Nevirapine versus ritonavir-boosted lopinavir for HIV-infected children.
BACKGROUND
Nevirapine-based antiretroviral therapy is the predominant (and often the only) regimen available for children in resource-limited settings. Nevirapine resistance after exposure to the drug for prevention of maternal-to-child human immunodeficiency virus (HIV) transmission is common, a problem that has led to the recommendation of ritonavir-boosted lopinavir in such settings. Regardless of whether there has been prior exposure to nevirapine, the performance of nevirapine versus ritonavir-boosted lopinavir in young children has not been rigorously established.


METHODS
In a randomized trial conducted in six African countries and India, we compared the initiation of HIV treatment with zidovudine, lamivudine, and either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 2 to 36 months of age who had no prior exposure to nevirapine. The primary end point was virologic failure or discontinuation of treatment by study week 24.


RESULTS
A total of 288 children were enrolled; the median percentage of CD4+ T cells was 15%, and the median plasma HIV type 1 (HIV-1) RNA level was 5.7 log(10) copies per milliliter. The percentage of children who reached the primary end point was significantly higher in the nevirapine group than in the ritonavir-boosted lopinavir group (40.8% vs. 19.3%; P<0.001). Among the nevirapine-treated children with virologic failure for whom data on resistance were available, more than half (19 of 32) had resistance at the time of virologic failure. In addition, the time to a protocol-defined toxicity end point was shorter in the nevirapine group (P=0.04), as was the time to death (P=0.06).


CONCLUSIONS
Outcomes were superior with ritonavir-boosted lopinavir among young children with no prior exposure to nevirapine. Factors that may have contributed to the suboptimal results with nevirapine include elevated viral load at baseline, selection for nevirapine resistance, background regimen of nucleoside reverse-transcriptase inhibitors, and the standard ramp-up dosing strategy. The results of this trial present policymakers with difficult choices. (Funded by the National Institute of Allergy and Infectious Diseases and others; P1060 ClinicalTrials.gov number, NCT00307151.).
Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
Avy
A
Violari
Jane C
JC
Lindsey
Michael D
MD
Hughes
Hilda A
HA
Mujuru
Linda
L
Barlow-Mosha
Portia
P
Kamthunzi
Benjamin H
BH
Chi
Mark F
MF
Cotton
Harry
H
Moultrie
Sandhya
S
Khadse
Werner
W
Schimana
Raziya
R
Bobat
Lynette
L
Purdue
Susan H
SH
Eshleman
Elaine J
EJ
Abrams
Linda
L
Millar
Elizabeth
E
Petzold
Lynne M
LM
Mofenson
Patrick
P
Jean-Philippe
Paul
P
Palumbo
D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002675:Child, Preschool; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D015658:HIV Infections / Q000401:mortality / Q000517:prevention & control*; D015497:HIV-1; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D061466:Lopinavir / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D019829:Nevirapine / Q000009:adverse effects / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000009:adverse effects / Q000627:therapeutic use; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use*
D044966:Anti-Retroviral Agents; D012367:RNA, Viral; D061466:Lopinavir; D019259:Lamivudine; D015215:Zidovudine; D019829:Nevirapine; D019438:Ritonavir