Research Article: Preterm delivery and small-for-gestation outcomes in HIV-infected pregnant women on antiretroviral therapy in rural South Africa: Results from a cohort study, 2010-2015

Date Published: February 22, 2018

Publisher: Public Library of Science

Author(s): Terusha Chetty, Claire Thorne, Anna Coutsoudis, Graciela Andrei.


Increasingly more women conceive on antiretroviral therapy (ART) with non-nucleoside reverse transcriptase-based regimens. This study assessed the effect of preconception tenofovir disoproxil fumarate (TDF)-lamivudine (3TC)/emtricitabine (FTC)-efavirenz (EFV) and post-conception TDF-(3TC/FTC)-EFV (versus other regimens) on preterm delivery (PTD) and small-for-gestational age (SGA) births.

We analysed data of 2549 HIV-infected women attending antenatal clinics in KwaZulu-Natal from 2010 through 2015 in this retrospective cohort study. Preconception, TDF-(3TC/FTC)-EFV was compared to nevirapine (NVP)-based regimens and other 3-drug EFV-based regimens. Post-conception, TDF-(3TC/FTC)-EFV was compared to NVP-based ART and zidovudine (ZDV) prophylaxis. Outcomes included PTD <37 weeks and SGA births. Generalized linear mixed effects were used to fit logistic regression models to account for repeat pregnancies. Among 2549 singleton live births, 10.4% (n = 264) were PTD and 10.4% (n = 265) SGA. PTD declined from 16.3% in 2010 to 9.3% in 2015 and SGA remained stable from 9.9% in 2010 to 10% in 2015. Preconception TDF-(3TC/FTC)-EFV and post-conception TDF-(3TC/FTC)-EFV were not associated with PTD or SGA, compared with other regimens. Increasing ART use merits further study of the optimum ART regimen for safe birth outcomes.

Partial Text

Triple antiretroviral therapy (ART) reduces perinatal HIV transmission [1–3] and improves maternal and infant survival [4,5]. However, ART may increase adverse birth outcomes, including preterm delivery (PTD) and small-for-gestational age (SGA) births in developed [6,7] and developing settings [8–11]. Until recently, birth data for ART-exposed pregnancies mostly came from cohorts in developed countries [6,12–16], frequently with small sample size [7,17,18] and with more information on protease inhibitor (PI)-based regimens then non-nucleoside reverse transcriptase inhibitors (NNRTI) [8,19].

Between 2010 and 2012, HIV-infected pregnant women attending any one of the 17 antenatal clinics in the Hlabisa HIV Treatment and Care Programme, northern KwaZulu-Natal, South Africa were eligible for inclusion [31]. Thereafter enrolment was limited to seven clinics within the Africa Centre surveillance area which allowed data linkage (clinics were from the original cohort with 40% of patients generally representative of Hlabisa) [32]; the additional clinic (Mtubatuba) was one of the busiest in the sub-district [33].

Of 4435 pregnancies in 4161 HIV-infected women, 299 (6.7%) were unexposed to ART, 1523 (34.3%) had under one month ARV exposure, and 20 (0.5%) had unknown ART timing (Fig 1). Of 2593 pregnancies remaining, 1002 initiate preconception ART and 1591 started post-conception ARV. Most of the post-conception group were on ZDV-prophylaxis or NNRTI-based regimens; we excluded nine pregnancies on d4T/ZDV-3TC-EFV as there were no adverse outcomes and one pregnancy with PI-based ART. Ten pregnancies on PI-based ART and 24 with pregnancy regimen changes were excluded from the preconception group, leaving 2549 pregnancies for this analysis; 968 (38.0%) were on preconception ART and 1581 (62.0%) on post-conception ARV.

In this study in a high HIV prevalent setting in rural South Africa, 9% of overall deliveries were PTD and 10% were SGA, with minimal overlap between outcomes. PTD births declined over time while SGA births remained relatively stable over six years. There were no significant differences in PTD or SGA risk among women on either preconception or post-conception TDF-(3TC/FTC)-EFV versus other regimens.

Preconception TDF-(3TC/FTC)-EFV and post-conception TDF-(3TC/FTC)-EFV was not associated with PTD and SGA versus other ART. As there was limited power to detect differences between ART groups, the results should be interpreted with caution. Larger studies are required to elucidate ART regimens, timing effect, and specific factors that determine safe birth outcomes in ART-exposed HIV-infected women in this setting.




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