Journal of Antimicrobial Chemotherapy (1999) 43, 379-388
© 1999 The British Society for Antimicrobial Chemotherapy
Are HIV-infected patients with rapid CD4 cell decline a subgroup who benefit from early antiretroviral therapy?
a Chelsea and Westminster Hospital, London; b MRC HIV Clinical Trials Centre, London, UK; c University of New South Wales, Sydney, Australia
We have developed a model to determine whether asymptomatic HIV-infected individuals who
have a rapid CD4 cell decline are a subgroup who might benefit from early antiretroviral
therapy. Data were obtained from a subgroup of participants in the Concorde and EACG020
trials, two randomized, double-blind, comparative trials of immediate (IMM) versus deferred
(DEF) zidovudine therapy in asymptomatic HIV-infected individuals. The subgroup comprised
297 patients (IMM = 154, DEF = 143) who had at least one CD4 cell count before
and after randomization. The median CD4 cell count at randomization was 491 x 106/L, and the median follow-up was 61 months. The rate of CD4 decline before and
after randomization was estimated using multi-level linear regression analysis, and patients were
stratified into quartiles according to the rate of CD4 cell decline before randomization. Outcome
measures were the development of AIDS, a 50% drop in CD4 count from the baseline, and
death.
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 randomization was associated with a greater reduction in the
rate of CD4 decline following IMM antiretroviral therapy (r= -0.5, P= 0.03). The greatest risk reduction in disease progression with IMM antiretroviral
therapy was seen in the quartile of patients with the highest rate of CD4 decline (
26 x
106 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, we found no evidence in
the EACG020
trial of any trend towards greater benefit in those with the most rapid CD4 cell decline. These
findings suggest that 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 include viral load data.
* Correspondence address. Department of HIV and Genitourinary Medicine, Kings College Hospital, 15-22 Caldecot Road, London SE5 9RS, UK. Tel: +44-171-346-4891.