Extensive Drug Resistance in HIV-Infected Cambodian Children Who Are Undetected as Failing First-Line Antiretroviral Therapy by WHO 2010 Guidelines

Coetzer, Mia; Westley, Benjamin; DeLong, Allison; Tray, Chhraing S.; Sophearin, Dim; Nerrienet, Eric; Schreier, Leeann; Kantor, Rami

doi:10.1089/aid.2013.0025

Cited by 9 publications

(11 citation statements)

References 34 publications

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“…All naive patients harbored viruses that were resistant to NVP/EFV with a majority of them showing the K103N/S mutation. The rates of 181C/I, K103N/S G190A and M184L/V mutations were also higher than in another recent study in Cambodia among patients having a median duration of 12 months up to 4 years on antiretroviral therapy [6], [7], [30]. The level of transmitted drug resistance (TDR) in naive patients needs to be assessed and could explain the high level of resistance mutations for this population potentially more recently infected than pre-treated patients.…”

Section: Discussionmentioning

confidence: 82%

Virological Failure and HIV-1 Drug Resistance Mutations among Naive and Antiretroviral Pre-Treated Patients Entering the ESTHER Program of Calmette Hospital in Cambodia

et al. 2014

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IntroductionIn resource limited settings, patients entering an antiretroviral therapy (ART) program comprise ART naive and ART pre-treated patients who may show differential virological outcomes.MethodsThis retrospective study, conducted in 2010–2012 in the HIV clinic of Calmette Hospital located in Phnom Penh (Cambodia) assessed virological failure (VF) rates and patterns of drug resistance of naive and pre-treated patients. Naive and ART pre-treated patients were included when a Viral Load (VL) was performed during the first year of ART for naive subjects or at the first consultation for pre-treated individuals. Patients showing Virological failure (VF) (>1,000 copies/ml) underwent HIV DR genotyping testing. Interpretation of drug resistance mutations was done according to 2013 version 23 ANRS algorithms.ResultsOn a total of 209 patients, 164 (78.4%) were naive and 45 (21.5%) were ART pre-treated. Their median initial CD4 counts were 74 cells/mm3 (IQR: 30–194) and 279 cells/mm3 (IQR: 103–455) (p<0.001), respectively. Twenty seven patients (12.9%) exhibited VF (95% CI: 8.6–18.2%), including 10 naive (10/164, 6.0%) and 17 pre-treated (17/45, 37.8%) patients (p<0.001). Among these viremic patients, twenty-two (81.4%) were sequenced in reverse transcriptase and protease coding regions. Overall, 19 (86.3%) harbored ≥1 drug resistance mutations (DRMs) whereas 3 (all belonging to pre-treated patients) harbored wild-types viruses. The most frequent DRMs were M184V (86.3%), K103N (45.5%) and thymidine analog mutations (TAMs) (40.9%)Two (13.3%) pre-treated patients harbored viruses that showed a multi-nucleos(t)ide resistance including Q151M, K65R, E33A/D, E44A/D mutations.ConclusionIn Cambodia, VF rates were low for naive patients but the emergence of DRMs to NNRTI and 3TC occurred relatively quickly in this subgroup. In pre-treated patients, VF rates were much higher and TAMs were relatively common. HIV genotypic assays before ART initiation and for ART pre-treated patients infection should be considered as well.

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Section: Discussionmentioning

confidence: 82%

Virological Failure and HIV-1 Drug Resistance Mutations among Naive and Antiretroviral Pre-Treated Patients Entering the ESTHER Program of Calmette Hospital in Cambodia

et al. 2014

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“…At that time, reports about children’s ART chiefly expressed concerns about the challenges of detecting treatment failures using only immunological and clinical criteria [ 16 ]. Later, with the development of HIV genotypic resistance testing, high resistance mutations were reported in children with virological failure on first-line ART [ 17 , 18 ]. However this testing was not yet routinely available.…”

Section: Discussionmentioning

confidence: 99%

“…Based on the WHO 2010 pediatric guidelines, without routine viral load monitoring, treatment failure were misclassified for children on first-line therapy [ 16 , 17 ]. In addition, extensive drug resistance to first-line ART was described among 51 HIV-infected children, who were undetected as first-line ART failures under the WHO 2010 guidelines [ 18 ]. Similarly the HIV/Hepatitis laboratory of the Pasteur Institute in Cambodia reported the occurrence of mutations in children from routine samples collected between December 2004 and January 2011 [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Factors associated with the failure of first and second-line antiretroviral therapies therapy, a case control study in Cambodian HIV-1 infected children

