Abstract
The study analyzed pregnancy outcomes among 498 women living with HIV in East Asia. We found 15% had pregnancies postdiagnosis, with 57% resulting in live births. Older age at antiretroviral therapy initiation and higher pre-antiretroviral therapy viral loads were negatively associated with pregnancy. High rates of unplanned pregnancies (61%) and terminations (26%) highlight the need for improved reproductive counseling.
Keywords: women living with HIV, pregnancy, antiretroviral therapy, caesarean section, infants
Introduction
The global scale-up of antiretroviral therapy (ART) has significantly improved the life expectancy and quality of life of women living with HIV (WLHIV), reducing HIV sexual and vertical HIV transmission. These changes may influence reproductive decisions. Studies from Western countries have shown WLHIV are now more likely to have children, with higher rates of unintended pregnancies [1]. Social and economic factors also play a role, including declining birth rates in fast-growing Asian economies. Achieving viral suppression during pregnancy is essential, though concerns about ART-related birth outcomes persist [2–4].
Objective.
This study aimed to identify factors associated with pregnancy after HIV diagnosis and describe pregnancy characteristics and outcomes to inform reproductive counseling and care for WLHIV in East Asia.
Methods.
We conducted a cross-sectional study at three HIV clinical sites in East Asia that contribute data to the TREAT Asia HIV Observational Database of International Epidemiology Databases to Evaluate AIDS Asia-Pacific, namely the National Center for Global Health and Medicine in Tokyo, Japan; Severance Hospital, Yonsei University in Seoul, South Korea; and Queen Elizabeth Hospital in Hong Kong Special Administrative Region, China. WLHIV aged between 18 and 45 years at HIV diagnosis who initiated ART and were in follow-up between January 2005 and December 2017 were included. HIV-related data were collected from the TREAT Asia HIV Observational Database. Information about pregnancies after HIV diagnosis and infants was collected from medical records at participating sites. Ethics approval was obtained by the University of New South Wales, Human Research Ethics Committee (IRB number 20181562) and the institutional review boards of all participating sites and the coordinating center (TREAT Asia/ amfAR). Pregnancy and infant outcomes were reported descriptively. Logistic regression was used to analyze factors associated with pregnancy, including age at ART initiation, HIV exposure mode, pre-ART CD4 and HIV viral load and US Centers for Disease Control and Prevention clinical category C diagnosis. Regression models were fitted using a backward stepwise selection process with P < 0.05 as the significance threshold. Analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC) and Stata version 16.1 (Stata Corp., College Station, TX).
Results
The 498 WLHIV participants had a median age at the time of ART initiation of 30 years [interquartile range (IQR): 26–36] (Table 1). The main mode of HIV exposure was heterosexual contact (95%). Median pre-ART CD4 count was 170 cells/μL (IQR: 44–308) and median pre-ART viral load was 47,000 copies/mL (IQR: 109,000–160,000). Among all WLHIV, 73 (15%) experienced 112 pregnancies and the average number of live births per WLHIV was 0.22.
Table 1.
Baseline characteristics of study participants and women living with HIV experiencing pregnancies and factors associated with pregnancy after HIV diagnosis.
| WLHIV Total | WLHIV experiencing pregnancies | Univariate | Multivariate | |||||
|---|---|---|---|---|---|---|---|---|
| N=498 | N=73 | OR | 95% CI | p | OR | 95% CI | p | |
| Median age at ART initiation (yr), median (IQR) | 30 (26–36) | 27 (24–30) | ||||||
| Age category at ART initiation (yr) | ||||||||
| ≤27 | 176 (35) | 40 (55) | 1 | 1 | ||||
| >27 | 322 (65) | 33 (45) | 0.39 | (0.23–0.64) | <0.001 | 0.40 | (0.24, 0.67) | <0.001 |
| HIV mode of exposure | ||||||||
| Heterosexual contact | 473 (95) | 72 (99) | 1 | |||||
| Injecting drug use | 11 (2) | 1 (1) | 0.56 | (0.07–4.42) | 0.580 | |||
| Other/Unknown | 14 (3) | 0 (0) | N/A | |||||
| CD4 (cells/μL) at ART initiation, n (%) | 0.077 | |||||||
| ≤50 | 114 (23) | 8 (11) | 0.34 | (0.15– 0.77) | 0.009 | |||
| 51–100 | 38 (8) | 5 (7) | 0.68 | (0.25–1.88) | 0.460 | |||
| 101–200 | 90 (18) | 13 (18) | 0.76 | (0.38–1.53) | 0.443 | |||
| >200 | 176 (35) | 32 (44) | 1 | |||||
| Not reported | 80 (16) | 15 (21) | ||||||
| Viral load (copies/mL) at ART initiation, n (%) | 0.009 | 0.010 | ||||||
| ≤50,000 | 204 (41) | 39 (53) | 1 | 1 | ||||
| 50,001–250,000 | 117 (23) | 15 (21) | 0.62 | (0.33–1.19) | 0.149 | 0.60 | (0.31–1.15) | 0.126 |
| >250,000 | 73 (15) | 2 (3) | 0.12 | (0.03– 0.51) | 0.004 | 0.13 | (0.03–0.54) | 0.005 |
| Not done | 104 (21) | 17 (23) | ||||||
| Ever had a CDC-C diagnosis, n (%) | ||||||||
| No | 345 (69) | 59 (81) | 1 | |||||
| Yes | 152 (31) | 14 (19) | 0.49 | (0.27–0.91) | 0.024 | |||
