The effectiveness of combination antiretroviral therapy in clinical practice

The results of clinical trials of combination antiretroviral therapy have ushered in an era of unprecedented optimism in the care of HIV-infected patients. However, the impact of these new drugs in clinical practice is not yet known. We analyzed the incidence rates of several opportunistic infections associated with advanced immunosuppression in HIV disease, hospitalisation, and death from 1991 through 1996 in a large clinical practice cohort. We also assessed the use of combination antiretroviral therapy, changes in CD4 level and HIV-1 RNA, and the association of these variables with these incidence rates. During 1996, there was a significant decrease in the incidence of cytomegalovirus disease (CMV) (Relative Risk=0.19; 95% CI: .06, .59), as well as non-significant decreases in toxoplasmosis (RR=0.44; 95% CI: .13,1.40), and Mycobacterium avium complex disease (MAC) (RR=0.65; 95% CI: .38,1.12) compared to earlier years. There was also a significant decrease in the rate of hospitalisation (RR=0.74; 95% CI: .62,.87). There was no appreciable decrease in the incidence of P. carinii pneumonia nor in the mortality rate in 1996. Compared to combination nucleoside therapy alone, patients receiving protease inhibitor therapy had significantly greater median declines in HIV-1 RNA (1.0 log decline vs. 0.5 log decline in the number of copies) and greater median increases in CD4 counts (+67 cells/mm³ vs. +24 cells/mm³). Use of combination antiretroviral therapy, increase in CD4 of >50 cells/mm³ and decrease in HIV-1 RNA to undetectable with combination therapy was associated with the decrease in rates of CMV, MAC, and toxoplasmosis. Incidence rates of opportunistic illness associated with advanced immuno- suppression and hospitalization rates have declined in 1996 and are associated with the use of combination antiretroviral therapy.