The Relationship of Preventable Opportunistic Infections, HIV-1 RNA, and CD4 Cell Counts to Chronic Mortality

Both HIV-1 RNA and absolute CD4 cell counts have been identified as important predictors of HIV-1 disease progression and mortality. The independent impact of opportunistic infections on the risk of chronic mortality, defined as death beyond 30 days of an opportunistic infection, has not been studied when controlling for HIV-1 RNA. Our objective was to determine the relationship between a history of any of five preventable opportunistic infections (Pneumocystis carinii pneumonia, Mycobacterium avium complex, toxoplasmosis, cytomegalovirus, and candida esophagitis) and chronic mortality.Using the Multicenter AIDS Cohort Study (MACS) public use data set of 2193 HIV-infected men in four U.S. cities, we employed a Cox regression model to estimate the impact of a history of preventable opportunistic infection on chronic mortality while controlling for maximum HIV-1 RNA, CD4 cell count, use of antiretroviral drugs, and age.The chronic mortality rate among individuals with a history of preventable opportunistic infection was 66.7 per 100 person-years compared with 2.3 per 100 person-years for those without a history of preventable opportunistic infection (RR = 28.4, 95% CI: 24.7-32.8). In the adjusted analysis, the relative hazard of death for those with a history of preventable opportunistic infections was 7.0 (5.8-8.3), whereas antiretroviral therapy was associated with a decreased risk of death (0.37 [0.30-0.44]). We found no association between maximum HIV-1 RNA and chronic mortality. There was statistically significant effect modification between preventable opportunistic infections and CD4 cell count (p <.0001).Preventable opportunistic infections cause not only short-term mortality in HIV-1 disease but appear to have a major impact on chronic mortality.