HIV pre-exposure prophylaxis for adolescent girls and young women in Africa: from efficacy trials to delivery

Connie L Celum, Sinead Delany-Moretlwe, Jared M Baeten, Ariane van der Straten, Sybil Hosek, Elizabeth A Bukusi, Margaret McConnell, Ruanne V Barnabas, Linda-Gail Bekker, Connie L Celum, Sinead Delany-Moretlwe, Jared M Baeten, Ariane van der Straten, Sybil Hosek, Elizabeth A Bukusi, Margaret McConnell, Ruanne V Barnabas, Linda-Gail Bekker

Abstract

Introduction: Adolescent girls and young women (AGYW) in Africa have high HIV incidence despite scale-up of HIV testing and HIV treatment. Placebo-controlled trials of tenofovir-based pre-exposure prophylaxi (PrEP) in diverse populations demonstrated that PrEP works with close to 100% effectiveness if taken with high, but not perfect, adherence. Divergent efficacy estimates among African AGYW led to demonstration and implementation projects to better understand motivations for HIV prevention, uptake, adherence and persistence to PrEP. To inform PrEP programmes, the design and initial findings from PrEP demonstration projects for AGYW are reviewed.

Discussion: Early lessons from PrEP implementation projects among young African women include: (1) awareness and demand creation with positive messaging about the benefits of PrEP are critical to motivate AGYW to consider this novel prevention technology and to foster awareness among peers, partners, parents and guardians to support AGYW's effective PrEP use; (2) PrEP initiation is high in projects that are integrating PrEP into youth-friendly clinics, family planning clinics and mobile clinics; (3) young African women at risk are initiating PrEP, based on behavioural characteristics, history of intimate partner violence, depression and 30% prevalence of chlamydia and/or gonorrhoea; (4) provision of youth-friendly PrEP delivery programmes that integrate reproductive health services, including contraception and the diagnosis and treatment of sexually transmitted infections, increase health impact; (5) messages that emphasize the necessity for high adherence while at potential risk of HIV exposure and support strategies that addresses AGYW's adherence challenges are essential; and, (6) a substantial proportion of AGYW do not persist with PrEP, and strategies are needed to help AGYW assess their ongoing need, motivation and challenges with persisting with PrEP.

Conclusions: PrEP is feasible to implement in integrated reproductive health service delivery models to reach African AGYW. While PrEP demonstration projects indicate that women with behavioural risks and high rates of sexually transmitted diseases are initiating PrEP; effective strategies to support AGYW's adherence and persistence with PrEP are needed. Lessons learned from oral PrEP delivery, a novel first generation HIV prevention product, are relevant to longer-acting and less adherence-dependent strategies which are currently in clinical trials.

Keywords: Africa; HIV prevention; adolescents; pre-exposure prophylaxis; young women.

© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.

