Risk of Extended Viral Resistance in Human Immunodeficiency Virus-1-Infected Mozambican Children After First-Line Treatment Failure

Chaix, Marie‐Laure; Jani, Ilesh; Macassa, Eugenia; Bila, Dulce; Vubil, Adolfo; Anderson, Soren; Rouzioux, Christine; Briand, Nelly; Blanche, Stéphane

doi:10.1097/inf.0b013e3181ba6c92

Cited by 20 publications

(21 citation statements)

References 31 publications

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“…31,32 Although there was a limited number of inclusions in the present series of children receiving a second-or third-line regimen, the rate of virological success was very low, with only 27% of children exhibiting an undetectable plasma viral load. In contrast, virological failure and NRTI-or NNRTIresistance mutations (even after excluding the M184V mutation) were much greater in children under a second-/ third-line treatment than in those under a first-line regimen.…”

Section: Discussionmentioning

confidence: 76%

Virological Response and Resistance Profiles After 18 to 30 Months of First- or Second-/Third-Line Antiretroviral Treatment: A Cross-Sectional Evaluation in HIV Type 1-Infected Children Living in the Central African Republic

Charpentier

Gody

Mbitikon

et al. 2012

AIDS Research and Human Retroviruses

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A total of 242 HIV-1-infected children were followed up at the Complexe Pédiatrique of Bangui, Central African Republic, including 165 receiving antiretroviral treatment in first- (n=150) or second-/third-line (n=15) regimens. They were prospectively included in a study, in 2009, to assess their virological status and prevalence of antiretroviral drug-resistance mutations in cases of virological failure, according to revised 2010 WHO criteria (e.g., HIV-1 RNA >3.7 log(10) copies/ml). Detectable plasma HIV-1 RNA was observed in 53% of children under first-line treatment, and virological failure was diagnosed in 40%, which was associated in 85% of cases with viruses harboring at least one drug-resistance mutation to nucleoside reverse transcriptase inhibitors (NRTI) or nonnucleoside reverse transcriptase inhibitors (NNRTI), and in 36% of cases with at least one major drug-resistance mutation to NRTI or NNRTI when excluding the M184V mutation. Overall, the proportion of children receiving a first-line regimen for a median of 18 months with virological failure associated with drug-resistance mutations, and thus eligible for a second-line treatment, was estimated at 34% of the whole cohort. In children under second-/third-line therapy, virological failure occurred in 47%, plus at least one major drug-resistance mutation to NRTI or NNRTI, though less commonly to protease inhibitors. Taken together, these findings argue in favor of the urgent need to improve distribution of pediatric antiretroviral drugs in the Central African Republic, to increase adherence by treated children, and to offer adequate HIV biological monitoring.

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Section: Discussionmentioning

confidence: 76%

Virological Response and Resistance Profiles After 18 to 30 Months of First- or Second-/Third-Line Antiretroviral Treatment: A Cross-Sectional Evaluation in HIV Type 1-Infected Children Living in the Central African Republic

Charpentier

Gody

Mbitikon

et al. 2012

AIDS Research and Human Retroviruses

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“…[9] Finally, several studies have reported on the outcome of antiretroviral treatment in children in Africa, but only a few reports are available on long-term outcomes and in adolescents. [19,23–25,35,37,39,40] …”

Section: Introductionmentioning

confidence: 99%

High levels of virological failure with major genotypic resistance mutations in HIV-1-infected children after 5 years of care according to WHO-recommended 1st-line and 2nd-line antiretroviral regimens in the Central African Republic

et al. 2017

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A large cohort of 220 HIV-1-infected children (median [range] age: 12 [4–17] years) was cared and followed up in the Central African Republic, including 198 in 1st-line and 22 in 2nd-line antiretroviral regimens. Patients were monitored clinically and biologically for HIV-1 RNA load and drug resistance mutations (DRMs) genotyping. A total of 87 (40%) study children were virological responders and 133 (60%) nonresponders. In children with detectable viral load, the majority (129; 97%) represented a virological failure. In children receiving 1st-line regimens in virological failure for whom genotypic resistance test was available, 45% displayed viruses harboring at least 1 DRM to NNRTI or NRTI, and 26% showed at least 1 major DRM to NNRTI or NRTI; more than half of children in 1st-line regimens were resistant to 1st-generation NNRTI and 24% of the children in 1st-line regimens had a major DRMs to PI. Virological failure and selection of DRMs were both associated with poor adherence. These observations demonstrate high rate of virological failure after 3 to 5 years of 1st-line or 2nd-line antiretroviral treatment, which is generally associated with DRMs and therapeutic failure. Overall, more than half (55%) of children receiving 1st-line antiretroviral treatment for a median of 3.4 years showed virological failure and antiretroviral-resistance and thus eligible to 2nd-line treatment. Furthermore, two-third (64%) of children under 2nd-line therapy were eligible to 3rd-line regimen. Taken together, these observations point the necessity to monitor antiretroviral-treated children by plasma HIV-1 RNA load to diagnose as early as possible the therapeutic failure and operate switch to a new therapeutic line.

