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Efficacy and safety of an extended nevirapine regimen in infants of breastfeeding mothers with HIV-1 infection for prevention of HIV-1 transmission (HPTN 046): 18-month results of a randomized, double-blind, placebo-controlled trial.

ABSTRACT: BACKGROUND:HPTN 046 compared the efficacy and safety of infant nevirapine (NVP) among HIV-exposed breastfed infants randomized at 6 weeks to 6 months to t NVP or placebo to prevent postnatal infection: we report final 18-month outcomes. METHODS:Randomized, placebo-controlled trial in 4 African countries. Infant diagnostic HIV testing was performed regularly from birth through 18 months. Kaplan-Meier analysis was used to assess 18-month cumulative infant HIV infection, HIV infection/or death, and mortality rates. RESULTS:Between 6 weeks and 6 months, postnatal HIV infection rates were significantly lower among infants receiving daily NVP from 6 weeks to 6 months 1.1% [95% confidence interval (CI): 0.2% to 1.8%], compared with placebo 2.4% (95% CI: 1.3% to 2.6%), P = 0.049, but not significantly lower thereafter. Eighteen-month postnatal infection rates were low: 2.2% (95% CI: 1.1% to 3.3%) versus 3.1% (95% CI: 1.9% to 4.4%), respectively, P = 0.28. Mortality and HIV infection/death did not differ between arms at any age. Infants of women receiving antiretroviral therapy (ART) for their own health had the lowest 18-month postnatal infection rates (0.5%, 95% CI: 0.0% to 1.1%). However, HIV infection/death rates at 18 months were not significantly different for infants of mothers on ART (3.7%, 95% CI: 1.9% to 5.5%), and infants of mothers with CD4 counts of ? 350 cells per cubic millimeter not receiving ART (4.8%, 95% CI: 2.7% to 6.8%; P = 0.46). There were no differences in adverse events between study arms. CONCLUSIONS:This trial demonstrated early but not late differences in postnatal HIV transmission among infants randomized at age 6 weeks to extended NVP or placebo, underscoring the importance of continued prophylaxis throughout breastfeeding.

SUBMITTER: Fowler MG

PROVIDER: S-EPMC3945386 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Efficacy and safety of an extended nevirapine regimen in infants of breastfeeding mothers with HIV-1 infection for prevention of HIV-1 transmission (HPTN 046): 18-month results of a randomized, double-blind, placebo-controlled trial.

Fowler Mary Glenn MG Coovadia Hoosen H Herron Casey M CM Maldonado Yvonne Y Chipato Tsungai T Moodley Dhayendre D Musoke Philippa P Aizire Jim J Manji Karim K Stranix-Chibanda Lynda L Fawzi Wafaie W Chetty Vani V Msweli Lindiwe L Kisenge Rodrick R Brown Elizabeth E Mwatha Anthony A Eshleman Susan H SH Richardson Paul P Allen Melissa M George Kathleen K Andrew Philip P Zwerski Sheryl S Mofenson Lynne M LM Jackson J Brooks JB

Journal of acquired immune deficiency syndromes (1999) 20140301 3

<h4>Background</h4>HPTN 046 compared the efficacy and safety of infant nevirapine (NVP) among HIV-exposed breastfed infants randomized at 6 weeks to 6 months to t NVP or placebo to prevent postnatal infection: we report final 18-month outcomes.<h4>Methods</h4>Randomized, placebo-controlled trial in 4 African countries. Infant diagnostic HIV testing was performed regularly from birth through 18 months. Kaplan-Meier analysis was used to assess 18-month cumulative infant HIV infection, HIV infectio ...[more]

PMID: 24189151

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Project description:BackgroundNevirapine given once-daily for the first 6, 14, or 28 weeks of life to infants exposed to HIV-1 via breastfeeding reduces transmission through this route compared with single-dose nevirapine at birth or neonatally. We aimed to assess incremental safety and efficacy of extension of such prophylaxis to 6 months.MethodsIn our phase 3, randomised, double-blind, placebo-controlled HPTN 046 trial, we assessed the incremental benefit of extension of once-daily infant nevirapine from age 6 weeks to 6 months. We enrolled breastfeeding infants born to mothers with HIV-1 in four African countries within 7 days of birth. Following receipt of nevirapine from birth to 6 weeks, infants without HIV infection were randomly allocated (by use of a computer-generated permuted block algorithm with random block sizes and stratified by site and maternal antiretroviral treatment status) to receive extended nevirapine prophylaxis or placebo until 6 months or until breastfeeding cessation, whichever came first. The primary efficacy endpoint was HIV-1 infection in infants at 6 months and safety endpoints were adverse reactions in both groups. We used Kaplan-Meier analyses to compare differences in the primary outcome between groups. This study is registered with ClinicalTrials.gov, number NCT00074412.FindingsBetween June 19, 2008, and March 12, 2010, we randomly allocated 1527 infants (762 nevirapine and 765 placebo); five of whom had HIV-1 infection at randomisation and were excluded from the primary analyses. In Kaplan-Meier analysis, 1·1% (95% CI 0·3-1·8) of infants who received extended nevirapine developed HIV-1 between 6 weeks and 6 months compared with 2·4% (1·3-3·6) of controls (difference 1·3%, 95% CI 0-2·6), equating to a 54% reduction in transmission (p=0·049). However, mortality (1·2% for nevirapine vs 1·1% for placebo; p=0·81) and combined HIV infection and mortality rates (2·3%vs 3·2%; p=0·27) did not differ between groups at 6 months. 125 (16%) of 758 infants given extended nevirapine and 116 (15%) of 761 controls had serious adverse events, but frequency of adverse events, serious adverse events, and deaths did not differ significantly between treatment groups.InterpretationNevirapine prophylaxis can safely be used to provide protection from mother-to-child transmission of HIV-1 via breastfeeding for infants up to 6 months of age.FundingUS National Institutes of Health.