References

    1. UNAIDS . Global AIDS update. Miles to go: closing gaps, breaking barriers, righting injustices. Geneva: UNAIDS; 2018.
    1. Baeten JM, Palanee‐Phillips T, Brown ER, Schwartz K, Soto‐Torres LE, Govender V, et al. Use of a vaginal ring containing dapivirine for HIV‐1 prevention in women. N Engl J Med. 2016;375:2121–32.
    1. Fonner VA, Dalglish SL, Kennedy CE, Baggaley R, O'Reilly KR, Koechlin FM, et al. Effectiveness and safety of oral HIV preexposure prophylaxis for all populations. AIDS. 2016;30(12):1973–83.
    1. Marrazzo JM, Ramjee G, Richardson BA, Gomez K, Mgodi N, Nair G, et al. Tenofovir‐based preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2015;372(6):509–18.
    1. Van Damme L, Corneli A, Ahmed K, Agot K, Lombaard J, Kapiga S, et al. Preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2012;367(5):411–22.
    1. Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363(27):2587–99.
    1. Baeten JM, Donnell D, Ndase P, Mugo NR, Campbell JD, Wangisi J, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367(5):399–410.
    1. Choopanya K, Martin M, Suntharasamai P, Sangkum U, Mock PA, Leethochawalit M, et al. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double‐blind, placebo‐controlled phase 3 trial. Lancet. 2013;381(9883):2083–90.
    1. Thigpen MC, Kebaabetswe PM, Paxton LA, Smith DK, Rose CE, Segolodi TM, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. 2012;367(5):423–34.
    1. Murnane PM, Celum C, Mugo N, Campbell JD, Donnell D, Bukusi E, et al. Efficacy of preexposure prophylaxis for HIV‐1 prevention among high‐risk heterosexuals: subgroup analyses from a randomized trial. AIDS. 2013;27(13):2155–60.
    1. Hanscom B, Janes HE, Guarino PD, Huang Y, Brown ER, Chen YQ, et al. Preventing HIV‐1 infection in women using oral pre‐exposure prophylaxis: a meta‐analysis of current evidence. J Acquir Immune Defic Syndr. 2016;73(5):606.
    1. Argo N, Krishnamurti T, Fischhof B. Should I take PrEP? A mental models assessment of young African women's motivations for and barriers to PrEP initiation and adherence. International AIDS Conference; July 23‐27; Amsterdam, The Netherlands; 2018.
    1. Corneli A, Perry B, Agot K, Ahmed K, Malamatsho F, Van Damme L. Facilitators of adherence to the study pill in the FEM‐PrEP clinical trial. PLoS ONE. 2015;10(4):e0125458.
    1. Katz A, Mensch B, Woeber K, Musara P, Etima J, van der Straten A. Understanding women's motivations to participate in MTN‐003/VOICE, an HIV prevention trial with low adherence. HIV Research for Prevention Conference (HIVR4P); October 17‐20; Chicago, IL; 2016.
    1. Macphail C, Delany‐Moretlwe S, Mayaud P. “It's not about money, it's about my health”: determinants of participation and adherence among women in an HIV‐HSV2 prevention trial in Johannesburg, South Africa. Patient Prefer Adherence. 2012;6:579–88.
    1. Magazi B, Stadler J, Delany‐Moretlwe S, Montgomery E, Mathebula F, Hartmann M, et al. Influences on visit retention in clinical trials: insights from qualitative research during the VOICE trial in Johannesburg, South Africa. BMC Womens Health. 2014;14:88.
    1. Corneli AL, McKenna K, Perry B, Ahmed K, Agot K, Malamatsho F, et al. The science of being a study participant: FEM‐PrEP participants’ explanations for overreporting adherence to the study pills and for the whereabouts of unused pills. J Acquir Immune Defic Syndr. 2015;68(5):578–84.
    1. van der Straten A, Stadler J, Luecke E, Laborde N, Hartmann M, Montgomery ET. Perspectives on use of oral and vaginal antiretrovirals for HIV prevention: the VOICE‐C qualitative study in Johannesburg, South Africa. J Int AIDS Soc. 2014;17(3 Suppl 2):19146.
    1. van der Straten A, Stadler J, Montgomery E, Hartmann M, Magazi B, Mathebula F, 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(2):e89118.
    1. van der Straten A, Musara P, Etima J, Woeber K, Montgomery ET, Hartmann M, et al. Disclosure of pharmacokinetic (PK) drug results promotes open discourse on non‐adherence among women in VOICE. AIDS Res Hum Retrov. 2014;30:A42–3.
    1. Laibson D. Golden eggs and hyperbolic discounting. Q J Econ. 1997;112(2):443–77.
    1. O'Donoghue T, Rabin M. Doing it now or later. Am Econ Rev. 1999;89(1):103–24.
    1. Linnemayr S. HIV prevention through the lens of behavioral economics. J Acquir Immune Defic Syndr. 2015;68(4):e61–3.
