Antiretroviral Treatment In HIV-infected Children Research Articles

Plasma metabolomic study in perinatally HIV-infected children using 1H NMR spectroscopy reveals perturbed metabolites that sustain during therapy.

BackgroundPerinatally HIV-infected children on anti-retroviral treatment (ART) are reported to have metabolic abnormalities such as dyslipidemia, lipodystrophy, and insulin resistance which potentially increase the risk of diabetes, kidney, liver and cardiovascular disease.ObjectiveTo elucidate HIV-mediated metabolic complications that sustain even during ART in perinatally HIV-infected children.MethodWe have carried out metabolic profiling of the plasma of treatment-naïve and ART-suppressed perinatally HIV-infected children and uninfected controls using 1H nuclear magnetic resonance (NMR) spectroscopy followed by statistical analysis and annotation.ResultValidated multivariate analysis showed clear distinction among our study groups. Our results showed elevated levels of lactate, glucose, phosphoenolpyruvic acid, propionic acid, 2-ketobutyric acid and tricarboxylic acid (TCA) cycle metabolites in untreated HIV-infected children compared to uninfected controls. ART normalized the levels of several metabolites, however the level of lactate, phosphoenolpyruvic acid, oxoglutaric acid, oxaloacetic acid, myoinositol and glutamine remained upregulated despite ART in HIV-infected children. Pathway analysis revealed perturbed propanoate metabolism, amino acid metabolism, glycolysis and TCA cycle in untreated and ART-suppressed HIV-infected children.ConclusionDeveloping therapeutic strategies targeting metabolic abnormalities may be beneficial for preventing diabetes, cardiovascular disease or other associated complications in perinatally HIV-infected children.

Escalating and sustained immunovirological dissociation among antiretroviral drug-experienced perinatally human immunodeficiency virus-1-infected children and adolescents living in the Central African Republic: A STROBE-compliant study.

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 HIV-infected 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 over time in most of the cases, suggesting slow immunorestoration. Notably, nearly half of the children (40.8% at baseline and 48.2% at follow-up) harbored discordant immunovirological responses with a paradoxically high CD4 T-cell count and HIV-1 RNA load, which are always associated with high levels of drug resistance mutations. The latter category showed a significant increase over time, with a growth rate of 1.23% per year of follow-up.Our STROBE-compliant study demonstrates the high heterogeneity of biological responses under ART in children with frequent passage from 1 category to another over time. Close biological evaluation with access to routine plasma HIV-1 RNA load monitoring is crucial for adapting the complex outcomes of ART in HIV-infected children born from infected mothers.

Utility of Mobile Communication Devices as a Tool to Improve Adherence to Antiretroviral Treatment in HIV-infected Children and Young Adults in Argentina.

Optimal adherence is critical to achieve the benefits of antiretroviral treatment (ART). The aim of the study is to evaluate the use of mobile devices as a strategy to improve adherence to ART, measured by viral load (VL) in HIV+ patients less than 25 years of age. A prospective study was conducted in a cohort of HIV+ patients less than 25 years of age. HIV+ patients, on ART, VL >1000 copies/mL, using mobile devices and suboptimal adherence were included. The intervention was based on a mobile generic contact twice a month using text message and Facebook during 32 weeks. Extended communications were generated by the patient. VL was performed before and after the intervention. Twenty-five patients were included. Three were excluded and 22 patients were enrolled. Mean age was 17.2 ± 6.1 years (range: 6-25); 15 (68%) were female; mean baseline VL was 25,100 copies/mL (range: 1020-500,000 copies/mL), mean log was 4.3 (range: 3-5.7 log). Each participant received a total of 16 contacts; 84% (296) were answered by the patient and 54% (189) of the contacts generated extended communications. After the strategy implementation, 20/22 VL results were available: 13/20 (65%) were undetectable, 14/20 (70%) had VL < 1000 copies/mL and 6/20 (30%) VLs had no changes. The use of mobile devices and social networks is a valid tool to improve ART adherence in HIV+ pediatric and young adults, evaluated through VL. The strategy is feasible. The reminder messages trigger additional communications between patients and health provider and better engagement with HIV care. Longer follow-up time is needed.

Multicentre analysis of second-line antiretroviral treatment in HIV-infected children: adolescents at high risk of failure.

