Risk of HIV Acquisition During Pregnancy and Postpartum: A Call for Action

Risk of HIV Acquisition During Pregnancy and Postpartum: A Call for Action Human immunodeficiency virus, pregnancy, postpartum, sexual transmission (See the Major Article by Thomson et al, on pages 16–25.) Prospective studies exploring the relationship between pregnancy and HIV acquisition in women have had inconsistent results, with some studies documenting an increased risk [1–3], while others finding no increase in risk — or even lower risk — after controlling for sexual behavior and other confounding factors such as sexually transmitted infections [4–7]. A meta-analysis of 19 cohort studies estimated a pooled HIV incidence during pregnancy and postpartum of 3.9 per 100 person-years (4.7 per 100 person-years during pregnancy and 2.9 per 100 person-years postpartum) [8], similar to that defined as “substantial risk” in nonpregnant individuals, such as female sex workers, by the World Health Organization (WHO) [9]. The pooled meta-analysis reported that HIV incidence was not significantly higher among pregnant or postpartum women than among nonpregnant/nonpostpartum women, but only 5 studies had appropriate data and were not able to control for a variety of confounding factors, limiting the power to detect associations. The study reported by Thomson and colleagues in this issue of the Journal of Infectious Diseases was unique in its ability to control for many factors that other studies of HIV acquisition risk in pregnancy were not able to [10]. The authors have taken advantage of detailed databases from 2 clinical trials (Partners in Prevention Herpes Simplex Virus/HIV Transmission Study and Partners PrEP study) which enrolled serodiscordant couples in 7 high HIV prevalence African countries with median follow-up of 2 years; the studies included detailed standardized collection of monthly reports of sexual behavior, and data on male circumcision, sexually transmitted infections, contraceptive use, partner viral load, and antiretroviral therapy (ART). An elegant analysis was conducted among 2751 African HIV-seronegative women enrolled in the trials, including 5069 person-years of follow-up and 615 incident pregnancies, to evaluate the risk of HIV acquisition during pregnancy and postpartum, comparing the per coital act HIV acquisition risk in early and late pregnancy (first 13 weeks compared to 14 weeks to gestation end) and through 6 months’ postpartum to nonpregnant/nonpostpartum intervals; visits were censored once the male partner reported initiation of ART, thus the study provides data on HIV acquisition risk in the absence of partner treatment. In addition to HIV antibody testing, the authors had archived quarterly plasma specimens; all seroconversions were tested for HIV RNA and, hence, the authors were able to more definitively determine the timing of acquisition of infection and assign infection events to the stage the woman was in near the time of HIV acquisition (early/late pregnant, postpartum, nonpregnant). Only genetically linked HIV acquisitions were included in the study, allowing linkage to the sexual behavior surveys of the partners. The authors report that HIV acquisition risk per condomless coital act was significantly increased during pregnancy through 6 months’ postpartum (adjusted relative risk [aRR] 2.76; 95% confidence interval [CI], 1.6–4.8) compared to nonpregnant/nonpostpartum time and was highest during late pregnancy (aRR 2.82; 95% CI, 1.3–6.2) and postpartum (aRR 3.97; 95% CI, 1.5–10.5). Additional analyses extending evaluation of the postpartum period through 52 weeks postdelivery found that the increased postpartum risk was concentrated in the first 6 months after delivery. The authors adjusted for time-varying measures of partner viral load and female use of active preexposure prophylaxis (PrEP) based on study arm, as well as age and additional demographic and clinical variables. There are several important implications of this study. From the pathophysiologic viewpoint, because the study was able to control for major behavioral, demographic, and clinical confounders, these data strongly point toward a biologic association of pregnancy with HIV-acquisition risk. Pregnancy is associated with a complex interaction between sexual hormones and the immune system that modulates the maternal immune response to enable