Adverse birth outcomes in pregnant women with HIV varied by ART regimen

Issue: March 2017

SEATTLE — The safety of ART for HIV–infected pregnant women, and its impact on adverse birth outcomes such as stillbirth and preterm delivery, varied by individual ART regimen, according to data presented at the annual Conference on Retroviruses and Opportunistic Infections (CROI).

Researchers found that Atripla (tenofovir disoproxil fumarate/emtricitabine [TDF/FTC]/efavirenz; Bristol-Myers Squibb/Gilead) was associated with the fewest adverse birth outcomes.

“More than 1.5 million HIV-infected women become pregnant every year, and because of expanded access to ART, an increasing number of these women become pregnant while already on ART,” Rebecca Zash, MD, of Beth Israel Deaconess Medical Center, said during a press conference. “Prior studies have found that women on ART at conception may have increased risk of adverse birth outcomes such as stillbirth, preterm delivery, and low birth-weight, but few studies have been able to evaluate these risks by individual ART regimen.”

Zash also noted, “Additionally, there is very little information about the safety of the WHO first-line recommended regimen in pregnancy, TDF/FTC/efavirenz.”

To determine the safety of current ART regimens, Zash and colleagues examined obstetric records at eight government hospitals in Botswana for adverse birth outcomes – including stillbirth, preterm delivery (<37 weeks gestation), small for gestational age, and neonatal death (<28 days after delivery) – among 47,180 infants between August 2014 and August 2016.

Among infants with an HIV–infected mother (n= 11,932), 52% (n=6,178) were continuously exposed to ART from the time of conception, 38% (n=4,557) were exposed to ART during pregnancy following conception, 9% (n=1,059) received no ART exposure, 1% (n=138) reported unknown timing for ART exposure.

When examining infants exposed to ART since conception, the researchers used adjusted models to compare the safety of the four other available individual ART regimens with the WHO–recommended first-line regimen. According to study results:

Regimens consisting of TDF/FTC/efavirenz were associated with the lowest risk for combined adverse birth outcomes.
Regimens consisting of Viread (tenofovir disoproxil fumarate, Gilead Sciences) plus lamivudine and Sustiva (efavirenz, Bristol Myers Squibb) were associated with the lowest risk of small-for-gestational-age outcomes.
Regimens consisting of Combivir (zidovudine/lamivudine [ZDV/3TC], ViiV Healthcare) plus Kaletra (ritonavir-boosted lopinavir, AbbVie) were associated with higher risk of preterm delivery and neonatal death.
Regimens consisting of ZDV/3TC plus Viramune (nevirapine, Boehringer Ingelheim) were associated with higher risk of stillbirth, preterm delivery and neonatal death.

“This is the first study to show that there may be significant differences in the risk of adverse birth outcomes from individual ART regimens when started prior to conception,” Zash said. “The good news is that TDF/FTC/efavirenz, the WHO first-line recommended regimen appears to be the safest. However, our findings do raise concerns about the first-line alternatives and second-line regimens being used in women of reproductive age and speak to the need for increased surveillance for the safety of ART in pregnancy as new antiretrovirals are rolled out.” – by Bob Stott

Reference:

Zash R, et al. Abstract 25. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 13-16, 2017; Seattle.

Disclosure: The researchers report no relevant financial disclosures.