Dimitri Van der Linden

The Young and the Resistant: HIV-Infected Adolescents at the Time of Transfer to Adult Care

Combined antiretroviral therapy allows children with human immunodeficiency virus (HIV) to reach adulthood. We studied 45 adolescents at the time of transfer to adult care. Despite universal healthcare access, over two-thirds of the adolescents were failing treatment, which was manifested by detectable HIV-1 viral load, CD4 counts <200 cells/ mm(3), and/or triple-class drug resistance.

Clinical practice treatment of HIV infection in children

Perinatal transmission remains the main cause of HIV infection in the pediatric population. Treatment of HIV-infected children has become less of a problem in resource-rich countries with a remarkable decrease of perinatal infections, resulting in an effective prevention of mother-to-child transmission and antiretroviral treatment of HIV infection in pediatrics because of differences in drug pharmacokinetics, the lack of available licensed drugs, the use of different immunologic markers and age-related adherence issues. This review, for the general pediatrician, summarizes the most recent pediatric data and guidelines for treatment of HIV. Recommendations for when to initiate therapy are more aggressive in children than in adults, particularly in infants because disease progression in children is more rapid. The indications to start therapy differ by age and are based on international immunologic and clinical classification system for HIV infection. At present, combination regimens of at least three drugs are recommended. Moreover, therapies must also consider the potential complications in these children currently treated for a long time.

Pediatric HIV: new opportunities to treat children.

Background: Treating HIV-infected children remains a challenge due to a lack of treatment options, appropriate drug formulations and, in countries with limited resources, insufficient access to diagnostic tests and treatment. Objective: To summarize current data concerning new opportunities to improve the treatment of HIV-infected children. Methods: This review includes data from the most recently published peer-reviewed publications, guidelines or presentations at international meetings concerning new ways to treat HIV-infected children. Results/conclusions: New WHO guidelines recommend starting combination antiretroviral treatment in all infants aged < 1 year. Although this is common practice in some high-income countries, implementation of these recommendations in countries with limited resources is still a challenge. There is still an important gap between the availability of licensed drugs in children compared with adults. There remains a need for further pharmacokinetic studies, and for more pediatric formulations of antiretroviral drugs with improved palatability.

Moving forward with treatment options for HIV-infected children

ABSTRACT Introduction: Current international guidelines recommend to treat all HIV-1 infected patients regardless of CD4 cell count. Despite the remarkable worldwide progress for universal access to antiretroviral during the last decade, the pediatric population remains fragile due to lack of randomized studies, inappropriate antiretroviral formulations, adherence difficulties, drug toxicity and development of resistance. Areas covered: This review summarizes the latest recommendations and advances for the treatment of HIV-infected children and highlights the potential complications of a lifelong antiretroviral treatment initiated early in life. Expert opinion: International guidelines recommend to start combination antiretroviral therapy (cART) as fast as possible in all children diagnosed with HIV-1. The principal goal is to improve survival and reduce mortality as well as rapidly decrease HIV reservoirs. This remains a challenge in resource-limited settings were diagnostic tools and treatment access may be limited. Different new strategies are in the pipeline such as immunotherapy in combination with very early cART initiation to seek remission or functional cure. For the time being and awaiting for long term remission or cure, there is a need for further pharmacokinetics studies, more pediatric formulations with improved palatability and implementation of randomized trials for the newer antiretroviral drugs.

Virological and Immunological Long-Term Outcome of Human Immunodeficiency Virus-1 Infected Children Treated before One Year and after Two Years of Age in a Resource-Limited Setting of South Africa

Introduction: Benefits of early Highly Active AntiRetroviral Therapy (HAART) to reduce infant mortality and morbidity have been demonstrated in resource-limited and rich settings. However, immunovirological data collected in Sub-Saharan Africa are scarce. This study describes the long-term outcome of South African children who started HAART before one year of age (Early Starters Cohort or ESC) and compare their immunovirological outcomes to children who started their therapy after two years of age (Late Starters Cohort or LSC). Immunovirological results will be compared in order to evaluate the long-term non-inferiority of early treatment initiation. Methods: Fifty-five children were included in the ESC (mean follow-up period 7.9 years) and 96 children were included in the LSC (mean follow-up period 6.3 years). Children from the ESC and the LSC were subdivided into three subgroups according to CD4+% at HAART initiation ( 100 cp/ml) was comparable in both cohorts but persistent undetectable viral load (<50 cp/ml) after initial virological suppression was more frequent in the ESC (p=0.008). Finally, the proportion of children with detectable viral loads (50 to 1000 cp/ml) at least one time during the entire follow-up period was higher in the LSC (p=0.0022). Conclusion: HAART appeared highly effective in terms of immunovirological outcomes both in children treated before one and after two years of age. The results of this study demonstrate that early treated children more often achieved normal CD4+%, tended to have higher mean CD4+% and more sustained virological suppression. These results encourage the current international recommendations to initiate HAART as soon as possible in RLS.