tolerance of the paternally derived fetal alloantigens, while maintaining reactivity against potential pathogens. With advancing pregnancy and increasing estradiol and progesterone levels, there is a decrease in natural killer cells and in the robustness of cytotoxic T-cell responses (T-helper cell type 1 immunity, Th1), with a shift toward the humoral T-cell response (T-helper cell type 2 immunity, Th2), while aspects of innate immunity as alpha-defensin levels and monocyte, dendritic cells, and polymorphonuclear cell activity are enhanced [11]. Pregnancy hormone-associated changes in the female genital tract, including changes in vaginal epithelial thickness, the vaginal and gut microbiome, and an increase in CCR5 coreceptor expression, may create a favorable milieu for HIV acquisition in the female genital tract during pregnancy [11–14]. The finding that the increased risk of HIV acquisition in the postpartum period was confined to the first 6 months postpartum is also consistent with this increased risk being related to biologic factors, as it takes weeks to months following delivery for the immunologic changes of pregnancy to reverse [15, 16]. The second and third trimesters of pregnancy and the early postpartum period through 6 months appeared to the periods of highest risk for HIV acquisition [10]. While there has been significant attention to the need to improve retention of HIV-positive women in care, little attention has been paid toward the need for repeat testing in pregnancy and postpartum following an initial HIV-negative test in early pregnancy. Transmission of HIV from mother-to-child (MTCT) among women who acquire HIV during pregnancy or breastfeeding is double to triple that of women who acquire HIV prior to pregnancy [8]. Elimination of MTCT will not occur without elimination of new infections among women. In a study in South Africa, an estimated 3.3% of mothers who had at least 1 HIV-negative test antenatally in 2011–2012 seroconverted during pregnancy; they accounted for 26% of early MTCT in infants age 4–8 weeks [17]. In a mathematical model of MTCT, the proportion of MTCT attributable to maternal seroconversion during late pregnancy or postpartum in South Africa was estimated to be 34% in 2014 [18]. Programs for prevention of MTCT have almost exclusively been directed toward women who are HIV seropositive at their first antenatal visit. Without incorporating interventions focused on keeping HIV-seronegative pregnant and breastfeeding women negative, control of the pediatric HIV epidemic will be difficult. Although many HIV-endemic countries recommend repeat testing of seronegative pregnant women in the third trimester, this is often not done [19], and few programs include HIV testing during the postpartum breastfeeding period. Male partner involvement in antenatal care and HIV testing of male partners of pregnant women are low and, thus, many women lack knowledge of their partners’ HIV serostatus [20–22]. The most effective way to limit transmission from women who seroconvert during pregnancy or breastfeeding is to prevent them from becoming infected in the first place. The data from Thomson et al point toward the critical need to prioritize interventions targeted to HIV seronegative pregnant and breastfeeding women to prevent HIV acquisition. Given the complexity of the HIV epidemic, this will require a multifaceted approach including structural, behavioral, and biomedical interventions. A community-based combination prevention intervention targeted to HIV-seronegative pregnant women was recently studied in South Africa. The intervention included lay community workers who provided individualized HIV prevention counseling and performed every-3-months home and clinic-based individual and couples’ HIV testing, with referral of male partners for circumcision, sexually transmitted infections, or HIV treatment, as appropriate [23]. The antenatal and postnatal HIV incidence was 1.49 and 1.03 infections per 100 person-years, respectively, substantially lower than historical seroconversion rates or the 4.8 per 100 person-years during pregnancy/postpartum in the meta-analysis [8]. Tenofovir-based preexposure prophylaxis is highly effective in preventing HIV acquisition among adherent women [24]. Although adherence in placebo-controlled clinical trials has been variable, experience outside of the clinical trial