strategies in the safer conception counselling sessions. (A) Treatment as prevention. (Top panel) The man is not taking ART, has a high viral load and there is a high risk of transmitting to his partner. (Down panel) The man is taking ART, has a suppressed viral load and the risk of transmitting to his partner is minimized. (B) PrEP. The man is not taking ART, has a high viral load and there is a high risk of transmitting to his partner. In (B), the woman is taking PrEP which protects her from acquiring HIV. (C) Timing condomless sex to peak fertility. In this image, the couple is evaluating a calendar to time condomless sex to peak fertility. ART, antiretroviral therapy; PrEP, pre-exposure prophylaxis.

References

    1. Matthews LT, Crankshaw T, Giddy J, et al. . Reproductive decision-making and periconception practices among HIV-positive men and women attending HIV services in Durban, South Africa. AIDS Behav 2013;17:461–70. 10.1007/s10461-011-0068-y
    1. Cooper D, Moodley J, Zweigenthal V, et al. . Fertility intentions and reproductive health care needs of people living with HIV in Cape Town, South Africa: implications for integrating reproductive health and HIV care services. AIDS Behav 2009;13(S1):38–46. 10.1007/s10461-009-9550-1
    1. Mindry D, Maman S, Chirowodza A, et al. . Looking to the future: South African men and women negotiating HIV risk and relationship intimacy. Cult Health Sex 2011;13:589–602. 10.1080/13691058.2011.560965
    1. Myer L, Morroni C, Rebe K. Prevalence and determinants of fertility intentions of HIV-infected women and men receiving antiretroviral therapy in South Africa. AIDS Patient Care STDS 2007;21:278–85. 10.1089/apc.2006.0108
    1. Thomson KA, Hughes J, Baeten JM, et al. . Increased risk of HIV acquisition among women throughout pregnancy and during the postpartum period: a prospective per-coital-act analysis among women with HIV-infected partners. J Infect Dis 2018;218:16–25. 10.1093/infdis/jiy113
    1. Human Sciences Research Council, S.A. South African national HIV prevalence, incidence, behaviour, and communication survey, 2017, 2018.
    1. Vandormael A, Akullian Adam N, Dobra Adrian, et al. . Sharp decline in male HIV incidence in a rural South African population (2004–2015); 4–7 March 2018, Boston, Massachusetts:CROI.
    1. Dovel K, Yeatman S, Watkins S, et al. . Men’s heightened risk of AIDS-related death: the legacy of gendered HIV testing and treatment strategies. AIDS 2015;29:1123–5. 10.1097/QAD.0000000000000655
    1. Mambanga P, Sirwali RN, Tshitangano T. Factors contributing to men’s reluctance to seek HIV counselling and testing at Primary Health Care facilities in Vhembe District of South Africa. Afr J Prim Health Care Fam Med 2016;8:e1–7. 10.4102/phcfm.v8i2.996
    1. Mitchell S, Cockcroft A, Lamothe G, et al. . Equity in HIV testing: evidence from a cross-sectional study in ten Southern African countries. BMC Int Health Hum Rights 2010;10:23 10.1186/1472-698X-10-23
    1. Osler M, Hilderbrand K, Goemaere E, et al. . The continuing burden of advanced HIV disease over 10 years of increasing antiretroviral therapy coverage in South Africa. Clin Infect Dis 2018;66:S118–S125. 10.1093/cid/cix1140
    1. Huerga H, Van Cutsem G, Ben Farhat J, et al. . Who needs to be targeted for HIV testing and treatment in KwaZulu-Natal? Results from a population-based survey. J Acquir Immune Defic Syndr 2016;73:411–8. 10.1097/QAI.0000000000001081
    1. World Health Organization. World Health Organization: PMTCT strategic vision 2010-2015: preventing mother-to-child transmission of HIV to reach the UNGASS and Millennium Development Goals. Geneva: World Health Organization, 2010.