Project description:BackgroundDaily nevirapine (NVP) prophylaxis to HIV-exposed infants significantly reduces breast-milk HIV transmission. We assessed NVP-resistance in Indian infants enrolled in the "six-week extended-dose nevirapine" (SWEN) trial who received single-dose NVP (SD-NVP) or SWEN for prevention of breast-milk HIV transmission but who also acquired subtype C HIV infection during the first year of life.Methods/findingsStandard population sequencing and cloning for viral subpopulations present at > or =5% frequency were used to determine HIV genotypes from 94% of the 79 infected Indian infants studied. Timing of infection was defined based on when an infant's blood sample first tested positive for HIV DNA. SWEN-exposed infants diagnosed with HIV by six weeks of age had a significantly higher prevalence of NVP-resistance than those who received SD-NVP, by both standard population sequencing (92% of 12 vs. 38% of 29; p = 0.002) and low frequency clonal analysis (92% of 12 vs. 59% of 29; p = 0.06). Likelihood of infection with NVP-resistant HIV through breast-milk among infants infected after age six weeks was substantial, but prevalence of NVP-resistance did not differ among SWEN or SD-NVP exposed infants by standard population sequencing (15% of 13 vs. 15% of 20; p = 1.00) and clonal analysis (31% of 13 vs. 40% of 20; p = 0.72). Types of NVP-resistance mutations and patterns of persistence at one year of age were similar between the two groups. NVP-resistance mutations did differ by timing of HIV infection; the Y181C variant was predominant among infants diagnosed in the first six weeks of life, compared to Y188C/H during late breast-milk transmission.Conclusions/significanceUse of SWEN to prevent breast-milk HIV transmission carries a high likelihood of resistance if infection occurs in the first six weeks of life. Moreover, there was a continued risk of transmission of NVP-resistant HIV through breastfeeding during the first year of life, but did not differ between SD-NVP and SWEN groups. As with SD-NVP, the value of preventing HIV infection in a large number of infants should be considered alongside the high risk of resistance associated with extended NVP prophylaxis.Trial registrationClinicalTrials.gov NCT00061321.

Project description:The 6-month exclusive breastfeeding rate in the Northeast region of Thailand has recently significantly decreased in contrast to all other regions in Thailand. The factors that have influenced this decrease remain unknown. Hence, it is suggested that an investigation into factors that could improve or hinder EBF for 6 months in Northeast Thailand may be required to inform the development of relevant interventions to improve this situation. This study aimed to identify perceived facilitators and barriers to providing exclusive breastfeeding for 6 months in Northeast Thailand among breastfeeding mothers.Six focus group discussions were conducted with a total of 30 mothers aged 20 to 40 years who had children aged between 4 and 6 months and were currently breastfeeding or had breastfeeding experience. Participants were recruited through self-selection sampling from Khonkaen hospital (urban), Numphong hospital (peri-urban) and private hospitals (urban) in Khonkaen, Thailand. Thematic analysis was employed to analyse the data.Five main themes, with 10 sub-themes, were identified as either facilitators (+) or barriers (-), or in some cases, as both (+/-). Breastfeeding knowledge, perceptions, maternal circumstances, support, and traditional food were the main identified themes. Mother's breastfeeding knowledge, intention to breastfeed, and social media were perceived as facilitators. Perceptions, employment, and formula milk promotion were perceived as barriers. Family, healthcare, and traditional food were perceived as both facilitators and barriers. The perception that social media was a way to access breastfeeding knowledge and support mothers in Northeast Thailand emerged as a new facilitating factor that had not previously been identified in Thai literature relating to facilitators and barriers to exclusive breastfeeding. Intention to breastfeed, family support, healthcare support and traditional food were mentioned by all groups, whereas mothers from urban areas specifically mentioned mother's breastfeeding knowledge, social media and employment sub-themes. Only mothers from the peri-urban area mentioned formula milk promotion and only mothers who had delivered in public hospitals mentioned the perceptions sub-theme.Knowledge about these facilitators and barriers may inform the design and development of specific and relevant interventions to improve the 6-month exclusive breastfeeding rate in the Northeast region of Thailand and be useful in other contexts. Social media emerged as a newly perceived facilitator in the Thai context and may be a useful inclusion in a 6-month exclusive breastfeeding intervention model.

Dataset Information

Efficacy and safety of an extended nevirapine regimen in infants of breastfeeding mothers with HIV-1 infection for prevention of HIV-1 transmission (HPTN 046): 18-month results of a randomized, double-blind, placebo-controlled trial.

Publications

Efficacy and safety of an extended nevirapine regimen in infants of breastfeeding mothers with HIV-1 infection for prevention of HIV-1 transmission (HPTN 046): 18-month results of a randomized, double-blind, placebo-controlled trial.

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