Article

Prevention of mother-to-child transmission of HIV-1 through breast-feeding by treating infants prophylactically with lamivudine in Dar es Salaam, Tanzania: the Mitra Study

Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.39). 08/2008; 48(3):315-23. DOI: 10.1097/QAI.0b013e31816e395c
Source: PubMed

ABSTRACT To investigate the possibility of reducing mother-to-child transmission (MTCT) of HIV-1 through breast-feeding by prophylactic antiretroviral (ARV) treatment of the infant during the breast-feeding period.
An open-label, nonrandomized, prospective cohort study in Tanzania (Mitra).
HIV-1-infected pregnant women were treated according to regimen A of the Petra trial with zidovudine (ZDV) and lamivudine (3TC) from week 36 to 1 week postpartum. Infants were treated with ZDV and 3TC from birth to 1 week of age (Petra arm A) and then with 3TC alone during breast-feeding (maximum of 6 months). Counseling emphasized exclusive breast-feeding. HIV transmission was analyzed using the Kaplan-Meier survival technique. Cox regression was used for comparison with the breast-feeding population in arm A of the Petra trial, taking CD4 cell count and other possible confounders into consideration.
There were 398 infants included in the transmission analysis in the Mitra study. The estimated cumulative proportion of HIV-1-infected infants was 3.8% (95% confidence interval [CI]: 2.0 to 5.6) at week 6 after delivery and 4.9% (95% CI: 2.7 to 7.1) at month 6. The median time of breast-feeding was 18 weeks. High viral load and a low CD4 T-cell count at enrollment were associated with transmission. The Kaplan-Meier estimated risk of HIV-1 infection at 6 months in infants who were HIV-negative at 6 weeks was 1.2% (95% CI: 0.0 to 2.4). The cumulative HIV-1 infection or death rate at 6 months was 8.5% (95% CI: 5.7 to 11.4). No serious adverse events related to the ARV treatment of infants occurred. The HIV-1 transmission rate during breast-feeding in the Mitra study up to 6 months after delivery was more than 50% lower than in the breast-feeding population of Petra arm A (relative hazard=2.61; P=0.001; adjusted values). The difference in transmission up to 6 months was significant also in the subpopulation of mothers with CD4 counts>or=200 cells/microL.
The rates of MTCT of HIV-1 in the Mitra study at 6 weeks and 6 months after delivery are among the lowest reported in a breast-feeding population in sub-Saharan Africa. Prophylactic 3TC treatment of infants to prevent MTCT of HIV during breast-feeding was well tolerated by the infants and could be a useful strategy to prevent breast milk transmission of HIV when mothers do not need ARV treatment for their own health.

