HIV Incidence Among Pregnant and Nonpregnant Women in the FACTS-001 Trial: Implications for HIV Prevention, Especially PrEP Use.
Adolescent
Adult
Female
HIV Infections
/ epidemiology
Humans
Incidence
Infectious Disease Transmission, Vertical
/ prevention & control
Pre-Exposure Prophylaxis
/ statistics & numerical data
Pregnancy
Pregnancy Complications, Infectious
/ epidemiology
Pregnant Women
Risk Factors
Sexual Behavior
South Africa
/ epidemiology
Tenofovir
/ administration & dosage
Young Adult
Journal
Journal of acquired immune deficiency syndromes (1999)
ISSN: 1944-7884
Titre abrégé: J Acquir Immune Defic Syndr
Pays: United States
ID NLM: 100892005
Informations de publication
Date de publication:
01 12 2021
01 12 2021
Historique:
received:
23
04
2020
accepted:
13
07
2021
entrez:
28
10
2021
pubmed:
29
10
2021
medline:
18
1
2022
Statut:
ppublish
Résumé
During pregnancy and postpartum period, the sexual behaviors of women and their partners change in ways that may either increase or reduce HIV risks. Pregnant women are a priority population for reducing both horizontal and vertical HIV transmission. Nine sites in 4 South African provinces. Women aged 18-30 years were randomized to receive pericoital tenofovir 1% gel or placebo gel and required to use reliable modern contraception. We compared HIV incidence in women before, during, and after pregnancy and used multivariate Cox Proportional hazards models to compare HIV incidence by pregnancy status. Rates of pregnancy were 7.1 per 100 woman-years (95% confidence interval [CI]: 6.3 to 8.1) and highest in those who reported oral contraceptive use (25.1 per 100 woman-years; adjusted hazard ratio 22.97 higher than other women; 95% CI: 5.0 to 105.4) or had 2 children. Birth outcomes were similar between trial arms, with 59.8% having full-term live births. No difference was detected in incident HIV during pregnancy compared with nonpregnant women (2.1 versus 4.3%; hazard ratio = 0.56, 95% CI: 0.14 to 2.26). Sexual activity was low in pregnancy and the early postpartum period, as was consistent condom use. Pregnancy incidence was high despite trial participation being contingent on contraceptive use. We found no evidence that rates of HIV acquisition were elevated in pregnancy when compared with those in nonpregnant women. Risks from reductions in condom use may be offset by reduced sexual activity. Nevertheless, high HIV incidence in both pregnant and nonpregnant women supports consideration of introducing antiretroviral-containing pre-exposure prophylaxis for pregnant and nonpregnant women in high HIV prevalence settings.
Sections du résumé
BACKGROUND
During pregnancy and postpartum period, the sexual behaviors of women and their partners change in ways that may either increase or reduce HIV risks. Pregnant women are a priority population for reducing both horizontal and vertical HIV transmission.
SETTING
Nine sites in 4 South African provinces.
METHODS
Women aged 18-30 years were randomized to receive pericoital tenofovir 1% gel or placebo gel and required to use reliable modern contraception. We compared HIV incidence in women before, during, and after pregnancy and used multivariate Cox Proportional hazards models to compare HIV incidence by pregnancy status.
RESULTS
Rates of pregnancy were 7.1 per 100 woman-years (95% confidence interval [CI]: 6.3 to 8.1) and highest in those who reported oral contraceptive use (25.1 per 100 woman-years; adjusted hazard ratio 22.97 higher than other women; 95% CI: 5.0 to 105.4) or had 2 children. Birth outcomes were similar between trial arms, with 59.8% having full-term live births. No difference was detected in incident HIV during pregnancy compared with nonpregnant women (2.1 versus 4.3%; hazard ratio = 0.56, 95% CI: 0.14 to 2.26). Sexual activity was low in pregnancy and the early postpartum period, as was consistent condom use.
CONCLUSIONS
Pregnancy incidence was high despite trial participation being contingent on contraceptive use. We found no evidence that rates of HIV acquisition were elevated in pregnancy when compared with those in nonpregnant women. Risks from reductions in condom use may be offset by reduced sexual activity. Nevertheless, high HIV incidence in both pregnant and nonpregnant women supports consideration of introducing antiretroviral-containing pre-exposure prophylaxis for pregnant and nonpregnant women in high HIV prevalence settings.
Identifiants
pubmed: 34710071
doi: 10.1097/QAI.0000000000002785
pii: 00126334-202112010-00008
doi:
Substances chimiques
Tenofovir
99YXE507IL
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
376-383Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors have no conflicts of interest to disclose.
Références
Keating MA, Hamela G, Miller WC, et al. High HIV incidence and sexual behavior change among pregnant women in Lilongwe, Malawi: implications for the risk of HIV acquisition. PLoS One. 2012;7:e39109.