setting has been promising. In a study of serodiscordant couples in Kenya and Uganda, 78% of women took ≥6 doses and 88% took ≥4 doses per week while on PrEP, providing an estimated 93% protection against HIV acquisition [25]. Similarly, a clinical trial in South Africa found 75% adherence to a daily PrEP regimen in women, with no seroconversions [26]. Even in the context of a placebo-controlled trial, high medication adherence was observed during the periconception periods in HIV-uninfected women in the Partners PrEP trial, with women who experienced pregnancy taking 97% of prescribed doses of study drug overall [27]. The Partners Demonstration Project in Kenya and Uganda demonstrated that integrated delivery of time-limited PrEP until sustained ART use and viral suppression in African HIV-1–serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of <0.5% per year compared to an expected incidence of >5% per year [28]. Increasing data on safety of tenofovir in pregnancy and breastfeeding indicate no increase in adverse birth/infant outcomes and minimal penetration of tenofovir into breast milk [29–32]. The article by Thomson and colleagues provides definitive evidence that the risk of HIV acquisition increases during pregnancy and the early postpartum period. These data serve to emphasize that HIV-seronegative pregnant and postpartum women in HIV-endemic areas need to be considered key populations at high risk for HIV acquisition, requiring urgent attention to the development of interventions to detect HIV seroconversion and initiate ART to prevent transmission to their infants and sexual partners and, even more critically, to maintain their HIV-seronegative status. Notes Potential conflicts of interest.  Author certifies no potential conflicts of interest. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. References 1. 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 – 8 . Google Scholar CrossRef Search ADS PubMed 2. Mugo NR , Heffron R , Donnell D et al. ; Partners in Prevention HSV/HIV Transmission Study Team . Increased risk of HIV-1 transmission in pregnancy: a prospective study among African HIV-1-serodiscordant couples . AIDS 2011 ; 25 : 1887 – 95 . Google Scholar CrossRef Search ADS PubMed 3. Moodley D , Esterhuizen TM , Pather T , Chetty V , Ngaleka L . High HIV incidence during pregnancy: compelling reason for repeat HIV testing . AIDS 2009 ; 23 : 1255 – 9 . Google Scholar CrossRef Search ADS PubMed 4. Morrison CS , Wang J , Van Der Pol B , Padian N , Salata RA , Richardson BA . Pregnancy and the risk of HIV-1 acquisition among women in Uganda and Zimbabwe . AIDS 2007 ; 21 : 1027 – 34 . Google Scholar CrossRef Search ADS PubMed 5. Chetty T , Vandormael A , Thorne C , Coutsoudis A . 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 . Google Scholar CrossRef Search ADS PubMed 6. 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 . Google Scholar CrossRef Search ADS PubMed 7. 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 – 13 . Google Scholar PubMed 8. Drake AL , Wagner A , Richardson B , John-Stewart G . 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 . Google Scholar CrossRef Search ADS PubMed 9. World Health Organization . Guidelines on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV . Geneva, Switzerland: WHO , 2015 . 10. Thomson KA , Hughes J , Baeten JM et al. Increased risk of female HIV-1 acquisition throughout pregnancy and postpartum: a prospective per-coital act analysis among women with HIV-1 infected partners . J Infect Dis 2018 ; 218 : 16 – 25 . 11. Kourtis AP , Read JS , Jamieson DJ . Pregnancy and infection . N Engl J Med 2014 ; 370 : 2211 – 8 . Google Scholar CrossRef Search ADS PubMed 12. Sheffield JS , Wendel GD Jr , McIntire DD , Norgard MV . The effect of progesterone levels and pregnancy on HIV-1 coreceptor expression . Reprod Sci 2009 ; 16 : 20 – 31 . Google Scholar CrossRef Search ADS PubMed 13. Pelzer E , Gomez-Arango LF , Barrett HL , Nitert MD . Review: Maternal health and the placental microbiome . Placenta 2017 ; 54 : 30 – 7 . Google Scholar CrossRef Search ADS PubMed 14. Koren O , Goodrich JK , Cullender TC et al. Host remodeling of the gut microbiome and metabolic changes during pregnancy . Cell 2012 ; 150 : 470 – 80 . Google Scholar CrossRef Search ADS PubMed 15. Groer MW , El-Badri N , Djeu J , Williams SN , Kane B , Szekeres K . Suppression of natural killer cell cytotoxicity in postpartum women: time course and potential mechanisms . Biol Res Nurs 2014 ; 16 : 320 – 6 . Google Scholar CrossRef Search ADS PubMed 16. Gillespie SL , Porter K , Christian LM . Adaptation of the inflammatory immune response across pregnancy and postpartum in Black and White women . J Reprod Immunol 2016 ; 114 : 27 – 31 . Google Scholar CrossRef Search ADS PubMed 17. 