Long-term virological outcome in children receiving first-line antiretroviral therapy (original) (raw)
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Long-term virological outcome in children on antiretroviral therapy in the UK and Ireland
AIDS, 2014
on behalf of the Collaborative HIV Paediatric Study Steering Committee Objective: To assess factors at the start of antiretroviral therapy (ART) associated with long-term virological response in children. Design: Multicentre national cohort. Methods: Factors associated with viral load below 400 copies/ml by 12 months and virologic failure among children starting 3/4-drug ART in the UK/Irish Collaborative HIV Paediatric Study were assessed using Poisson models. Results: Nine hundred and ninety-seven children started ART at a median age of 7.7 years (inter-quartile range 2.9-11.7), 251 (25%) below 3 years: 411 (41%) with efavirenz and two nucleoside reverse transcriptase inhibitors (EFV þ 2NRTIs), 264 (26%) with nevirapine and two NRTIs (NVP þ 2NRTIs), 119 (12%; 106 NVP, 13 EFV) with non-nucleoside reverse transcriptase inhibitor and three NRTIs (NNRTI þ 3NRTIs), and 203 (20%) with boosted protease inhibitor-based regimens. Median follow-up after ART initiation was 5.7 (3.0-8.8) years. Viral load was less than 400 copies/ml by 12 months in 92% [95% confidence interval (CI) 91-94%] of the children. Time to suppression was similar across regimens (P ¼ 0.10), but faster over calendar time, with older age and lower baseline viral load. Three hundred and thirtynine (34%) children experienced virological failure. Although progression to failure varied by regimen (P < 0.001) and was fastest for NVP þ 2NRTIs regimens, risk after 2 years on therapy was similar for EFV þ 2NRTIs and NVP þ 2NRTIs, and lowest for NNRTI þ 3NRTIs regimens (P-interaction ¼ 0.03). Older age, earlier calendar periods and maternal ART exposure were associated with increased failure risk. Early treatment discontinuation for toxicity occurred more frequently for NVP-based regimens, but 5-year cumulative incidence was similar: 6.1% (95% CI 3.9-8.9%) NVP, 8.3% (95% CI 5.6-11.6) EFV, and 9.8% (95% CI 5.7-15.3%) protease inhibitor-based regimens (P ¼ 0.48). Conclusion: Viral load suppression by 12 months was high with all regimens. NVP þ 3NRTIs regimens were particularly efficacious in the longer term and may be a good alternative to protease inhibitor-based ART in young children.
2020
Background: Many HIV-infected African children gained access to antiretroviral treatment (ART) through expansion of PEPFAR programs since 2004 and introduction of "Test and Treat" WHO guidelines in 2015. As ART access increases and children transition from adolescence to adulthood, treatment failure is inevitable. Viral load (VL) monitoring in Uganda was introduced in 2016 replacing clinical monitoring. However, there's limited data on the comparative effectiveness of these two strategies among HIVinfected children in resource-limited settings (RLS). Methods: HIV-infected Ugandan children aged 1-12 years from HIV-care programs with >1 year of rst-line ART using only immunologic and clinical criteria to monitor response to treatment were screened in 2010. Eligible children were strati ed by VL ≤ 400 and >400 copies/ml randomized to clinical and immunological (control) versus clinical, immunological and VL monitoring to determine treatment failure with follow-up at 12, 24, 36, and 48 weeks. Plasma VL was analyzed retrospectively for controls. Mixedeffects logistic regression models were used to compare the prevalence of viral suppression between study arms and identify factors associated with viral suppression. Results: At baseline all children (n=142) were on NNRTI based ART (75% Nevirapine, 25% efavirenz). One third of ART-experienced children had detectable VL at baseline despite high CD4%. Median age was 6 years (interquartile range [IQR]: 5-9) and 43% were female. Overall, the odds of viral suppression were not different between study arms: (arm by week interaction, p=0.63), adjusted odds ratio [aOR]: 1.07; 95%CI: 0.53, 2.17, p=0.57) and did not change over time (aOR: 0 vs 24 week: 1.15; 95% CI: 0.91, 1.46, p=0.24 and 0 vs 48 weeks: 1.26; 95%CI: 0.92, 1.74, p=0.15). Longer duration of a child's ART exposure was associated with lower odds of viral suppression (aOR: 0.61; 95% CI: 0.42, 0.87, p<.01). Only 13% (9/71) of children with virologic failure were switched to second-line ART, in spite of access to real-time VL. Conclusion: With increasing ART exposure, viral load monitoring is critical for early detection of treatment failure in RLS. Clinicians need to make timely informed decisions to switch failing children to second-line ART.
Virologic, immunologic and clinical response of infants to antiretroviral therapy in Kampala, Uganda
BMC Pediatrics, 2013
Background: Antiretroviral therapy (ART) is known to save lives. Among HIV-infected infants living in resource constrained settings, the short and long term benefits of ART are only partially known. This study was designed to determine the virologic, immunologic and clinical outcomes of antiretroviral therapy in a cohort of HIV-infected infants receiving care from an outpatient clinic in Kampala, Uganda.