Gray RH, Li X, Kigozi G, et al. Increased risk of incident HIV during pregnancy in Rakai, Uganda: a prospective study. Lancet. 2005;366:1182–1188.
Morrison CS, Wang J, Van Der Pol B, et al. Pregnancy and the risk of HIV-1 acquisition among women in Uganda and Zimbabwe. AIDS. 2007;21:1027–1034.
Drake AL, Wagner A, Richardson B, et al. Incident HIV during pregnancy and postpartum and risk of mother-to-child HIV transmission: a systematic review and meta-analysis. PLoS Med. 2014;11:e1001608.
Chetty T, Vandormael A, Thorne C, et al. Incident HIV during pregnancy and early postpartum period: a population-based cohort study in a rural area in KwaZulu-Natal, South Africa. BMC Pregnancy Childbirth. 2017;17:248.
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.
Marston M, Newell ML, Crampin A, et al. Is the risk of HIV acquisition increased during and immediately after pregnancy? A secondary analysis of pooled HIV community-based studies from the ALPHA network. PLoS One. 2013;8:e82219.
Mugo NR, Heffron R, Donnell D, et al. Increased risk of HIV-1 transmission in pregnancy: a prospective study among African HIV-1-serodiscordant couples. AIDS. 2011;25:1887–1895.
Groer M, El-Badri N, Djeu J, et al. Suppression of natural killer cell cytotoxicity in postpartum women. Am J Reprod Immunol. 2010;63:209–213.
Elenkov IJ, Wilder RL, Bakalov VK, et al. IL-12, TNF-alpha, and hormonal changes during late pregnancy and early postpartum: implications for autoimmune disease activity during these times. J Clin Endocrinol Metab. 2001;86:4933–4938.
Morrison C, Fichorova RN, Mauck C, et al. Cervical inflammation and immunity associated with hormonal contraception, pregnancy, and HIV-1 seroconversion. J Acquir Immune Defic Syndr. 2014;66:109–117.
Sheffield JS, Wendel GD Jr, McIntire DD, et al. The effect of progesterone levels and pregnancy on HIV-1 coreceptor expression. Reprod Sci. 2009;16:20–31.
MacIntyre DA, Chandiramani M, Lee YS, et al. The vaginal microbiome during pregnancy and the postpartum period in a European population. Sci Rep. 2015;5:8988.
Irungu E, Chersich MF, Sanon C, et al. Changes in sexual behaviour among HIV-infected women in west and east Africa in the first 24 months after delivery. AIDS. 2012;26:997–1007.
Joseph Davey DL, Nyemba DC, Gomba Y, et al. Prevalence and correlates of sexually transmitted infections in pregnancy in HIV-infected and- uninfected women in Cape Town, South Africa. PLoS One. 2019;14:e0218349.
Pintye J, Beima-Sofie KM, Makabong OP, et al. HIV-uninfected Kenyan adolescent and young women share perspectives on using pre-exposure prophylaxis during pregnancy. AIDS Patient Care STDS. 2018;32:538–544.
WHO. Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection: Recommendations for a Public Health Approach. Geneva, Switzerland: WHO; 2013.
Joseph Davey D, West S, Umutoni V, et al. A systematic review of the current status of safer conception strategies for HIV affected heterosexual couples in sub-Saharan Africa. AIDS Behav. 2018;22:2916–2946.
Siemieniuk RAC, Lytvyn L, Mah Ming J, et al. Antiretroviral therapy in pregnant women living with HIV: a clinical practice guideline. BMJ. 2017;358:j3961.
Fowler MG, Qin M, Fiscus SA, et al. Benefits and risks of antiretroviral therapy for perinatal HIV prevention. N Engl J Med. 2016;375:1726–1737.
Nachega JB, Uthman OA, Mofenson LM, et al. Safety of tenofovir disoproxil fumarate-based antiretroviral therapy regimens in pregnancy for HIV-infected women and their infants: a systematic review and meta-analysis. J Acquir Immune Defic Syndr. 2017;76:1–12.
Mofenson LM, Baggaley RC, Mameletzis I. Tenofovir disoproxil fumarate safety for women and their infants during pregnancy and breastfeeding. AIDS. 2017;31:213–232.
Chou R, Evans C, Hoverman A, et al. Pre-Exposure Prophylaxis for the Prevention of HIV Infection: A Systematic Review for the U.S. Preventive Services Task Force . Rockville, MD: US Preventive Services Task Force; 2019.
Mugwanya KK, John-Stewart G, Baeten J. Safety of oral tenofovir disoproxil fumarate-based HIV pre-exposure prophylaxis use in lactating HIV-uninfected women. Expert Opin Drug Saf. 2017;16:867–871.