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“…Moreover, specific resistance mutations have been described for non-B subtype viruses. In particular, the child harbouring a C subtype, who was initially treated in Mozambique with suboptimal control of HIV-1 replication because of limited access to antiretrovirals [10], did not respond to etravirine. The recently described E138A mutation, along with an accumulation of baseline resistance mutations observed in our patient, might have compromised susceptibility to etravirine in patients with non-B subtypes [11].…”

Section: Betweenmentioning

confidence: 99%

Etravirine-based highly active antiretroviral therapy in HIV-1-infected paediatric patients

et al. 2011

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We evaluated the efficacy, safety and tolerability of etravirine in paediatric patients vertically infected with HIV-1. MethodsA multicentre retrospective study of 23 multidrug-resistant paediatric patients (five children and 18 adolescents) enrolled in the study from 1 September 2007 to 28 February 2010 was carried out. We performed a longitudinal analysis of immunological, virological and clinical data. ResultsThe median age of the patients was 14.2 years [interquartile range (IQR) 12.5-15.8 years]. At baseline, the median HIV-1 RNA was 29 000 (4.5 log 10 ) HIV-1 RNA copies/mL (range 4300-83 000 copies/mL), the median CD4 T-cell count was 445 cells/mL (range 221-655 cells/mL) and the median CD4 percentage was 19.6% (IQR 13.0-31.0). Remarkably, 16 of 23 patients (70%) harboured one or more etravirineassociated resistance mutations. The backbone regimen included at least two fully active drugs in 91% of patients. After etravirine-based therapy, 20 patients (87%) achieved HIV-1 RNAo400 copies/mL and 18 of 23 (78%) achieved HIV-1 RNAo50 copies/mL: three (13%) within the first month, seven (30%) within the first 4 months, and six (26%) between the 5th and 8th months. CD4 T-cell recovery was observed in 19 patients (83%). The median follow-up time was 48.4 weeks .4 weeks); four patients (17%) were exposed to etravirine for 4120 weeks. Three mild/short-term and two moderate skin rashes were observed in the adolescents. Laboratory abnormalities included hypercholesterolaemia (11 of 23 patients), hypertriglyceridaemia (eight of 23 patients), and reduced high-density lipoprotein cholesterol (10 of 23 patients). Adherence was complete in seven patients (30%). No patients showed complete resistance to etravirine after follow-up. However, three of 21 patients (14%) who initially showed intermediate resistance interrupted etravirine treatment because of virological failure. ConclusionsWe observed a sustained antiviral response and improved immunological parameters in multidrugresistant paediatric patients, most of whom had received etravirine as part of salvage regimens with at least two fully active drugs.

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Risk of Extended Viral Resistance in Human Immunodeficiency Virus-1-Infected Mozambican Children After First-Line Treatment Failure

Cited by 20 publications

References 31 publications

Virological Response and Resistance Profiles After 18 to 30 Months of First- or Second-/Third-Line Antiretroviral Treatment: A Cross-Sectional Evaluation in HIV Type 1-Infected Children Living in the Central African Republic

Virological Response and Resistance Profiles After 18 to 30 Months of First- or Second-/Third-Line Antiretroviral Treatment: A Cross-Sectional Evaluation in HIV Type 1-Infected Children Living in the Central African Republic

High levels of virological failure with major genotypic resistance mutations in HIV-1-infected children after 5 years of care according to WHO-recommended 1st-line and 2nd-line antiretroviral regimens in the Central African Republic

Etravirine-based highly active antiretroviral therapy in HIV-1-infected paediatric patients

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