HIV This Week

Jaspan HB, Berrisford AE, Boulle AM. Two-Year Outcomes of Children on Non-Nucleoside Reverse Transcriptase Inhibitor and Protease Inhibitor Regimens in a South African Pediatric Antiretroviral Program. Pediatr Infect Dis 2008;27(11):993-8

Few data exist on the efficacy of the limited regimens for children with HIV, which are available in sub-Saharan Africa. Jaspan and colleagues conducted a retrospective cohort study to evaluate the clinical and laboratory outcomes of 391 children who received protease inhibitor (PI) or non-nucleoside reverse transcription inhibitor (nNRTI)-containing highly active antiretroviral regimens (HAART) from a Cape Town clinic. Endpoints included CD4% and count, viral loads, weight-for-age Z score, survival, drug changes, and loss to follow-up over 24 months. A generalized estimating equation population-averaged model was used to identify associations with virological suppression, and a log-rank test explored associations with survival. Overall, this cohort achieved a sustained doubling of median CD4% from baseline, steady increase of median weight-for-age Z score, and survival of 91%, despite only 49% virologic suppression at 24 months. However, when analyzed according to regimen, PI-containing regimens had better virologic suppression at all time points. There were no differences in immunologic and growth endpoints between regimens or in survival. In a multivariate model predicting virologic suppression at any duration up to 24 months and adjusting for baseline CD4%, regimen, age, baseline weight-for-age Z score, duration of HAART, and year of HAART initiation, nNRTI-based regimens (odds ratio [OR]: 0.38; 95% confidence interval [CI]: 0.19-0.77) and length of time on HAART were inversely associated with virologic suppression. Age (OR: 1.23 per year; 95% CI: 1.09-1.39) was positively associated with virologic suppression. The benefits of antiretroviral treatment are substantial in this setting, although PI regimens achieved greater virologic suppression than nNRTIs. Further exploration of regimens and dosing of antiretrovirals for children in these settings is needed.

Editors’ note: This retrospective cohort study was not designed to compare treatment regimens but did find that protease inhibitor-based therapy was strongly associated with a greater probability of viral suppression, likely because of the strong genetic barrier to resistance mutations conferred by boosted lopinavir (LPV/r). The high early mortality seen in this study reinforces the need to initiate antiretroviral therapy in children before severe immune suppression develops.