    1. Montgomery ET, Mensch B, Musara P, Hartmann M, Woeber K, Etima J, et al. Misreporting of product adherence in the MTN‐003/VOICE trial for HIV prevention in Africa: participants’ explanations for dishonesty. AIDS Behav. 2017;21(2):481–91.
    1. Hartmann M, McConnell M, Bekker LG, Celum C, Bennie T, Zuma J, et al. Motivated reasoning and HIV risk? Views on relationships, trust, and risk from young women in Cape Town, South Africa, and implications for oral PrEP. AIDS Behav. 2018;22(11):3468–79.
    1. Palanee‐Phillips T, Roberts ST, Reddy K, Vaneshree G, Naidoo L, Siva S, et al. Impact of partner‐related social harms on women's adherence to the dapivirine vaginal ring during a phase III trial. J Acquir Immune Defic Syndr. 2018;79:580.
    1. Roberts ST, Haberer J, Celum C, Mugo N, Ware NC, Cohen CR, et al. Intimate partner violence and adherence to HIV pre‐exposure prophylaxis (PrEP) in African women in HIV serodiscordant relationships: a prospective cohort study. J Acquir Immune Defic Syndr. 2016;73(3):313–22.
    1. Cabral A, Ngure K, Velloza J, Odoyo J, Celum C, Muwonge T, et al. Intimate partner violence and self‐reported pre‐exposure prophylaxis interruptions among HIV‐negative partners in HIV serodiscordant couples in Kenya and Uganda. J Acquir Immune Defic Syndr. 2018;77(2):154–9.
    1. Montgomery ET, van der Straten A, Stadler J, Hartmann M, Magazi B, Mathebula F, et al. Male partner influence on women's HIV prevention trial participation and use of pre‐exposure prophylaxis: the importance of “understanding.” AIDS Behav. 2015;19(5):784–93.
    1. Geier CF. Adolescent cognitive control and reward processing: implications for risk taking and substance use. Horm Behav. 2013;64(2):333–42.
    1. Smith AR, Chein J, Steinberg L. Impact of socio‐emotional context, brain development, and pubertal maturation on adolescent risk‐taking. Horm Behav. 2013;64(2):323–32.
    1. Romer D. Adolescent risk taking, impulsivity, and brain development: implications for prevention. Dev Psychobiol. 2010;52(3):263–76.
    1. Perez KM, Patel NJ, Lord JH, Savin KL, Monzon AD, Whittemore R, et al. Executive function in adolescents with type 1 diabetes: relationship to adherence, glycemic control, and psychosocial outcomes. J Pediatr Psychol. 2017;42(6):636–46.
    1. O'Hara LK, Holmbeck GN. Executive functions and parenting behaviors in association with medical adherence and autonomy among youth with spina bifida. J Pediatr Psychol. 2013;38(6):675–87.
    1. Bagner DM, Williams LB, Geffken GR, Silverstein JH, Storch EA. Type 1 diabetes in youth: the relationship between adherence and executive functioning. Children's Health Care. 2007;36(2):169–79.
    1. Reed‐Knight B, Blount RL, Gilleland J. The transition of health care responsibility from parents to youth diagnosed with chronic illness: a developmental systems perspective. Fam Syst Health. 2014;32(2):219–34.
    1. Gutierrez‐Colina AM, Eaton CK, Lee JL, Reed‐Knight B, Loiselle K, Mee LL, et al. Executive functioning, barriers to adherence, and nonadherence in adolescent and young adult transplant recipients. J Pediatr Psychol. 2016;41(7):759–67.
    1. Luecke EH, Cheng H, Woeber K, Nakyanzi T, Mudekunye‐Mahaka IC, van der Straten A. Stated product formulation preferences for HIV pre‐exposure prophylaxis among women in the VOICE‐D (MTN‐003D) study. J Int AIDS Soc. 2016;19(1):20875.
    1. van der Straten A, Shapley‐Quinn MK, Reddy K, Cheng H, Etima J, Woeber K, et al. Favoring “peace of mind”: a qualitative study of african women's HIV prevention product formulation preferences from the MTN‐020/ASPIRE trial. AIDS Patient Care STDs. 2017;31(7):305–14.
    1. Minnis AM, Roberts ST, Agot K, Weinrib R, Ahmed K, Manenzhe K, et al. Young women's ratings of three placebo multipurpose prevention technologies for HIV and pregnancy prevention in a randomized, cross‐over study in Kenya and South Africa. AIDS Behav. 2018;22(8):2662–73.
    1. van der Straten A, Agot K, Ahmed K, Weinrib R, Browne EN, Manenzhe K, et al. The tablets, ring, injections as options (TRIO) study: what young African women chose and used for future HIV and pregnancy prevention. J Int AIDS Soc. 2018;21(3):e25094.
