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      Progress in the Prevention of Mother to Child Transmission of HIV in Three Regions of Tanzania: A Retrospective Analysis

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          Abstract

          Background

          Mother to child transmission (MTCT) of HIV-1 remains an important problem in sub-Saharan Africa where most new pediatric HIV-1 infections occur. Early infant diagnosis of HIV-1 using dried blood spot (DBS) PCR among exposed infants provides an opportunity to assess current MTCT rates.

          Methods

          We conducted a retrospective data analysis on mother-infant pairs from all PMTCT programs in three regions of northern Tanzania to determine MTCT rates from 2008–2010. Records of 3,016 mother-infant pairs were assessed to determine early transmission among HIV-exposed infants in the first 75 days of life.

          Results

          Of 2,266 evaluable infants in our cohort, 143 had a positive DBS PCR result at ≤75 days of life, for an overall transmission rate of 6.3%. Transmission decreased substantially over the period of study as more effective regimens became available. Transmission rates were tightly correlated to maternal regimen: 14.9% (9.5, 20.3) of infants became infected when women received no therapy; 8.8% (6.9, 10.7) and 3.6% (2.4, 4.8) became infected when women received single-dose nevirapine (sdNVP) or combination prophylaxis, respectively; the lowest MTCT rates occurred when women were on HAART, with 2.1% transmission (0.3, 3.9). Treatment regimens changed dramatically over the study period, with an increase in combination prophylaxis and a decrease in the use of sdNVP. Uptake of DBS PCR more than tripled over the period of study for the three regions surveyed.

          Conclusions

          Our study demonstrates significant reductions in MTCT of HIV-1 in three regions of Tanzania coincident with increased use of more effective PMTCT interventions. The changes we demonstrate for the period of 2008–2010 occurred prior to major changes in WHO PMTCT guidelines.

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          Most cited references18

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          Prevention of mother-to-child HIV transmission in resource-poor countries: translating research into policy and practice.

          Each year, an estimated 590,000 infants acquire human immunodeficiency virus type 1 (HIV) infection from their mothers, mostly in developing countries that are unable to implement interventions now standard in the industrialized world. In resource-poor settings, the HIV pandemic has eroded hard-won gains in infant and child survival. Recent clinical trial results from international settings suggest that short-course antiretroviral regimens could significantly reduce perinatal HIV transmission worldwide if research findings could be translated into practice. This article reviews current knowledge of mother-to-child HIV transmission in developing countries, summarizes key findings from the trials, outlines future research requirements, and describes public health challenges of implementing perinatal HIV prevention interventions in resource-poor settings. Public health efforts must also emphasize primary prevention strategies to reduce incident HIV infections among adolescents and women of childbearing age. Successful implementation of available perinatal HIV interventions could substantially improve global child survival.
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            Combination antiretroviral strategies for the treatment of pregnant HIV-1-infected women and prevention of perinatal HIV-1 transmission.

            The Women and Infants Transmission Study is a prospective natural history study that has been enrolling HIV-1-infected pregnant women and their infants since 1989. To evaluate the impact of different antiretroviral regimens on perinatal HIV-1 transmission at the population level. Prospective cohort study. Plasma HIV-1 RNA levels were serially measured in 1542 HIV-1-infected women with singleton live births between January 1990 and June 2000. HIV-1 status of the infant. HIV-1 transmission was 20.0% (95% confidence interval [CI], 16.1%-23.9%) for 396 women who not receiving prenatal antiretroviral therapy; 10.4% (95% CI, 8.2%-12.6%) for 710 receiving zidovudine monotherapy; 3.8% (95% CI, 1.1%-6.5%) for 186 receiving dual antiretroviral therapy with no or one highly active drug (Multi-ART); and 1.2% (95% CI, 0-2.5%) for 250 receiving highly active antiretroviral therapy (HAART). Transmission also varied by maternal delivery HIV RNA level: 1.0% for 30,000 copies/mL (p =.0001 for trend). The odds of transmission increased 2.4-fold (95% CI, 1.7-3.5) for every log10 increase in delivery viral load. In multivariate analyses adjusting for maternal viral load, duration of therapy, and other factors, the odds ratio for transmission for women receiving Multi-ART and HAART compared with those receiving ZDV monotherapy was 0.30 (95% CI, 0.09-1.02) and 0.27 (95% CI, 0.08-0.94), respectively. Levels of HIV-1 RNA at delivery and prenatal antiretroviral therapy were independently associated with transmission. The protective effect of therapy increased with the complexity and duration of the regimen. HAART was associated with the lowest rates of transmission.
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              Efficacy of three short-course regimens of zidovudine and lamivudine in preventing early and late transmission of HIV-1 from mother to child in Tanzania, South Africa, and Uganda (Petra study): a randomised, double-blind, placebo-controlled trial.

