Ritonavir-based highly active antiretroviral therapy in human immunodeficiency virus type 1-infected infants younger than 24 months of age.
ABSTRACT Few data are available regarding clinical outcomes or dosing requirements for the protease inhibitor ritonavir in human immunodeficiency virus (HIV)-infected children younger than under 24 months of age.
This prospective, multicenter phase I/II open label treatment trial used ritonavir, zidovudine and lamivudine to treat protease inhibitor-naive, HIV-infected infants between the ages of 4 weeks and 24 months. Two sequential dosing cohorts were treated with 350 or 450 mg/m(2) ritonavir every 12 hours; this report includes results of pharmacokinetics, safety, tolerability and efficacy through 104 weeks of follow-up of all subjects.
Fifty HIV-infected children were treated. By week 16, 36 had achieved HIV-1 RNA <400 copies/mL (72% intent-to-treat, 84% as-treated analysis); by week 104, 18 maintained durable viral suppression (36% intent-to-treat, 46% as-treated). Poor medication adherence by caregiver report contributed to virologic failure. Few subjects experienced treatment-limiting toxicity: emesis or ritonavir refusal in 6 (12%); and severe but reversible anemia or elevated serum hepatic transaminases in 1 (4%) each. Apparent oral clearance was higher and the median predose concentrations were substantially lower than those found in adults. Median z scores for weight and height for age/gender were below normal at baseline but improved by week 104.
A combination regimen of ritonavir, zidovudine and lamivudine was generally safe and produced sustained viral suppression in more than one-third of infants who initiated therapy before 2 years of age. Improved palatability of liquid preparations of protease inhibitors, supporting infrastructure and behavioral approaches to improve medication adherence with antiretrovirals will likely be necessary to further improve efficacy.
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ABSTRACT: Adherence to antiretroviral therapy (ART) in children is complicated may be because of many factors such as child characteristics, caregiver and family characteristics, regimen characteristics, etc. Therefore, it is important to identify factors associated with adherence in HIV infected children in order to reduce the risk of developing treatment failure or drug resistance through interventions. This survey was planned to find out the rate of adherence to ART and its associated factors among the children in Mekelle, Tigray region, Ethiopia. A cross-sectional survey was conducted in two hospitals in Mekelle: Ayder Referral Hospital and Mekelle Hospital, during the months of February to March 2013. A structured questionnaire was administered to caregivers to assess patient's adherence. Out of a total of 193 patients, 83.4% as reported by caregivers were adherent to ART in the past seven days before the interview. On multivariate logistic regression model, it was found that the children whose caregivers were unmarried (AOR = 15.17, 95% CI: 3.36-68.43) and married (AOR = 3.54, 95% CI: 1.23-10.13) were more likely to adhere to their ART treatment than those whose caregivers were divorced/separated. Similarly, children whose caregivers' age groups of 25-34 (AOR = 22.27, 95% CI: 4.34-114.29) and 35-44 (AOR = 7.14, 95% CI: 1.65-30.95) were more likely to adhere than their counterparts. The major reasons reported by caregivers for missing medicines include: child being depressed (24.4%), drug side effects (16.3%), too many pills (15.5%) and difficulty in swallowing pills (13.3%). The prevalence of adherence to ART among children was found to be high and comparable to that of other similar setups. Nevertheless, encouraging the fundamental role of caregivers is so significant to improve adherence among those who missed a dose or more and consequently treatment outcomes of children with HIV.BMC Pediatrics 04/2014; 14(1):114. DOI:10.1186/1471-2431-14-114 · 1.92 Impact Factor
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ABSTRACT: Background. Early initiation of combination antiretroviral therapy (cART) to human immunodeficiency virus type 1 (HIV-1)-infected infants controls HIV-1 replication and reduces mortality. Methods. Plasma viremia (lower limit of detection, <2 copies/mL), T-cell activation, HIV-1-specific immune responses, and the persistence of cells carrying replication-competent virus were quantified during long-term effective combination antiretroviral therapy (cART) in 4 perinatally HIV-1-infected youth who received treatment early (the ET group) and 4 who received treatment late (the LT group). Decay in peripheral blood mononuclear cell (PBMC) proviral DNA levels was also measured over time in the ET youth. Results. Plasma viremia was not detected in any ET youth but was detected in all LT youth (median, 8 copies/mL; P=.03). PBMC proviral load was significantly lower in ET youth (median, 7 copies per million PBMCs) than in LT youth (median, 181 copies; P=.03). Replication-competent virus was recovered from all LT youth but only 1 ET youth. Decay in proviral DNA was noted in all 4 ET youth in association with limited T-cell activation and with absent to minimal HIV-1-specific immune responses. Conclusions. Initiation of early effective cART during infancy significantly limits circulating levels of proviral and replication-competent HIV-1 and promotes continuous decay of viral reservoirs. Continued cART with reduction in HIV-1 reservoirs over time may facilitate HIV-1 eradication strategies.The Journal of Infectious Diseases 05/2014; 210(10). DOI:10.1093/infdis/jiu297 · 5.78 Impact Factor
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ABSTRACT: Pharmacokinetics, safety and antiviral activity of fosamprenavir (FPV) with ritonavir (RTV) twice daily were evaluated in HIV-1-infected infants and children 4 weeks to <2years over 48 weeks. Results from intensive pharmacokinetic sampling of subjects enrolled in single dose visits was used to determine individualized dosing for the first 6-10 subjects in each of two cohorts (4 weeks to <6 months, 6 months to <2 years); steady state pharmacokinetic data were then used to select the dosage regimen for the remaining subjects recruited to the cohort. Intensive pharmacokinetic sampling was performed at Week 2 or 8; pre-dose samples were collected every 4-12 weeks thereafter. Safety and plasma HIV-1 RNA were monitored every 4-12 weeks. Fifty-nine subjects received study medication. FPV 45 mg/kg boosted with RTV 7 to 10 mg/kg BID achieved average plasma amprenavir AUC(0-τ) values 26 to 28% lower and Cmax similar to historical adult data for FPV/RTV 700/100 mg BID; amprenavir Cτ values were lower in the subjects <6months of age. At Week 48, 35/54, 65% subjects had achieved plasma HIV-1 RNA <400 copies/mL and 33/54, 61% had plasma HIV-1 RNA values <50 copies/mL. The most common adverse events were diarrhea, upper respiratory tract infection, gastroenteritis and otitis media. Final FPV/RTV dosing regimens achieved plasma amprenavir exposures comparable to those from regimens approved in adults, with the exception of trough exposures in the <6 month old infants. The FPV/RTV regimens led to viral suppression in 61% of patients, and were generally well tolerated.The Pediatric Infectious Disease Journal 06/2013; DOI:10.1097/INF.0b013e3182a1123a · 3.14 Impact Factor