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Is the interruption of antiretroviral treatment during pregnancy an additional major risk factor for mother-to-child transmission of HIV type 1?

Galli L, Puliti D, Chiappini E et al. Clin Infect Dis 2009;48:1310–7. • This prospective study investigated the effects of discontinuing ART during pregnancy on the rate of mother-to-child transmission.
• Among 937 HIV-positive pregnant women, ART was interrupted in 81 (8.6%) in the first and 11 (1.2%) in the third trimester. The rate of mother-to-child transmission was 1.3% (95% CI: 0.7–2.3%) overall, 4.9% (95% CI: 1.9–13.2%) with first-trimester interruption and 18.2% (95% CI, 4.5%–72.7%) with third- trimester interruption.
• Conclusion: Discontinuing ART during pregnancy increases the rate of mother-to-child transmission of HIV-1.
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Public Health Service Task Force recommendations for use of antiretroviral drugs in pregnant HIV-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States.

Perinatal HIV Guidelines Working Group April 29, 2009; pp 1–90. Available at http://aidsinfo.nih.gov/ContentFiles/PerinatalGL.pdf • These guidelines are structured to reflect the management of an individual mother-child pair. They are organised into principles for the management of the woman and her infant during the antepartum, intrapartum and postpartum period.
• Key issues and new information in the report include: lessons learned from clinical trials, neonatal post-natal care, preclinical and clinical data relevant to the use of ARVs in pregnancy and safety and toxicity of individual ARVs in pregnancy.
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Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1.

Wind-Rotolo M, Durand C, Cranmer L, et al. J Infect Dis 2009;199:1301–1309. • This study investigated NVP resistance in women from South Africa and Uganda >6 months after they had received single-dose NVP for prevention of mother-to-child transmission of HIV-1.
• Although only a small number of latently infected cells were present in each blood sample (mean, 162 cells), NVP resistance mutations (K103N and G190A) were found in the latent reservoir in four of 50 (8%) evaluable women.
• Conclusions: Single-dose NVP can establish ARV resistance within the latent reservoir resulting in a potentially lifelong risk of re-emergence of NVP-resistant virus. This emphasises the need for strategies to prevent transmission that do not compromise successful future therapy.
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Rapid advice: antiretroviral therapy for HIV infection in adults and adolescents.

WHO guidelines • These three new WHO guidelines update the previous versions published in 2006.
• The guidelines aim to optimise outcomes, including QoL and survival, and to act as a reference tool for countries to adopt and adapt according to their national circumstances.
• The WHO has reviewed emerging evidence on when to initiate ART, which drug regimens to use, the management of co-infections and treatment failure, when to start and what ART to use in pregnancy, to reduce the risk of mother-to-child transmission and when breast feeding.
• The evidence was assembled following systematic reviews, GRADE profile preparation and analysis, consultations with HIV+ individuals, cost and economic impact studies, country-level feasibility assessment, and comparisons of current country guidelines.
• The aim of the guidelines is to outline standards for high-quality care by providing evidence-based recommendations, while considering the risks and benefits, acceptability, feasibility, cost and financial implications.
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Rapid advice: use of antiretroviral drugs for treating pregnant women and preventing HIV infection in infants.

WHO guidelines • These three new WHO guidelines update the previous versions published in 2006.
• The guidelines aim to optimise outcomes, including QoL and survival, and to act as a reference tool for countries to adopt and adapt according to their national circumstances.
• The WHO has reviewed emerging evidence on when to initiate ART, which drug regimens to use, the management of co-infections and treatment failure, when to start and what ART to use in pregnancy, to reduce the risk of mother-to-child transmission and when breast feeding.
• The evidence was assembled following systematic reviews, GRADE profile preparation and analysis, consultations with HIV+ individuals, cost and economic impact studies, country-level feasibility assessment, and comparisons of current country guidelines.
• The aim of the guidelines is to outline standards for high-quality care by providing evidence-based recommendations, while considering the risks and benefits, acceptability, feasibility, cost and financial implications.
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Rapid advice: infant feeding in the context of HIV.

WHO guidelines • These three new WHO guidelines update the previous versions published in 2006.
• The guidelines aim to optimise outcomes, including QoL and survival, and to act as a reference tool for countries to adopt and adapt according to their national circumstances.
• The WHO has reviewed emerging evidence on when to initiate ART, which drug regimens to use, the management of co-infections and treatment failure, when to start and what ART to use in pregnancy, to reduce the risk of mother-to-child transmission and when breast feeding.
• The evidence was assembled following systematic reviews, GRADE profile preparation and analysis, consultations with HIV+ individuals, cost and economic impact studies, country-level feasibility assessment, and comparisons of current country guidelines.
• The aim of the guidelines is to outline standards for high-quality care by providing evidence-based recommendations, while considering the risks and benefits, acceptability, feasibility, cost and financial implications.
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New WHO HIV treatment and prevention guidelines.

Crowley S et al. Lancet 2009 Nov 30. • These three new WHO guidelines update the previous versions published in 2006.
• The guidelines aim to optimise outcomes, including QoL and survival, and to act as a reference tool for countries to adopt and adapt according to their national circumstances.
• The WHO has reviewed emerging evidence on when to initiate ART, which drug regimens to use, the management of co-infections and treatment failure, when to start and what ART to use in pregnancy, to reduce the risk of mother-to-child transmission and when breast feeding.
• The evidence was assembled following systematic reviews, GRADE profile preparation and analysis, consultations with HIV+ individuals, cost and economic impact studies, country-level feasibility assessment, and comparisons of current country guidelines.
• The aim of the guidelines is to outline standards for high-quality care by providing evidence-based recommendations, while considering the risks and benefits, acceptability, feasibility, cost and financial implications.
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Decline in early life mortality in a high HIV prevalence rural area of South Africa: evidence of HIV prevention or treatment impact?

Ndirangu J et al. AIDS 2010;24:593–602. • This retrospective study investigated the temporal and spatial associations between early life mortality rates and a prevention of mother-to-child transmission (PMTCT) programme (single-dose NVP), an HIV treatment programme and maternal HIV in a largely rural population with a high prevalence of antenatal HIV.
• Mortality was independently associated with birth season (adjusted HR: 1.16; 95% CI: 1.02–1.33), maternal education (HR: 1.21; 95% CI: 1.02–1.43), maternal HIV (HR: 4.34; 95% CI: 3.11–6.04) and ART availability (HR: 0.46; 95% CI: 0.33–0.65).
• Children born at home (unlikely to have received PMTCT) had a 35% higher risk of dying than children born in a facility where PMTCT was available (HR: 1.35; 95% CI: 1.04–1.74).
• Conclusions: The results confirm the importance of maternal survival and show the importance of the PMTCT and maternal HIV treatment in improving the survival of their young children.
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Antiretroviral regimens in pregnancy and breast-feeding in Botswana.

Shapiro RL et al. N Engl J Med 2010;362:2282–94. • This randomised study investigated the efficacy HAART regimens to prevent mother-to-child transmission of HIV-1.
• Women received ABC/3TC/AZT (NRTI group), LPV/r + AZT/3TC (PI group) or NVP/3TC/AZT (observational group). Infants received single-dose NVP and 4 weeks of AZT.
• The rate of virological suppression to <400 copies/mL was high and did not differ significantly between the three groups at delivery (NRTI 96%, PI 93% and observational 94%) or during breast feeding (NRTI 92%, PI 93% and observational 95%).
• By 6 months of age, 8/709 live-born infants (1.1%) were infected (95% CI: 0.5–2.2): six were infected in utero (four in the NRTI, one in the PI and one in the observational group) and two were infected during breast feeding (in the NRTI group).
• Treatment-limiting adverse events occurred in 2% of women in the NRTI and PI groups and 11% of women in the observational group.
• Conclusions: All regimens resulted in high rates of virological suppression, with an overall mother-to-child transmission rate of 1.1%.
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Maternal or infant antiretroviral drugs to reduce HIV-1 transmission.

Chasela CS et al. N Engl J Med 2010;362:2271–81. • This study investigated the efficacy of a maternal triple-drug ARV regimen or infant NVP prophylaxis for 28 weeks during breast-feeding to reduce post-natal transmission of HIV-1 in Malawi.
• All mothers and infants received perinatal prophylaxis with single-dose NVP and 1 week of AZT plus 3TC.
• Among mother-infant pairs, 5.0% of infants were HIV+ at 2 weeks.
• The estimated risk of HIV-1 transmission at 2–28 weeks was higher in the control group (5.7%) than in either the maternal- (2.9%, p=0.009) or the infant-regimen group (1.7%, p<0.001).
• The estimated risk of infant HIV-1 infection or death at 2–28 weeks was 7.0% in the control group, 4.1% in the maternal- (p=0.02), and 2.6% in the infant-regimen group (p<0.001).
• Conclusions: The use of either a maternal ARV regimen or infant NVP for 28 weeks was effective in reducing HIV-1 transmission during breast feeding.
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