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 . Google Scholar CrossRef Search ADS PubMed 18. Johnson LF , Stinson K , Newell ML et al. The contribution of maternal HIV seroconversion during late pregnancy and breastfeeding to mother-to-child transmission of HIV . J Acquir Immune Defic Syndr 2012 ; 59 : 417 – 25 . Google Scholar CrossRef Search ADS PubMed 19. Rogers AJ , Akama E , Weke E et al. Implementation of repeat HIV testing during pregnancy in southwestern Kenya: progress and missed opportunities . J Int AIDS Soc 2017 ; 20 : e25036 . Google Scholar CrossRef Search ADS 20. De Schacht C , Mabunda N , Ferreira OC et al. High HIV incidence in the postpartum period sustains vertical transmission in settings with generalized epidemics: a cohort study in Southern Mozambique . J Int AIDS Soc 2014 ; 17 : 18808 . Google Scholar CrossRef Search ADS PubMed 21. Hensen B , Taoka S , Lewis JJ , Weiss HA , Hargreaves J . Systematic review of strategies to increase men’s HIV-testing in sub-Saharan Africa . AIDS 2014 ; 28 : 2133 – 45 . Google Scholar CrossRef Search ADS PubMed 22. Manjate Cuco RM , Munguambe K , Bique Osman N , Degomme O , Temmerman M , Sidat MM . Male partners’ involvement in prevention of mother-to-child HIV transmission in sub-Saharan Africa: A systematic review . SAHARA J 2015 ; 12 : 87 – 105 . Google Scholar CrossRef Search ADS PubMed 23. Fatti G , Shaikh N , Jackson D et al. Low HIV incidence in pregnant and postpartum women receiving a community-based combination HIV prevention intervention in a high HIV incidence setting in South Africa . PLoS One 2017 ; 12 : e0181691 . Google Scholar CrossRef Search ADS PubMed 24. Hanscom B , Janes HE , Guarino PD et al. Brief report: preventing HIV-1 infection in women using oral preexposure prophylaxis: a meta-analysis of current evidence . J Acquir Immune Defic Syndr 2016 ; 73 : 606 – 8 . Google Scholar CrossRef Search ADS PubMed 25. Pyra M , Haberer JE , Heffron R et al. ; Partners Demonstration Project Team . Brief report: PrEP use during periods of HIV risk among East African Women in serodiscordant relationships . J Acquir Immune Defic Syndr 2018 ; 77 : 41 – 5 . Google Scholar PubMed 26. Bekker LG , Roux S , Sebastien E et al. ; HPTN 067 (ADAPT) study team . 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 – 78 . Google Scholar CrossRef Search ADS PubMed 27. Matthews LT , Heffron R , Mugo NR et al. ; Partners PrEP Study Team . 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 . Google Scholar CrossRef Search ADS PubMed 28. Baeten JM , Heffron R , Kidoguchi L et al. ; Partners Demonstration Project Team . 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 : e1002099 . Google Scholar CrossRef Search ADS PubMed 29. Mofenson LM , Baggaley RC , Mameletzis I . Tenofovir disoproxil fumarate safety for women and their infants during pregnancy and breastfeeding . AIDS 2017 ; 31 : 213 – 32 . Google Scholar CrossRef Search ADS PubMed 30. Pintye J , Baeten JM , Celum C et al. Maternal tenofovir disoproxil fumarate use during pregnancy is not associated with adverse perinatal outcomes among HIV-infected East African women: a prospective study . J Infect Dis 2017 ; 216 : 1561 – 8 . Google Scholar CrossRef Search ADS PubMed 31. Waitt C , Olagunju A , Nakelema S et al. Plasma and breast milk pharmacokinetics of emtricitabine, tenofovir and lamivudine using dried blood spots and breast milk spots in nursing African mother-infant pairs [published online ahead of print 4 January, 2018]. J Antimicrob Chemother , doi: 10.1093/jac/dkx507 . 32. Mugwanya KK , Hendrix CW , Mugo NR et al. Pre-exposure prophylaxis use by breastfeeding HIV-uninfected women: a prospective short-term study of antiretroviral excretion in breast milk and infant absorption . PLoS Med 2016 ; 13 : e1002132 . Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. 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Risk of HIV Acquisition During Pregnancy and Postpartum: A Call for Action