    1. Matthews LT, Beyeza-Kashesya J, Cooke I, et al. . Consensus statement: supporting safer conception and pregnancy for men and women living with and affected by HIV. AIDS Behav 2018;22:1713–24. 10.1007/s10461-017-1777-7
    1. Matthews LT, Baeten JM, Celum C, et al. . Periconception pre-exposure prophylaxis to prevent HIV transmission: benefits, risks, and challenges to implementation. AIDS 2010;24:1975–82. 10.1097/QAD.0b013e32833bedeb
    1. Heffron R, Pintye J, Matthews LT, et al. . PrEP as peri-conception HIV prevention for women and men. Curr HIV/AIDS Rep 2016;13:131–9. 10.1007/s11904-016-0312-1
    1. Mofenson LM, Baggaley RC, Mameletzis I. Tenofovir disoproxil fumarate safety for women and their infants during pregnancy and breastfeeding. AIDS 2017;31:213–32. 10.1097/QAD.0000000000001313
    1. Haberer JE. Current concepts for PrEP adherence in the PrEP revolution: from clinical trials to routine practice. Curr Opin HIV AIDS 2016;11:10–17. 10.1097/COH.0000000000000220
    1. Heffron R, Thomson K, Celum C, et al. . Fertility Intentions, Pregnancy, and Use of PrEP and ART for Safer Conception Among East African HIV Serodiscordant Couples. AIDS Behav 2018;22:1758–65. 10.1007/s10461-017-1902-7
    1. Ngure K, Kimemia G, Dew K, et al. . Delivering safer conception services to HIV serodiscordant couples in Kenya: perspectives from healthcare providers and HIV serodiscordant couples. J Int AIDS Soc 2017;20(Suppl 1):21309 10.7448/IAS.20.2.21309
    1. Schwartz SR, Bassett J, Holmes CB, et al. . Client uptake of safer conception strategies: implementation outcomes from the Sakh’umndeni Safer Conception Clinic in South Africa. J Int AIDS Soc 2017;20(Suppl 1):21291 10.7448/IAS.20.2.21291
    1. Matthews LT, Heffron R, Mugo NR, et al. . High medication adherence during periconception periods among HIV-1-uninfected women participating in a clinical trial of antiretroviral pre-exposure prophylaxis. J Acquir Immune Defic Syndr 2014;67:91–7. 10.1097/QAI.0000000000000246
    1. Heffron R, Ngure K, Odoyo J, et al. . Pre-exposure prophylaxis for HIV-negative persons with partners living with HIV: uptake, use, and effectiveness in an open-label demonstration project in East Africa. Gates Open Res 2017;1:3 10.12688/gatesopenres.12752.1
    1. Bekker LG, Roux S, Sebastien E, et al. . Daily and non-daily pre-exposure prophylaxis in African women (HPTN 067/ADAPT Cape Town Trial): a randomised, open-label, phase 2 trial. Lancet HIV 2018;5:e68–e78. 10.1016/S2352-3018(17)30156-X
    1. Brofenbrenner U. The ecology of human development. American Psychology 1979;32:513–31.
    1. van der Straten A, Stadler J, Montgomery E, et al. . Women’s experiences with oral and vaginal pre-exposure prophylaxis: the VOICE-C qualitative study in Johannesburg, South Africa. PLoS One 2014;9:e89118 10.1371/journal.pone.0089118
    1. Crankshaw TL, Matthews LT, Giddy J, et al. . A conceptual framework for periconception HIV transmission risk reduction among HIV serodiscordant couples. Reprod Health Matters 2012;20:50–60. 10.1016/S0968-8080(12)39639-0
    1. National Department of Health. S.A., National antenatal sentinel HIV and syphilis prevalence survey in South Africa, 2011. Pretoria: National Department of Health, 2012.
    1. Bekker LG, Rebe K, Venter F, et al. . Southern African guidelines on the safe use of pre-exposure prophylaxis in persons at risk of acquiring HIV-1 infection. South Afr J HIV Med 2016;17:455 10.4102/sajhivmed.v17i1.455
    1. Matthews LT, Moore L, Crankshaw TL, et al. . South Africans with recent pregnancy rarely know partner’s HIV serostatus: implications for serodiscordant couples interventions. BMC Public Health 2014;14:843 10.1186/1471-2458-14-843
    1. Bunting L, Boivin J. Development and preliminary validation of the fertility status awareness tool: FertiSTAT. Hum Reprod 2010;25:1722–33. 10.1093/humrep/deq087
    1. Harichund C, Haripersad K, Ramjee R. Participant verification: prevention of co-enrolment in clinical trials in South Africa. S Afr Med J 2013;103:491–3. 10.7196/SAMJ.6674
    1. Department of Health Republic of South Africa. National contraception and fertility planning policy and service delivery guidelines. Pretoria, 2012.
