Associations Between HIV, Antiretroviral Therapy and Preterm Birth in the US Women's Interagency HIV Study, 1995–2018

A Prospective Cohort

Kartik K. Venkatesh; Andrew Edmonds; Daniel Westreich; Jodie Dionne-Odom; Deborah Jones Weiss; Anandi N. Sheth; Helen Cejtin; Dominika Seidman; Seble Kassaye; Howard Minkoff; Jessica Atrio; Lisa Rahangdale; Adaora A. Adimora


HIV Medicine. 2022;23(4):406-416. 

In This Article

Abstract and Introduction


Objective: To evaluate the associations of HIV infection with preterm birth (PTB), and of HIV antiretroviral therapy (ART) with PTB.

Methods: We analysed singleton live-born pregnancies among women from 1995 to 2019 in the Women's Interagency HIV Study, a prospective cohort of US women with, or at risk for, HIV. The primary exposures were HIV status and ART use before delivery [none, monotherapy or dual therapy, or highly active antiretroviral therapy (HAART)]. The primary outcome was PTB < 34 weeks, and, secondarily, < 28 and < 37 weeks. We analysed self-reported birth data, and separately modelled the associations between HIV and PTB, and between ART and PTB, among women with HIV. We used modified Poisson regression, and adjusted for age, race, parity, tobacco use and delivery year, and, when modelling the impact of ART, duration from HIV diagnosis to delivery, nadir CD4 count, and pre-pregnancy viral load and CD4 count.

Results: We analysed 488 singleton deliveries (56% exposed to HIV) to 383 women. The risk of PTB < 34 weeks was similar among women with and without HIV, but the risk of PTB < 37 weeks was higher [32% vs. 23%; adjusted risk ratio (aRR) = 1.43; 95% confidence interval (CI): 1.07–1.91] among women with HIV. The risk of PTB < 34 weeks was lower among women with HIV receiving HAART than among those receiving no ART (7% vs. 26%; aRR:0.19; 95% CI: 0.08–0.44). The associations between HAART and PTB < 28 and < 37 weeks were similar.

Conclusions: Antiretroviral therapy exposure was associated with a decreased risk of PTB among a US cohort of women with HIV. Given the growing concerns about ART and adverse pregnancy outcomes, this finding that ART may be protective for PTB is reassuring.


Antiretroviral therapy (ART) during pregnancy nearly eliminates the risk of mother-to-child transmission of HIV and improves health and survival for women with HIV.[1,2] Despite over two decades of clinical experience of ART use in pregnancy, the debate about whether ART increases the risk of adverse perinatal outcomes continues due to conflicting data.[3,4] HIV without ART increases the risk of preterm birth (PTB), low infant birthweight (which may also be a proxy for PTB), and stillbirth.[5–7] Recent clinical trials primarily conducted in low- and middle-income countries suggest that ART increases the risk of PTB.[8]

Pooled estimates across regional settings suggest that ART may be associated with an increased adjusted odds of PTB (1.32–1.71).[9–14] This association persists regardless of individual antiretroviral (ARV) drugs prescribed or when ART was started (before vs. during pregnancy).[15–17] However, not all observational studies have found that ART increases the risk of PTB.[10,11,18–21] It is possible that the observed increased risk noted in low- and middle-income countries may be due in part to inaccurate determination of gestational age at birth because of unknown last menstrual period (LMP) date and lack of access to prenatal ultrasound dating,[22] as well as late entry to prenatal care with initiation of ART in the setting of advanced immunodeficiency.[23]

In contrast to low- and middle-income countries, most women with HIV in high-income countries initiate ART before pregnancy, but a recent meta-analysis suggests that women who started ART before conception were at higher risk of PTB compared with those who started after conception.[24] In the US, the PTB rate among women with HIV has declined in the era of increasing ART access.[25] A recent analysis from two US multicentre observational cohorts did not find a higher risk of PTB with ART.[13] However, studies from Europe have identified ART as an independent risk factor for PTB.[26–28] Limitations of prior observational data include lack of a comparison population of women at high risk of HIV who are concurrently at high risk of PTB, small sample size, as well as not adequately addressing natural history of HIV prior to pregnancy in analyses.

We evaluated the associations of HIV with PTB, and ART with PTB in the Women's Interagency HIV Study (WIHS). Given the ongoing debate of the impact of HIV and ART on adverse perinatal outcomes, it remains important to understand these associations in well-characterized longitudinal cohorts of women with, or at risk for, HIV.[29]