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    • "In high-income countries, the use of prophylactic ART combined with elective caesarean section and avoidance of breastfeeding has almost eliminated mother-to-child transmission (MTCT) of HIV but this is not the case in resource-poor settings [1]. Earlier studies in low-income countries have shown that PMTCT, involving ART during the late stages of pregnancy and postnatally, combined with exclusive breastfeeding for six months, can reduce MTCT to between 1% and 5% at 6 months after delivery [3-7]. "
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    ABSTRACT: Background In a study of prevention of mother-to-child transmission of HIV (PMTCT) by triple antiretroviral therapy (ART) in Dar es Salaam, Tanzania (the Mitra Plus study), retrospective viral load testing revealed a high and increasing frequency of detectable viral load during follow-up for two years postnatally in women given continuous ART for their own health suggesting poor adherence. This study explored women’s own perceived barriers to adherence to ART post-delivery so as to identify ways to facilitate better drug adherence among women in need of ART for their own health. Methods Semi-structured interviews were conducted with 23 of the 48 women who had detectable viral load at 24 months postnatally. Content analysis was used to analyze the data. Results Most women in the study did not acknowledge poor adherence until confronted with the viral load figures. Then, however, they revealed multiple reasons for failing to adhere. They said that their motivation to take ART decreased once they had protected their children from becoming infected and successfully weaned them. Feeling well for some, and a feeling of hopelessness for others, also decreased motivation to continue ART. The overwhelming demands of everyday life, poverty and lack of empowerment also posed significant barriers to long-term adherence. The need to keep their HIV status a secret and not let anyone see them taking the drugs was another steep barrier. Conclusion Reasons for postnatal failure to adhere by mothers put on ART for life during pregnancy included lack of motivation to continue ART after weaning the child, poverty and stigma. Projects that simultaneously address stigma, poverty and women’s lack of empowerment may be necessary for PMTCT and ART to reach their full potential. Our results indicate that the new WHO proposal to start all HIV-infected pregnant women on lifelong ART regardless of CD4 cell count needs to address the challenging realities of women in resource-poor contexts if it is to be successful.
    BMC Public Health 05/2013; 13(1):450. DOI:10.1186/1471-2458-13-450 · 2.32 Impact Factor
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    • "Tolerance of extended NVP was acceptable although 15% of babies experienced NVP-related side effects, while no drug-related severe adverse events were reported with 3TC [13]. Major concerns arose from a sub-study of SWEN in India which reported that 92% of babies infected despite NVP prophylaxis harboured viruses resistant to NVP, thus jeopardizing the use of any drug of this therapeutic class (NNRTI) for future treatment of these infants, which restricts considerably the number of ART drugs available in low-income countries. "
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    ABSTRACT: BACKGROUND: Postnatal transmission of HIV-1 through breast milk remains an unsolved challenge in many resource-poor settings where replacement feeding is not a safe alternative. WHO now recommends breastfeeding of infants born to HIV-infected mothers until 12 months of age, with either maternal highly active antiretroviral therapy (HAART) or peri-exposure prophylaxis (PEP) in infants using nevirapine. As PEP, lamivudine showed a similar efficacy and safety as nevirapine, but with an expected lower rate of resistant HIV strains emerging in infants who fail PEP, and lower restrictions for future HIV treatment. Lopinavir/ritonavir (LPV/r) is an attractive PEP candidate with presumably higher efficacy against HIV than nevirapine or lamivudine, and a higher genetic barrier to resistance selection. It showed an acceptable safety profile for the treatment of very young HIV-infected infants. The ANRS 12174 study aims to compare the risk of HIV-1 transmission during and safety of prolonged infant PEP with LPV/r (40/10 mg twice daily if 2-4 kg and 80/20 mg twice daily if >4 kg) versus Lamivudine (7,5 mg twice daily if 2-4 kg, 25 mg twice daily if 4-8 kg and 50 mg twice daily if >8 kg) from day 7 until one week after cessation of BF (maximum 50 weeks of prophylaxis) to prevent postnatal HIV-1 acquisition between 7 days and 50 weeks of age. METHODS: The ANRS 12174 study is a multinational, randomised controlled clinical trial conducted on 1,500 mother-infant pairs in Burkina Faso, South Africa, Uganda and Zambia. We will recommend exclusive breastfeeding (EBF) until 26th week of life and cessation of breastfeeding at a maximum of 49 weeks in both trial arms.HIV-uninfected infants at day 7 (+/- 2 days) born to HIV-1 infected mothers not eligible for HAART who choose to breastfeed their infants.The primary endpoint is the acquisition of HIV-1 (as assessed by HIV-1 DNA PCR) between day 7 and 50 weeks of age. Secondary endpoints are safety (including resistance, adverse events and growth) until 50 weeks and HIV-1-free survival until 50 weeks. DISCUSSION: This study will provide a new evidence-based intervention to support HIV-1-infected women not eligible for HAART to safely breastfeed their babies.Trial registration number (www.clinicaltrials.gov)NCT00640263.
    BMC Infectious Diseases 10/2012; 12(1):246. DOI:10.1186/1471-2334-12-246 · 2.61 Impact Factor
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    • "Among factors that contributed to the decline, prevention of mother to child HIV transmission (PMTCT) programmes were the most significant, according to this report. Currently, a highly efficacious and safe prophylaxis regimen and/or lifelong antiretroviral treatment (ART) that can reduce mother to child transmission (MTCT) to less than 5% are made available in many resource-poor settings [2]. In those settings, however, ensuring uptake and adherence remains a challenge. "
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    ABSTRACT: Prevention of mother to child HIV transmission (PMTCT) programmes have great potential to achieve virtual elimination of perinatal HIV transmission provided that PMTCT recommendations are properly followed. This study assessed mothers and infants adherence to medication regimen for PMTCT and the proportions of exposed infants who were followed up in the PMTCT programme. A prospective cohort study was conducted among 282 HIV-positive mothers attending 15 health facilities in Addis Ababa, Ethiopia. Descriptive statistics, bivariate and mulitivariate logistic regression analyses were done. Of 282 mothers enrolled in the cohort, 232 (82%, 95% CI 77-86%) initiated medication during pregnancy, 154 (64%) initiated combined zidovudine (ZDV) prophylaxis regimen while 78 (33%) were initiated lifelong antiretroviral treatment (ART). In total, 171 (60%, 95% CI 55-66%) mothers ingested medication during labour. Of the 221 live born infants (including two sets of twins), 191 (87%, 95% CI 81-90%) ingested ZDV and single-dose nevirapine (sdNVP) at birth. Of the 219 live births (twin births were counted once), 148 (68%, 95% CI 61-73%) mother-infant pairs ingested their medication at birth. Medication ingested by mother-infant pairs at birth was significantly and independently associated with place of delivery. Mother-infant pairs attended in health facilities at birth were more likely (OR 6.7 95% CI 2.90-21.65) to ingest their medication than those who were attended at home. Overall, 189 (86%, 95% CI 80-90%) infants were brought for first pentavalent vaccine and 115 (52%, 95% CI 45-58%) for early infant diagnosis at six-weeks postpartum. Among the infants brought for early diagnosis, 71 (32%, 95% CI 26-39%) had documented HIV test results and six (8.4%) were HIV positive. We found a progressive decline in medication adherence across the perinatal period. There is a big gap between mediation initiated during pregnancy and actually ingested by the mother-infant pairs at birth. Follow up for HIV-exposed infants seem not to be organized and is inconsistent. In order to maximize effectiveness of the PMTCT programme, the rate of institutional delivery should be increased, the quality of obstetric services should be improved and missed opportunities to exposed infant follow up should be minimized.
    Journal of the International AIDS Society 10/2011; 14:50. DOI:10.1186/1758-2652-14-50 · 4.21 Impact Factor
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