Introduction: The number of HIV-infected children and adolescents requiring second-line antiretroviral treatment (ART) is increasing in low- and middle-income countries (LMIC). However, the effectiveness of paediatric second-line ART and potential risk factors for virologic failure are poorly characterized. We performed an aggregate analysis of second-line ART outcomes for children and assessed the need for paediatric third-line ART. Methods: We performed a multicentre analysis by systematically reviewing the literature to identify cohorts of children and adolescents receiving second-line ART in LMIC, contacting the corresponding study groups and including patient-level data on virologic and clinical outcomes. Kaplan–Meier survival estimates and Cox proportional hazard models were used to describe cumulative rates and predictors of virologic failure. Virologic failure was defined as two consecutive viral load measurements >1000 copies/ml after at least six months of second-line treatment. Results: We included 12 cohorts representing 928 children on second-line protease inhibitor (PI)-based ART in 14 countries in Asia and sub-Saharan Africa. After 24 months, 16.4% (95% confidence interval (CI): 13.9–19.4) of children experienced virologic failure. Adolescents (10–18 years) had failure rates of 14.5 (95% CI 11.9–17.6) per 100 person-years compared to 4.5 (95% CI 3.4–5.8) for younger children (3–9 years). Risk factors for virologic failure were adolescence (adjusted hazard ratio [aHR] 3.93, p < 0.001) and short duration of first-line ART before treatment switch (aHR 0.64 and 0.53, p = 0.008, for 24–48 months and >48 months, respectively, compared to <24 months). Conclusions: In LMIC, paediatric PI-based second-line ART was associated with relatively low virologic failure rates. However, adolescents showed exceptionally poor virologic outcomes in LMIC, and optimizing their HIV care requires urgent attention. In addition, 16% of children and adolescents failed PI-based treatment and will require integrase inhibitors to construct salvage regimens. These drugs are currently not available in LMIC.

A prospective study of haematological changes after switching from stavudine to zidovudine-based antiretroviral treatment in HIV-infected children

Long-term use of stavudine is associated with a high incidence of lipodystrophy, warranting its substitution with zidovudine in first-line antiretroviral therapy (ART) regimens. In a prospective observational study, we determined the spectrum and severity of haematological changes after switching from stavudine- to zidovudine-based ART in Indian children aged 2-18 years who had received a stavudine-based ART regimen for at least 48 weeks. They were followed for 48 weeks for changes in haematological parameters and CD4 cell counts after switching to zidovudine. Of the 60 children analysed, 45 (75%) showed a significant fall in Hb (>1 g/dl). A majority developed grade 1 anaemia (14 [31%]) while only three (6%) developed grade 4 anaemia. The lowest Hb was recorded between 12 and 16 weeks with spontaneous improvement noticed after 28 weeks. A significant drop in absolute neutrophil count (5067 cells/mm3 to 3625 cells/mm3; p = 0.004) was also observed but none developed severe neutropenia. No significant changes were observed in platelet and CD4 cell counts. Since the incidence of severe drug toxicity was low with zidovudine and the majority of children recovered without intervention, drug toxicity should not preclude its routine use in poor countries.

P001: Utility of mobile communication devices as a tool to improve adherence to antiretroviral treatment in HIV-infected children and adolescents in Argentina

P001: Utility of mobile communication devices as a tool to improve adherence to antiretroviral treatment in HIV-infected children and adolescents in Argentina

Prevalence and Determinants of Virological Failure in HIV-Infected Children on Antiretroviral Therapy in Rural Cameroon: A Cross-Sectional Study

In Africa, success of antiretroviral treatment (ART) seems to lag behind in children compared with adults, and high therapeutic failure rates have been reported. We aimed to identify prevalence and determinants of virological failure in HIV-infected children treated under programmatic conditions. All patients <18 years on ART presenting to the HIV clinic at the Bamenda Regional Hospital, a secondary referral hospital in rural Cameroon, from September 2010 to August 2011, were enrolled in this cross-sectional study. Clinical data, self-reported adherence, CD4(+) T-cell counts and viral load were recorded. Therapeutic drug monitoring was performed on stored plasma samples. Determinants of virological failure were identified using descriptive statistics and logistic regression. A total of 230 children with a mean age of 8.9 years (sd 3.7) were included. At the time of analysis, the mean duration of HAART was 3.5 years (sd 1.7) and 12% had a CD4(+) T-cell count <200 cells/µl. In total, 53% of children experienced virological failure (>200 copies/ml). Among children on nevirapine (NVP), plasma levels were subtherapeutic in 14.2% and supratherapeutic in 42.2%. Determinants of virological failure included male sex, lower CD4(+) T-cell counts, subtherapeutic drug levels, longer time on ART and a deceased mother. Poor adherence was associated with subtherapeutic NVP plasma levels and advanced disease stages (WHO stage 3/4). This study demonstrates high virological failure rates and a high variability of NVP plasma levels among HIV-infected children in a routine ART programme in rural Cameroon. Strategies to improve adherence to ART in HIV-infected children are urgently needed.

