Risk Factors for Preterm Birth Among HIV-Infected Pregnant Ugandan Women Randomized to Lopinavir/Ritonavir- or Efavirenz-Based Antiretroviral Therapy

Abstract

Background Protease inhibitor-based antiretroviral therapy (ART) has been associated with preterm birth in some studies. We examined risk factors for preterm birth among women randomized to lopinavir/ritonavir- or efavirenz-based ART. Methods This was a planned secondary analysis of the PROMOTE-Pregnant Women and Infants Study, an open-label, randomized controlled trial comparing the risk of placental malaria among HIV-infected, ART-naïve pregnant Ugandan women assigned to initiate lopinavir/ritonavir- or efavirenz-based ART at 12 to 28 weeks gestation. Gestational age was determined based on last menstrual period and ultrasound biometry. All women received bednets and trimethoprim-sulfamethoxazole. Stillbirths, spontaneous abortions, and multiple gestations were excluded from the primary analysis. Potential risk factors for preterm birth (<37 weeks gestation) were evaluated by univariate and multivariate logistic regression. Results 356 women were included in this analysis. At enrollment, median gestational age was 21 weeks, median CD4 cell count was 368 cells/mm3. 14.7% of deliveries in the efavirenz arm and 16.2% in the lopinavir/ritonavir arm were preterm. Preterm birth was associated with gestational weight gain below 0.1 kg/week versus 0.1 kg/week or more (OR = 2.49, 95% CI: 1.38–4.47, p = 0.003). Neither ART regimen of lopinavir/ritonavir versus efavirenz (OR = 1.12, 95% CI: 0.63–2.00, p = 0.69) nor placental malaria (OR = 0.74, 95% CI: 0.38–1.44, p = 0.37) was associated with preterm birth. Conclusions Lopinavir/ritonavir was not associated with an increased risk of preterm birth compared to efavirenz. However, interventions are needed to address modifiable risk factors for preterm birth, such as nutritional status. (ClinicalTrials.gov, NCT00993031.)

Safety and efficacy of Option B+ ART in Malawi: few severe maternal toxicity events or infant HIV infections among pregnant women initiating tenofovir/lamivudine/efavirenz

“…EFV-based regimens have demonstrated a null or protective relationship with preterm birth when compared to nevirapine-or dolutegravir-based regimens [49][50][51][52][53] and are widely available. Among infants in our study, birth outcomes were comparable to or more favourable than results from other sub-Saharan African countries for both preterm birth [52,[54][55][56][57] and low birth weight [55,56,58]. We did not observe pregnancy outcomes for women lost to follow-up, so our results may underestimate adverse birth outcomes and MTCT events.…”

Efficacy and safety of lopinavir/ritonavir versus efavirenz-based antiretroviral therapy in HIV-infected pregnant Ugandan women

“…There were no differences between study arms in the numbers of stillbirths, preterm deliveries, low birth weight infants, or neonatal deaths. [15, 20]…”

A Worldwide Epidemic: The Problem and Challenges of Preterm Birth in Low- and Middle-Income Countries

“…95 In contrast, a secondary analysis of the Pregnant Women and Infants Study (PROMOTE) placental malaria study found no difference in PTB among 356 HIV-infected gravidas randomized to receive either a PI (ritonavir-boosted lopinavir) or non-nucleoside reverse transcriptase inhibitor (efavirenz) regimen. 96…”