Hubert

Virak²,

Raffi

et al. 2016

BMC Res Notes

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BackgroundLittle is known about the efficacy of first and and second-line antiretroviral therapies (ART) for HIV-1 infected children in resource limited Southeast Asian settings. Previous studies have shown that orphans are at a higher risk for virological failure (VF) in Cambodia. Consequently most of them required transfer to second-line ART. We assessed the factors associated with VF among HIV-1 infected children who were either under first-line (mostly 3TC + D4T + NVP) or under second-line (mostly ABC + DDI + LPV) therapies at a referral hospital in Cambodia.MethodsA case-control study was conducted from February to July 2013 at the National Pediatric Hospital among HIV-1 infected children (aged 1–15 years) under second-line ART (cases) or first-line (matched controls at a ratio of 1:3) regimens. Children were included if a HIV-1 RNA plasma viral load (VL) result was available for the preceding 12 months. A standardized questionnaire explored family sociodemographics, HIV history, and adherence to ART. Associations between VF (HIV-1 RNA levels ≥1000 copies/ml) and the children’s characteristics were assessed using bivariate and multivariate analyses.ResultsA total of 232 children, 175 (75.4 %) under first-line and 57 (24.6 %) under second-line ART, for a median of 72.0 (IQR: 68.0–76.0) months, were enrolled. Of them, 94 (40.5 %) were double orphans and 51 (22.0 %) single orphans, and 77 (33.2 %) were living in orphanages. A total of 222 children (95.6 %) were deemed adherent to ART. Overall, 18 (7.7 %; 95 % CI 4.6–11.9) showed a VF, 14 (8.6 %; 95 % CI 4.8–14.0) under first-line and 4 (7.0 %; 95 % CI 1.9–17.0) under second-line ART (p = 0.5). Their median CD4 percentage was 8 % (IQR 2.9–12.9) at ART initiation. Children under second-line ART were older; more often double orphans, and had lower CD4 cell counts at the last control.In the multivariate analysis, having the last CD4 percentage below 15 % was the only factor associated with VF for ART regimen separately or when combined (OR 40.4; 95 % CI 11–134).ConclusionsThe pattern of risk factors for VF in children is changing in Cambodia. Improved adherence evaluation and intensified monitoring of children with low CD4 counts is needed to decrease the risk of VF.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-016-1884-y) contains supplementary material, which is available to authorized users.

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“…Since the reported sensitivity of clinical/immunological monitoring in detecting treatment failure is low, 29 %-33 % [ 36 ], many of these children will continue to be on failing first-line regimens. Several studies have shown that delayed detection of virological failure to first-line therapy often leads to development of drug resistance, jeopardizing potential second-line treatments [ 11 , 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Viral load monitoring and antiretroviral treatment outcomes in a pediatric HIV cohort in Ghana

et al. 2015

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BackgroundHIV-infected children in sub-Saharan Africa may be at a high risk of staying on a failing first-line regimen and developing drug-resistance HIV variants due to lack of routine viral load monitoring. We investigated whether cumulative viral load, measured as viremia copy-years (VCY) could predict morbidity in a setting where viral load is not routinely monitored.MethodsThis was a single-center prospective observational longitudinal study of HIV-infected children initiating antiretroviral therapy (ART) at the Pediatric HIV/AIDS Care program at Korle-Bu Teaching Hospital in Accra, Ghana. The main outcome was morbidity measured as frequency of hospitalizations, opportunistic infections, and outpatient sick visits. The main explanatory variable was viral load measured as VCY.ResultsThe study included 140 children who initiated ART between September 2009 and May 2013 and had at least 2 viral load measurements. There were 184 hospitalizations, with pneumonia being the most common cause (22.8 %). A total of 102 opportunistic infections was documented, with tuberculosis being the most common opportunistic infection (68 %). A total of 823 outpatient sick visits was documented, with upper respiratory infections (14.2 %) being the most common cause. Forty-four percent of our study participants had >4 log10 VCY. Children in this sub-cohort had a higher frequency of sick visits compared with those with <4 log10 VCY (p = 0.03). Only 6.5 % of children with >4 log10 VCY had been identified as treatment failure using WHO clinical and immunological treatment failure criteria.ConclusionsHigh level of cumulative viral load may translate to virological failure and subsequent increased all-cause morbidity. Our finding of potential utility of VCY in pediatrics warrants further investigations. VCY may be a good alternate to routine viral load measurement as its determination may be less frequent and could be personalized to save cost.

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Extensive Drug Resistance in HIV-Infected Cambodian Children Who Are Undetected as Failing First-Line Antiretroviral Therapy by WHO 2010 Guidelines

Cited by 9 publications

References 34 publications

Virological Failure and HIV-1 Drug Resistance Mutations among Naive and Antiretroviral Pre-Treated Patients Entering the ESTHER Program of Calmette Hospital in Cambodia

Virological Failure and HIV-1 Drug Resistance Mutations among Naive and Antiretroviral Pre-Treated Patients Entering the ESTHER Program of Calmette Hospital in Cambodia

Factors associated with the failure of first and second-line antiretroviral therapies therapy, a case control study in Cambodian HIV-1 infected children

Viral load monitoring and antiretroviral treatment outcomes in a pediatric HIV cohort in Ghana

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