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

OBJECTIVES 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. METHODS 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. RESULTS 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 NVP-based regimens [adjusted odds ratio (aOR) 0.66; 95% CI 0.27-1.63] and other 3-drug EFV-based regimens (aOR 0.72; 95% CI 0.24-2.12) were not associated with PTD versus TDF-(3TC/FTC)-EFV. NVP-based (aOR 0.75; 95% CI 0.40-1.42) and other 3-drug EFV-based regimens (aOR 1.55; 95% CI 0.76-3.16) were not associated with SGA births versus TDF-(3TC/FTC)-EFV. Post-conception NVP-based ART (1.77; 95% CI 0.89-3.51) and ZDV (1.03; 95% CI 0.68-1.58) were not associated with PTD versus TDF-(3TC/FTC)-EFV. NVP-based ART (1.55; 95% CI 0.66-3.61) and ZDV (0.89; 95% CI 0.53-1.47) were not associated with SGA versus TDF-(3TC/FTC)-EFV. CONCLUSIONS 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.