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Health Implications of Low CD4-Cell Counts

Data presented at the 14th Retrovirus Conference confirm that the risk for non-AIDS-related death increases as CD4-cell counts fall.

Potent combination antiretroviral therapy has dramatically reduced AIDS-related morbidity and mortality, but how does persistent partial immunodeficiency, as reflected by low CD4-cell counts, affect overall health? Previous reports from both the DAD study (ACC Mar 21 2005) and the SMART study (ACC Nov 29 2006) indicate an increase in non-AIDS-related deaths (from kidney, liver, and cardiovascular disease and from non-AIDS-related cancer) with lower CD4-cell counts. Now, data from the 14th Retrovirus Conference confirm these reports.

In a French study comparing causes of death among HIV-infected people in 2005 versus 2000 [Abstract 976], AIDS remained the most common cause of death (mostly from non-Hodgkin lymphoma), but the proportion of deaths due to non-AIDS-related cancer and to liver, kidney, and heart disease increased and was generally explained by comorbidities. In another study from France [Abstract 525], the absolute risk for death after first AIDS-defining illness was similar for AIDS- and non-AIDS-defining causes. And in an analysis from the Antiretroviral Cohort Collaboration [Abstract 972], estimated life expectancy was lower for patients who started potent antiretroviral therapy at CD4 counts <200 cells/mm³ (31 years) than among those who started at CD4 counts 350 cells/mm³ (38 years).

In an updated analysis from the DAD study, fatal non-AIDS-related cancer was more common than AIDS-defining cancer among patients on potent antiretroviral therapy [Abstract 84]. Viral load did not influence rates of death from non-AIDS-defining cancer, but latest CD4-cell count did (relative risk, 15 for CD4 counts <50 vs. >500 cells/mm³). A report from the FIRST study described the relation between nonopportunistic disease and CD4-cell count in a randomized clinical trial in which all subjects were receiving antiretroviral treatment [Abstract 37]. As latest CD4-cell counts increased, risk for nonopportunistic diseases decreased, but to a lesser degree than seen with AIDS-defining diseases. At CD4 counts >200 cells/mm³, morbidity and mortality were most often due to non-AIDS-defining events. After adjustment for other factors, latest CD4-cell count predicted risk for non-AIDS-defining events.

Cumulatively, these results indicate that we need to broaden our view of what constitutes HIV-related disease, both in clinical trials and in practice. If low CD4-cell counts are bad for health, then seeing patients early in disease affords them the best opportunity to achieve optimal health. Unfortunately, many HIV-infected people continue to access care late (at CD4 counts <200 cells/mm³) in both resource-rich and resource-poor settings (ACC Apr 2 2007), highlighting our continuing failure to identify infected persons early and connect them with effective care.

— Keith Henry, MD

Dr. Henry was a coauthor on the report from the FIRST study (Abstract 37).

Published in AIDS Clinical Care April 2, 2007