Article

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: 9.42). 09/2012; 56(1). DOI: 10.1093/cid/cis808
Source: PubMed

ABSTRACT Background. 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.Methods. 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.Results. 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).Conclusions. 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.

Download full-text

Full-text

Available from: Lynne M Mofenson, Aug 29, 2014
0 Followers
 · 
140 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To compare the effectiveness of multi-stage and one-stage alternating low-pressure air mattresses (ALPAM) and alternating pressure air mattress (APAM) overlays in preventing pressure ulcers among hospitalized patients, data were pooled (N = 617) from a study of patients allocated to multi-stage ALPAM (n = 252) or one-stage ALPAM (n = 264), and another study of patients allocated to APAM overlay (n = 101). Cumulative pressure ulcer incidence was 4.9% (n = 30) over 14 days. Fewer ulcers developed on multi-stage ALPAM compared with APAM overlay (OR = 0.33; 95% CI [0.11, 0.97]), but no difference was found between one-stage ALPAM and APAM overlay (OR = 0.40; 95% CI [0.14, 1.10]). Time to develop ulcers did not differ by mattress type. © 2013 Wiley Periodicals, Inc. Res Nurs Health.
    Research in Nursing & Health 08/2013; DOI:10.1002/nur.21557 · 1.16 Impact Factor
  • [Show abstract] [Hide abstract]
    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; DOI:10.1097/COH.0b013e3283632ba2 · 4.39 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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 · 4.77 Impact Factor