Nevirapine is generally safe and well tolerated by children according to a UK paper published in the July 25th edition of AIDS. However, investigators found that effective virological control was most likely to be achieved when children received a dose higher than that currently recommended by the drug’s manufacturer.
The use of the NNRTI nevirapine has been available for the treatment of HIV in children as part of HAART since 1997, however, there is little information on its use and efficacy. Accordingly investigators at St Mary’s Hospital in London and the North Manchester Hospital conducted a retrospective case note review involving 74 children who were prescribed nevirapine between 1997 and 1999. The investigators wished to establish the drug’s safety and impact on HIV disease progression, CD4 cell count, HIV viral load, and which dose of nevirapine proved the safest and most effective.
At enrollment, 28 of the children had never taken anti-HIV treatment before. Average age was 5.2 years, median viral load was 126,000 copies/mL and average CD4 cell percentage was 13.5%. Nevirapine was prescribed with two NRTIs to 58 of the children, and twelve children were also treated with a protease inhibitor. The remaining four children discontinued therapy due to adverse events. Nevirapine was provided in three different doses. If the dose was greater than 300mg/m2 per day it was classified as 'high', 'recommended' if it was between 300mg/m2 per day, and low if it was below 240mg/m2 a day.
Nevirapine was provided twice daily to 35 of the children receiving the drug with NRTIs, with the remaining 17 children on NNRTI and NRTI therapy taking the drug once daily. A dose higher than the 300mg/m2 (or the equivalent liquid dose) daily was provided to 14 of the children taking once-daily therapy and one child on twice-daily treatment.
Both the liquid suspension of nevirapine and the pill formulation were well tolerated, and by the end of the study, 79% of treatment naïve children and 63% of those with pre-treatment were still taking nevirapine. HIV disease progressed in four children during the study, in all cases during the initial months of nevirapine therapy.
In an intention to treat analysis, 33% (n=20) children had an HIV viral load below 400 copies at week 96 (42% in on-treatment analysis). There was a non-significant trend for treatment naïve children to have an undetectable viral load, and none of the children who had nevirapine added to a failing protease inhibitor-containing HAART regimen achieved a viral load below 400 copies/mL.
Amongst the children taking nevirapine and two NRTIs, a dose of nevirapine higher than the manufacturer’s recommended 300mg daily was found to be significantly associated with achieving and maintaining an undetectable viral load by the end of the study (60% versus 17% on 240mg/m2 dose).
Baseline CD4 cell counts were available for 54 children, and these increased by an average of 29% by the end of the study (p<0.001). Height and weight also increased significantly (p<0.001).
The most commonly observed side-effect was rash, which developed in 20% of children, and was severe enough for nevirapine therapy to be stopped in four children. The rash developed an average of nine days after treatment with nevirapine was initiated and lasted for a median of ten days. There were no cases of the potentially life-threatening Stevens-Johnson syndrome. The development of rash was not significantly associated with the dose of nevirapine provided.
The investigators conclude that nevirapine was generally well tolerated and was associated with “encouraging” clinical, virological and immunological responses. For optimum virological suppression a daily dose of 300mg/m2 or more a day is needed, they conclude, higher than the manufacturer’s recommended dose is needed.
Further information on this website
Nevirapine - overview
Verweel G et al. Nevirapine use in HIV-1-infected children. AIDS 17: 1639 – 1647, 2003.