Are HIV-infected patients with rapid CD4 cell decline a subgroup who benefit from early antiretroviral therapy?

We have developed a model to determine whether asymptomatic HIV-infected in dividuals who have a rapid CD4 cell decline are a subgroup who might benefi t from early antiretroviral therapy. Data were obtained from a subgroup of participants in the Concorde and EACG020 trials, two randomized, double-bli nd, comparative trials of immediate (IMM) versus deferred (DEF) zidovudine therapy in asymptomatic HIV-infected individuals. The subgroup comprised 29 7 patients (IMM = 154, DEF = 143) who had at least one CD4 cell count befor e and after randomization. The median CD4 cell count at randomization was 4 91 x 10(6)/L, and the median follow-up was 61 months. The rate of CD4 decli ne before and after randomization was estimated using multi-level linear re gression analysis, and patients were stratified into quartiles according to the rate of CD4 cell decline before randomization. Outcome measures were t he development of AIDS, a 50% drop in CD4 count from the baseline, and deat h. A Cox proportional hazards model was used to examine whether the effect of zidovudine on disease progression varied according to the previous rate of CD4 decline. We found that a more rapid rate of CD4 decline before rando mization was associated with a greater reduction in the rate of CD4 decline following IMM antiretroviral therapy (r = -0.5, P = 0.03). The greatest ri sk reduction in disease progression with IMM antiretroviral therapy was see n in the quartile of patients with the highest rate of CD4 decline (greater than or equal to 26 x 10(6) cells/L per 6 months) (hazards ratio (HR) = 0. 61, 95% CI = 0.35-1.05). However, this effect was statistically significant in only the Concorde trial (HR = 0.48, 95% CI = 0.29-0.89). In contrast, w e found no evidence in the EACG020 trial of any trend towards greater benef it in those with the most rapid CD4 cell decline. These findings suggest th at asymptomatic patients with rapid CD4 cell decline are a subgroup likely to benefit from early antiretroviral therapy. This analytic approach should now be replicated in trials of combination therapy, and these should inclu de viral load data.