Dataset Information

Comparative safety and effectiveness of perinatal antiretroviral therapies for HIV-infected women and their children: Systematic review and network meta-analysis including different study designs.

ABSTRACT:

Background

Nearly all newly infected children acquire Human Immunodeficiency virus (HIV) via mother-to-child transmission (MTCT) during pregnancy, labour or breastfeeding from untreated HIV-positive mothers. Antiretroviral therapy (ART) is the standard care for pregnant women with HIV. However, evidence of ART effectiveness and harms in infants and children of HIV-positive pregnant women exposed to ART has been largely inconclusive. The aim of our systematic review and network meta-analysis (NMA) was to evaluate the comparative safety and effectiveness of ART drugs in children exposed to maternal HIV and ART (or no ART/placebo) across different study designs.

Methods

We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (inception until December 7, 2015). Primary outcomes were any congenital malformations (CMs; safety), including overall major and minor CMs, and mother-to-child transmission (MTCT; effectiveness). Random-effects Bayesian pairwise meta-analyses and NMAs were conducted. After screening 6,468 citations and 1,373 full-text articles, 90 studies of various study designs and 90,563 patients were included.

Results

The NMA on CMs (20 studies, 7,503 children, 16 drugs) found that none of the ART drugs examined here were associated with a significant increase in CMs. However, zidovudine administered with lamivudine and indinavir was associated with increased risk of preterm births, zidovudine administered with nevirapine was associated with increased risk of stillbirths, and lamivudine administered with stavudine and efavirenz was associated with increased risk of low birth weight. A NMA on MTCT (11 studies, 10,786 patients, 6 drugs) found that zidovudine administered once (odds ratio [OR] = 0.39, 95% credible interval [CrI]: 0.19-0.83) or twice (OR = 0.43, 95% CrI: 0.21-0.68) was associated with significantly reduced risk of MTCT.

Conclusions

Our findings suggest that ART drugs are not associated with an increased risk of CMs, yet some may increase adverse birth events. Some ART drugs (e.g., zidovudine) effectively reduce MTCT.

SUBMITTER: Veroniki AA

PROVIDER: S-EPMC6005568 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Comparative safety and effectiveness of perinatal antiretroviral therapies for HIV-infected women and their children: Systematic review and network meta-analysis including different study designs.

Veroniki Areti Angeliki AA Antony Jesmin J Straus Sharon E SE Ashoor Huda M HM Finkelstein Yaron Y Khan Paul A PA Ghassemi Marco M Blondal Erik E Ivory John D JD Hutton Brian B Gough Kevin K Hemmelgarn Brenda R BR Lillie Erin E Vafaei Afshin A Tricco Andrea C AC

PloS one 20180618 6

<h4>Background</h4>Nearly all newly infected children acquire Human Immunodeficiency virus (HIV) via mother-to-child transmission (MTCT) during pregnancy, labour or breastfeeding from untreated HIV-positive mothers. Antiretroviral therapy (ART) is the standard care for pregnant women with HIV. However, evidence of ART effectiveness and harms in infants and children of HIV-positive pregnant women exposed to ART has been largely inconclusive. The aim of our systematic review and network meta-analy ...[more]

PMID: 29912896

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Project description:BackgroundAntiretroviral therapy reduces mother-to-child transmission of human immunodeficiency virus (HIV) during pregnancy, delivery, and breastfeeding. However, these agents have been associated with preterm birth, anemia and low birth weight. We aim to evaluate the comparative safety and effectiveness of the use of antiretroviral drugs among HIV-infected women and the effects on their infants and children through a systematic review and network meta-analysis.Methods/designStudies examining the effects of six antiretroviral drug classes (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, fusion inhibitors, co-receptor inhibitors) administered to HIV-infected pregnant women will be included. We will include randomized clinical trials (RCTs), quasi-RCTs, non-RCTs, controlled before-after, interrupted time series, cohort, registry, and case-control studies. No limitations will be imposed on publication status (that is, unpublished studies are eligible for inclusion), duration of follow-up, study conduct period, and language of dissemination. Comprehensive literature searches will be conducted in major electronic databases, including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. Gray literature will be identified through searching dissertation databases, trial protocol registries, and conference abstracts.Two team members will independently screen all citations, full-text articles, and abstract data; conflicts will be resolved through discussion. The risk of bias and methodological quality will be appraised using appropriate tools (for example, Cochrane Collaboration's tool for assessing risk of bias, Newcastle-Ottawa Scale, and McMaster Quality Assessment Scale of Harms). If feasible and appropriate, we will conduct random effects meta-analysis. Network meta-analysis will be considered for outcomes with the greatest number of treatment comparisons available that fulfill network meta-analysis assumptions (for example, consistency of evidence between direct and indirect data, and low statistical heterogeneity between included studies).The primary effectiveness outcome is mother-to-child transmission of HIV, and the primary safety outcome is major congenital malformation (overall and specific types) among newborns of HIV-infected women. Secondary safety outcomes include stillbirths, infant/child death, preterm delivery, overall and specific minor congenital malformations, and small for gestational age infants.DiscussionOur systematic review will be of utility to healthcare providers, policy-makers, and HIV-positive women regarding the use of antiretroviral drugs.Trial registrationPROSPERO registry number: CRD42014009071.

