Pooled Individual Data Analysis of 5 Randomized Trials of Infant Nevirapine Prophylaxis to Prevent Breast-Milk HIV-1 Transmission

University of North Carolina at Chapel Hill.
Clinical Infectious Diseases (Impact Factor: 8.89). 09/2012; 56(1). DOI: 10.1093/cid/cis808
Source: PubMed


In resource-limited settings, mothers infected with human immunodeficiency virus type 1 (HIV-1) face a difficult choice: breastfeed their infants but risk transmitting HIV-1 or not breastfeed their infants and risk the infants dying of other infectious diseases or malnutrition. Recent results from observational studies and randomized clinical trials indicate daily administration of nevirapine to the infant can prevent breast-milk HIV-1 transmission.

Data from 5396 mother-infant pairs who participated in 5 randomized trials where the infant was HIV-1 negative at birth were pooled to estimate the efficacy of infant nevirapine prophylaxis to prevent breast-milk HIV-1 transmission. Four daily regimens were compared: nevirapine for 6 weeks, 14 weeks, or 28 weeks, or nevirapine plus zidovudine for 14 weeks.

The estimated 28-week risk of HIV-1 transmission was 5.8% (95% confidence interval [CI], 4.3%-7.9%) for the 6-week nevirapine regimen, 3.7% (95% CI, 2.5%-5.4%) for the 14-week nevirapine regimen, 4.8% (95% CI, 3.5%-6.7%) for the 14-week nevirapine plus zidovudine regimen, and 1.8% (95% CI, 1.0%-3.1%) for the 28-week nevirapine regimen (log-rank test for trend, P < .001). Cox regression models with nevirapine as a time-varying covariate, stratified by trial site and adjusted for maternal CD4 cell count and infant birth weight, indicated that nevirapine reduces the rate of HIV-1 infection by 71% (95% CI, 58%-80%; P < .001) and reduces the rate of HIV infection or death by 58% (95% CI, 45%-69%; P < .001).

Extended prophylaxis with nevirapine or with nevirapine and zidovudine significantly reduces postnatal HIV-1 infection. Longer duration of prophylaxis results in a greater reduction in the risk of infection.

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Available from: Lynne M Mofenson, Aug 29, 2014
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    • "Initial studies showed that intrapartum single-dose nevirapine (sdNVP) prophylaxis reduced the risk of MTCT by half [7] but lacked efficacy to prevent breast milk HIV transmission. More recently, extended NVP prophylaxis regimens reduced breast milk transmission when compared to sdNVP [8]. Though convenient, inexpensive, and effective, sdNVP prophylaxis selects for NVP-resistant (NVP-R) variants in a high proportion of women (19–75%) and their infected infants (33–87%) [9,10] and these variants remain detectable for a year or more [10-12]. "
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    ABSTRACT: Intrapartum administration of single-dose nevirapine (sdNVP) reduces perinatal HIV-1 transmission in resource-limiting settings by half. Yet this strategy has limited effect on subsequent breast milk transmission, making the case for new treatment approaches to extend maternal/infant antiretroviral prophylaxis through the period of lactation. Maternal and transmitted infant HIV-1 variants frequently develop NVP resistance mutations following sdNVP, complicating subsequent treatment/prophylaxis regimens. However, it is not clear whether NVP-resistant viruses are transmitted via breastfeeding or arise de novo in the infant. We performed a detailed HIV genetic analysis using single genome sequencing to identify the origin of drug-resistant variants in an sdNVP-treated postnatally-transmitting mother-infant pair. Phylogenetic analysis of HIV sequences from the child revealed low-diversity variants indicating infection by a subtype C single transmitted/founder virus that shared full-length sequence identity with a clonally-amplified maternal breast milk virus variant harboring the K103N NVP resistance mutation. In this mother/child pair, clonal amplification of maternal NVP-resistant HIV variants present in systemic and mammary gland compartments following intrapartum sdNVP represents one source of transmitted NVP-resistant variants that is responsible for the acquisition of drug resistant virus by the breastfeeding infant. This finding emphasizes the need for combination antiretroviral prophylaxis to prevent mother-to-child HIV transmission.
    Retrovirology 08/2013; 10(1):88. DOI:10.1186/1742-4690-10-88 · 4.19 Impact Factor
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    ABSTRACT: Considerable advances have been made in the effort to prevent mother-to-child HIV transmission (PMTCT) in sub-Saharan Africa. Clinical trials have demonstrated the efficacy of antiretroviral regimens to interrupt HIV transmission through the antenatal, intrapartum, and postnatal periods. Scientific discoveries have been rapidly translated into health policy, bolstered by substantial investment in health infrastructure capable of delivering increasingly complex services. A new scientific agenda is also emerging, one that is focused on the challenges of effective and sustainable program implementation. Finally, global campaigns to "virtually eliminate" pediatric HIV and dramatically reduce HIV-related maternal mortality have mobilized new resources and renewed political will. Each of these developments marks a major step in regional PMTCT efforts; their convergence signals a time of rapid progress in the field, characterized by an increased interdependency between clinical research, program implementation, and policy. In this review, we take stock of recent advances across each of these areas, highlighting the challenges-and opportunities-of improving health services for HIV-infected mothers and their children across the region.
    Current HIV/AIDS Reports 02/2013; 10(2). DOI:10.1007/s11904-013-0154-z · 3.80 Impact Factor
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    ABSTRACT: Purpose of review: In the past 5 years, research has identified antiretroviral drug interventions that significantly reduce HIV transmission through breastfeeding. This evidence is reflected in WHO guidelines that now recommend national health authorities to adopt a public health approach for HIV and infant feeding, namely to promote and support a single infant feeding practice to all HIV-infected mothers. In most developing countries where diarrhoea, pneumonia and malnutrition are common causes of infant mortality, this means breastfeeding and providing antiretroviral drugs. Scaling-up these approaches is essential to eliminate new paediatric infections and to improve maternal health. The review examined knowledge and implementation of these interventions, and considered areas for future research. Recent findings: Most recent reports focus on approaches for resolving implementation challenges rather than investigating new clinical interventions. Wherever WHO guidelines have been implemented, significant reductions in HIV transmission and improved survival are reported. Health system inefficiencies and social barriers continue to impede progress. A limited number of studies examined mechanisms of transmission and how breastmilk and viral factors influence these processes. Summary: The findings of recent research should give confidence to health workers and policy makers that major improvements in HIV-related child and maternal mortality are attainable and justify intensified efforts.
    Current opinion in HIV and AIDS 06/2013; 8(5). DOI:10.1097/COH.0b013e3283632ba2 · 4.68 Impact Factor
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