Combination Antiretroviral Use and Preterm Birth

Watts, D. Heather; Williams, Paige L.; Kacanek, Deborah; Griner, Raymond; Rich, Kenneth; Hazra, Rohan; Mofenson, Lynne; Mendez, Hermann

doi:10.1093/infdis/jis728

Cited by 112 publications

(113 citation statements)

References 33 publications

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“…There are inconsistent findings regarding protease inhibitor-based ART and preterm delivery. 3,[18][19][20][21] Some studies have shown that protease inhibitors reduce progesterone production in the trophoblast in vitro and that low progesterone levels are associated with preterm delivery. [22][23][24][25] However, other studies have shown that nevirapine-based ART is also associated with a higher rate of preterm delivery than zidovudine plus single-dose nevirapine.…”

Section: Discussionmentioning

confidence: 99%

Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention

Fowler¹,

Qin²,

Fiscus³

et al. 2017

Obstetrical &Amp; Gynecological Survey

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Section: Discussionmentioning

confidence: 99%

Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention

Fowler¹,

Qin²,

Fiscus³

et al. 2017

Obstetrical &Amp; Gynecological Survey

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“…Additionally, recent clinical studies have shown that in utero PI exposure is associated with preterm birth, although the mechanism is not yet clear. 42 Future studies should examine whether dysfunctional FAO in the context of in utero PI exposure plays a role in gestation length and birth weight in HEU neonates, both of which are important for future and adult health.…”

Section: Discussionmentioning

confidence: 99%

Acylcarnitine Profiles in HIV-Exposed, Uninfected Neonates in the United States

Kirmse

Yao

Hofherr

et al. 2016

AIDS Research and Human Retroviruses

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We sought to determine the prevalence of abnormal acylcarnitine profiles (ACP) in HIV-exposed uninfected (HEU) newborns and to explore the association of abnormal ACP with clinical laboratory outcomes and antiretroviral drug exposures. Clinically, ACP are used to assess for fatty acid oxidation (FAO) dysfunction and normal FAO is necessary for optimal fetal/neonatal growth and development. We analyzed serum ACP in 522 HEU neonates enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study of the Pediatric HIV/AIDS Cohort Study (PHACS) and evaluated the associations of abnormal ACP with in utero exposure to combination antiretroviral therapy (cART) in logistic regression models, adjusting for maternal demographic, disease, and behavioral characteristics. We evaluated the associations of abnormal ACP with laboratory parameters and measures of neurodevelopment and growth. Of 522 neonates, 89 (17%) had abnormal ACP. In adjusted analyses, in utero exposure to a protease inhibitor (PI) was associated with higher odds of having an abnormal ACP [adjusted odds ratio (aOR) = 2.35, 95% CI: 0.96, 5.76, p = 0.06] with marginal significance while exposure to a nonnucleoside reverse transcriptase inhibitor (NNRTI) was associated with lower odds (aOR = 0.23, 95% CI: 0.07, 0.80, p = 0.02). Mean ALT levels were slightly higher in those with abnormal ACP, but no differences in lactate, glucose, or CPK were observed. ACP status was not associated with neurodevelopment at 1 year or growth at 2 and 3 years of age. Abnormal ACP in HEU neonates are associated with exposure to PIcontaining as opposed to NNRTI-containing antiretroviral (ARV) regimens but are not associated with serious postnatal clinical problems. Further studies are needed to determine the long-term health implications of abnormal acylcarnitine metabolism at birth in HEU children.

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“…Recently, a study evaluating 1869 singleton births in the United States found that of 18.6% of preterm births, 10.2% were spontaneous. 33 Additionally, the odds of preterm birth and spontaneous preterm birth were significantly greater among mothers who used PIs in the first trimester but not among mothers who used non-nucleoside reverse transcriptase inhibitors or triple nucleoside regimens during the first trimester. Individual PIs associated with a preterm birth were saquinavir, ritonavir, and LPV/r.…”

Section: Prematuritymentioning

confidence: 90%

A Randomized Controlled Trial to Assess Safety, Tolerability, and Antepartum Viral Load with Increased Lopinavir/Ritonavir Dosage in Pregnancy

Bonafé

Costa

Vaz

et al. 2013

AIDS Patient Care and STDs

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HIV mother-to-child transmission (MTCT) is significantly reduced if antepartum viral load (apVL) is < 50 copies/mL. Pharmacokinetic studies suggest increasing the dosage of lopinavir/ritonavir (LPV/r) in pregnancy. It is important to assess tolerance, safety, and rate of patients presenting a apVL < 50 copies/mL when treating with increased dose of LPV/r during pregnancy. Confirmed HIV-infected pregnant women with a fetus at a gestational age of 14-33 weeks were randomly assigned to receive LPV/r 400/100 or 600/150 mg b.i.d. plus two nucleoside analogues (NRTIs). Treatment was discontinued in the case of alanine transaminase (ALT) of grade III elevation or higher, glucose, or triglycerides. Thirty-two women were randomized to the LPV/r 400/ 100 mg dose, and 31 women were randomized to the 600/150 mg dose. Overall, 9.4% of the women receiving the conventional dose, and 17.2% receiving the increased dose, discontinued treatment because of adverse events ( p = 0.29). The rates of gastrointestinal (GI) symptoms, laboratory abnormalities, preterm delivery, and low birth weight were similar in both groups. There were no cases of HIV MTCT. Among the women with a baseline VL > 50 copies/mL assigned to the conventional dose group, 45% (95% confidence interval [CI] 62.5-27.5%) had a apVL > 50 copies/mL compared with 10.5% (95% CI 21.6-0.6%) of those assigned to the increased dose group ( p = 0.01). There was no significant difference found for the patients with a baseline VL < 50 copies/mL. In pregnant women with a baseline VL > 50 copies/mL, it may be warranted to initiate LPV/r dosing at 600/ 150 mg, whereas the conventional dose is sufficient for pregnant women with a baseline VL < 50 copies/mL.

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Combination Antiretroviral Use and Preterm Birth

Abstract: Protease inhibitor use early in pregnancy may be associated with increased risk for prematurity.

Cited by 112 publications

References 33 publications

Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention

Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention

Acylcarnitine Profiles in HIV-Exposed, Uninfected Neonates in the United States

A Randomized Controlled Trial to Assess Safety, Tolerability, and Antepartum Viral Load with Increased Lopinavir/Ritonavir Dosage in Pregnancy

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