Joint effects of HIV-1 RNA levels and CD4 lymphocyte cells on the risk of specific opportunistic infections

Objectives: To evaluate the predictive value of baseline plasma HIV-1 RNA levels and CD4 lymphocyte counts and early changes in these markers after initiating antiretroviral therapy on the risk of development of specific opportunistic infections (OIs). Design: Patient data from four antiretroviral therapy studies were combined for a retrospective analysis. The analysis included 837 participants from the virology substudies of these trials who had baseline measurements for both HIV-1 RNA levels and CD4 cell counts. Methods: Cox proportional hazards models were used to assess the joint effects of baseline CD4 cell count and HIV-1 RNA level and early treatment-associated changes in these values on the risk of development of Pneumocystis carinii pneumonia (PCP), cytomegalovirus (CMV), or Mycobacterium avium complex (MAC). The effects of potential confounders such as prior prophylaxis and previous OIs were also addressed. Results: Baseline CD4 cell counts and HIV-1 RNA measurements showed significant associations with the risk of PCP, CMV, and MAC. Patients with higher levels of HIV-1 RNA were estimated to have three to six times the risk of these OIs than those with lower levels. Reductions in viral load were linked to significantly reduced risks of PCP, CMV, and MAC. Early decreases in RNA were generally more predictive of risk than were early increases in CD4 cell counts. Conclusions: Baseline viral load and reductions in viral load during therapy appeared to influence the risk of these OIs independently of the CD4 cell count. Future guidelines for the initiation of prophylaxis for these OIs may be improved by incorporating information on viral load.