Antiretroviral therapy in pregnancy is not associated with an increased risk of preterm delivery

PMTCT Option B+ does not increase preterm birth risk and may prevent extreme prematurity: A retrospective cohort study in Malawi.

Chagomerana MB, Miller WC, Pence BW, Hosseinipour MC, Hoffman IF, Flick RJ, Tweya H, Mumba S, Chibwandira F, Powers KA. J Acquir Immune Defic Syndr. 2016 Nov 21. [Epub ahead of print]

Objective: To estimate preterm birth risk among infants of HIV-infected women in Lilongwe, Malawi according to maternal antiretroviral therapy (ART) status and initiation time under Option B+.

Design: Retrospective cohort study of HIV-infected women delivering at ≥27 weeks of gestation, April 2012- November 2015. Among women on ART at delivery, we restricted our analysis to those who initiated ART before 27 weeks of gestation.

Methods: We defined preterm birth as a singleton live birth at ≥27 and <37 weeks of gestation, with births at <32 weeks classified as extremely to very preterm. We used log-binomial models to estimate risk ratios (RR) and 95% confidence intervals (CIs) for the association between ART and preterm birth.

Results: Among 3074 women included in our analyses, 731 preterm deliveries were observed (24%). Overall preterm birth risk was similar in women who had initiated ART at any point before 27 weeks and those who never initiated ART (RR = 1.14; 95% CI: 0.84 - 1.55), but risk of extremely to very preterm birth was 2.33 (1.39 - 3.92) times as great in those who never initiated ART compared to those who did at any point before 27 weeks. Among women on ART before delivery, ART initiation before conception was associated with the lowest preterm birth risk.

Conclusions: ART during pregnancy was not associated with preterm birth, and it may in fact be protective against severe adverse outcomes accompanying extremely to very preterm birth. As pre-conception ART initiation appears especially protective, long-term retention on ART should be a priority to minimize preterm birth in subsequent pregnancies.

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Editor’s notes: Effectively delivered antiretroviral therapy (ART) in pregnancy virtually eliminates the risk of mother-to-child HIV transmission and has been widely adopted. Option B+ is a strategy to start all HIV-positive pregnant women on ART regardless of their CD4 count or other HIV parameters and to continue it indefinitely after delivery to further protect the mother’s health. Balanced against the substantial health gains from the use of ART in pregnancy have been concerns that they may make some adverse pregnancy outcomes more common. Concerns about teratogenicity and birth defects with commonly-used drugs have largely gone as more data has accumulated but prematurity has remained an issue. There has been conflicting evidence from previous studies. Some have suggested an increased risk of preterm birth but others, including meta-analysis, have not. Many earlier studies were predominantly of women with advanced HIV disease, a group with an already-increased risk of preterm birth, and included single- or dual-drug regimens that are no longer recommended. Thus, the results of earlier studies may not be generalizable to women with early stage HIV disease who are being offered newer ART regimens in the context of Option B+.

This study has shown no increase in preterm birth associated with ART in pregnancy, and in fact a statistically and clinically significant protective effect for very early birth (before 32 weeks gestational age). It is a large, thorough and impressive piece of work but has the limitations of any observational study. The risk of unmeasured confounders can never be eliminated; in this case perhaps economic status or level of education. No precise data are presented on the ARV combinations used but it is implied that the great majority of women received efavirenz-based treatment, in accordance with national guidelines in Malawi. Previous studies have suggested that protease inhibitors may be responsible for increased preterm birth. The present study cannot address this question.

This large study of pregnancy outcomes from Option B+ should reassure HIV-positive women and their clinicians that no significant harms were found to be associated with this strategy.  

Africa
Malawi
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