Management of paediatric HIV-1 resistance

Rk, Gupta; Gibb, Diana M; Pillay, Deenan

doi:10.1097/qco.0b013e3283298f1f

Cited by 26 publications

(34 citation statements)

References 63 publications

(69 reference statements)

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“…14 The transmission of HIV through breastfeeding is estimated to be about 10% but when extended prophylaxis with 6 weeks of NVP is given, this transmission rate can be reduced by half. 15 Thior et al 16 in the Mashi Study also reported that breastfeeding with antiretroviral prophylaxis is not as effective as formula feeding with similar intervention in curtailing post-natal HIV transmission but it reduces mortality in infants of HIV-infected mothers at 7 months. However, this study revealed there was no difference in the DNA PCR results between mothers who chose to exclusively breastfeed (EBF) and those who opted for exclusive formula feeding (EFF).…”

Section: Choice Of Infant Feedingmentioning

confidence: 99%

Evaluation of the prevention of mother-to-child transmission programme at a primary health care centre in South Africa

Akinsanya

Wiseberg-Firtell

Akpomiemie

et al. 2017

South African Family Practice

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Aim:To evaluate the effectiveness of the prevention of mother-to-child transmission (PMTCT) of the HIV programme at Levai Mbatha Community Health Centre (CHC), Evaton, South Africa. Methods: A retrospective analysis of HIV-infected mother-infant pairs was conducted between 1 August 2009 and 31 July 2010. The infants' HIV status was determined using HIV-specific qualitative DNA polymerase chain reaction (PCR). Demographic characteristics, mode of mother to child transmission (MTCT), choice of infant feeding, mode of delivery and CD4 count were included. Results: Of the 206 mothers, 10 infants had positive DNA PCR results at 6 weeks. The MTCT rate was 4.9%. The mean age of HIVinfected mothers was 28 years (SD 5.7, range 16-42 years). Overall, 74.2% (152) Conclusions:The PMTCT programme at Levai Mbatha CHC is effective in reducing the MTCT of HIV. Lack of ART prophylaxis and low CD4 count were the significant determinants of MTCT in the study.

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Section: Choice Of Infant Feedingmentioning

confidence: 99%

Evaluation of the prevention of mother-to-child transmission programme at a primary health care centre in South Africa

Akinsanya

Wiseberg-Firtell

Akpomiemie

et al. 2017

South African Family Practice

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“…Infants have a higher risk of developing resistance compared with adolescents and adults because younger children have higher viral loads, and during treatment, their family members cannot provide accurate dosing, because of the limitations in formulations of antiretroviral drugs, which can lead to subtherapeutic drug concentrations (17).…”

Section: Discussionmentioning

confidence: 99%

“…Children infected perinatally are usually exposed to many ART regimens, and once in adolescence and young adulthood, they have typically accumulated drug-resistant viruses that can be significantly difficult to control (17). Infants have a higher risk of developing resistance compared with adolescents and adults because younger children have higher viral loads, and during treatment, their family members cannot provide accurate dosing, because of the limitations in formulations of antiretroviral drugs, which can lead to subtherapeutic drug concentrations (17).…”

Section: Discussionmentioning

confidence: 99%

Genotype-guided antiretroviral regimens in children with multidrug-resistant HIV-1 infection

