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High rates of virological failure and drug resistance in perinatally HIV-1-infected children and adolescents receiving lifelong antiretroviral therapy in routine clinics in Togo.

ABSTRACT: INTRODUCTION:Antiretroviral treatment (ART) has been scaled up over the last decade but compared to adults, children living with HIV are less likely to receive ART. Moreover, children and adolescents are more vulnerable than adults to virological failure (VF) and emergence of drug resistance. In this study we determined virological outcome in perinatally HIV-1-infected children and adolescents receiving ART in Togo. METHODS:HIV viral load (VL) testing was consecutively proposed to all children and adolescents who were on ART for at least 12 months when attending HIV healthcare services for their routine follow-up visit (June to September 2014). Plasma HIV-1 VL was measured using the m2000 RealTime HIV-1 assay (Abbott Molecular, Des Plaines, IL, USA). Genotypic drug resistance was done for all samples with VL>1000 copies/ml. RESULTS AND DISCUSSION:Among 283 perinatally HIV-1-infected children and adolescents included, 167 (59%) were adolescents and 116 (41%) were children. The median duration on ART was 48 months (interquartile range: 28 to 68 months). For 228 (80.6%), the current ART combination consisted of two nucleoside reverse transcriptase inhibitors (NRTIs) (zidovudine and lamivudine) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) (nevirapine or efavirenz). Only 28 (9.9%) were on a protease inhibitor (PI)-based regimen. VL was below the detection limit (i.e. 40 copies/ml) for 102 (36%), between 40 and 1000 copies/ml for 35 (12.4%) and above 1000 copies/ml for 146 (51.6%). Genotypic drug-resistance testing was successful for 125/146 (85.6%); 110/125 (88.0%) were resistant to both NRTIs and NNRTIs, 1/125 (0.8%) to NRTIs only, 4/125 (3.2%) to NNRTIs only and three harboured viruses resistant to reverse transcriptase and PIs. Overall, 86% (108/125) of children and adolescents experiencing VF and successfully genotyped, corresponding thus to at least 38% of the study population, had either no effective ART or had only a single effective drug in their current ART regimen. CONCLUSIONS:Our study provided important information on virological outcome on lifelong ART in perinatally HIV-1-infected children and adolescents who were still on ART and continued to attend antiretroviral (ARV) clinics for follow-up visits. Actual conditions for scaling up and monitoring lifelong ART in children in resource-limited countries can have dramatic long-term outcomes and illustrate that paediatric ART receives inadequate attention.

SUBMITTER: Salou M

PROVIDER: S-EPMC4850147 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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High rates of virological failure and drug resistance in perinatally HIV-1-infected children and adolescents receiving lifelong antiretroviral therapy in routine clinics in Togo.

Salou Mounerou M Dagnra Anoumou Y AY Butel Christelle C Vidal Nicole N Serrano Laetitia L Takassi Elom E Konou Abla A AA Houndenou Spero S Dapam Nina N Singo-Tokofaï Assetina A Pitche Palokinam P Atakouma Yao Y Prince-David Mireille M Delaporte Eric E Peeters Martine M

Journal of the International AIDS Society 20160427 1

<h4>Introduction</h4>Antiretroviral treatment (ART) has been scaled up over the last decade but compared to adults, children living with HIV are less likely to receive ART. Moreover, children and adolescents are more vulnerable than adults to virological failure (VF) and emergence of drug resistance. In this study we determined virological outcome in perinatally HIV-1-infected children and adolescents receiving ART in Togo.<h4>Methods</h4>HIV viral load (VL) testing was consecutively proposed to ...[more]