              (2002)
              Large reductions in transmission of HIV-1 from mother to child have been achieved in more-developed countries due to the use of antiretrovirals. Short-course regimens, suitable for resource-poor countries, have also been shown to significantly reduce peripartum HIV-1 transmission. We assessed the efficacy of short-course regimens with zidovudine and lamivudine in a predominantly breastfeeding population. We did a randomised, double-blind, placebo-controlled trial in South Africa, Uganda, and Tanzania. Between June, 1996, and January, 2000, HIV-1-infected mothers were randomised to one of four regimens: A, zidovudine plus lamivudine starting at 36 weeks' gestation, followed by oral intrapartum dosing and by 7 days' postpartum dosing of mothers and infants; B, as regimen A, but without the prepartum component; C, intrapartum zidovudine and lamivudine only; or placebo. From Feb 18, 1998, onward, women were only randomised to one of the active treatment groups. Primary outcomes were HIV-1 infection and child mortality at week 6 and month 18 after birth. Analysis was by intention to treat of those randomised before Feb 18, 1998. 1797 HIV-1-infected women were identified. Week 6 HIV-1 transmission rates were 5.7% for group A, 8.9% for group B, 14.2% for group C, and 15.3% for the placebo group. Respective relative risks for HIV-1 transmission in the treatment groups compared with placebo were 0.37 (95% CI 0.21-0.65), 0.58 (0.36-0.94), and 0.93 (0.62-1.40). For the combined endpoint of HIV-1 infection and infant mortality at week 6 rates were 7.0%, 11.6%, 17.5%, and 18.1%, respectively, with relative risks of 0.39 (0.24-0.64), 0.64 (0.42-0.97), and 0.97 (0.68-1.38). 1081 (74%) of the women analysed initiated breastfeeding. Based on an interval-censored survival analysis, HIV-1 infection rates at month 18 were 15% (95% CI 9-23), 18% (12-26), 20% (13-30) and 22% (16-30), respectively. Although at week 6 after birth, regimens A and B were effective in reducing HIV-1 transmission, benefits have diminished considerably after 18 months of follow-up. Introduction of short-course regimens to prevent mother-to-child transmission of HIV-1 in less-developed countries should be accompanied by interventions to minimise the risk of subsequent transmission via breastfeeding.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                13 February 2014
                : 9
                : 2
                : e88679
                Affiliations
                [1 ]Kilimanjaro Christian Medical Centre, Moshi, Tanzania
                [2 ]Division of Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, United States of America
                [3 ]Duke Global Health Institute, Duke University, Durham, North Carolina, United States of America
                [4 ]Ministry of Health and Social Welfare, Dar es Salaam, Tanzania
                [5 ]Kilimanjaro Christian Medical Centre Clinical Laboratory, Moshi, Tanzania
                [6 ]Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina, United States of America
                [7 ]Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America
                [8 ]Elizabeth Glaser Pediatric AIDS Foundation, Dar es Salaam, Tanzania
                University of British Columbia, Canada
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: AMB JAB CKC CGM WS AS. Performed the experiments: BN RM. Analyzed the data: DED SF. Contributed reagents/materials/analysis tools: BN. Wrote the paper: AMB DED CGM BN AS RM SF JAB CKC WS.

                Article
                PONE-D-13-27231
                10.1371/journal.pone.0088679
                3923804
                24551134
                dec647e0-49dd-4baa-8f49-485862e5701f
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 2 July 2013
                : 10 January 2014
                Page count
                Pages: 7
                Funding
                This research was supported by the President’s Emergency Plan for AIDS Relief (PEPFAR) through a supplement to the National Institute of Allergy and Infectious Diseases (NIAID): NOT-A1-10-023 (3UO1 A1069484 A4S2); the Duke Clinical Trials Unit and Clinical Research Sites (U01 AI069484 to CKC, JAB, and AMB); the Duke Center for AIDS Research (5P30 AI064518 to CKC and AMB); the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) training grant to the Division of Infectious Diseases, Department of Pediatrics, Duke University Medical Center (T32 HD060558 to DED); and HRSA grant T84HS21123 and NIH grants P30AI064518, D43CA153722, and D43TW06732 to JAB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine
                Clinical research design
                Retrospective studies
                Global health
                Infectious diseases
                Sexually transmitted diseases
                AIDS
                Viral diseases
                HIV
                HIV epidemiology
                HIV opportunistic infections
                HIV prevention
                Infectious disease control
                Obstetrics and gynecology
                Genitourinary infections
                HIV
                Pregnancy
                Public health
                Child health
                Health screening

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                Uncategorized

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