Reassuring Birth Outcomes With Tenofovir/Emtricitabine/Efavirenz Used for Prevention of Mother-to-Child Transmission of HIV in Botswana

Abstract

Background Prior to introduction of tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV), 3-drug antiretroviral treatment (ART) was associated with increased adverse birth outcomes when used for prevention of mother-to-child HIV transmission (PMTCT) in Botswana. Methods We extracted obstetric records from all women at the 2 largest maternities in Botswana from 2009-11 when Botswana National Guidelines recommended ZDV from 28 weeks gestational age (GA) for CD4 ≥350 and ART for CD4 <350, and again in 2013-14 after implementation of TDF/FTC/EFV for PMTCT regardless of CD4 or GA. We compared use of TDF/FTC/EFV in pregnancy with other 3-drug ART regimens, and with initiation of ZDV, among women with similar CD4 cell counts. Outcomes included small for gestational age (SGA), preterm delivery (PTD) (<37 weeks GA), and stillbirths (SB). Results Among 9445 HIV-infected women delivering during the study period, 170 were on TDF/FTC/EFV at conception and 1468 initiated TDF/FTC/EFV during pregnancy. Adverse birth outcomes were high overall (3% SB, 21% PTD, and 18% SGA), and among women receiving TDF/FTC/EFV (3% SB, 22% PTD and 12% SGA). There was no difference in PTD or SB among women initiating TDF/FTC/EFV compared with ZDV or other 3-drug ART, but initiating TDF/FTC/EFV was associated with fewer SGA infants than other 3-drug ART (aOR 0.4, 95% CI 0.2,0.7). Conclusions Adverse birth outcomes remain high among HIV–infected women. TDF/FTC/EFV was at least as safe as other ART, and associated with fewer SGA infants when initiated during pregnancy. Larger studies are needed to evaluate birth outcomes and congenital abnormalities among women on TDF/FTC/EFV at conception.

Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention

“…However, the Botswana data are reassuring in that the combination of tenofovir, emtricitabine, and efavirenz was not associated with higher rates of adverse pregnancy outcomes than zidovudine-based ART. 12 In conclusion, the PROMISE trial showed superior efficacy of triple-drug ART, as compared with zidovudine plus single-dose nevirapine, for the prevention of mother-to-child transmission in HIV-infected women with high CD4 cell counts but also showed higher rates of adverse events. On the basis of recent trials, the WHO recommends ART for HIV-infected persons regardless of CD4 cell count, and there are clear benefits of ART for the prevention of mother-to-child transmission and maternal health.…”

“…A study in Botswana that compared birth outcomes in women receiving tenofovir-based ART (with efavirenz) or zidovudine-based ART (primarily with nevirapine) showed no significant differences in preterm delivery or stillbirth. 12 A potential biologic cause may be a pharmacokinetic interaction between lopinavir-ritonavir and tenofovir; decreased renal clearance of tenofovir and increased plasma and intracellular levels, particularly in women, have been reported with concomitant administration. [13][14][15] In the PROMISE trial, the lopinavir-ritonavir dose was increased during the third trimester because pharmacokinetic studies showed decreased lopinavir-ritonavir levels with standard doses in late pregnancy.…”

Timing of initiation of antiretroviral therapy and adverse pregnancy outcomes: a systematic review and meta-analysis

“…Prematurity was reported in ten studies. 9,10,16,21,[23][24][25][26][27][28] ART initiation before conception was associated with signifi cantly higher risk of prematurity than ART initiation after conception (pooled RR 1·20, 95% CI 1·01-1·44; fi gure 2). Between-study heterogeneity was signifi cant (I²=77%, 95% CI 57·3-87·4; p=0·0001), suggesting that about three-quarters of the variability in the measures of the association is due to heterogeneity between studies rather than chance (fi gure 2).…”

“…After review of the title and abstract, 187 full-text articles were selected for reading, and 11 studies met inclusion criteria (fi gure 1). 9,10,16,[21][22][23][24][25][26][27][28] The studies included participants recruited during the period 1986-2012 (table 1). Three were done in the UK, 10,23,26 two in Botswana, 9,28 and one each in Brazil, 24 France, 27 South Africa, 25 and Tanzania; 16 the remaining two studies 21,22 included participants from the European Collaborative Study (ECS).…”

Methods of gestational age assessment influence the observed association between antiretroviral therapy exposure, preterm delivery, and small-for-gestational age infants: a prospective study in Cape Town, South Africa

“…6 Thus in high HIV prevalence settings it is essential to understand how ART use may influence the risk of preterm delivery. Findings on the association between ART use and adverse birth outcomes, including PTD, are conflicting 7,8 and possibly associated with ART regimen used, timing of initiation and ART eligibility criteria.…”