BMC Infectious Diseases, 2014
Background: In Tanzania, HIV-1 RNA testing is rarely available and not standard of care. Determining virologic failure is challenging and resistance mutations accumulate, thereby compromising second-line therapy. We evaluated durability of antiretroviral therapy (ART) and predictors of virologic failure among a pediatric cohort at four-year follow-up. Methods: This was a prospective cross-sectional study with retrospective chart review evaluating a perinatally HIV-infected Tanzanian cohort enrolled in 2008-09 with repeat HIV-1 RNA in 2012-13. Demographic, clinical, and laboratory data were extracted from charts, resistance mutations from 2008-9 were analyzed, and prospective HIV RNA was obtained. Results: 161 (78%) participants of the original cohort consented to repeat HIV RNA. The average age was 12.2 years (55% adolescents ≥12 years). Average time on ART was 6.4 years with 41% receiving second-line (protease inhibitor based) therapy. Among those originally suppressed on a first-line (non-nucleoside reverse transcriptase based regimen) 76% remained suppressed. Of those originally failing first-line, 88% were switched to second-line and 72% have suppressed virus. Increased level of viremia and duration of ART trended with an increased number of thymidine analogue mutations (TAMs). Increased TAMs increased the odds of virologic failure (p = 0.18), as did adolescent age (p < 0.01). Conclusions: After viral load testing in 2008-09 many participants switched to second-line therapy. The majority achieved virologic suppression despite multiple resistance mutations. Though virologic testing would likely hasten the switch to second-line among those failing, methods to improve adherence is critical to maximize durability of ART and improve virologic outcomes among youth in resource-limited settings.
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2014
Background-In the PROMOTE-pediatrics trial, HIV-infected Ugandan children randomized to receive lopinavir-ritonavir (LPV/r)-based antiretroviral therapy (ART) experienced a lower incidence of malaria compared to children receiving non-nucleoside-reverse-transcriptaseinhibitor (NNRTI)-based-ART. Here we present the results of the non-inferiority (NI) analysis of virologic efficacy and comparison of immunologic outcomes. Methods-ART-naïve or-experienced (HIV RNA < 400 copies/ml) children ages 2 months to 6 years received either LPV/r or NNRTI-based-ART. The proportion of children with virologic suppression (HIV RNA <400copies/ml) at 48 weeks was compared using a pre-specified NI margin of −11% in per-protocol analysis. Time to virologic failure by 96 weeks, change in CD4 counts and percentages, and incidence of adverse event rates were also compared. Results-Of 185 children enrolled, 91 initiated LPV/r and 92 initiated NNRTI-based ART. At baseline, the median age was 3.1 years (range: 0.4 to 5.9) and 131 (71%) were ART-naïve. The proportion of children with virologic suppression at 48 weeks was 80% (67/84) in the LPV/r-arm vs. 76% (59/78) in the NNRTI-arm, a difference of 4% (95%CI: −9% to +17%). Time to virologic failure, CD4 changes, and the incidence of DAIDS grade III/IV adverse events were similar between arms.
Clinico-immunological profile and outcome of antiretroviral therapy in HIV-positive children
Public Health Nutrition, 2012
Objectives: To study the clinico-immunological, nutritional and growth characteristics of HIV-infected children and the impact of antiretroviral therapy (ART) on these parameters. Design: Retrospective study. Setting: Out-patient department of a paediatric ART centre, Delhi, India. Subjects: HIV-positive children registered at the paediatric ART centre of the hospital were enrolled (n 130). Anthropometric measurements were used to classify children into the type of malnutrition according to definitions of the WHO and US Centers for Disease Control and Prevention. Clinical and immunological status of the children was recorded as per WHO guidelines. First-line ART was started based on guidelines of the National AIDS Control Organization. Nutritional status and clinico-immunological characteristics were followed up annually in children receiving ART. Results: Of children #5 years of age (n 54), stunting was noted in 42?5 % contrary to wasting seen in only 12?9 %. In children .5 years of age (n 76), short stature (40?7 %) and underweight (39?4 %) were seen in almost equal proportions. Asymptomatic presentation was noted in 60?0 %. Following ART, a reduction in wasting was noted in 75?0 % of children #5 years of age, whereas only 44?4 % of underweight children .5 years of age showed an improvement after therapy. Stunting and short stature continued to persist in all in children (#5 years and .5 years, respectively). Clinico-immunologically, 67?5 % improved in clinical status and 62?5 % showed immunological improvement.
Medicine, 2020
Sub-Saharan Africa has the vast majority (∼90%) of new pediatric acquired immunodeficiency syndrome cases worldwide. Biologically monitoring HIV-infected pediatric populations remains challenging. The differential interest of human immunodeficiency virus (HIV)-1 RNA loads and CD4 T-cell counts is debated for the treatment of pediatric acquired immunodeficiency syndrome patients. Long-term antiretroviral treatment (ART) outcomes regarding immunological and virological surrogate markers were longitudinally evaluated between 2009 and 2014 (over 57 months) in 245 perinatally HIV-1-infected children and adolescents born from HIVinfected mothers, treated at inclusion for at least 6 months by the World Health Organization-recommended ART in Bangui, Central African Republic. Patients were monitored over time biologically for CD4 T-cell counts, HIV-1 RNA loads, and drug resistance mutation genotyping. Children lost to follow-up totaled 6%. Four categories of immunovirological responses to ART were observed. At baseline, therapeutic success with sustained immunological and virological responses was observed in 80 (32.6%) children; immunological and virologic nonresponses occurred in 32 (13.0%) children; finally, the majority (133; 54.2%) of the remaining children showed discordant immunovirological responses. Among them, 33 (13.4%) children showed rapid virological responses to ART with an undetectable viral load, whereas immunological responses remained absent after 6 months of treatment and increased progressively