In Utero Exposure to Zidovudine and Heart Anomalies in the ANRS French Perinatal Cohort and the Nested PRIMEVA Randomized Trial

Sibiude, Jeanne; Chenadec, Jérôme Le; Bonnet, Damien; Tubiana, Roland; Faye, Albert; Dollfus, Catherine; Mandelbrot, Laurent; Delmas, Sandrine; Lelong, Nathalie; Khoshnood, Babak; Warszawski, Josiane; Blanche, Stéphane

doi:10.1093/cid/civ260

Cited by 51 publications

(37 citation statements)

References 33 publications

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“…ZDV and didanosine (ddI), drugs that were introduced in the 1990s have only recently shown associations with congenital cardiac defects and cancer, [51,52] respectively, which would not have been apparent without many years of data. Given the changing drugs and changing populations without safety data from clinical trials, ongoing ARV safety surveillance in pregnancy is clearly needed.…”

Section: In-utero Antiretroviral Therapy Exposurementioning

confidence: 99%

“…The study has provided critical insight on the link between preterm birth and in utero ART exposure, and birth weight, which was not found to be associated with ART in this cohort [64]. Due to its large size, this study has also allowed evaluation of rarer adverse endpoints, such as congenital heart defects and cancer [13,52,65,66]. Although infant follow-up is limited to two years, precluding evaluation of most long-term outcomes, examination of cancer risk was possible through linkage with a national pediatric cancer registry.…”

Section: Art Safety Surveillance Programsmentioning

confidence: 99%

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Surveillance monitoring for safety of in utero antiretroviral therapy exposures: current strategies and challenges

Zash

Williams

Sibiude

et al. 2016

Expert Opinion on Drug Safety

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Introduction The use of antiretroviral therapy (ART) in pregnancy to prevent vertical HIV transmission has been one of the most successful public health programs in the last decade. As a result, an unprecedented number of women are taking ART at conception and during pregnancy. Given few randomized studies evaluating safety of different ART regimens in pregnancy, ongoing drug safety surveillance is critical. Areas Covered This review aims to provide a rationale for ART drug safety surveillance, describe changing patterns of ART use and summarize current surveillance efforts in both low-resource and high-resource settings. Additionally, biostatistical approaches to and challenges in analysis of observational surveillance data are discussed. Expert Opinion The global landscape of ART use in pregnancy is rapidly increasing and evolving. Any increase in adverse effects of in-utero exposure to ART has the potential to reduce the impact of improvements in infant morbidity and mortality gained from decreased vertical HIV transmission. ART drug safety surveillance should therefore be a critical piece of programs to prevent mother to child transmission in both high- and low-resource settings. Current surveillance efforts could be strengthened with long-term follow-up of exposed children, pooling of data across cohorts and standardized approaches to analysis.

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Section: In-utero Antiretroviral Therapy Exposurementioning

confidence: 99%

Section: Art Safety Surveillance Programsmentioning

confidence: 99%

Surveillance monitoring for safety of in utero antiretroviral therapy exposures: current strategies and challenges

Zash

Williams

Sibiude

et al. 2016

Expert Opinion on Drug Safety

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“…There have been several recent and notable studies investigating cardiac function in ART-exposed, HEU infants [48–51]. While most studies failed to show any evidence of gross cardiac toxicity by echocardiography between children exposed to ART in utero and those who were not exposed, a number of subclinical findings are quite concerning.…”

Section: Cardiac Function and Cardiovascular Disease Riskmentioning

confidence: 99%

“…For example, several studies demonstrated that in utero ART exposure may be associated with some degree of LV diastolic dysfunction, changes in LV shortening fraction, lower stress-velocity z-scores, and posterior wall thickening. One particularly alarming study showed a higher risk of congenital heart disease, particularly ventricular septal defects, among female subjects exposed to ZDV in utero •[51]. The long-term implications of these findings are yet unclear, but the possibility that cardiac contractility may eventually be compromised in some of these HEU patients should be considered and closely monitored.…”

Section: Cardiac Function and Cardiovascular Disease Riskmentioning

confidence: 99%

Complications of Treatment in Youth with HIV

et al. 2016

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While combination antiretroviral therapy allows HIV-infected patients to have life expectancies similar to that of the general population, it may also contribute to the development of co-morbidities, such as cardiovascular disease and osteoporosis. Such complications could compromise long-term quality of life, especially in HIV-infected youth whose lifetime cumulative exposure to antiretrovirals is likely to be many decades. Recent studies continue to demonstrate abnormalities associated with antiretroviral therapy, although clinical manifestations are rare in this younger population, especially with modern antiretrovirals. The purpose of this paper is to review the most recent literature on complications of treatment in youth with HIV.

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“…Some epidemiological studies have found that zidovudine use, especially in the first trimester, is associated with modest elevations in the risk of overall malformations,[4] cardiac malformations,[5–7] and male genital malformations. [8,9] However, a number of other studies have not replicated the increased risk.…”

Section: Introductionmentioning

confidence: 99%

Zidovudine use in pregnancy and congenital malformations

Rough

Sun

Seage³

et al. 2017

Aids

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Objective There is inconsistent evidence that zidovudine use during pregnancy increases overall, cardiac, and male genital malformations. Design We conducted a systematic review and meta-analysis of zidovudine use and malformations and, using Bayesian methods, combined it with data from a cohort study of mother-infant pairs in the nationwide Medicaid Analytic eXtract (MAX). Methods Using MAX data (2000–2010), we identified pregnant women with HIV treated with antiretroviral therapy (ART). Women with ≥1 zidovudine dispensing during the first trimester were compared to women receiving ART without zidovudine in the first trimester. Malformation outcomes were defined using diagnosis/procedure codes. To adjust for confounding, we performed 1:1 propensity score matching. Bayesian methods require specification of a prior, which we developed in the meta-analysis. Logistic regression models combined MAX data with the prior, estimating odds ratios (ORs) and 95% credible intervals. Results Fourteen articles contributed information on overall malformations, 7 on cardiac malformations, and 5 on male genital malformations. In MAX, matching led to a sample of 735 women each in the zidovudine and comparator groups. When comparing first trimester zidovudine use to other ART, the Bayesian procedure yielded OR estimates slightly above the null for overall (OR=1.11, 95% credible interval [0.80–1.55]) and cardiac (OR=1.30 [0.63–2.71]) malformations. There were no zidovudine-exposed cases of male genital malformations in MAX, but the meta-analysis yielded elevated OR estimates (OR=2.57 [1.26–5.24]). Conclusions For most malformations, first trimester zidovudine was not associated with increased risk. The potential increase in male genital malformations was small in absolute terms, and should be evaluated further.

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In Utero Exposure to Zidovudine and Heart Anomalies in the ANRS French Perinatal Cohort and the Nested PRIMEVA Randomized Trial

Abstract: NCT00424814.

Cited by 51 publications

References 33 publications

Surveillance monitoring for safety of in utero antiretroviral therapy exposures: current strategies and challenges

Surveillance monitoring for safety of in utero antiretroviral therapy exposures: current strategies and challenges

Complications of Treatment in Youth with HIV

Zidovudine use in pregnancy and congenital malformations

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