Highly Active Antiretroviral Therapy and Adverse Birth Outcomes Among HIV-Infected Women in Botswana

Chen, Jennifer Y.; Ribaudo, Heather J.; Souda, Sajini; Parekh, Natasha; Ogwu, Anthony; Lockman, Shahin; Powis, Kathleen M.; Dryden‐Peterson, Scott; Creek, Tracy; Jimbo, William; Madidimalo, Tebogo; Makhema, Joseph; Essex, Max; Shapiro, Roger

doi:10.1093/infdis/jis553

Cited by 291 publications

(335 citation statements)

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“…In a review of published literature, studies that have examined the association between ZDV use in pregnancy and adverse outcomes have typically looked at preterm delivery as the outcome of interest 13, 14, 15. These studies also compared the use of highly active antiretroviral therapy (HAART) during pregnancy and ZDV monotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…In some studies that have compared HAART use to ZDV monotherapy, an increased risk of preterm delivery among HAART users has been reported 14, 15. However, Tuomala et al 16.…”

Section: Discussionmentioning

confidence: 99%

“…In studies that have examined the relationship between HAART or ZDV monotherapy use during pregnancy, HAART was associated with a higher risk of stillbirth 14, 20, 21. Tuomala et al.…”

Section: Discussionmentioning

confidence: 99%

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Association between in utero zidovudine exposure and nondefect adverse birth outcomes: analysis of prospectively collected data from the Antiretroviral Pregnancy Registry

Vannappagari

Koram

Albano

et al. 2015

BJOG

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ObjectiveTo examine the association between nondefect adverse birth outcomes and in utero exposure to zidovudine (ZDV)‐containing regimens versus non‐ZDV antiretroviral (ARV) regimens.DesignAnalysis of prospectively‐collected data.SettingGlobal.Population HIV‐infected pregnant women prenatally exposed to antiretrovirals.MethodsEstimation of prevalence of and risk for nondefect adverse birth outcomes among HIV‐infected women.Main outcome measuresPrevalence of and risk for nondefect adverse birth outcomes.ResultsAmong 12 780 singleton birth outcomes with in utero ZDV exposure, 96.1% were live births; 3.9% were spontaneous abortions, induced abortions or stillbirths. Among live births, 16.4% were low birthweight (LBW); 12.3% were premature. Among 1904 outcomes with in utero exposure to non‐ZDV ARV regimens, 85.8% were live births; 14.2% were spontaneous abortions, induced abortions or stillbirths. Among live births, 14.1% were LBW; 12.4% were premature. Relative risk comparing exposure to ZDV‐containing ARV regimens to non‐ZDV ARV regimens for spontaneous abortions was 0.18 (95% confidence interval [95% CI] 0.14–0.22); induced abortions 0.28 (95% CI 0.22–0.36); stillbirths 0.76 (95% CI 0.51–1.12); premature births 1.00 (95% CI 0.87–1.15) and LBW 1.17 (95% CI 1.02–1.33).ConclusionPrevalence of nondefect adverse birth outcomes is lower among outcomes with in utero ZDV exposure versus in utero non‐ZDV ARV exposure. The risks for spontaneous and induced abortions were no different for ZDV‐containing regimens versus non‐ZDV ARV regimens. For premature births and stillbirths, there was no significant difference in risk between the two regimens. The risk of LBW was statistically significantly higher among ZDV‐containing regimens versus non‐ZDV ARV regimens.Tweetable abstract ZDV‐containing regimens do not increase the risk for nondefect adverse birth outcomes.

