Relationship between CD4 cell count and serious long-term complications among HIV-positive individuals

To summarize recent findings on the relationship between CD4 cell count metrics and selected serious clinical outcomes, and to deduce implications for CD4 cell count monitoring in treated HIV infection and the timing of combination antiretroviral therapy initiation.

In treated HIV infection, a higher latest CD4 cell count is associated with a lower short-term risk of serious non-AIDS events (often composite endpoints) even in CD4 cell count strata more than 350/μl. Knowledge of alternate CD4 cell count metrics, such as CD4 cell count slope, nadir level and time spent under specific CD4 cell count thresholds, does not seem to confer additional prognostic information beyond that achieved by current CD4 cell count. Latest CD4 cell count is strongly associated with a short-term risk of infection-related non-AIDS malignancies, and serious hepatic events; however, the evidence is inconsistent for cardiovascular outcomes. Studies vary significantly in definitions of composite endpoints as well as the rigorousness of outcome ascertainment, which could explain the heterogeneity in results.

Current CD4 cell count, but not other metrics, could be an important clinical tool to predict the short-term risk of serious non-AIDS events in treated HIV-positive individuals. An earlier initiation of therapy at CD4 cell count more than 350/μl or above 500/μl is likely to improve long-term CD4 cell count metrics. Whether it provides net individual clinical benefit requires a randomized trial.