PROGRESSIVE CD4 CELL DEPLETION AND DEATH IN ZIDOVUDINE-TREATED PATIENTS

Preliminary evidence suggests that a CD4 cell count <50 cells/mm3 is a ssociated with a particularly poor short-term prognosis, and is both n ecessary and sufficient for death associated with HIV infection. We so ught to validate these findings in a cohort of 1,415 zidovudine (ZDV)- treated patients, with advanced HIV infection, and to examine more clo sely the profile of CD4 cell decline over the 2 years prior to death. As of December 31, 1991, 432 patients had died. The cumulative 2 year survival of patients once their CD4 cell count fell to less-than-or-eq ual-to 50 cells/mm3 (median survival = 17.3 months) was substantially shorter at 25.7%, than from when their CD4 cell counts first fell with in the range 51-100/mm3 (51.4%); 101-150/mm3 (67.3%); or 151-200/mm3 ( 76.5%). The percent of patients with a CD4 count <50 cells/mm3, increa sed from 33% at 24 months prior to death to 58% at 12 months and 86% a t 1 month. Patients with a CD4 count less-than-or-equal-to 50 cells/mm 3 in the month prior to death, were significantly older (p <0.001) and had higher CD4 cell counts (p <0.05) at initiation of ZDV compared to those with a CD4 count <50 cell/mm3. There were no important differen ces in HIV risk category, duration of ZDV therapy or use of PCP prophy laxis between the two groups. These findings highlight the importance of more intensive monitoring of patients with CD4 counts <50 cells/mm3 , since life-threatening opportunistic infections are more likely to s upervene at this stage. A CD4 count <50 may also be a useful surrogate endpoint for survival in clinical trials.