PMID: 27125320

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Project description:To assess and compare the prevalence of persistent hepatic abnormalities, including nonalcoholic fatty liver disease (NAFLD) and/or hepatic fibrosis, among perinatally HIV-monoinfected Asian adolescents with history of abnormal hepatic enzymes to those without, using noninvasive diagnostic tools. A multicenter cohort study was conducted in Thailand and Indonesia. Adolescents aged 10-25 years who were on antiretroviral treatment (ART), had virologic suppression (HIV RNA<400 copies/mL within the past 6 months), and had no history of chronic hepatitis B/C infection were enrolled. Participants were pre-classified into 2 subgroups (1:1 ratio) as participants with history of elevated versus normal aminotransferase enzymes. NAFLD was defined as hepatic steatosis (any severity) evaluated by liver ultrasonography. Significant hepatic fibrosis was defined as liver stiffness ?7.4 kPa evaluated by transient elastography. Participants who met the criteria for protocol-defined NAFLD and/or hepatic fibrosis were re-assessed to evaluate disease progression (persistent versus transient hepatic abnormalities) at one year later. Of 120 participants, 62 (51.7%) were male, 7 (5.8%) had central obesity, and 19 (15.8%) had insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR] >3.16). At enrollment, the median age and duration of ART (IQR) were 17.0 (14.6-19.2) years and 10.5 (7.1-12.0) years, respectively. Persistent hepatic abnormalities were identified in 5/60 participants listed in the group having history of elevated aminotransferases, corresponding to the prevalence of 8.3% (95% CI: 2.8-18.4%), whereas none (0/60) were among the group having history of normal hepatic enzymes. All 5 participants had persistent aminotransferase elevation (?2 episodes within the past 12 months). Baseline alanine aminotransferase (ALT) >30 U/L (adjusted odds ratio [aOR]: 29.1; 95% CI: 1.7-511.8), and HOMA-IR >3.16 (aOR: 17.9; 95% CI: 1.1-289.7) were independently associated with persistent hepatic abnormalities. Among perinatally HIV-monoinfected Asian adolescents with history of elevated aminotransferase enzymes, persistent hepatic abnormalities are not uncommon. Screening for liver complications by noninvasive diagnostic tools might be considered in at risk individuals, including those with persistent ALT elevation and insulin resistance.

Project description:IntroductionThe potential impact of socio-economic condition on virological suppression during antiretroviral treatment (ART) in sub-Saharan Africa is largely unknown. In this case-control study, we compared socio-economic factors among Ethiopian ART recipients with lack of virological suppression to those with undetectable viral load (VL).MethodsCases (VL>1000 copies/ml) and controls (VL<150 copies/ml) aged ≥15years, with ART for >6 months and with available VL results within the last 3 months, were identified from registries at public ART clinics in Central Ethiopia. Questionnaire-based interviews on socio-economic characteristics, health condition and transmission risk behavior were conducted. Univariate variables associated with VL>1000 copies/ml (p<0.25) were added to a multivariable logistic regression model.ResultsAmong 307 participants (155 cases, 152 controls), 61.2% were female, and the median age was 38 years (IQR 32-46). Median HIV-RNA load among cases was 6,904 copies/ml (IQR 2,843-26,789). Compared to controls, cases were younger (median 36 vs. 39 years; p = 0.004), more likely to be male (46.5% vs. 30.9%; p = 0.005) and had lower pre-ART CD4 cell counts (170 vs. 220 cells/μl; p = 0.009). In multivariable analysis of urban residents (94.8%), VL>1000 copies/ml was associated with lower relative wealth (adjusted odds ratio [aOR] 2.98; 95% CI 1.49-5.94; p = 0.016), geographic work mobility (aOR 6.27, 95% CI 1.82-21.6; p = 0.016), younger age (aOR 0.94 [year], 95% CI 0.91-0.98; p = 0.011), longer duration of ART (aOR 1.19 [year], 95% CI 1.07-1.33; p = 0.020), and suboptimal (aOR 3.83, 95% CI 1.33-10.2; p = 0.048) or poor self-perceived wellbeing (aOR 9.75, 95% CI 2.85-33.4; p = 0.012), after correction for multiple comparisons. High-risk sexual behavior and substance use was not associated with lack of virological suppression.ConclusionGeographic work mobility and lower relative wealth were associated with lack of virological suppression among Ethiopian ART recipients in this predominantly urban population. These characteristics indicate increased risk of treatment failure and the need for targeted interventions for persons with these risk factors.