CDC-C indicates US Centers for Disease Control and Prevention clinical category C; CI, confidence interval; OR, odds ratio
Among those with pregnancies, the median age at ART initiation was 27 years (IQR: 24–30) (Table 1). Median pre-ART CD4 cell count was 254 cells/μL (IQR: 126–380) and median pre-ART viral load was 21,056 copies/mL (IQR: 3400–55,000). WLHIV age >27 years at ART initiation, compared with those age ≤27 years at ART initiation, were less likely to become pregnant (odds ratio = 0.40, 95% confidence interval: 0.24–0.67, P < 0.001). WLHIV with high pre-ART viral load of >250,000 copies/mL, compared with those with viral load ≤50,000 copies/mL, were also less likely to become pregnant (odds ratio = 0.13, 95% confidence interval: 0.03–0.54, P = 0.005).
Among the 112 pregnancies, 82 (73%) were in legal or de facto marriages. Partner HIV status was available for 82 pregnancies; 13 (12%) had male partners living with HIV. Information about pregnancy intention was available for 108 pregnancies; 68 (61%) were reported as unplanned. Of 40 (36%) planned pregnancies (36%), 30 (75%) used assisted reproductive technologies, including 27 self- or artificial inseminations and 2 in vitro fertilizations. Twenty-eight (25%) WLHIV were in HIV care but were not receiving ART at the time of conception. Sixty-six (59%) WLHIV were known to have conceived while virally suppressed (<50 copies/mL), whereas 12 (11%) conceptions occurred at a viral load > 1000 copies/mL. Of 108 pregnancies with detailed outcome information, 62 (57%) were live births, 28 (26%) induced abortions, 13 (12%) previable fetal losses, 4 (3.7%) ectopic pregnancies and 1 (1.0%) hydatiform mole. Of 62 live births, the 59 (95%) with available delivery information all had cesarean sections: 47 (76%) elective surgeries at 35–37 weeks of gestational age based on local vertical transmission prevention protocols and 11 (18%) emergency surgeries, including 3 caused by preterm premature rupture of the membranes. At delivery, 48 (77%) of WLHIV were virally suppressed and 3 (5%) had viral loads >1000 copies/mL. Data were available for 60 (97%) infants. Median weight was 2786 g (IQR: 2372–3077) at birth, 7710g (IQR: 7095–8400) at 6 months and 9190g (IQR: 8720–10,170) at 12 months. Sixteen (27%) of infants were at low birth weight (<2500 g), and 2 were small for gestational age (less than 10th percentile for gestational age). Low Apgar scores <7 were seen in 3 (5%). After a median of 625 days (range 38 – 3919) of follow-up in 60 infants, there were no vertical HIV transmissions or deaths; no infant was breastfed.
Discussion.
In our study, 15% of WLHIV experienced pregnancies after HIV diagnosis, of which 57% ended in live births. The average number of live births was 0.22, considerably lower than general fertility rates in Japan (1.2), Hong Kong (0.75) and South Korea (0.72) in 2023 (World Bank). Older age and higher baseline viral load were associated with lower pregnancy rates.
Approximately 61% of the pregnancies were reported as unplanned. This was like or lower than rates reported for WLHIV in the United States [1] but higher than the 43%–48% reported in the general population in Japan [5]. The 26% overall elective termination rate was comparable to rates in previous reports among WLHIV in East Asia [6,7] but higher than the estimated 10%–15% elective termination rate in the general population in the region [8]. Many (28%) used assisted reproductive treatments, possibly to reduce partner HIV transmission risk but not necessarily to improve fertility. Although reasons for the high rates of unplanned pregnancy and terminations were not assessed in the study, our findings emphasize the importance of implementing effective reproductive counseling in clinical settings accessed by WLHIV in East Asia.
Recommendations for elective cesarean section in vertical prevention guidelines have changed over time from a strong recommendation to avoid transmission to allowing vaginal delivery for WLHIV who are fully suppressed on ART. However, in our study, cesarean section was chosen in all deliveries, 76% of which were elective, regardless of viral load at delivery. Although national guidelines in Japan, South Korea and Hong Kong are broadly consistent in permitting vaginal delivery under these conditions, differences in clinical practice may reflect how individual healthcare providers interpret and communicate the residual risk of mother-to-child transmission. Earlier studies from other regions showed varied preferences for vaginal delivery, but with more recent vertical prevention guidelines, many studies have shown an increasing trend of vaginal deliveries.9 This suggests that delivery mode may be influenced not only by patient counseling but also by local clinical norms and provider perceptions. It highlights the importance of ensuring consistent, evidence-based counseling while also addressing provider-level factors that may shape delivery decisions.
