Two-year clinical and immune outcomes in human immunodeficiency virus-infected children who reconstitute CD4 T cells without control of viral replication after combination antiretroviral therapy.

OBJECTIVE: To evaluate 96-week clinical and immune outcomes to protease inhibitor-containing antiretroviral therapy. METHODS: A prospective study was conducted of 40 human immunodeficiency virus (HIV)-infected children who displayed viral suppression (VS) with successful immune reconstitution (IS), failure to suppress virus (VF) or develop immune reconstitution (IF), or discordant immune and viral responses (VF/IS) at 24 weeks posttherapy. All children enrolled had viral RNA >4.0 log10 copies per mL and were Centers for Disease Control ad Prevention immune stage 2 or 3. Clinical, viral, and immune outcomes were assessed during the subsequent 72 weeks. RESULTS: VS/IS and VF/IS groups displayed similar sustained increases in CD4 T cells, although viral levels rebounded by 48 and 96 weeks posttherapy to pretherapy levels in the discordant group. The VF/IS outcome group had significant increases in height and weight z scores compared with entry and were similar to the VS/IS group. After treatment, antigen-specific responses after tetanus immunization were similar in the VF/IS and VS/IS groups. Prevalence of HIV-associated illnesses decreased in both VS/IS and VF/IS but not in VF/IF response groups. CONCLUSIONS: The findings indicate that viral replication under the selective pressure of protease inhibitors fails to exhibit the same deleterious impact on T-cell immunity as pretherapy viruses. CD4 T-cell counts may be a better predictor of disease progression and improvement in growth than viral burden in HIV-infected children who receive a protease inhibitor as part of a highly active antiretroviral therapy regimen.

Duke Scholars

Author John William Sleasman Pediatrics, Allergy and Immunology