Extended Antiretroviral Prophylaxis to Reduce Breast-Milk HIV-1 Transmission

Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
New England Journal of Medicine (Impact Factor: 55.87). 07/2008; 359(2):119-29. DOI: 10.1056/NEJMoa0801941
Source: PubMed


Effective strategies are urgently needed to reduce mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) through breast-feeding in resource-limited settings.
Women with HIV-1 infection who were breast-feeding infants were enrolled in a randomized, phase 3 trial in Blantyre, Malawi. At birth, the infants were randomly assigned to one of three regimens: single-dose nevirapine plus 1 week of zidovudine (control regimen) or the control regimen plus daily extended prophylaxis either with nevirapine (extended nevirapine) or with nevirapine plus zidovudine (extended dual prophylaxis) until the age of 14 weeks. Using Kaplan-Meier analyses, we assessed the risk of HIV-1 infection among infants who were HIV-1-negative on DNA polymerase-chain-reaction assay at birth.
Among 3016 infants in the study, the control group had consistently higher rates of HIV-1 infection from the age of 6 weeks through 18 months. At 9 months, the estimated rate of HIV-1 infection (the primary end point) was 10.6% in the control group, as compared with 5.2% in the extended-nevirapine group (P<0.001) and 6.4% in the extended-dual-prophylaxis group (P=0.002). There were no significant differences between the two extended-prophylaxis groups. The frequency of breast-feeding did not differ significantly among the study groups. Infants receiving extended dual prophylaxis had a significant increase in the number of adverse events (primarily neutropenia) that were deemed to be possibly related to a study drug.
Extended prophylaxis with nevirapine or with nevirapine and zidovudine for the first 14 weeks of life significantly reduced postnatal HIV-1 infection in 9-month-old infants. ( number, NCT00115648.)

