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

<div><p>Objectives</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>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.</p><p>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.</p><p>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.</p><p>Conclusions</p><p>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.</p></div

Study inclusions and exclusions.

<p>Study inclusions and exclusions.</p

Delivery characteristics by antiretroviral regimen.

<p>Delivery characteristics by antiretroviral regimen.</p

Maternal, pregnancy and delivery characteristics by antiretroviral regimen.

<p>Maternal, pregnancy and delivery characteristics by antiretroviral regimen.</p

Risk factors for preterm and SGA deliveries between 2010 and 2015 in women initiating post-conception ARV (n = 1581).

<p>Risk factors for preterm and SGA deliveries between 2010 and 2015 in women initiating post-conception ARV (n = 1581).</p

PTD and SGA trends by year and PMTCT regimen.

<p>PTD and SGA trends by year and PMTCT regimen.</p

Posterior probability density functions for <i>β</i>₀, <i>β</i>₁, <i>β</i>₂, <i>β</i>₃, <i>β</i>₄ and <i>β</i>₅ for the four Markov chains used for sampling.

(TIF)</p

S1 Data -

(CSV)</p

Posterior means, 95% credible intervals and interval widths for <i>β</i>₀, <i>β</i>₁, <i>β</i>₂, <i>β</i>₃, <i>β</i>₄ and <i>β</i>₅ for different prior distributions.

The t-distributions have the same variance. Normal distributions are parameterized by their means and standard deviations. (DOCX)</p

Estimated number of livebirths to HCV seropositive women per 100,000 livebirths, together with 95% credible intervals.

Estimated number of livebirths to HCV seropositive women per 100,000 livebirths, together with 95% credible intervals.</p