    1. McCormack S, Dunn DT, Desai M, Dolling DI, Gafos M, Gilson R, et al. Pre‐exposure prophylaxis to prevent the acquisition of HIV‐1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open‐label randomised trial. Lancet. 2016;387(10013):53–60.
    1. Heffron R, Ngure K, Odoyo J, Bulya N, Tindimwebwa E, Hong T, 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.
    1. Baeten J, Heffron R, Kidoguchi L, Mugo N, Katabira E, Bukusi E, et al. Integrated delivery of antiretroviral treatment and pre‐exposure prophylaxis to HIV‐1–serodiscordant couples: a prospective implementation study in Kenya and Uganda. PLoS Med. 2016;13(8):e1002099.
    1. Baeten J, Palanee‐Philips T, Mgodi N, Mayo A, Nel A, Rosenberg Z, et al. High uptake and reduced HIV‐1 incidence in an open‐label, trial of the dapivirine ring. Conference on Retroviruses and Opportunistic Infections (CROI); March 4‐7; Boston, MA; 2018.
    1. Bekker LG, Roux S, Sebastien E, Yola N, Amico KR, Hughes JP, 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(2):e68–78.
    1. Hosek SG, Landovitz RJ, Kapogiannis B, Siberry GK, Rudy B, Rutledge B, et al. Safety and feasibility of antiretroviral preexposure prophylaxis for adolescent men who have sex with men aged 15 to 17 years in the United States. JAMA Pediatr. 2017;171(11):1063–71.
    1. World Health Organization . WHO implementation guidance for pre‐exposure prophylaxis of HIV infection. Geneva, Switzerland: World Health Organization; 2016.
    1. Haberer JE, Kidoguchi L, Heffron R, Mugo N, Bukusi E, Katabira E, et al. Alignment of adherence and risk for HIV acquisition in a demonstration project of pre‐exposure prophylaxis among HIV serodiscordant couples in Kenya and Uganda: a prospective analysis of prevention‐effective adherence. J Int AIDS Soc. 2017;20(1):21842.
    1. Meyers L, Bekker L‐G, Aunger R, van der Straten A, Morton J, McConnell M, et al. A behaviour‐centered design approach to creating demand for oral PrEP among young women in Masiphumelele, South Africa. International AIDS Conference; July 23‐27; Amsterdam, The Netherlands; 2018.
    1. Wagner LD, Roberts S, O'Rourke S, Celum C, Baeten J, Bukusi E, et al. Challenges with oral pre‐exposure prophylaxis (PrEP) disclosure among adolescent girls and young women (AGYW) in Kenya and South Africa. The HIV Research For Prevention Conference (HIVR4P); October 21‐25; Madrid, Spain; 2018.
    1. Celum C, Mgodi N, Bekker L‐G, Hosek S, Donnell D, Anderon P, et al. Adherence 3 months after PrEP initiation among young African women in HPTN 082. Conference on Retroviruses and Opportunistic Infections (CROI); March 4‐7; Seattle, WA; 2019.
    1. Delany‐Moretlwe S, Mgodi N, Bekker L‐G, Baeten J, Pathak S, Donnell D, et al. High curable STI prevalence and incidence in HPTN 082. Conference on Retroviruses and Opportunistic Infections (CROI); March 4‐7; Seattle, WA; 2019.
    1. Rousseau‐Jemwa E, Bekker L‐G, Bukusi E, Delany‐Moretlwe S, Omollo V, Traveill D, et al. Early persistence of HIV pre‐exposure prophylaxis (PrEP) in African adolescent girls and young women (AGYW) from Kenya and South Africa. HIV Research for Prevention Meeting (HIVR4P); October 21‐25; Madrid, Spain; 2018.
    1. Celum C, Delany‐Moretlwe S, Hosek S, Dye B, Bekker L, Mgodi N, et al. Risk behavior, perception, and reasons for PrEP among young African women in HPTN 082. Conference on Retroviruses and Opportunistic Infections (CROI); March 4‐7; Boston, MA; 2018.
    1. Celum C, Gill K, Morton J, Stein G, van der Straten A, Baeten J, et al. High adherence among young women in Cape Town in the first 3 months after PrEP START. Conference on Retroviruses and Opportunistic Infections (CROI); March 4‐7; Seattle, WA; 2019.
    1. Simoni JM, Huh D, Frick PA, Pearson CR, Andrasik MP, Dunbar PJ, et al. Peer support and pager messaging to promote antiretroviral modifying therapy in Seattle: a randomized controlled trial. J Acquir Immune Defic Syndr. 2009;52(4):465–73.
    1. Spiegel HM, Futterman DC. Adolescents and HIV: prevention and clinical care. Curr HIV/AIDS Rep. 2009;6(2):100–7.
    1. Denison JA, Banda H, Dennis AC, Packer C, Nyambe N, Stalter RM, et al. “The sky is the limit”: adhering to antiretroviral therapy and HIV self‐management from the perspectives of adolescents living with HIV and their adult caregivers. J Int AIDS Soc. 2015;18(1):19358.
