203   CD4⁺Cell Count Is a Better Predictor of Disease Progression than HIV RNA Level in Persons with Advanced HIV Infection on Highly Active Antiretroviral Therapy.

R. D. MacArthur*, G. Perez, S. Walmsley, J. Baxter, J. Neaton, and D. Wentworth.
Wayne State Univ., Detroit, MI; North Jersey Community Res. Initiative, Newark; Toronto Gen. Hosp., Ontario, Canada;.Cooper Hosp./Univ. Med. Ctr., Camden, NJ;.Univ. of Minnesota, Minneapolis; Terry Beirn Community Programs for Clin. Res. on AIDS 042/045 Protocol Teams; and Canadian Trials Network 102 Protocol Team.

Background:For persons on HAART, the relative prognostic importance of proximal (prox) follow-up (f/u) levels of CD4⁺cells (CD4s) and viral load (VL), vs baseline values, for progression to AIDS/death has not been established. This issue was investigated in CPCRA 042/045-CTN 102, a study of AR-naïve or -experienced HIV⁺persons with CD4s <200 cells/mL who were randomized to different HAART regimens and followed for progression to AIDS or death.

Methods:CD4s, VL, and clinical events were recorded at least every 4 months. Using all f/u values, tertiles (Tls) for CD4s and VL were determined. Using proportional hazards regression with time-dependent covariates corresponding to prox (updated every 4 months) CD4s and VL, considered simultaneously, hazard ratios for the lower 2 Tls of CD4s compared to the highest Tl and for the upper 2 Tls of VL compared to the lowest Tl were estimated.

Results:610 persons were followed for an average of 2.5 yrs. Median (med) baseline CD4 was 42 cells/mL; med baseline VL was 119,000 copies/ml. CD4s increased to a med of 137 cells/mL after 12 months and to 154 cells/mL after 24 months. 172 persons (28%) developed a disease progression event or died. Of these 172 patients, only 5 (3%) had CD4s of <250 cells/mL immediately preceding the event. Compared to the highest Tl of CD4s (>190 cells/mL), the hazard ratios for the lower two Tls (<80 cells/mL and 80—190 cells/mL) were 7.0 (95% CI: 3.3—15.0) and 2.4 (95% CI: 1.1—5.3), after adjustment for prox VL. Compared to the lowest Tl of VL (<400 copies/ml), the hazard ratios for the upper 2 Tls (>50,000 copies/ml and 400—50,000 copies/ml) were 2.2 (95% CI: 1.2—4.1) and 1.4 (95% CI: 0.8—2.5), after adjustment for prox CD4s.

Conclusions:Both prox CD4s and VL data provide information on disease prognosis in persons on HAART. For persons with advanced HIV infection on HAART, risk of disease progression is predicted better by prox CD4s than by prox VL.