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    • "However, replacement feeding in resource-poor countries is associated with increased mortality from diarrheal disease, pneumonia, and other infectious diseases [4]. In these regions, the World Health Organization recommends that HIV-infected women breastfeed their infants in the setting of maternal and/or infant antiretroviral prophylaxis, which considerably reduces postnatal HIV-1 transmission [5–7]. "
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    ABSTRACT: HIV-1 and CMV are important pathogens transmitted via breastfeeding. Furthermore, perinatal CMV transmission may impact growth and disease progression in HIV-exposed infants. Although maternal antiretroviral therapy reduces milk HIV-1 RNA load and postnatal transmission, its impact on milk CMV load is unclear. We examined the relationship between milk CMV and HIV-1 load (4-6 weeks postpartum) and the impact of antiretroviral treatment in 69 HIV-infected, lactating Malawian women and assessed the relationship between milk CMV load and postnatal growth in HIV-exposed, breastfed infants through six months of age. Despite an association between milk HIV-1 RNA and CMV DNA load (0.39 log10 rise CMV load per log10 rise HIV-1 RNA load, 95% CI 0.13-0.66), milk CMV load was similar in antiretroviral-treated and untreated women. Higher milk CMV load was associated with lower length-for-age (-0.53, 95% CI: -0.96, -0.10) and weight-for-age (-0.40, 95% CI: -0.67, -0.13) Z-score at six months in exposed, uninfected infants. As the impact of maternal antiretroviral therapy on the magnitude of postnatal CMV exposure may be limited, our findings of an inverse relationship between infant growth and milk CMV load highlight the importance of defining the role of perinatal CMV exposure on growth faltering of HIV-exposed infants.
    Infectious Diseases in Obstetrics and Gynecology 03/2014; 2014:989721. DOI:10.1155/2014/989721
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    • "Currently, the US remains the only country where antiretrovirals (ARVs) are licensed for use as PrEP. The rationale for the use of ARV prophylaxis is based on its efficacy in infants exposed to HIV-1 during birth and breast feeding [21], and its partial or full protection against simian or simian/human immunodeficiency virus (SIV/SHIV) challenged in primates [22], [23], [24]. Up to now, eight randomized double-blind placebo-controlled clinical trials of PrEP have been completed or are ongoing worldwide [25]. "
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    ABSTRACT: Acceptability of pre-exposure prophylaxis (PrEP) and willingness to participate in a clinical trial for both safety and efficacy of PrEP were investigated among female sex workers (FSWs) in Guangxi, China. A cross-sectional study was performed in three cities in Guangxi. Structured, self-administered questionnaires were used to assess the acceptability of PrEP and the willingness to participate in a clinical trial. Multivariable logistic regression models were fitted to identify predictors. Among 405 participants, 15.1% had heard of PrEP. If PrEP was deemed to be effective, safe and provided for free, 85.9% reported that they would accept it, and 54.3% of those who accepted PrEP said that they would participate in a clinical trial. The increased acceptability of PrEP was associated with working in male dominated venues, higher income, a poor family relationship, better HIV/AIDS knowledge, not realizing HIV risk from unfamiliar clients, not being forced to use condoms by the gatekeepers, consistent use of condoms, and use of drugs to prevent STD infection. The increased willingness to participate in a clinical trial was associated with a poor family relationship, better HIV/AIDS knowledge, not realizing HIV risk from unfamiliar clients, a willingness to adhere to daily PreP use, and not being concerned about discrimination by others. The main reason for rejecting PrEP or participating in a clinical trial was the concern about the side effects of PrEP. Acceptability of PrEP among Guangxi FSWs is relatively high, indicating that PrEP intervention programs may be feasible for Chinese FSWs. Given the fact that most of the participants had never heard of PrEP before, and that family, gatekeepers, and social discrimination could significantly affect its acceptability, a comprehensive mix of multiple interventions is necessary for the successful implementation of a PrEP program among this population in Guangxi.
    PLoS ONE 01/2014; 9(1):e86200. DOI:10.1371/journal.pone.0086200 · 3.23 Impact Factor
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    • "Most of the mothers (>65%) in this study breastfed their children beyond 6 months, which would be associated with higher postnatal HIV transmission to their infants [33]. In situations where breastfeeding cannot be avoided, extended ARV prophylaxis would help reduce risk of postnatal infection [34]. "
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    ABSTRACT: Zimbabwe is one of the five countries worst affected by the HIV/AIDS pandemic with HIV infection contributing increasingly to childhood morbidity and mortality. Among the children born to HIV positive mothers participating in the PMTCT programme, 25% tested positive to HIV. We investigated factors associated with HIV infection among children born to mothers on the PMTCT programme. A 1:1 unmatched case-control study was conducted at Chitungwiza Hospital, Zimbabwe, 2008. A case was defined as a child who tested HIV positive, born to a mother who had been on PMTCT programme. A control was a HIV negative child born to a mother who had been on PMTCT programme. An interviewer-administered questionnaire was used to collect data on demographic characteristics, risk factors associated with HIV infection and immunization status. A total of 120 mothers were interviewed. Independent risk factors associated with HIV infection among children included maternal CD4 count of less than 200 during pregnancy [aOR = 7.1, 95% CI (2.6-17)], mixed feeding [aOR = 29, 95% CI (4.2-208)], being hospitalized since birth [aOR = 2.9, 95% CI (1.2-4.8)] whilst being exclusively breast fed for less than 6 months [aOR = 0.1 (95% CI 0.03-0.4)] was protective. HIV infection among children increased if the mother's CD4 count was <=200 cells/muL and if the child was exposed to mixed feeding. Breastfeeding exclusively for less than six months was protective. We recommended exclusive breast feeding period for the first six months and stop breast feeding after 6 months if affordable, sustainable and safe.
    BMC Public Health 12/2013; 13(1):1181. DOI:10.1186/1471-2458-13-1181 · 2.26 Impact Factor
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