Children can achieve undetectable viral loads with therapy. Dr. Garrett Tudor-Williams, of a London clinic, talked about a four-drug regimen for infants that did not include a protease inhibitor (PI). He said the four drugs were able to bring viral load down to undetectable, which does not always happen in children who use a three-drug regimen with a PI. (In fact, U.S. guidelines state that "although suppression of HIV RNA to undetectable levels ... is desirable, few data among children indicate that such suppression is always achievable.")
The London infants had less than 50 viral load (undetectable) after 24 weeks. Also, their weight and CD4 counts were normal after a year of therapy.
The quadruple therapy consisted of four "palatable" suspensions taken twice a day without food restrictions. The medications were Retrovir, Epivir, Ziagen and Viramune. Protease inhibitors for children, he noted, are not easy to use long-term because of taste, formula and difficulty getting the dose right, as with Viracept.
His clinic provided the quadruple regimen to 18 infants who had no perinatal treatment. Half of them had PCP (pneumocystis carinii pneumonia) and six had disseminated cytomegalovirus infection (CMV). Three had encephalitis (swelling of the brain). Only one had no symptoms of disease.
Three of the children stopped therapy by 24 weeks (six months), two of them because of hepatitis due to the Viramune and one because of intolerance to Ziagen, although none of the infants had hypersensitivity to Ziagen. This child was switched to Kaletra (a protease inhibitor) and "is doing fine." If you take into consideration these three children, the undetectable rate was 60%, as opposed to 100% for the 15 children who stayed on therapy.
Dr. Tudor-Williams said the tiny number of children discussed here is problematic for evaluating the four-drug regimen, but that further evaluation is warranted, especially for children with a very high initial viral load, as with these children.
Michelle McConnell of the U.S. Centers for Disease Control and Prevention (CDC) reported on changes in children's HIV therapy between 1998 and 2000. Her report was based on the Pediatric Spectrum of Disease (PSD), a chart review of HIV-positive children from six sites. McConnell said that antiviral therapy is safe and effective in children, and that protease inhibitors have been associated with improved survival both in the U.S. and in Europe. Happily, the median age of the children in the PSD increased from four years in 1994 to nine in 2000, as HIV-positive children live longer.
Of the 1,541 children looked at in 2000, 98% were on antiviral therapy. Ninety-six percent of them were on nucleoside analogs (for example, Retrovir or Epivir), 70% were taking a protease inhibitor and 40% were taking a non-nucleoside analog (such as Sustiva or Viramune). The most commonly used medications were Zerit and Epivir (67% each) and the protease inhibitor Viracept (46%). Drugs with increasing use between 1998 and 2000 were the nuceloside Ziagen (up from 3% to 12%), Sustiva (up from 3% to 17%) and the protease inhibitor Agenerase (up from 0.4% to 9.3%). The only other protease inhibitor with increasing use in pediatrics was Kaletra.
Drug failure (detectable viral load) accounted for a third of the changes made to children's therapy in 2000, while inadherence and side effects each accounted for 14%. Fifteen to 20% of the children are on dual drugs only. More and more of the children are on their second or third drug regimen.
Italian researchers looked at adverse drug reactions (ADRs) in children. This report also came from data collected between 1998 and 2000. Of 486 children, 191 (39%) reported at least one ADR. The total number of ADRs was 239. Thirteen percent were considered serious (grades 3 or 4). All of the ADRs resolved completely, except for two children who were left with permanent conditions (one with increased creatine levels and one with diarrhea). One child died.
What were the most common side effects? Lipodystrophy (abnormal increase or decrease of body fat) occurred in 20% of the children. Both lipodystrophy and high lipid levels (triglyceride or cholesterol) were also twice as likely to occur in kids over the age of 10. Bone marrow toxicity occurred in 11%.
However, 67% of cardiac disturbances and "alterations in pancreatic function" were considered severe, as were a quarter of the kidney stone cases and bone marrow toxicities. The researchers concluded that, "ADRs to HAART (highly active antiretroviral therapy) in HIV-positive children are similar to those decribed in adults. Even if they appear of mild severity (85% score grade 1-2), they can compromise compliance to therapy. Lipodystrophy and alterations of lipids were less frequent than expected, probably in relation to the lack of clear diagnostic criteria in childhood. Further analysis will help to clarify whether our results reflect a true lower incidence or is the effect of underreporting." The presenter also noted that CD4 count was only "marginally" related to side effects, but that taking more than three drugs increased the risk for ADRs.