Flynn PM, Mirochnick M, Shapiro DE, et al. Pharmacokinetics and safety of single-dose tenofovir disoproxil fumarate and emtricitabine in HIV-1-infected pregnant women and their infants. Antimicrob Agents Chemother. 2011;55:5914–5922.
Heffron R, Mugo N, Hong T, et al. Pregnancy outcomes and infant growth among babies with in-utero exposure to tenofovir-based preexposure prophylaxis for HIV prevention. AIDS. 2018;32:1707–1713.
Hu X, Wang L, Xu F. Guides concerning tenofovir exposure via breastfeeding: a comparison of drug dosages by developmental stage. Int J Infect Dis. 2019;87:8–12.
Joseph Davey DL, Pintye J, Baeten JM, et al. Emerging evidence from a systematic review of safety of pre-exposure prophylaxis for pregnant and postpartum women: where are we now and where are we heading? J Int AIDS Soc. 2020;23:e25426.
Fairlie L, Waitt C, Lockman S, et al. Inclusion of pregnant women in antiretroviral drug research: what is needed to move forwards? J Int AIDS Soc. 2019;22:e25372.
WHO. Technical Brief: Preventing HIV During Pregnancy and Breastfeeding in the Context of Pre-exposure Prophylaxis (PrEP). Geneva, Switzerland: WHO; 2017. CC BY-NC-SA 3.0 IGO.
WHO. Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection: Recommendations for a Public Health Approach. 2nd ed. Geneva, Switzerland: WHO; 2016.
Marrazzo JM, del Rio C, Holtgrave DR, et al. HIV prevention in clinical care settings: 2014 recommendations of the International Antiviral Society-USA Panel. JAMA. 2014;312:390–409.
Delany-Moretlwe S, Lombard C, Baron D, 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;18:1241–1250.
Tien D, Schnaare RL, Kang F, et al. In vitro and in vivo characterization of a potential universal placebo designed for use in vaginal microbicide clinical trials. AIDS Res Hum Retroviruses. 2005;21:845–853.
Sibeko S, Baxter C, Yende N, et al. Contraceptive choices, pregnancy rates, and outcomes in a microbicide trial. Obstet Gynecol. 2011;118:895–904.
Akello CA, Bunge KE, Nakabiito C, et al. Contraceptive use and pregnancy incidence among women participating in an HIV prevention trial. J Womens Health (Larchmt). 2017;26:670–676.
Van Damme L, Corneli A, Ahmed K, et al. Preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2012;367:411–422.
Callahan R, Nanda K, Kapiga S, et al. Pregnancy and contraceptive use among women participating in the FEM-PrEP trial. J Acquir Immune Defic Syndr. 2015;68:196–203.
Reid SE, Dai JY, Wang J, et al. Pregnancy, contraceptive use, and HIV acquisition in HPTN 039: relevance for HIV prevention trials among African women. J Acquir Immune Defic Syndr. 2010;53:606–613.
Pleaner M, Morroni C, Smit J, et al. Lessons learnt from the introduction of the contraceptive implant in South Africa. S Afr Med J. 2017;107:933–938.
Trussell J. Contraceptive efficacy. In: Hatcher RA, Trussell J, Nelson AL, et al, eds. Contraceptive Technology: Twentieth Revised Edition. New York, NY: Ardent Media; 2011.
Desgrees-du-Lou A, Brou H. Resumption of sexual relations following childbirth: norms, practices and reproductive health issues in Abidjan, Cote d'Ivoire. Reprod Health Matters. 2005;13:155–163.
Dinh TH, Delaney KP, Goga A, et al. Impact of maternal HIV seroconversion during pregnancy on early mother to child transmission of HIV (MTCT) measured at 4-8 weeks postpartum in South Africa 2011-2012: a national population-based evaluation. PLoS One. 2015;10:e0125525.
Joseph Davey DL, Bekker LG, Gorbach PM, et al. Delivering preexposure prophylaxis to pregnant and breastfeeding women in Sub-Saharan Africa: the implementation science frontier. AIDS. 2017;31:2193–2197.
Vazquez L, Moll AP, Kacin A, et al. Perceptions of HIV preexposure prophylaxis among young pregnant women from rural KwaZulu-Natal, South Africa. AIDS Patient Care STDS. 2019;33:214–219.
van der Straten A, Ryan JH, Reddy K, et al. Influences on willingness to use vaginal or oral HIV PrEP during pregnancy and breastfeeding in Africa: the multisite MAMMA study. J Int AIDS Soc. 2020;23:e25536.
Serris A, Zoungrana J, Diallo M, et al. Getting pregnant in HIV clinical trials: women's choice and safety needs. The experience from the ANRS12169-2LADY and ANRS12286-MOBIDIP trials. HIV Clin Trials. 2016;17:233–241.