    1. Massy M, Bauermeister JA, Victor M, Judith B, Kiweewa F, Snow RC, et al. Psychosocial challenges and strategies for coping with HIV among adolescents in Uganda: a qualitative study. AIDS Patient Care STDS. 2015;29(2):86–94.
    1. Sung‐Hee K, Susan M, Samuel K, Caroline F, Sarah F. Importance of self‐motivation and social support in medication adherence in HIV‐infected adolescents in the United Kingdom and Ireland: a multicentre HYPNet study. AIDS Patient Care STDS. 2015;29(6):354–64.
    1. Fisher EB, Boothroyd RI, Coufal MM, Baumann LC, Mbanya JC, Rotheram‐Borus MJ, et al. Peer support for self‐management of diabetes improved outcomes in international settings. Health Aff. 2012;31(1):130–9.
    1. Scorgie F, Stadler J, Baron D, Ju S, Ikaneng T, Mabude Z, et al. “It was not my aim to sleep there”: the impact of timing and location of sex on adherence to coitally‐dependent hiv pre‐exposure prophylaxis. AIDS Behav. 2018;22(11):3692–704.
    1. Delany‐Moretlwe S, Lombard C, Baron D, Bekker L‐G, Nkala B, Ahmed K, et al. Tenofovir 1% vaginal gel for prevention of HIV‐1 infection in women in South Africa (FACTS‐001): a phase 3, randomised, double‐blind, placebo‐controlled trial. Lancet Infect Dis. 2018;18(11):1241–50.
    1. Mudhune S, Delany‐Moretlwe S, Baron D, Pato S, Stadler J, Ngcobo N, et al. Motivating, measuring and monitoring adherence in the FACTS 001 tenofovir gel microbicide study. HIV Research For Prevention Conference (HIVR4P); October 27‐31; Cape Town, South Africa; 2014.
    1. Ramskin L, Baron D, Makgamathe K, Schutzman J, Stangl A, Sievwright K, et al. EMPOWER clubs for young women using oral PrEP as part of an HIV prevention package: what we've learned so far. Adherence to HIV prevention and treatment. Adherence to HIV Prevention and Treatment; April 26‐27; Harare, Zimbabwe; 2018.
    1. Mani A, Mullainathan S, Shafir E, Zhao J. Poverty impedes cognitive function. Science. 2013;341(6149):976–80.
    1. Linnemayr S, Stecher C, Mukasa B. Behavioral economic incentives to improve adherence to antiretroviral medication. AIDS. 2017;31(5):719–26.
    1. Dupas P. Health behavior in developing countries. Annu Rev Econom. 2011;3(1):425–49.
    1. Loewenstein G, Price J, Volpp K. Habit formation in children: evidence from incentives for healthy eating. J Health Econ. 2016;45:47–54.
    1. Vannakit R, Kim M, Charoenying S, Mills S, Avery M, Phanuphak PN, et al. Key population‐led health services (KP‐LHS) critical to PrEP introduction among MSM and TG in Thailand. International AIDS Conference; July 23‐27; Amsterdam, The Netherlands; 2018.
    1. Tsondai PR, Wilkinson LS, Grimsrud A, Mdlalo PT, Ullauri A, Boulle A. High rates of retention and viral suppression in the scale‐up of antiretroviral therapy adherence clubs in Cape Town, South Africa. J Int AIDS Soc. 2017;20 Suppl 4:21649.
    1. McGillen JB, Anderson SJ, Hallett TB. PrEP as a feature in the optimal landscape of combination HIV prevention in sub‐Saharan Africa. J Int AIDS Soc. 2016;19(7 Suppl 6):21104.
    1. Peebles K, Mugwanya K, Irungu E, Odoyo J, Wamoni E, Morton J, et al. Low costs and opportunities for efficiency in the first year of programmatic PrEP delivery in Kenya's Public Sector. HIV Research for Prevention Conference (HIVR4P); October 21‐25; Madrid, Spain; 2018.
    1. Roberts A. The role of costing in the introduction and scale up of pre‐exposure prophylaxis: evidence from integrating PrEP into routine maternal and child health and family planning clinics in western Kenya. J Int AIDS Soc. Submitted.
    1. Gill K. Evaluation of PrEP demand creation and uptake among young women in a Cape Town township: the 3P study. International AIDS Conference; July 23‐27; Amsterdam, The Netherlands; 2018.
    1. Rousseau‐Jemwa E, Celum C, Baeten J, Bekker L‐G. A comparative study of risk among adolescent girls and young women who accept or decline PrEP uptake from a community‐based mobile clinic. International AIDS Conference; July 23‐27; Amsterdam, The Netherlands; 2018.
    1. Morton J, Bukusi E, Delaney‐Moretlwe S, Bekker L‐G, Omollo V, Travill D, et al. High prevalence of curable STIs among young women initiating PrEP in Kenya and South Africa. International AIDS Conference; July 23‐27; Amsterdam, The Netherlands; 2018.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit