Impact of Antiretroviral Drugs in Pregnant Women and Their Children in Africa: HIV Resistance and Treatment Outcomes.
ABSTRACT The global community has committed itself to eliminating new pediatric HIV infections by 2015 and improving maternal, newborn, and child health and survival in the context of HIV. Such objectives require regimens to prevent mother-to-child transmission (pMTCT) which, while being highly efficacious, protect the efficacy of future first-line antiretroviral therapy (ART). Major obstacles to eliminating vertical transmissions globally include low rates of adherence to ART and non-completion of the 'pMTCT cascade' due to programmatic and structural challenges faced by healthcare systems in low-income countries. Providing all pregnant women with lifelong ART regardless of CD4 count/disease stage (Option B+) could be the most effective option to prevent both HIV transmission and resistance, assuming adherence is successfully maintained. This strategy is more likely to achieve sustained undetectable HIV viremia, does not involve ART interruptions, is simpler to implement, and is cost-effective. Where Option B+ is not available, options A (short course zidovudine with single-dose nevirapine and an ARV "tail") and B (combination ART during pregnancy and breastfeeding, with ART cessation after weaning in women not qualifying for ART for their own health) are also efficacious, highly cost-effective and associated with infrequent resistance selection if taken properly.
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ABSTRACT: 2-Chloro-3-amino-4-picoline (CAPIC) is a strategic building block for the preparation of nevirapine, a widely-prescribed non-nucleosidic reverse transcriptase inhibitor for the treatment of HIV-infected patients. A continuous synthesis to the bromo derivative of a CAPIC intermediate, 2-bromo-4-methylnicotinonitrile, that terminates in a dead-end crystallization is described. The route uses inexpensive, acyclic commodity-based raw materials and has the potential to enable lower cost production of nevirapine as well as other value added structures that contain complex pyridines. The route terminates in a batch crystallization yielding high purity CAPIC. This outcome is expected to facilitate regulatory implementation of the overall process.Beilstein Journal of Organic Chemistry 01/2013; 9:2570-8. DOI:10.3762/bjoc.9.292 · 2.80 Impact Factor
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ABSTRACT: The World Health Organization (WHO) recommends periodic surveillance of transmitted drug resistance (TDR) in communities where antiretroviral therapy (ART) has been scaled-up for greater than 3 years. We conducted a survey of TDR mutations among newly detected HIV infected antiretroviral (ARV)-naïve pregnant women. From May 2010 to March 2012, 38 ARV-naive pregnant women were recruited in three hospitals in Jos, Plateau state, north central Nigeria. Eligible subjects were recruited using a modified version of the binomial sequential sampling technique recommended by WHO. HIV-1 genotyping was performed and HIV-1 drug resistance mutations characterized according to WHO 2009 surveillance drug resistance mutation (SDRM) list. HIV subtypes were determined by phylogenetic analysis. The women's median age was 25.5 years; the median CD4+ cell counts was 317 cells/µl and median viral load of 16, 261copies/ml. Of the 38 samples tested, 34 (89%) were successfully genotyped. The SDRM rate was <5% for all ART drug classes, with 1/34 (2.9%) for NRTIs/NNRTIs and none for protease inhibitors 0/31 (0%). The specific SDRM detected were M41L for NRTI and G190A for NNRTI. HIV-1 subtypes detected were CRF02_AG (38.2%), G' (41.2%), G (14.7%), CRF06-CPX (2.9%) and a unique AG recombinant form (2.9%). The single ARV-native pregnant woman with SDRMS was infected with HIV-1 subtype G'. Access to ART has been available in the Jos area for over 8 years. The prevalence of TDR lower than 5%, suggests proper ART administration although continued surveillance is warranted.AIDS research and human retroviruses 10/2013; DOI:10.1089/AID.2013.0074 · 2.46 Impact Factor
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ABSTRACT: In the era of more efficacious prevention of mother-to-child transmission (PMTCT) regimens, documenting the profile of drug resistance in HIV-infected infants and young children is critical to our efforts to improve care and treatment for children. HIV drug resistance mutations in plasma virus were ascertained using population sequencing among 230 newly diagnosed HIV-infected children under 2 years of age recruited in Johannesburg, South Africa, during 2011. By this time, more effective PMTCT regimens, including combination antiretroviral therapy for pregnant women, were being implemented. Two-thirds (67.4%) of HIV-infected children had been exposed to some form of maternal (89%) and/or infant (97%) PMTCT. Among PMTCT-exposed, 56.8% had nonnucleoside reverse transcriptase inhibitor (NNRTI), 14.8% nucleoside reverse transcriptase inhibitor (NRTI), and 1.3% protease inhibitor mutations. NNRTI mutations were strongly related to younger age. The remaining third (32.6%) had no reported or recorded PMTCT exposures, but resistance to NNRTI was detected in 24.0%, NRTI in 10.7%, and protease inhibitor in 1.3%. The new PMTCT strategies dramatically reduce the number of children who acquire infection, but among those who do become infected, NNRTI resistance prevalence is high. In this South African setting with high PMTCT coverage, almost a quarter of children with no reported or recorded PMTCT also have drug resistance mutations. PMTCT history is an inadequate means of ruling out pretreatment drug resistance. Our results support the use of protease inhibitor-based first-line regimens in HIV-infected infants and young children regardless of PMTCT history.AIDS (London, England) 04/2014; 28(11). DOI:10.1097/QAD.0000000000000261 · 6.56 Impact Factor