Ritonavir-Based Highly Active Antiretroviral Therapy in Human Immunodeficiency Virus Type 1-Infected Infants Younger Than 24 Months of Age
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.
Available from: Tadele Eticha
- "Adherence is therefore a determinant of viral suppression and fundamental to successful ART treatment. There is a direct correlation between risk of virologic failure and proportion of missed doses of antiretroviral drugs
. Adherence is a complex health behavior which may be influenced by the dosage regimen prescribed, patient and family factors, and characteristics of health care providers
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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 · 1.93 Impact Factor
Available from: Valeriane Leroy
- "The Children with HIV Early ART (CHER) trial in South Africa recently demonstrated a 76% reduction in morbidity, a 75% reduction in mortality, and notable short-term cost reductions when HIV-infected infants initiated ART before 3 months of age and before clinical signs and symptoms of HIV developed [33,34]. Based on this trial and a growing body of observational data [35-37], WHO pediatric treatment guidelines now recommend ART initiation for all HIV-infected infants under 24 months of age [6,32]. In order to facilitate ART initiation as soon as possible after infection, WHO recommends HIV diagnostic testing for all HIV-exposed infants (infants born to HIV-infected mothers) at 4-6 weeks of age . "
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ABSTRACT: Early infant diagnosis (EID) of HIV-1 infection confers substantial benefits to HIV-infected and HIV-uninfected infants, to their families, and to programs providing prevention of mother-to-child transmission (PMTCT) services, but has been challenging to implement in resource-limited settings. In order to correctly inform parents/caregivers of infant infection status and link HIV-infected infants to care and treatment, a 'cascade' of events must successfully occur. A frequently cited barrier to expansion of EID programs is the cost of the required laboratory assays. However, substantial implementation barriers, as well as personnel and infrastructure requirements, exist at each step in the cascade. In this update, we review challenges to uptake at each step in the EID cascade, highlighting that even with the highest reported levels of uptake, nearly half of HIV-infected infants may not complete the cascade successfully. We next synthesize the available literature about the costs and cost effectiveness of EID programs; identify areas for future research; and place these findings within the context of the benefits and challenges to EID implementation in resource-limited settings.
BMC Medicine 05/2011; 9(1):59. DOI:10.1186/1741-7015-9-59 · 7.25 Impact Factor
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ABSTRACT: Several guidelines are available to guide the initiation of highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV)-infected children. The recommendations in these guidelines show significant variability. Because there is no well-established evidence on when to start HAART, it is left to the discretion of the pediatrician which guidelines to follow. We conducted a survey concerning the indications for starting antiretroviral therapy among pediatricians involved in the treatment of HIV-infected patients in Europe and the United States. We compared the results of this survey with the guidelines available at the time, the recently adapted guidelines and literature evidence. Our results indicate that in clinical practice HAART was initiated at higher viral loads and lower CD4 counts than recommended by the guidelines. American guidelines recommended and still recommend more aggressive treatment than the European guidelines, and this is reflected in clinical practice. Until recently all guidelines were based on long term risk analyses of progression to acquired immunodeficiency syndrome (AIDS) and death performed in cohort data. A recent short term risk analysis makes it possible to calculate the 6 or 12-month risk for progression to AIDS or death for an individual child. Because viral load and CD4 count are typically measured every 3 months, one can argue that it is clinically more relevant to base the decision of when to start HAART on the short term probability of disease progression. Guidelines in Europe are now based on this type of analysis. The American guidelines only adopted the thresholds for CD4 and viral load. The short term risk analysis also shows that the risk for developing AIDS varies markedly with age. This should be reflected in all guidelines. Determining the acceptable risk of disease progression is difficult and influenced by patient-, doctor- and culture-related factors. The controversy over whether or not to treat asymptomatic infants is unresolved as well. All infants have a very high risk of disease progression regardless of their viral load or CD4 count, but lifelong treatment with a potential for significant toxicities and risk of developing resistance is also not an appealing option. We recommend an attempt to achieve a consensus among the different working groups to reduce the number of different guidelines, which should be based on the literature evidence. Because all risk analyses are based on information from the pre-HAART era, a head-to-head trial comparing early versus deferred HAART would be useful. This may be difficult to accomplish. The first step could be an analysis of retrospective data from collaborative cohort data.
The Pediatric Infectious Disease Journal 12/2006; 25(11):987-94. DOI:10.1097/01.inf.0000242670.11693.56 · 2.72 Impact Factor
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