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Tenofovir exposure in utero and linear growth in HIV-exposed, uninfected infants.

ABSTRACT: OBJECTIVE:Tenofovir (TDF) affects bone health and is widely used in pregnancy but data are limited on the effects of TDF exposure in utero. We examined the association between duration of in-utero TDF exposure and linear growth in HIV-exposed, uninfected (HEU) infants. DESIGN:A prospective cohort of pregnant women initiating TDF-containing regimens at primary care services in Cape Town, South Africa, were enrolled and followed with their breastfeeding infants through 12 months postpartum. METHODS:Length-for-age z scores (LAZ) were calculated from infant lengths reported at birth and measured at 6, 12, 24, 36 and 48 weeks, using Fenton and WHO standards. Linear mixed-effects models were used to examine the association between duration of TDF exposure and LAZ over time. RESULTS:In 464 singleton mother-infant pairs (median CD4 at ART initiation, 346?cells/?l; viral load (VL), 4.0?log10 copies/ml), the median duration of in-utero TDF exposure was 16.7 weeks (interquartile range, IQR 11.0-22.0) with 31, 44 and 25% of infants exposed to less than 12, 12-22 and more than 22 weeks of TDF, respectively. Overall, 12% of children were stunted (LAZ < -2) at 48 weeks. Duration of exposure was not associated with LAZ: adjusted mean difference for more than 22 vs less than 12 weeks, -0.12 (95% CI -0.47 to 0.23); 12-22 vs less than 12 weeks, -0.06 (95% CI -0.35 to 0.24). Mean LAZ was 0.15 lower per log increase in maternal VL at ART initiation (95% CI -0.29 to -0.0001). CONCLUSION:These data suggest no association between duration of TDF exposure in utero and early linear growth.

SUBMITTER: M le Roux S

PROVIDER: S-EPMC5814299 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Tenofovir exposure in utero and linear growth in HIV-exposed, uninfected infants.

M le Roux Stanzi S Jao Jennifer J Brittain Kirsty K Phillips Tamsin K TK Olatunbosun Seun S Ronan Agnes A Zerbe Allison A Abrams Elaine J EJ Myer Landon L

AIDS (London, England) 20170101 1

<h4>Objective</h4>Tenofovir (TDF) affects bone health and is widely used in pregnancy but data are limited on the effects of TDF exposure in utero. We examined the association between duration of in-utero TDF exposure and linear growth in HIV-exposed, uninfected (HEU) infants.<h4>Design</h4>A prospective cohort of pregnant women initiating TDF-containing regimens at primary care services in Cape Town, South Africa, were enrolled and followed with their breastfeeding infants through 12 months pos ...[more]

PMID: 27898591

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Project description:Most studies examining the association of prenatal antiretroviral (ARV) exposures with congenital anomalies (CAs) in children born to human immunodeficiency virus (HIV)-infected women have been reassuring, but some evidence suggests an increased risk with specific ARV agents.To evaluate the association of in utero ARV exposures with CAs in HIV-exposed uninfected children.Prospective cohort study design. The Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring of ART Toxicities (SMARTT) Study was performed at 22 US medical centers among 2580 HIV-exposed uninfected children enrolled in the SMARTT Study between March 23, 2007, and June 18, 2012.First-trimester exposure to any ARV and to specific ARV medications.The primary end point was a CA based on physician review of infant physical examinations according to the Antiretroviral Pregnancy Registry modification of the Metropolitan Atlanta Congenital Defects Program. Rates of CAs were estimated overall and by birth year. Logistic regression models were used to evaluate the association of CAs with first-trimester ARV exposures, adjusting for demographic and maternal characteristics.Congenital anomalies occurred in 175 of 2580 children, yielding a prevalence of 6.78% (95% CI, 5.85%-7.82%); 242 major CAs were confirmed, including 72 musculoskeletal and 55 cardiovascular CAs. The prevalence of CAs increased significantly among successive birth cohorts (3.8% for children born before 2002 and up to 8.3% for those born 2008-2010). In adjusted models, no association of first-trimester exposures with CAs was found for any ARV, for combination ARV regimens, or for any drug class. No individual ARV in the reverse transcriptase inhibitor drug classes was associated with an increased risk of CAs. Among protease inhibitors, higher odds of CAs were observed for atazanavir sulfate (adjusted odds ratio [aOR], 1.95; 95% CI, 1.24-3.05) and for ritonavir used as a booster (aOR, 1.56; 95% CI, 1.11-2.20). With first-trimester atazanavir exposure, risks were highest for skin (aOR, 5.23) and musculoskeletal (aOR, 2.55) CAs.Few individual ARVs and no drug classes were associated with an increased risk of CAs in HIV-exposed infants after adjustment for calendar year and maternal characteristics. While the overall risk remained low, a relative increase was observed in successive years and with atazanavir exposure. Given the low absolute CA risk, the benefits of recommended ARV therapy use during pregnancy still outweigh such risks, although further studies are warranted.

Dataset Information

Tenofovir exposure in utero and linear growth in HIV-exposed, uninfected infants.

Publications

Tenofovir exposure in utero and linear growth in HIV-exposed, uninfected infants.

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