Antiretroviral Therapy in Children: Recent Advances (original) (raw)

Treatment of pediatric HIV infection

Current Infectious Disease Reports, 2007

HIV-infected children require a peculiar management when compared to infected adults. Antiretroviral therapy has been quite well adapted to children, but new studies are needed to answer many unsolved questions, such as when to start therapy in asymptomatic infected children. Recently, several guidelines have been updated. In this review, we compare these recommendations together with the latest studies concerning the treatment of HIV in children. A triple-drug combination therapy based either on nonnucleoside reverse transcriptase inhibitors or protease inhibitors is the recommended initial therapy. After treatment failure, a second-line therapy should be based on switching between these two regimens. Antiretroviral therapy should be managed by an expert in pediatric and adolescent HIV infection. The importance of children's adherence to therapy is a crucial point, particularly in adolescents.

Treatment of children with HIV infection

Current HIV/AIDS Reports, 2007

The treatment of pediatric HIV infection has seen vast improvements in terms of better long-term suppression of HIV replication and subsequent improvements in the longevity and quality of life in children. This has been realized, in part, by development of newer antiretroviral medications, better knowledge about the pharmacokinetics of these drugs in children, and improved insight on drug toxicities in children. This review will discuss some of the newer agents that may be available for children in the near future, in addition to new pharmacokinetic and toxicity data that are specific to the pediatric patient. New information on key vaccines that should be administered to children with HIV infection is also discussed.

Optimization of antiretroviral therapy in HIV-infected children under 3 years of age

AIDS, 2014

Background: Treatment of young HIV-infected children is challenging because of rapid disease progression, high viral loads and few drug options. This review was undertaken to update evidence on the management of young HIV-infected children and to inform the development of the 2013 WHO guidelines for antiretroviral therapy (ART) in low and middle-income countries. Design: A systematic review and meta-analysis. Methods: We identified and critically assessed randomized controlled trials that evaluated treatment strategies in perinatally HIV-infected infants and young children (aged <3 years). Results: Eight studies were included. Antiretroviral therapy (ART) initiation in asymptomatic infants led to 74% reduction in mortality or disease progression [hazard ratio 0.36, 95% confidence interval (CI) 0.18-0.74, P ¼ 0.0002]. Regardless of previous exposure to prevention of mother to child transmission (PMTCT), treatment failure at 24 weeks was more likely in children starting nevirapine-based than in those starting lopinavir/ritonavir (lopinavir/r)-based ART (hazard ratio 1.79, 95% CI 1.33-2.41, P ¼ 0.0001). Infants starting lopinavir/r-based ART and substituting lopinavir/r with nevirapine once virologic suppression was achieved were less likely to experience viral load more than 50 copies/ml (hazard ratio 0.62, 95% CI 0.41-0.92, P ¼ 0.02) but more likely to have confirmed virologic failure (>1000 copies/ml) than those remaining on lopinavir/r (hazard ratio 10.19, 95% CI 2.36-43.94, P ¼ 0.002). Children receiving induction-maintenance ART (four-drug NNRTIbased regimen for 36 weeks followed by three-drug ART) showed better short-term immunologic and virologic responses, but no long-term benefits. The only trial comparing continuous ART from infancy with interrupted ART beyond infancy was terminated early because the duration of treatment interruption was less than 3 months in most infants. Conclusion: ART initiation in asymptomatic infants reduces morbidity and mortality. Lopinavir/r-based first-line ART is superior to nevirapine-based regimens in young children, regardless of PMTCT exposure, but lopinavir/r use is challenging. Substituting lopinavir/r with nevirapine following virologic suppression may be feasible where viral load testing is available. Considering current evidence, induction-maintenance and treatment interruption strategies are not recommended. This review contributed to the evidence base for the 2013 WHO guidelines on antiretroviral therapy, which recommend that all children below 3 years start lopinavir/r-based ART and that lopinavir/r can be substituted with nevirapine once sustained virologic suppression is achieved.