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© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
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Abstract

Human immunodeficiency virus, pregnancy, postpartum, sexual transmission (See the Major Article by Thomson et al, on pages 16–25.) Prospective studies exploring the relationship between pregnancy and HIV acquisition in women have had inconsistent results, with some studies documenting an increased risk [1–3], while others finding no increase in risk — or even lower risk — after controlling for sexual behavior and other confounding factors such as sexually transmitted infections [4–7]. A meta-analysis of 19 cohort studies estimated a pooled HIV incidence during pregnancy and postpartum of 3.9 per 100 person-years (4.7 per 100 person-years during pregnancy and 2.9 per 100 person-years postpartum) [8], similar to that defined as “substantial risk” in nonpregnant individuals, such as female sex workers, by the World Health Organization (WHO) [9]. The pooled meta-analysis reported that HIV incidence was not significantly higher among pregnant or postpartum women than among nonpregnant/nonpostpartum women, but only 5 studies had appropriate data and were not able to control for a variety of confounding factors, limiting the power to detect associations. The study reported by Thomson and colleagues in this issue of the Journal of Infectious Diseases was unique in its ability to control for many factors that other studies of HIV acquisition risk in pregnancy were not able to [10]. The authors have taken advantage of detailed databases from 2 clinical trials (Partners in Prevention Herpes Simplex Virus/HIV Transmission Study and Partners PrEP study) which enrolled serodiscordant couples in 7 high HIV prevalence African countries with median follow-up of 2 years; the studies included detailed standardized collection of monthly reports of sexual behavior, and data on male circumcision, sexually transmitted infections, contraceptive use, partner viral load, and antiretroviral therapy (ART). An elegant analysis was conducted among 2751 African HIV-seronegative women enrolled in the trials, including 5069 person-years of follow-up and 615 incident pregnancies, to evaluate the risk of HIV acquisition during pregnancy and postpartum, comparing the per coital act HIV acquisition risk in early and late pregnancy (first 13 weeks compared to 14 weeks to gestation end) and through 6 months’ postpartum to nonpregnant/nonpostpartum intervals; visits were censored once the male partner reported initiation of ART, thus the study provides data on HIV acquisition risk in the absence of partner treatment. In addition to HIV antibody testing, the authors had archived quarterly plasma specimens; all seroconversions were tested for HIV RNA and, hence, the authors were able to more definitively determine the timing of acquisition of infection and assign infection events to the stage the woman was in near the time of HIV acquisition (early/late pregnant, postpartum, nonpregnant). Only genetically linked HIV acquisitions were included in the study, allowing linkage to the sexual behavior surveys of the partners. The authors report that HIV acquisition risk per condomless coital act was significantly increased during pregnancy through 6 months’ postpartum (adjusted relative risk [aRR] 2.76; 95% confidence interval [CI], 1.6–4.8) compared to nonpregnant/nonpostpartum time and was highest during late pregnancy (aRR 2.82; 95% CI, 1.3–6.2) and postpartum (aRR 3.97; 95% CI, 1.5–10.5). Additional analyses extending evaluation of the postpartum period through 52 weeks postdelivery found that the increased postpartum risk was concentrated in the first 6 months after delivery. The authors adjusted for time-varying measures of partner viral load and female use of active preexposure prophylaxis (PrEP) based on study arm, as well as age and additional demographic and clinical variables. There are several important implications of this study. From the pathophysiologic viewpoint, because the study was able to control for major behavioral, demographic, and clinical confounders, these data strongly point toward a biologic association of pregnancy with HIV-acquisition risk. Pregnancy is associated with a complex interaction between sexual hormones and the immune system that modulates the maternal immune response to