SIZE AND DURATION OF ZIDOVUDINE BENEFIT IN 1003 HIV-INFECTED PATIENTS- US ARMY, NAVY, AND AIR-FORCE NATURAL-HISTORY DATA

Objectives: The study's objectives were to determine the size and dura tion of benefits of early versus delayed versus late treatment with zi dovudine (ZDV) on disease progression and mortality in HIV-infected pa tients, and whether patients rapidly progressing before ZDV treatment had a different outcome from those not rapidly progressing before ZDV. Design: The design was an inception cohort of 1003 HIV-infected patie nts. One hundred and seventy-four of the 1003 patients were treated be fore CD4 counts fell to 1400 x 10(9)/L, (''early treatment''); 183 of 1003 patients were treated after CD4 counts fell to <400 x 10(9)/L but before clinical disease developed (''delayed treatment''); and 646 of the 1003 patients had either been treated after clinical disease deve loped or had not been treated at all by the end of follow-up (''late t reatment''). Outcomes were progression to clinical HIV disease and mor tality. Results: The relative risk (RR) of progression for early versu s delayed treatment was 0.58 (p < .03), and durability of ZDV benefits on progression was estimated at no more than 2.0 years; however, this estimate had wide confidence intervals. The RR of progression for del ayed versus late treatment was 0.54 p < .0001, and durability of ZDV b enefits was estimated at 1.74 years; this estimate had narrow confiden ce intervals. Survival was better for the early versus delayed treatme nt (RR = 0.55), but this difference was not statistically significant. In the subgroup of patients with more rapid CD4 decline prior to ZDV therapy, significant benefits on progression were observed for early v ersus delayed ZDV therapy (RR = 0.42, p = .02) and delayed versus late ZDV therapy (RR = 0.51; p = .0004). Duration of benefit was estimated to be 4.5 years (early versus delayed) and 1.7 years (delayed versus late). For patients with less rapid pre-ZDV decline in CD4 levels, a s ignificant progression benefit was observed for delayed versus late th erapy (RR = 0.50; p = .02). Duration of benefit in this subgroup was e stimated to be 1.8 years. No significant benefit was found for early v ersus delayed treatment (RR = 1.12) in the less rapid pre-ZDV CD4 cell decline subgroup. Conclusions: Early treatment compared with delayed treatment was associated with a sizable reduction in HIV progression, but the duration of benefits was estimated to last only about 2 years. Delayed treatment compared with late treatment with ZDV was associate d with substantial reduction of progression, but this reduction was al so clearly limited in duration. Benefits on progression and mortality for the early treatment group were heavily dependent on the pre-ZDV CD 4 slope. In the subgroup of patients with the most rapid pre-ZDV CD4 c ell declines, the duration of benefit was much longer, possibly as lon g as 4 years.