Prevalence and effect of pre-treatment drug resistance on the virological response to antiretroviral treatment initiated in HIV-infected children – a EuroCoord-CHAIN-EPPICC joint project

Abstract

BackgroundFew studies have evaluated the impact of pre-treatment drug resistance (PDR) on response to combination antiretroviral treatment (cART) in children. The objective of this joint EuroCoord-CHAIN-EPPICC/PENTA project was to assess the prevalence of PDR mutations and their association with virological outcome in the first year of cART in children.MethodsHIV-infected children <18 years initiating cART between 1998 and 2008 were included if having at least one genotypic resistance test prior to cART initiation. We used the World Health Organization 2009 resistance mutation list and Stanford algorithm to infer resistance to prescribed drugs. Time to virological failure (VF) was defined as the first of two consecutive HIV-RNA > 500 copies/mL after 6 months cART and was assessed by Cox proportional hazards models. All models were adjusted for baseline demographic, clinical, immunology and virology characteristics and calendar period of cART start and initial cART regimen.ResultsOf 476 children, 88 % were vertically infected. At cART initiation, median (interquartile range) age was 6.6 years (2.1–10.1), CD4 cell count 297 cells/mm3 (98–639), and HIV-RNA 5.2 log10copies/mL (4.7–5.7). Of 37 children (7.8 %, 95 % confidence interval (CI), 5.5–10.6) harboring a virus with ≥1 PDR mutations, 30 children had a virus resistant to ≥1 of the prescribed drugs. Overall, the cumulative Kaplan-Meier estimate for virological failure was 19.8 % (95 %CI, 16.4–23.9). Cumulative risk for VF tended to be higher among children harboring a virus with PDR and resistant to ≥1 drug prescribed than among those receiving fully active cART: 32.1 % (17.2–54.8) versus 19.4 % (15.9–23.6) (P = 0.095). In multivariable analysis, age was associated with a higher risk of VF with a 12 % reduced risk per additional year (HR 0.88; 95 %CI, 0.82–0.95; P < 0.001).ConclusionsPDR was not significantly associated with a higher risk of VF in children in the first year of cART. The risk of VF decreased by 12 % per additional year at treatment initiation which may be due to fading of PDR mutations over time. Lack of appropriate formulations, in particular for the younger age group, may be an important determinant of virological failure.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1968-2) contains supplementary material, which is available to authorized users.

Rates and Correlates of Short Term Virologic Response among Treatment-Naïve HIV-Infected Children Initiating Antiretroviral Therapy in Ethiopia: A Multi-Center Prospective Cohort Study

“…However, previous studied have reported conflicting results. Several African and multinational studies reported a positive association between PDR and virologic suppression while other studies and in contrast to other African and Asian studies reported the lack of any association between PDR and virological suppression [39,40]. Our study showed that, after adjusting for other baseline factors, presence of any PDR was associated with reduced rates of virological suppression.…”

“…The impact of PDR on virologic outcomes among newly-diagnosed HIV infected children is not well established in resource-limited settings [22,[36][37][38][39]. In theory, PDR could compromise the efficacy of first-line cART regimens, thereby reducing rates of virological suppression and increasing subsequent rates of virological treatment failure.…”

Incidence and predictors of treatment failure among children on first-line antiretroviral therapy in Amhara Region Referral Hospitals, northwest Ethiopia 2018: A retrospective study

“…Evidences showed that different predictors affect treatment failure. The most common predictors are age [7, 10–14], gender [10–12], being orphan [15], time from ART initiation [15], poor adherence to ART failure [10, 11, 16–18] [19], nevirapine (NVP)-based regimen [13, 20], drug side-effects, drug toxicity [10, 11, 16, 17], nutritional status [11], pretreatment CD4 count [1, 10, 11, 13, 14, 16, 19, 21], WHO clinical stage [9–11, 16, 19, 21] and tuberculosis co-infection [9, 19]. A previous study [22] does not address important predictor like repeated measurement for CD4 which this includes.…”

AIDS Therapy Evaluation in the Netherlands (ATHENA) national observational HIV cohort: cohort profile

“… 39 ATHENA collaborates with other research groups and observational cohorts in western Europe, the USA and Canada. Data sharing and collaboration has taken place or is ongoing with the Collaboration of Observational HIV Epidemiological Research Europe (COHERE), 40 EuroSIDA, 41 the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) 42 within the Paediatric European Network for the Treatment of AIDS (PENTA), the European Coordinating Committee for the Integration of Ongoing Coordination Actions Related to Clinical and Epidemiological HIV Research (EuroCoord); A Collaboration on HIV-2 infection (ACHI E V 2E ) 43 ; Antiretroviral Therapy Cohort Collaboration (ART-CC) 44 ; Data collection on Adverse events of anti-HIV Drugs (D:A:D) 45 ; HIV Cohorts Analysed Using Structural Approaches to Longitudinal data (HIV-CAUSAL) Collaboration 46 ; Bridging the Evolution and Epidemiology of HIV in Europe (BEEHIVE) 47 ; HIV Resistance Response Database Initiative (RDI) 48 49 ; and International epidemiology Databases to Evaluate AIDS (IeDEA). 50 …”