enable tolerance of the paternally derived fetal alloantigens, while maintaining reactivity against potential pathogens. With advancing pregnancy and increasing estradiol and progesterone levels, there is a decrease in natural killer cells and in the robustness of cytotoxic T-cell responses (T-helper cell type 1 immunity, Th1), with a shift toward the humoral T-cell response (T-helper cell type 2 immunity, Th2), while aspects of innate immunity as alpha-defensin levels and monocyte, dendritic cells, and polymorphonuclear cell activity are enhanced [11]. Pregnancy hormone-associated changes in the female genital tract, including changes in vaginal epithelial thickness, the vaginal and gut microbiome, and an increase in CCR5 coreceptor expression, may create a favorable milieu for HIV acquisition in the female genital tract during pregnancy [11–14]. The finding that the increased risk of HIV acquisition in the postpartum period was confined to the first 6 months postpartum is also consistent with this increased risk being related to biologic factors, as it takes weeks to months following delivery for the immunologic changes of pregnancy to reverse [15, 16]. The second and third trimesters of pregnancy and the early postpartum period through 6 months appeared to the periods of highest risk for HIV acquisition [10]. While there has been significant attention to the need to improve retention of HIV-positive women in care, little attention has been paid toward the need for repeat testing in pregnancy and postpartum following an initial HIV-negative test in early pregnancy. Transmission of HIV from mother-to-child (MTCT) among women who acquire HIV during pregnancy or breastfeeding is double to triple that of women who acquire HIV prior to pregnancy [8]. Elimination of MTCT will not occur without elimination of new infections among women. In a study in South Africa, an estimated 3.3% of mothers who had at least 1 HIV-negative test antenatally in 2011–2012 seroconverted during pregnancy; they accounted for 26% of early MTCT in infants age 4–8 weeks [17]. In a mathematical model of MTCT, the proportion of MTCT attributable to maternal seroconversion during late pregnancy or postpartum in South Africa was estimated to be 34% in 2014 [18]. Programs for prevention of MTCT have almost exclusively been directed toward women who are HIV seropositive at their first antenatal visit. Without incorporating interventions focused on keeping HIV-seronegative pregnant and breastfeeding women negative, control of the pediatric HIV epidemic will be difficult. Although many HIV-endemic countries recommend repeat testing of seronegative pregnant women in the third trimester, this is often not done [19], and few programs include HIV testing during the postpartum breastfeeding period. Male partner involvement in antenatal care and HIV testing of male partners of pregnant women are low and, thus, many women lack knowledge of their partners’ HIV serostatus [20–22]. The most effective way to limit transmission from women who seroconvert during pregnancy or breastfeeding is to prevent them from becoming infected in the first place. The data from Thomson et al point toward the critical need to prioritize interventions targeted to HIV seronegative pregnant and breastfeeding women to prevent HIV acquisition. Given the complexity of the HIV epidemic, this will require a multifaceted approach including structural, behavioral, and biomedical interventions. A community-based combination prevention intervention targeted to HIV-seronegative pregnant women was recently studied in South Africa. The intervention included lay community workers who provided individualized HIV prevention counseling and performed every-3-months home and clinic-based individual and couples’ HIV testing, with referral of male partners for circumcision, sexually transmitted infections, or HIV treatment, as appropriate [23]. The antenatal and postnatal HIV incidence was 1.49 and 1.03 infections per 100 person-years, respectively, substantially lower than historical seroconversion rates or the 4.8 per 100 person-years during pregnancy/postpartum in the meta-analysis [8]. Tenofovir-based preexposure prophylaxis is highly effective in preventing HIV acquisition among adherent women [24]. Although adherence in placebo-controlled clinical trials has been variable, experience outside of the clinical