ABSTRACT
PENTA Guidelines aim to provide practical recommendations for treating children with HIV infection in Europe. Changes to guidance since 2004 have been informed by new evidence and by expectations of better outcomes following the ongoing success of antiretroviral therapy (ART). Participation in PENTA trials of simplifying treatment is encouraged. The main changes are in the following sections: 'When to start ART': Treatment is recommended for all infants, and at higher CD4 cell counts and percentages in older children, in line with changes to adult guidelines. The number of age bands has been reduced to simplify and harmonize with other paediatric guidelines. Greater emphasis is placed on CD4 cell count in children over 5 years, and guidance is provided where CD4% and CD4 criteria differ. 'What to start with': A three-drug regimen of two nucleoside reverse transcriptase inhibitors (NRTIs) with either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (PI) remains the first choice combination. Lamivudine and abacavir are the NRTI backbone of choice for most children, based on long-term follow-up in the PENTA 5 trial. Stavudine is no longer recommended. Whether to start with an NNRTI or PI remains unclear, but PENPACT 1 trial results in 2009 may help to inform this. All PIs should be ritonavir boosted. Recommendations on use of resistance testing, therapeutic drug monitoring and HLA testing draw from data in adults and from European paediatric cohort studies. Recently updated US and WHO paediatric guidelines provide more detailed review of the evidence base. Differences between guidelines are highlighted and explained.
Subject(s)
Anti-Retroviral Agents/therapeutic use , Antiretroviral Therapy, Highly Active/methods , HIV Infections/drug therapy , HIV-1 , Adolescent , Adult , Age Factors , Anti-Infective Agents/therapeutic use , Child , Child, Preschool , Drug Resistance, Viral , Europe , Female , HIV Infections/diagnosis , HIV Infections/transmission , HIV Long-Term Survivors , Hepatitis, Viral, Human/complications , Hepatitis, Viral, Human/drug therapy , Humans , Infant , Infant, Newborn , Infectious Disease Transmission, Vertical , Patient Education as Topic , Pneumonia, Pneumocystis/prevention & control , Pregnancy , RNA, Viral/blood , Randomized Controlled Trials as Topic , Treatment Failure , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , Tuberculosis/complications , Tuberculosis/drug therapy , Young AdultABSTRACT
The development of effective antiretroviral therapy for HIV has led to significant virological suppression and immune reconstitution, and resulted in dramatic reductions in HIV-related morbidity and mortality. However, in children initial regimens were unpalatable and inconvenient due to a high pill burden. Management was further compromised by a paucity of pharmacokinetic data and the late development of associated toxicities. These factors have resulted in the emergence of drug-resistant virus in many treated children and adolescents. In this review, therapeutic options that may be available for treatment-experienced pediatric individuals are summarized on the basis of data from adult clinical trials evaluating protease, non-nucleoside reverse transcriptase, fusion, integrase and CCR5 inhibitors.