Modeling changes in CD4-positive T-lymphocyte counts after the start of highly active antiretroviral therapy and the relation with risk of opportunistic infections - The Aquitaine Cohort, 1996-1997

After initiation of a treatment for human immunodeficiency virus type 1 inf ection containing a protease inhibitor, immune restoration associated with increases in CD4-positive (CD4+)T lymphocyte count may be delayed. In a sam ple of patients who had been prescribed protease inhibitors for the first t ime, the authors tested to see whether there was a minimal duration of CD4 cell count increase before the increase had an impact on the occurrence of opportunistic infections. The evolution (difference between time t and bas eline) of CD4+ cell count was modeled using a mixed effects linear model. C hanges in CD4+ count estimated by this model were then included as time-dep endent covariates in a proportional hazards model. Finally, the authors tes ted for the existence of a CD4+ change x time interaction. The authors used a sample of 553 French patients first prescribed protease inhibitors in 19 96 and followed for a median of 16 months. During the first 120 days, there was no association between CD4+ change and the rate of opportunistic infec tions. After 120 days, each 50-cell/mm(3) increase in CD4+ count was associ ated with a 60% (95% confidence interval: 45, 72) reduction in the incidenc e of opportunistic infections. These results, based on modeling of CD4+ cel l response, at least indirectly reinforce the concept of a delayed but poss ible immune recovery with the use of protease inhibitors. The findings supp ort the potential for interruption of certain types of prophylaxis against opportunistic infections under reasonable conditions of duration of antiret roviral therapy and sustained CD4+ cell response.