Project description:BackgroundPeripartum administration of single-dose nevirapine reduces mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but selects for nevirapine-resistant virus.MethodsIn seven African countries, women infected with HIV-1 whose CD4+ T-cell counts were below 200 per cubic millimeter and who either had or had not taken single-dose nevirapine at least 6 months before enrollment were randomly assigned to receive antiretroviral therapy with tenofovir–emtricitabine plus nevirapine or tenofovir-emtricitabine plus lopinavir boosted by a low dose of ritonavir. The primary end point was the time to confirmed virologic failure or death.ResultsA total of 241 women who had been exposed to single-dose nevirapine began the study treatments (121 received nevirapine and 120 received ritonavir-boosted lopinavir). Significantly more women in the nevirapine group reached the primary end point than in the ritonavir-boosted lopinavir group (26% vs. 8%) (adjusted P=0.001). Virologic failure occurred in 37 (28 in the nevirapine group and 9 in the ritonavir-boosted lopinavir group), and 5 died without prior virologic failure (4 in the nevirapine group and 1 in the ritonavir-boosted lopinavir group). The group differences appeared to decrease as the interval between single-dose nevirapine exposure and the start of antiretroviral therapy increased. Retrospective bulk sequencing of baseline plasma samples showed nevirapine resistance in 33 of 239 women tested (14%). Among 500 women without prior exposure to single-dose nevirapine, 34 of 249 in the nevirapine group (14%) and 36 of 251 in the ritonavir-boosted lopinavir group (14%) had virologic failure or died.ConclusionsIn women with prior exposure to peripartum single-dose nevirapine (but not in those without prior exposure), ritonavir-boosted lopinavir plus tenofovir–emtricitabine was superior to nevirapine plus tenofovir–emtricitabine for initial antiretroviral therapy. (Funded by the National Institute of Allergy and Infectious Diseases and the National Research Center; ClinicalTrials.gov number, NCT00089505.).

Project description:OBJECTIVES:To respond to the primary safety objective of the Perinatal HIV Prevention Trial 1 (PHPT-1) by studying the evolution of haematological parameters according to zidovudine exposure duration in HIV-1-infected pregnant women. DESIGN:Multicenter, randomized, double-blind, controlled trial of different durations of zidovudine prophylaxis. SETTING:27 hospitals in Thailand. PARTICIPANTS:1,436 HIV-infected pregnant women in PHPT-1. INTERVENTION:Zidovudine prophylaxis initiation at 28 or 35 wk gestation. OUTCOME MEASURES:Haemoglobin level, leucocytes, total lymphocyte counts, and absolute neutrophil counts were measured at 26, 32, and 35 wk and at delivery. The evolution of haematological parameters was estimated between 26 and 35 wk (zidovudine/placebo) and between 35 wk and delivery to compare a long versus short zidovudine exposure. For each parameter, linear mixed models were adjusted on baseline sociodemographic variables, HIV clinical stage, CD4 count, and viral load. RESULTS:Between 26 and 35 wk, haemoglobin, leucocytes, and absolute neutrophil counts decreased in zidovudine-exposed compared to unexposed women (mean difference [95% CI] -0.4 [-0.5 to -0.3], -423 [-703 to -142], -485 [-757 to -213], respectively). However, between 35 wk and delivery, the haematological parameters increased faster in women exposed to long rather than short durations of zidovudine (0.1 [0.0 to 0.1]; 105 [18 to 191]; 147 [59 to 234], respectively). At delivery, the differences were not statistically significant, except for mean haemoglobin level, which remained slightly lower in the long zidovudine treatment group (difference: 0.2 g/dl). Zidovudine had no negative impact on the absolute lymphocyte counts. CONCLUSION:Zidovudine initiated at 28 wk gestation rather than 35 wk had a transient negative impact on the evolution of haematological parameters, which was largely reversed by delivery despite continuation of zidovudine. This result provides reassurance about the safety of early initiation of zidovudine prophylaxis during pregnancy to maximize prevention of perinatal HIV.

Dataset Information

Comparative safety and effectiveness of perinatal antiretroviral therapies for HIV-infected women and their children: Systematic review and network meta-analysis including different study designs.

Background

Methods

Results

Conclusions

Publications

Comparative safety and effectiveness of perinatal antiretroviral therapies for HIV-infected women and their children: Systematic review and network meta-analysis including different study designs.

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