    1. Khidir H, Psaros C, Greener L, et al. . Developing a safer conception intervention for men living with HIV in South Africa. AIDS Behav 2018;22:1725–35. 10.1007/s10461-017-1719-4
    1. Matthews LT, Burns BF, Bajunirwe F, et al. . Beyond HIV-serodiscordance: partnership communication dynamics that affect engagement in safer conception care. PLoS One 2017;12:e0183131 10.1371/journal.pone.0183131
    1. Bolton P, Bass J, Neugebauer R, et al. . Group interpersonal psychotherapy for depression in rural Uganda: a randomized controlled trial. JAMA 2003;289:3117–24. 10.1001/jama.289.23.3117
    1. Hays RB, Rebchook GM, Kegeles SM. The Mpowerment project: community-building with young gay and bisexual men to prevent HIV1. Am J Community Psychol 2003;31:301–12. 10.1023/A:1023966905973
    1. Latkin CA, Knowlton AR. Micro-social structural approaches to HIV prevention: a social ecological perspective. AIDS Care 2005;17(Suppl 1):102–13. 10.1080/09540120500121185
    1. Haberer JE, Bangsberg DR, Baeten JM, et al. . Defining success with HIV pre-exposure prophylaxis: a prevention-effective adherence paradigm. AIDS 2015;29:1277–85. 10.1097/QAD.0000000000000647
    1. U.S. Public Health Service, Centers for Disease Control and Prevention, and U.S. Department of Health and Human Services. Preexposure prophylaxis for the prevention of HIV infection in the United States - 2014, 2014. Clinical Providers' Supplement.
    1. World Health Organization. Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV. Geneva: W.H.O., 2015.
    1. Donnell D, Baeten JM, Bumpus NN, et al. . HIV protective efficacy and correlates of tenofovir blood concentrations in a clinical trial of PrEP for HIV prevention. J Acquir Immune Defic Syndr 2014;66:340–8. 10.1097/QAI.0000000000000172
    1. Hendrix CW. Exploring concentration response in HIV pre-exposure prophylaxis to optimize clinical care and trial design. Cell 2013;155:515–8. 10.1016/j.cell.2013.09.030
    1. Castillo-Mancilla JR, Searls K, Caraway P, et al. . Short communication: tenofovir diphosphate in dried blood spots as an objective measure of adherence in HIV-infected women. AIDS Res Hum Retroviruses 2015;31:428–32. 10.1089/aid.2014.0229
    1. Best BM, Burchett S, Li H, et al. . Pharmacokinetics of tenofovir during pregnancy and postpartum. HIV Med 2015;16:502–11. 10.1111/hiv.12252
    1. Anderson PL, Liu AY, Castillo-Mancilla JR, et al. . Intracellular Tenofovir-Diphosphate and Emtricitabine-Triphosphate in Dried Blood Spots following Directly Observed Therapy. Antimicrob Agents Chemother 2018;62 10.1128/AAC.01710-17
    1. Patton M, Research Q. Qualitative research and evaluation methods. 3rd edn Thousand Oaks, CA: Sage Publications, 2002.
    1. García-Lerma JG, Otten RA, Qari SH, et al. . Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir. PLoS Med 2008;5:e28 10.1371/journal.pmed.0050028
    1. Haberer JE, Baeten JM, Campbell J, et al. . Adherence to antiretroviral prophylaxis for HIV prevention: a substudy cohort within a clinical trial of serodiscordant couples in East Africa. PLoS Med 2013;10:e1001511 10.1371/journal.pmed.1001511
    1. Grant RM, Lama JR, Anderson PL, et al. . Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010;363:2587–99. 10.1056/NEJMoa1011205
    1. Abdool Karim Q, Abdool Karim SS, Frohlich JA, et al. . Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 2010;329:1168–74. 10.1126/science.1193748
    1. Baeten JM, Donnell D, Ndase P, et al. . Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med 2012;367:399–410. 10.1056/NEJMoa1108524
    1. Cottrell ML, Garrett KL, Prince HMA, et al. . Single-dose pharmacokinetics of tenofovir alafenamide and its active metabolite in the mucosal tissues. J Antimicrob Chemother 2017;72:1731–40. 10.1093/jac/dkx064
    1. Little R, Rubin D. Statistical analysis with missing data. Hoboken, NJ: Wiley John & Sons, 2002.
    1. Scharfstein DO, Rotnitzky A, Robins JM. Adjusting for nonignorable drop-out using semiparametric nonresponse models. ‎J Am Stat Assoc 1999;94.
    1. Tsai AC, Kohrt BA, Matthews LT, et al. . Promises and pitfalls of data sharing in qualitative research. Soc Sci Med 2016;169:191–8. 10.1016/j.socscimed.2016.08.004

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