trial setting has been promising. In a study of serodiscordant couples in Kenya and Uganda, 78% of women took ≥6 doses and 88% took ≥4 doses per week while on PrEP, providing an estimated 93% protection against HIV acquisition [25]. Similarly, a clinical trial in South Africa found 75% adherence to a daily PrEP regimen in women, with no seroconversions [26]. Even in the context of a placebo-controlled trial, high medication adherence was observed during the periconception periods in HIV-uninfected women in the Partners PrEP trial, with women who experienced pregnancy taking 97% of prescribed doses of study drug overall [27]. The Partners Demonstration Project in Kenya and Uganda demonstrated that integrated delivery of time-limited PrEP until sustained ART use and viral suppression in African HIV-1–serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of <0.5% per year compared to an expected incidence of >5% per year [28]. Increasing data on safety of tenofovir in pregnancy and breastfeeding indicate no increase in adverse birth/infant outcomes and minimal penetration of tenofovir into breast milk [29–32]. The article by Thomson and colleagues provides definitive evidence that the risk of HIV acquisition increases during pregnancy and the early postpartum period. These data serve to emphasize that HIV-seronegative pregnant and postpartum women in HIV-endemic areas need to be considered key populations at high risk for HIV acquisition, requiring urgent attention to the development of interventions to detect HIV seroconversion and initiate ART to prevent transmission to their infants and sexual partners and, even more critically, to maintain their HIV-seronegative status. Notes Potential conflicts of interest.  Author certifies no potential conflicts of interest. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. References 1. 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 – 8 . Google Scholar CrossRef Search ADS PubMed 2. Mugo NR , Heffron R , Donnell D et al. ; Partners in Prevention HSV/HIV Transmission Study Team . Increased risk of HIV-1 transmission in pregnancy: a prospective study among African HIV-1-serodiscordant couples . AIDS 2011 ; 25 : 1887 – 95 . Google Scholar CrossRef Search ADS PubMed 3. Moodley D , Esterhuizen TM , Pather T , Chetty V , Ngaleka L . High HIV incidence during pregnancy: compelling reason for repeat HIV testing . AIDS 2009 ; 23 : 1255 – 9 . Google Scholar CrossRef Search ADS PubMed 4. Morrison CS , Wang J , Van Der Pol B , Padian N , Salata RA , Richardson BA . Pregnancy and the risk of HIV-1 acquisition among women in Uganda and Zimbabwe . AIDS 2007 ; 21 : 1027 – 34 . Google Scholar CrossRef Search ADS PubMed 5. Chetty T , Vandormael A , Thorne C , Coutsoudis A . 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 . Google Scholar CrossRef Search ADS PubMed 6. 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 . Google Scholar CrossRef Search ADS PubMed 7. 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 – 13 . Google Scholar PubMed 8. Drake AL , Wagner A , Richardson B , John-Stewart G . 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 . Google Scholar CrossRef Search ADS PubMed 9. World Health Organization . Guidelines on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV . Geneva, Switzerland: WHO , 2015 . 10. Thomson KA , Hughes J , Baeten JM et al. Increased risk of female HIV-1 acquisition throughout pregnancy and postpartum: a prospective per-coital act analysis among women with HIV-1 infected partners . J Infect Dis 2018 ; 218 : 16 – 25 . 11. Kourtis AP , Read JS , Jamieson DJ . Pregnancy and infection . N Engl J Med 2014 ; 370 : 2211 – 8 . Google Scholar CrossRef Search ADS PubMed 12. Sheffield JS , Wendel GD Jr , McIntire DD , Norgard MV . The effect of progesterone levels and pregnancy on HIV-1 coreceptor expression . Reprod Sci 2009 ; 16 : 20 – 31 . Google Scholar CrossRef Search ADS PubMed 13. Pelzer E , Gomez-Arango LF , Barrett HL , Nitert MD . Review: Maternal health and the placental microbiome . Placenta 2017 ; 54 : 30 – 7 . Google Scholar CrossRef Search ADS PubMed 14. Koren O , Goodrich JK , Cullender TC et al. Host remodeling of the gut microbiome and metabolic changes during pregnancy . Cell 2012 ; 150 : 470 – 80 . Google Scholar CrossRef Search ADS PubMed 15. Groer MW , El-Badri N , Djeu J , Williams SN , Kane B , Szekeres K . Suppression of natural killer cell cytotoxicity in postpartum women: time course and potential mechanisms . Biol Res Nurs 2014 ; 16 : 320 – 6 . Google Scholar CrossRef Search ADS PubMed 16. Gillespie SL , Porter K , Christian LM . Adaptation of the inflammatory immune response across pregnancy and postpartum in Black and White women . J Reprod Immunol 2016 ; 114 : 27 – 31 . Google Scholar CrossRef Search ADS PubMed 17. 