PENTA guidelines for the use of antiretroviral therapy, 2004.

There have been few major advances in paediatric HIV management over the last 2 years. Decisions about starting antiretroviral therapy can now be based on a recent large meta-analysis of the predictive value of CD4 and HIV RNA viral load (VL) in nearly 4000 untreated children, which is discussed in these updated guidelines. Risk estimates for progression to AIDS and death using surrogate markers can now be broken down by age, allowing more accurate discussion with families. In addition, there is increasing recognition of the problems of long-term adherence, drug resistance and cumulative toxicity in adults and children. The controversy over whether to treat asymptomatic infants continues. For older children more data on the efficacy of ritonavir boosted protease inhibitor (PI) regimens suggests that these may be the PI option of first choice. There is still no adult or paediatric trial evidence on which to base decisions about whether to start with PI- or non-nucleoside reverse transcriptase inhibitor (NNRTI)- based regimens, but the PENPACT 1 trial, which is addressing this question, is ongoing. There are increasing moves to provide simpler antiretroviral therapy (ART) regimens, including once daily dosing, but these lag behind adult regimens because of the paucity of pharmacokinetic data. Resistance assays should now be performed in all HIV-infected infants exposed to ART in pregnancy. Therapeutic drug monitoring may be very important in children because of high between- and within-child variability in drug absorption and metabolism. A trial to evaluate this should start shortly in Europe (PENTA 14 trial). The value of resistance tests for choice of second-line and subsequent choices of ART regimens remain unproven (the PERA trial will report late in 2004), but resistance assays are increasingly being used. The issue of when to switch therapy also remains unanswered and is being addressed within the PENPACT 1 trial. Regular formal assessment of adherence is now the standard of care, and routine monitoring in the clinic for lipodystrophy syndrome (LDS) and other ART toxicities is increasingly important. These guidelines will be updated again in 2006.