Prediction and prevention of preterm birth in pregnant women living with HIV on antiretroviral therapy

ABSTRACT

Introduction

The rate of spontaneous preterm-birth among pregnant women living with HIV on antiretroviral therapy (ART) is 3- to 4-fold higher when compared to HIV-negative women. The pathophysiology of preterm-birth related to HIV or ART remains unknown, especially as women living with HIV are often excluded from preterm birth studies.

Areas covered

This review discusses the currently available evidence on the prediction and prevention of preterm-birth in pregnant women living with HIV. A review of the literature was conducted of primary articles between 2005 and 2021 measuring the association or lack thereof between combination ART and preterm birth, as well as of other predisposing factors to preterm birth in women living with HIV, including cervical length, vaginal microbiome, and cervico-vaginal biomarkers.

Expert opinion

Further research into the effect of ART exposure on preterm-birth risk is critical, and development of preterm-birth predictive tools in this population should be a priority. Vaginal progesterone supplementation deserves further investigation as a therapeutic option to prevent recurrent preterm birth in pregnant women living with HIV. The ProSPAR study, a multicenter randomized controlled trial studying progesterone supplementation in pregnant women on protease inhibitor-based regimens, has been designed but is not yet recruiting patients.

KEYWORDS:

• Antiretroviral therapy (ART)
• HIV AIDS
• preterm birth
• prediction
• prevention
• pregnancy

Article highlights

• Preterm birth continues to be a major cause of perinatal morbidity and mortality, especially in women living with HIV. The rate of spontaneous preterm birth among pregnant women living with HIV is three to four-fold higher when compared to pregnant women without HIV.

• For patients living with HIV, a unique set of risk factors are relevant for prediction of preterm birth, including ART exposure, cervical length, cervico-vaginal biomarkers, vaginal microbiota, and imaging modalities.

• There are conflicting data regarding the association between combination ART and preterm birth risk in pregnant women living with HIV. Pertinently, analyses exploring the role of timing of ART initiation or duration of ART in relation to preterm birth risk are prone to selection bias because pregnancies delivered preterm have less opportunity to start ART in the later weeks of pregnancy. Careful monitoring of this population for preterm birth should be a priority while maintaining ART for suppression of viral load per current guidelines.

• Several large randomized clinical trials and meta-analyses have demonstrated the efficacy of vaginal progesterone for the prevention of preterm birth and neonatal outcomes. A multicenter randomized controlled pilot trial has been designed to study progesterone supplementation for pregnant women living with HIV on protease inhibitor-based regimens (the ProSPAR study). The group hypothesizes that pregnant women living with HIV on protease inhibitor regimens may benefit from vaginal progesterone supplementation, as studies have also suggested that protease inhibitor use during pregnancy is associated with a decline in progesterone levels. This trial is not yet recruiting patients (ClinicalTrials.gov Identifier: NCT02400021).

• The evidence indicates that 17-alpha progesterone caproate is unlikely to reduce spontaneous preterm birth or stillbirth among women whose risk derives solely from HIV infection. Cervical cerclage is an option for reducing risk of preterm birth in women living with HIV with shortened cervical length. Cervical pessary has not been studied for prevention of preterm birth in the population of women living with HIV.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose.

Author contributions

A Eke conceptualized and designed this study. A Jones interpreted the data and wrote the initial draft of the paper. U Eke revised the second draft of the paper. All authors critically analyzed the paper for intellectual content, revised it, and approved the final version of this manuscript, and are accountable for all aspects of the work.

Additional information

Funding

This manuscript was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the National Institutes of Health (NIH) under the Grant number 1K23HD104517-02, and the Johns Hopkins Center for AIDS Research (CFAR) under the Grant number P30AI094189. The content is solely the responsibility of the author and does not necessarily represent the official views of the NIH.