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 . Google Scholar CrossRef Search ADS PubMed 18. Johnson LF , Stinson K , Newell ML et al. The contribution of maternal HIV seroconversion during late pregnancy and breastfeeding to mother-to-child transmission of HIV . J Acquir Immune Defic Syndr 2012 ; 59 : 417 – 25 . Google Scholar CrossRef Search ADS PubMed 19. Rogers AJ , Akama E , Weke E et al. Implementation of repeat HIV testing during pregnancy in southwestern Kenya: progress and missed opportunities . J Int AIDS Soc 2017 ; 20 : e25036 . Google Scholar CrossRef Search ADS 20. De Schacht C , Mabunda N , Ferreira OC et al. High HIV incidence in the postpartum period sustains vertical transmission in settings with generalized epidemics: a cohort study in Southern Mozambique . J Int AIDS Soc 2014 ; 17 : 18808 . Google Scholar CrossRef Search ADS PubMed 21. Hensen B , Taoka S , Lewis JJ , Weiss HA , Hargreaves J . Systematic review of strategies to increase men’s HIV-testing in sub-Saharan Africa . AIDS 2014 ; 28 : 2133 – 45 . Google Scholar CrossRef Search ADS PubMed 22. Manjate Cuco RM , Munguambe K , Bique Osman N , Degomme O , Temmerman M , Sidat MM . Male partners’ involvement in prevention of mother-to-child HIV transmission in sub-Saharan Africa: A systematic review . SAHARA J 2015 ; 12 : 87 – 105 . Google Scholar CrossRef Search ADS PubMed 23. Fatti G , Shaikh N , Jackson D et al. Low HIV incidence in pregnant and postpartum women receiving a community-based combination HIV prevention intervention in a high HIV incidence setting in South Africa . PLoS One 2017 ; 12 : e0181691 . Google Scholar CrossRef Search ADS PubMed 24. Hanscom B , Janes HE , Guarino PD et al. Brief report: preventing HIV-1 infection in women using oral preexposure prophylaxis: a meta-analysis of current evidence . J Acquir Immune Defic Syndr 2016 ; 73 : 606 – 8 . Google Scholar CrossRef Search ADS PubMed 25. Pyra M , Haberer JE , Heffron R et al. ; Partners Demonstration Project Team . Brief report: PrEP use during periods of HIV risk among East African Women in serodiscordant relationships . J Acquir Immune Defic Syndr 2018 ; 77 : 41 – 5 . Google Scholar PubMed 26. Bekker LG , Roux S , Sebastien E et al. ; HPTN 067 (ADAPT) study team . 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 – 78 . Google Scholar CrossRef Search ADS PubMed 27. Matthews LT , Heffron R , Mugo NR et al. ; Partners PrEP Study Team . 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 . Google Scholar CrossRef Search ADS PubMed 28. Baeten JM , Heffron R , Kidoguchi L et al. ; Partners Demonstration Project Team . 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 : e1002099 . Google Scholar CrossRef Search ADS PubMed 29. Mofenson LM , Baggaley RC , Mameletzis I . Tenofovir disoproxil fumarate safety for women and their infants during pregnancy and breastfeeding . AIDS 2017 ; 31 : 213 – 32 . Google Scholar CrossRef Search ADS PubMed 30. Pintye J , Baeten JM , Celum C et al. Maternal tenofovir disoproxil fumarate use during pregnancy is not associated with adverse perinatal outcomes among HIV-infected East African women: a prospective study . J Infect Dis 2017 ; 216 : 1561 – 8 . Google Scholar CrossRef Search ADS PubMed 31. Waitt C , Olagunju A , Nakelema S et al. Plasma and breast milk pharmacokinetics of emtricitabine, tenofovir and lamivudine using dried blood spots and breast milk spots in nursing African mother-infant pairs [published online ahead of print 4 January, 2018]. J Antimicrob Chemother , doi: 10.1093/jac/dkx507 . 32. Mugwanya KK , Hendrix CW , Mugo NR et al. Pre-exposure prophylaxis use by breastfeeding HIV-uninfected women: a prospective short-term study of antiretroviral excretion in breast milk and infant absorption . PLoS Med 2016 ; 13 : e1002132 . Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

The Journal of Infectious DiseasesOxford University Press

Published: Mar 5, 2018

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