Severe morbidity and mortality in untreated HIV-infected children in a paediatric care programme in Abidjan, Côte d'Ivoire, 2004-2009

BackgroundClinical evolution of HIV-infected children who have not yet initiated antiretroviral treatment (ART) is poorly understood in Africa. We describe severe morbidity and mortality of untreated HIV-infected children.MethodsAll HIV-infected children enrolled from 2004-2009 in a prospective HIV programme in two health facilities in Abidjan, Côte d'Ivoire, were eligible from their time of inclusion. Risks of severe morbidity (the first clinical event leading to death or hospitalisation) and mortality were documented retrospectively and estimated using cumulative incidence functions. Associations with baseline characteristics were assessed by competing risk regression models between outcomes and antiretroviral initiation.Results405 children were included at a median age of 4.5 years; at baseline, 66.9% were receiving cotrimoxazole prophylaxis, and 27.7% met the 2006 WHO criteria for immunodeficiency by age. The risk of developing a severe morbid event was 14% (95%CI: 10.7 - 17.8) at 18 months; this risk was lower in children previously exposed to any prevention of mother-to-child-transmission (PMTCT) intervention (adjusted subdistribution hazard ratio [sHR]: 0.16, 95% CI: 0.04 - 0.71) versus those without known exposure. Cumulative mortality reached 5.5% (95%CI: 3.5 - 8.1) at 18 months. Mortality was associated with immunodeficiency (sHR: 6.02, 95% CI: 1.28-28.42).ConclusionsHaving benefited from early access to care minimizes the severe morbidity risk for children who acquire HIV. Despite the receipt of cotrimoxazole prophylaxis, the risk of severe morbidity and mortality remains high in untreated HIV-infected children. Such evidence adds arguments to promote earlier access to ART in HIV-infected children in Africa and improve care interventions in a context where treatment is still not available to all.

Growth response to antiretroviral treatment in HIV-infected children: a cohort study from Lilongwe, Malawi

Malnutrition is common in HIV-infected children in Africa and an indication for antiretroviral treatment (ART). We examined anthropometric status and response to ART in children treated at a large public-sector clinic in Malawi. All children aged <15 years who started ART between January 2001 and December 2006 were included and followed until March 2008. Weight and height were measured at regular intervals from 1 year before to 2 years after the start of ART. Sex- and age-standardized z-scores were calculated for weight-for-age (WAZ) and height-for-age (HAZ). Predictors of growth were identified in multivariable mixed-effect models. A total of 497 children started ART and were followed for 972 person-years. Median age (interquartile range; IQR) was 8 years (4-11 years). Most children were underweight (52% of children), stunted (69%), in advanced clinical stages (94% in WHO stages 3 or 4) and had severe immunodeficiency (77%). After starting ART, median (IQR) WAZ and HAZ increased from -2.1 (-2.7 to -1.3) and -2.6 (-3.6 to -1.8) to -1.4 (-2.1 to -0.8) and -1.8 (-2.4 to -1.1) at 24 months, respectively (P < 0.001). In multivariable models, baseline WAZ and HAZ scores were the most important determinants of growth trajectories on ART. Despite a sustained growth response to ART among children remaining on therapy, normal values were not reached. Interventions leading to earlier HIV diagnosis and initiation of treatment could improve growth response.

Effects of Antiretroviral Drug Recall on Perception of Therapy Benefits and on Adherence to Antiretroviral Treatment in HIV-Infected Children

In June 2007, the European Medicines Agency announced the recall by Roche of nelfinavir from European Union markets because of contamination of tablets with ethyl mesylate. Based on this event, we investigated the effect of switching therapy because of nelfinavir recall or for other reasons on the perception of therapy benefits and adherence to treatment in HIV-infected children and their caregivers. Thirty-eight children (mean age 12.1+/-6.7 years) were enrolled. A 35-item questionnaire was administered to the caregivers of enrolled children. Adherence was evaluated through a 4-day recall adherence instrument. Enrolled children were divided into 3 groups: patients who were shifted because of nelfinavir recall (group A, 8 patients); patients who were shifted for other reasons (group B, 12 patients); patients who were not shifted in the last 6 months (group C, 18 patients). All caregivers considered antiretroviral therapy necessary and effective for their children. However, drug shifting generated anxiety in most of them, irrespective of the reason for shifting. At baseline, 74% patients adhered to therapy. Adherence rate was related to the type of caregivers being higher in children cared for by foster parents than in children cared for by biological parents or second-degree relatives. Adherence rates did not change significantly in groups A and B after switching. Drug-switching raises concern in caregivers of HIV-infected children and induces a negative feeling irrespective of the reason for switching. However, switching, including the shift due to nelfinavir recall, did not affect adherence rates.

Stopping antiretroviral therapy in ‘prematurely treated' HIV-1-infected children with full viral supression is safe

Stopping antiretroviral therapy in ‘prematurely treated' HIV-1-infected children with full viral supression is safe