342   Diminished Effectiveness of Antiretroviral Therapy among Patients Initiating Therapy with CD4⁺Cell Counts Below 200/mm³.

R. S. Hogg, B. Yip, E. Wood, K. Chan, K. J. P. Craib, M. V. O'Shaughnessy, and J. S. G. Montaner.
BC Ctr. for Excellence in HIV/AIDS and Univ. of British Columbia, Vancouver, Canada.

Background:To what extent delaying initiation of antiretroviral therapy may compromise its effectiveness remains unknown. The objective of this study was to characterize the effectiveness of antiretroviral therapy initiated at various CD4 and plasma HIV-RNA thresholds.

Methods:This is a population-based analysis of antiretroviral-therapy-naïve HIV⁺persons 18 years and older who initiated triple combination therapy between August 1, 1996 and September 30, 1999. Rates of progression from the initiation of antiretroviral therapy to death were determined to be stratified using various CD4 and plasma HIV-RNA thresholds. Risk ratios of factors associated with mortality were estimated using Cox- proportional hazard models. An intent-to-treat principle was used in all analyses.

Results:A total of 1,219 persons (909 receiving PI- and 310 receiving NNRTI-containing regimens) were eligible. As of January 31, 2000, 72 patients had died of AIDS-related causes, for a crude mortality rate of 5.9%. The cumulative mortality rate at 12 months was 3.2% + 0.5%. In univariate analyses, a prior AIDS diagnosis, CD4⁺cell count, and HIV-RNA levels were found to be associated with mortality. There was no difference in mortality by age, gender, or PI use. In multivariate analyses, only CD4⁺cell count remained significantly associated with death. After controlling for AIDS diagnosis and baseline plasma HIV-RNA levels, the adjusted risk ratio was 7.36 (95% CI: [3.82, 14.21]; p < 0.001) and 3.17 (95% CI: 1.69, 5.93; p < 0.001) for patients with CD4⁺cell counts <50 cells/mm³

and 50 to 199 cells/mm³

respectively, compared to those with CD4⁺cell counts *200 cells/mm³.

Conclusions:Our data demonstrates that the effectiveness of antiretroviral therapy is independent of age, gender, AIDS diagnosis, protease-inhibitor use, and plasma HIV-RNA levels, but dependent on CD4 levels. More importantly, the effectiveness of antiretroviral therapy on survival is compromised in patients initiating therapy with CD4⁺cell counts <200 cells/mm³.