Commentary: When to start and what to use in children--recommendations and rationale

AIDS (London, England), 2014

The 2013 WHO consolidated guidelines recommend treating all HIV-infected children under the age of 5 years regardless of CD4 þ T-cell count or WHO clinical stage, and treating children aged 5 years and older according to the same criteria as for adults: WHO clinical stage 3 or 4 or CD4 þ T-cell count of 500 cells/ml or less [1]. Guideline recommendations for what drugs to use for initial antiretroviral therapy (ART) vary by age group: less than 3 years, 3-10 years and above 10 years.

Unresolved Antiretroviral Treatment Management Issues in HIV-Infected Children

JAIDS Journal of Acquired Immune Deficiency Syndromes, 2012

Antiretroviral therapy in children has expanded dramatically in low-income and middle-income countries. The World Health Organization revised its pediatric HIV guidelines to recommend initiation of antiretroviral therapy in all HIV-infected children younger than 2 years, regardless of CD4 count or clinical stage. The number of children starting life-long antiretroviral therapy should therefore expand dramatically over time. The early initiation of antiretroviral therapy has indisputable benefits for children, but there is a paucity of definitive information on the potential adverse effects. In this review, a comprehensive literature search was conducted to provide an overview of our knowledge about the complications of treating pediatric HIV. Antiretroviral therapy in children, as in adults, is associated with enhanced survival, reduction in opportunistic infections, improved growth and neurocognitive function, and better quality of life.

Antiretroviral therapy in children: Indian experience

Indian pediatrics, 2007

There is a paucity of reports on Highly Active Antiretroviral therapy (HAART) in children. We studied feasibility and effectiveness fixed dose combination (FDC) of lamivudine, nevirapine and stavudine in HIV infected children. Interventional study. A Tertiary care center. Twenty five consecutive HIV positive antiretroviral naive children older than 18 months. The study subjects were started on weight-appropriate doses of the FDC and followed up for 6 months. Weight, CD4 counts, absolute lymphocyte count (ALC) and number of episodes of illness were assessed before and after HAART. Adherence and barriers to adherence were studied. Mean weight increased from 15.2 to 16.8 kg (P < 0.001) while mean CD4 counts increased from 488/cmm to 765/cmm (P < 0.001). Only 2 cases of drug associated adverse event were encountered. Improvement in Center for Disease Control (CDC) immunological classification of the subjects was significant while that in World Health Organization (WHO) clinical st...

A Trial of Three Antiretroviral Regimens in HIV-1–Infected Children

New England Journal of Medicine, 2004

Depletion of CD4 T-cell counts or progression of human immunodeficiency virus (HIV) disease occurs rapidly in children, but few data address the efficacy of aggressive therapy for HIV-infected children. We evaluated the safety, tolerability, and activity of three regimens of antiretroviral therapy in a multicenter, open-label, phase 1-2 trial. Children infected with HIV type 1 (HIV-1) were stratified at entry according to age--three months or younger (early therapy) or older than three months (delayed therapy)--and assigned sequentially to one of three regimens. Children continued to receive treatment for up to 200 weeks if the plasma HIV-1 RNA level was less than 1000 copies per milliliter by 16 weeks. Plasma HIV-1 RNA levels fell from a median of 5.3 log copies per milliliter (range, 3.3 to 6.4 log copies per milliliter) at baseline to less than 1000 copies per milliliter at 16 weeks in 32 of 52 infants (62 percent). Plasma HIV-1 RNA levels were below 400 copies per milliliter at 48 weeks in 26 infants (50 percent) and at 200 weeks in 23 infants (44 percent). An intention-to-treat analysis revealed that significantly more children who received stavudine, lamivudine, nevirapine, and nelfinavir had plasma HIV-1 RNA levels of less than 400 copies per milliliter at 48 weeks (83 percent) and 200 weeks (72 percent) than children who received reverse-transcriptase inhibitors alone (P=0.001 and P=0.01, respectively). Fewer infants in the delayed-therapy group than in the early-therapy group (30 percent vs. 60 percent) had plasma HIV-1 RNA levels of less than 400 copies per milliliter at 200 weeks (P=0.03). Treatment-associated adverse effects were infrequent. In this phase 1-2 trial involving HIV-1-infected children, an age of three months or younger at the initiation of therapy and treatment with stavudine, lamivudine, nevirapine, and nelfinavir were associated with improved long-term viral suppression. Larger, randomized trials are required to define the optimal time to initiate therapy and the optimal regimen for these infants.