et al. 2016

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Background: Genotyping tests were developed to attenuate the impact of viral resistance. Information about the efficacy in genotype base antiretroviral therapy in children is rare and even more in low-and middle-income countries. Methods: Sixteen children with antiretroviral therapy (ART) failure and triple-class drug-resistant viruses were included in this study. Protease and retrotranscriptase genotypes were available for all patients. Switch of ART regimen was guided by genotyping data. The primary end point was virological suppression (<50 copies/ml) and immunological improvement after 48 wk of treatment with the new ART regimen. results: The median age of the patients was 14.5 y (interquartile range (IQR) 11-16.5). Median HIV-1 RNA viral load was 4.2 log 10 (IQR: 3.4-4.8). The primary end point was found in 11 children (69%), and 13 children (81%) had an HIV-1 RNA viral load <200 copies/ml. Median (IQR) for the baseline CD4 + cell count was 382 cells/μl (281-686 cells/μl), whereas after 48 wk of treatment with the new ART regimen, it was 640 cells/μl (361-936 cells/μl) (P < 0.001). conclusion: Darunavir/ritonavir, raltegravir, and etravirine were well tolerated in the present pediatric population. These drugs provide good options for children exposed to extensive ART. Regimens guided by genotyping data were effective for children who had ART failure and multidrug-resistant HIV-1 infection.i nfants and children who were infected perinatally are now surviving to adulthood with lifelong HIV infection and longterm exposure to combined antiretroviral therapy (ART) (1). Data from the United Kingdom Collaborative HIV Pediatric Study cohort demonstrated that over one-third of children had experienced virological treatment failure and were on a second or subsequent line of therapy at the time of their transition to adult care (2). In the pediatric setting, virological treatment failure occurs most frequently because of poor adherence to ART, and whenever viral replication is inefficiently controlled, virological treatment failure occurs more quickly, allowing the selection of HIV-1 quasispecies resistant to antiretroviral (ARV) drugs (3).Many innate and external factors have been associated with HIV drug resistance mutations in children, such as being infected perinatally, and extremely high viral load during the first steps of the infection, which can take longer to suppress than that in older children or adults, even when they are on fully active ART regimens (4).Interpretation of resistance tests in this context can be complex, particularly in the presence of expanding options for ARV drugs, and treatment decisions should be made with the support of pharmacists and clinicians who have expertise in the field (5).Currently, more than 20 different ARV drugs with six different classes of action have been approved for use in children or adolescents with HIV infection worldwide; most of them are used in Mexico (6).A good level of adherence is particularly difficult during adolescence, especially with a complex regimen ...

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“…Nevertheless, an analysis of children treated in South Africa showed that the probability of virological suppression at age 12 months was only 56% (8). This may be due to the higher viral loads and challenges associated with accurate dosing in infants, placing them at a potentially greater risk for developing PI drug resistance than adult patients (9).…”

mentioning

confidence: 99%

Contribution of Gag and Protease to HIV-1 Phenotypic Drug Resistance in Pediatric Patients Failing Protease Inhibitor-Based Therapy

Giandhari

Basson

Sutherland

et al. 2016

Antimicrob Agents Chemother

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f Protease inhibitors (PIs) are used as a first-line regimen in HIV-1-infected children. Here we investigated the phenotypic consequences of amino acid changes in Gag and protease on lopinavir (LPV) and ritonavir (RTV) susceptibility among pediatric patients failing PI therapy. The Gag-protease from isolates from 20 HIV-1 subtype C-infected pediatric patients failing an LPV and/or RTV-based regimen was phenotyped using a nonreplicative in vitro assay. Changes in sensitivity to LPV and RTV relative to that of the matched baseline (pretherapy) sample were calculated. Gag and protease amino acid substitutions associated with PI failure were created in a reference clone by site-directed mutagenesis and assessed. Predicted phenotypes were determined using the Stanford drug resistance algorithm. Phenotypic resistance or reduced susceptibility to RTV and/or LPV was observed in isolates from 10 (50%) patients, all of whom had been treated with RTV. In most cases, this was associated with protease resistance mutations, but substitutions at Gag cleavage and noncleavage sites were also detected. Gag amino acid substitutions were also found in isolates from three patients with reduced drug susceptibilities who had wild-type protease. Site-directed mutagenesis confirmed that some amino acid changes in Gag contributed to PI resistance but only in the presence of major protease resistance-associated substitutions. The isolates from all patients who received LPV exclusively were phenotypically susceptible. Baseline isolates from the 20 patients showed a large (47-fold) range in the 50% effective concentration of LPV, which accounted for most of the discordance seen between the experimentally determined and the predicted phenotypes. Overall, the inclusion of the gag gene and the use of matched baseline samples provided a more comprehensive assessment of the effect of PI-induced amino acid changes on PI resistance. The lack of phenotypic resistance to LPV supports the continued use of this drug in pediatric patients.

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Management of paediatric HIV-1 resistance

Cited by 26 publications

References 63 publications

Evaluation of the prevention of mother-to-child transmission programme at a primary health care centre in South Africa

Evaluation of the prevention of mother-to-child transmission programme at a primary health care centre in South Africa

Genotype-guided antiretroviral regimens in children with multidrug-resistant HIV-1 infection

Contribution of Gag and Protease to HIV-1 Phenotypic Drug Resistance in Pediatric Patients Failing Protease Inhibitor-Based Therapy

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