In our study, 25% of WLHIV were engaged in HIV care but not receiving ART at conception. This may reflect earlier guidelines that deferred ART until the second trimester unless there was evidence of advanced immunosuppression. Personal concerns may also have contributed, highlighting the need for integrated reproductive and HIV care that supports earlier ART initiation and addresses both structural and individual barriers.
Despite the high proportion of infants with low birth weight (27%) observed in the study, the proportion of those small for gestational age was low (3%), which may have been because most were born by elective cesarean sections performed earlier than 37 weeks of gestational age. Previous studies have reported high rates of preterm births and low birth weight among infants born to WLHIV compared with women without HIV [3]. Many of the study participants received protease inhibitor-based ART regimens, possibly due to past fears of teratogenicity with efavirenz. Although there have been studies suggesting an association of protease inhibitor-based ART regimens and preterm labor [10], it was difficult to assess this due to the small sample size.
A key limitation of our study was the relatively small number of WLHIV with prior pregnancies. This was primarily due to the low prevalence of HIV among women in East Asia. Despite the long study period, women comprise a small proportion of people living with HIV in the participating countries. The retrospective design of the study and incomplete medical records prevented us from collecting some key information, including uptake of contraceptives. In addition, the study was limited by the lack of data available after 2017. More recent data could provide further insight into the impact of updated clinical guidelines on pregnancy outcomes among WLHIV. Future studies using updated datasets are warranted to capture these evolving trends.
Conclusion.
We observed low pregnancy rates after HIV diagnosis and high unplanned pregnancies and elective termination rates in WLHIV in three East Asian countries. These findings highlight the need for comprehensive reproductive counselling and care to support WLHIV in low-prevalence settings.
Acknowledgements
This study is an initiative of TREAT Asia, a program of amfAR, The Foundation for AIDS Research, with support from the U.S. National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute on Child Health and Human Development, the National Cancer Institute, the National Institute of Mental Health, the National Institute on Drug Abuse, the National Heart, Lung, and Blood Institute, the National Institute on Alcohol Abuse, and Alcoholism, the National Institute of Diabetes and Digestive and Kidney Diseases, and the Fogarty International Center, as part of the International Epidemiology Databases to Evaluate AIDS (IeDEA; U01AI069907). The Kirby Institute is funded by the Australian Government Department of Health and Ageing, and is affiliated with the Faculty of Medicine, UNSW Sydney. This publication is the result of funding in whole or in part by the NIH. It is subject to the NIH Public Access Policy. Through acceptance of this federal funding, NIH has been given a right to make this manuscript publicly available in PubMed Central upon the Official Date of Publication, as defined by NIH. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of any of the governments or institutions mentioned above.
Footnotes
Ethics approval: Ethics approvals for the study were obtained from the local ethics committees of all participating sites, the data management and biostatistical program (the Kirby Institute, UNSW Sydney), and the coordinating center (TREAT Asia/amfAR).
Patient consent: Since all data were anonymized and part of an observational study of routinely collected data, informed consent was not required by the study unless specified by a local IRB. At one site (NCGM, Tokyo), informed consent was obtained in the form of an opt-out option as required by the IRB, and those who declined were excluded.
Disclosure of conflict of interest: AHS has received grants to her institution from ViiV Healthcare and Gilead Sciences. Other authors have declared no competing interest.
Data availability:
Due to restrictions from the study organizers and local ethics committees, the data in the study cannot be made publicly available. External investigator(s) wishing to access the study data can contact the study Project Manager for further information. Boondarika (Tor) Petersen, TREAT Asia, amfAR – The Foundation for AIDS Research Exchange Tower, 21st Floor, Suite 2104 388 Sukhumvit Road, Klongtoey, Bangkok 10110 Thailand T: +66 (0) 2663 7561 ×113 F: +66 (0) 2663 7562 tor.nakornsri@treatasia.org.
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Associated Data
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Data Availability Statement
Due to restrictions from the study organizers and local ethics committees, the data in the study cannot be made publicly available. External investigator(s) wishing to access the study data can contact the study Project Manager for further information. Boondarika (Tor) Petersen, TREAT Asia, amfAR – The Foundation for AIDS Research Exchange Tower, 21st Floor, Suite 2104 388 Sukhumvit Road, Klongtoey, Bangkok 10110 Thailand T: +66 (0) 2663 7561 ×113 F: +66 (0) 2663 7562 tor.nakornsri@treatasia.org.