Perinatal acquisition of drug-resistant HIV-1 infection: mechanisms and long-term outcome

Delaugerre, Constance; Chaix, Marie‐Laure; Blanche, Stéphane; Warszawski, Josiane; Cornet, Dorine; Dollfus, Catherine; Schneider, Véronique; Burgard, Marianne; Faye, Albert; Mandelbrot, Laurent; Tubiana, Roland; Rouzioux, Christine

doi:10.1186/1742-4690-6-85

Cited by 26 publications

(14 citation statements)

References 37 publications

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“…If available, the antiretroviral history of the mother or other source case should also be documented. In view of the possibility of transmitted drug resistance 18, 19 and unreported prior ART exposure, HIV genotypic resistance testing is recommended at baseline (including reverse transcriptase, protease and integrase resistance testing when available). If available, the results of resistance testing of the source case, as close as possible to the time of transmission, should also be documented.…”

Section: Diagnosis Baseline Investigations and Pretreatment Monitoringmentioning

confidence: 99%

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

et al. 2015

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The 2015 Paediatric European Network for Treatment of AIDS (PENTA) guidelines provide practical recommendations on the management of HIV‐1 infection in children in Europe and are an update to those published in 2009. Aims of treatment have progressed significantly over the last decade, moving far beyond limitation of short‐term morbidity and mortality to optimizing health status for adult life and minimizing the impact of chronic HIV infection on immune system development and health in general. Additionally, there is a greater need for increased awareness and minimization of long‐term drug toxicity. The main updates to the previous guidelines include: an increase in the number of indications for antiretroviral therapy (ART) at all ages (higher CD4 thresholds for consideration of ART initiation and additional clinical indications), revised guidance on first‐ and second‐line ART recommendations, including more recently available drug classes, expanded guidance on management of coinfections (including tuberculosis, hepatitis B and hepatitis C) and additional emphasis on the needs of adolescents as they approach transition to adult services. There is a new section on the current ART ‘pipeline’ of drug development, a comprehensive summary table of currently recommended ART with dosing recommendations. Differences between PENTA and current US and World Health Organization guidelines are highlighted and explained.

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Section: Diagnosis Baseline Investigations and Pretreatment Monitoringmentioning

confidence: 99%

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

et al. 2015

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“…In contrast, resistant viruses selected when ART fails [19–21] or acquired at the time of HIV-1 infection [22, 23] can persist for years. If mutant concentrations wane below the threshold of detection in the absence of drug pressure, the mutants can persist as viable proviruses, even after only a single dose of nevirapine [24], and if selective pressure is resumed, these can replicate and repopulate the blood [25].…”

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confidence: 99%

Nevirapine Resistance by Timing of HIV Type 1 Infection in Infants Treated with Single‐Dose Nevirapine

et al. 2010

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Background In women, single-dose nevirapine for prophylaxis against mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) selects for nevirapine-resistant HIV-1, which subsequently decays rapidly. We hypothesized that the selection, acquisition, and decay of nevirapine-resistant HIV-1 differs in infants, varying by the timing of HIV-1 infection. Methods We conducted a prospective, observational study of 740 Mozambican infants receiving single-dose nevirapine prophylaxis and determined the timing of infection and concentrations of nevirapine-resistant HIV-1 over time. Results Infants with established in utero infection had a high rate (87.0%) of selection of nevirapine-resistant HIV-1 mutants, which rapidly decayed to undetectable levels. The few without nevirapine resistance received zidovudine with single-dose nevirapine and/or their mothers took alternative antiretroviral drugs. Infants with acute in utero infection had a lower rate of nevirapine-resistant HIV-1 (33.3%; P =.006, compared with established in utero infection), but mutants persisted over time. Infants with peripartum infection also had a lower rate of nevirapine-resistant HIV-1 (38.1%; P =.001, compared with established in utero infection) but often acquired 100% mutant virus that persisted over time (P =.017, compared with established in utero infection). Conclusions The detection and persistence of nevirapine-resistant HIV-1 in infants after single-dose nevirapine therapy vary by the timing of infection and the antiretroviral regimen. In infants with persistent high-level nevirapine-resistant HIV-1, nevirapine-based antiretroviral therapy is unlikely to ever be efficacious because of concentrations in long-lived viral reservoirs. However, the absence or decay of nevirapine-resistant HIV-1 in many infants suggests that nevirapine antiretroviral therapy may be effective if testing can identify these individuals.

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“…The presence of BC recombinants in Indian HIV-1 infected adult patients has been recently observed [ 23 , 24 ], hence, emphasis should be on early subtyping in HIV-1 infected children, for the design of appropriate prevention strategies. There is an enhanced need for an early drug resistance genotyping in infants born to mothers who received suboptimal antiretroviral prophylaxis; due to the plausible vertical transmission of the drug resistant HIV-1 [ 25 ]. Limited information is available so far on the HIV-1 drug resistance in children from India and most of these are addressed in children on single dose drug therapy.…”

Section: Discussionmentioning

confidence: 99%

Mutations in the Reverse Transcriptase and Protease Genes of Human Immunodeficiency Virus-1 from Antiretroviral Naïve and Treated Pediatric Patients

Bure

Makhdoomi

Lodha³

et al. 2015

Viruses

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The success of highly active antiretroviral therapy (HAART) is challenged by the emergence of resistance-associated mutations in human immunodeficiency virus-1 (HIV-1). In this study, resistance associated mutations in the reverse transcriptase (RT) and protease (PR) genes in antiretroviral therapy (ART) naïve and treated HIV-1 infected pediatric patients from North India were evaluated. Genotyping was successfully performed in 46 patients (30 ART naive and 16 treated) for the RT gene and in 53 patients (27 ART naive and 26 treated) for PR gene and mutations were identified using Stanford HIV Drug Resistance Database. A major drug resistant mutation in RT gene, L74I (NRTI), and two such mutations, K101E and G190A (NNRTI), were observed in two ART naïve patients, while M184V was detected in two ART treated patients. Overall, major resistance associated mutations in RT gene were observed in nine (30%) and seven (36%) of ART naïve and treated children respectively. Minor mutations were identified in PR gene in five children. Few non-clade C viral strains (≈30%) were detected, although subtype C was most predominant. The screening of ART naïve children for mutations in HIV-1 RT and protease genes, before and after initiation of ART is desirable for drug efficacy and good prognosis.

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Perinatal acquisition of drug-resistant HIV-1 infection: mechanisms and long-term outcome

Abstract: Background: Primary-HIV-1-infection in newborns that occurs under antiretroviral prophylaxis that is a high risk of drug-resistance acquisition. We examine the frequency and the mechanisms of resistance acquisition at the time of infection in newborns.

Cited by 26 publications

References 37 publications

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

Nevirapine Resistance by Timing of HIV Type 1 Infection in Infants Treated with Single‐Dose Nevirapine

Mutations in the Reverse Transcriptase and Protease Genes of Human Immunodeficiency Virus-1 from Antiretroviral Naïve and Treated Pediatric Patients

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