Project description:BackgroundExisting studies have suggested decreased adherence and rebound in mortality in perinatally HIV-infected adolescents receiving antiretroviral therapy (ART) as compared to adults and young children.MethodsWe used both quantitative and qualitative approaches to identify factors influencing adherence among perinatally infected adolescents in Thailand. We analyzed data from 568 pairs of perinatally infected adolescents (aged 12-19) and their primary caregivers in the Teens Living With Antiretrovirals (TEEWA) study, a cross-sectional survey conducted in 2010-2012. We also conducted 12 in-depth interviews in 2014 with infected adolescents or their primary caregivers to elicit experiences of living with long-term ART.ResultsFrom the quantitative analysis, a total of 275 (48.4%) adolescents had evidence of suboptimal adherence based on this composite outcome: adolescents self-reported missing doses in the past 7 days, caregiver rating of overall adherence as suboptimal, or latest HIV-RNA viral load ≥1000 copies/ml. In multivariate logistic regression analysis, younger age, having grandparents or extended family members as the primary caregiver, caregiver-assessed poor intellectual ability, having a boy/girlfriend, frequent online chatting, self-reported unhappiness and easiness in asking doctors questions were significantly associated with suboptimal adherence. From the in-depth interviews, tensed relationships with caregivers, forgetfulness due to busy schedules, and fear of disclosing HIV status to others, especially boy/girlfriends, were important contributors to suboptimal adherence. Social and emotional support and counseling from peer group was consistently reported as a strong adherence-promoting factor.ConclusionOur findings highlight unique barriers of ART adherence among the perinatally infected adolescents. Future interventions should be targeted at helping adolescents to improve interpersonal relationships and build adaptive skills in recognizing and addressing challenging situations related to ART taking.

Project description:ObjectivesThe aim of the study was to determine the time to, and risk factors for, triple-class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection.MethodsWe analysed individual patient data from cohorts in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). A total of 5972 participants starting antiretroviral therapy (ART) from 1998, aged < 20 years at the start of ART for those with perinatal infection and 15-29 years for those with heterosexual infection, with ART containing at least two nucleoside reverse transcriptase inhibitors (NRTIs) and a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (bPI), were followed from ART initiation until the most recent viral load (VL) measurement. Virological failure of a drug was defined as VL > 500 HIV-1 RNA copies/mL despite ≥ 4 months of use. TCVF was defined as cumulative failure of two NRTIs, an NNRTI and a bPI.ResultsThe median number of weeks between diagnosis and the start of ART was higher in participants with perinatal HIV infection compared with participants with heterosexually acquired HIV infection overall [17 (interquartile range (IQR) 4-111) vs. 8 (IQR 2-38) weeks, respectively], and highest in perinatally infected participants aged 10-14 years [49 (IQR 9-267) weeks]. The cumulative proportion with TCVF 5 years after starting ART was 9.6% [95% confidence interval (CI) 7.0-12.3%] in participants with perinatally acquired infection and 4.7% (95% CI 3.9-5.5%) in participants with heterosexually acquired infection, and highest in perinatally infected participants aged 10-14 years when starting ART (27.7%; 95% CI 13.2-42.1%). Across all participants, significant predictors of TCVF were those with perinatal HIV aged 10-14 years, African origin, pre-ART AIDS, NNRTI-based initial regimens, higher pre-ART viral load and lower pre-ART CD4.ConclusionsThe results suggest a beneficial effect of starting ART before adolescence, and starting young people on boosted PIs, to maximize treatment response during this transitional stage of development.

Dataset Information

High rates of virological failure and drug resistance in perinatally HIV-1-infected children and adolescents receiving lifelong antiretroviral therapy in routine clinics in Togo.

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High rates of virological failure and drug resistance in perinatally HIV-1-infected children and adolescents receiving lifelong antiretroviral therapy in routine clinics in Togo.

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