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Section: Discussionmentioning

confidence: 99%

“…In some studies that have compared HAART use to ZDV monotherapy, an increased risk of preterm delivery among HAART users has been reported 14, 15. However, Tuomala et al 16.…”

Section: Discussionmentioning

confidence: 99%

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Association between in utero zidovudine exposure and nondefect adverse birth outcomes: analysis of prospectively collected data from the Antiretroviral Pregnancy Registry

Vannappagari

Koram

Albano

et al. 2015

BJOG

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“…Additional measures including selective caesarean or avoidance of breastfeeding are strongly recommended. However, adverse pregnancy outcome have been increasingly reported by several observational studies in HIV‐infected women exposed to HAART 6, 7, 8, 9, 10, 11. Anti‐retrovirals and HIV‐infection have been associated with pre‐eclampsia, stillbirth, pre‐term labour, low birth weight and intrauterine growth restriction (IUGR) 12, 13, 14, 15, 16, 17.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial toxicity and caspase activation in HIV pregnant women

Hernández

Morén

Catalán-García

et al. 2016

J Cellular Molecular Medi

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To assess the impact of HIV‐infection and highly active anti‐retroviral treatment in mitochondria and apoptotic activation of caspases during pregnancy and their association with adverse perinatal outcome. Changes of mitochondrial parameters and apoptotic caspase activation in maternal peripheral blood mononuclear cells were compared at first trimester of pregnancy and delivery in 27 HIV‐infected and ‐treated pregnant women versus 24 uninfected pregnant controls. We correlated immunovirological, therapeutic and perinatal outcome with experimental findings: mitochondrial DNA (mtDNA) content, mitochondrial protein synthesis, mitochondrial function and apoptotic caspase activation. The HIV pregnancies showed increased adverse perinatal outcome (OR: 4.81 [1.14–20.16]; P < 0.05) and decreased mtDNA content (42.66 ± 5.94%, P < 0.01) compared to controls, even higher in naïve participants. This depletion caused a correlated decrease in mitochondrial protein synthesis (12.82 ± 5.73%, P < 0.01) and function (20.50 ± 10.14%, P < 0.001), not observed in controls. Along pregnancy, apoptotic caspase‐3 activation increased 63.64 ± 45.45% in controls (P < 0.001) and 100.00 ± 47.37% in HIV‐pregnancies (P < 0.001), in correlation with longer exposure to nucleoside analogues. HIV‐infected women showed increased obstetric problems and declined genetic and functional mitochondrial parameters during pregnancy, especially those firstly exposed to anti‐retrovirals. The apoptotic activation of caspases along pregnancy is emphasized in HIV pregnancies promoted by nucleoside analogues. However, we could not demonstrate direct mitochondrial or apoptotic implication in adverse obstetric outcome probably because of the reduced sample size.

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“…For illustration, the methods are presented throughout in the context of data from the Botswana Birth Outcomes Surveillance Study, that we use to estimate the e¤ects of maternal HIV infection on SGA . 5 Estimating SACE for a continuous outcome The causal DAG also includes a variable U , which we will suppose is an unobserved common cause of S and Y . The presence of U ensures that Y and S remain dependent even after conditioning on observed risk factors included in C: We will also consider the counterfactual outcome S(a) which stands for infant stillbirth status under maternal HIV status a = 0; 1: For S(a) = 1; a live birth under exposure a; we de…ne the corresponding counterfactual birthweight Y (a); however for S(a) = 0, a stillbirth under exposure value a; birthweight is unde…ned.…”

Section: Introductionmentioning

confidence: 99%

A Simple Regression-based Approach to Account for Survival Bias in Birth Outcomes Research

2015

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Highly Active Antiretroviral Therapy and Adverse Birth Outcomes Among HIV-Infected Women in Botswana

Abstract: HAART receipt during pregnancy was associated with increased PTD, SGA, and SB.

Cited by 291 publications

References 47 publications

Association between in utero zidovudine exposure and nondefect adverse birth outcomes: analysis of prospectively collected data from the Antiretroviral Pregnancy Registry

Association between in utero zidovudine exposure and nondefect adverse birth outcomes: analysis of prospectively collected data from the Antiretroviral Pregnancy Registry

Mitochondrial toxicity and caspase activation in HIV pregnant women

A Simple Regression-based Approach to Account for Survival Bias in Birth Outcomes Research

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