Pa. Volberding et Nmh. Graham, INITIATION OF ANTIRETROVIRAL THERAPY IN HIV-INFECTION - A REVIEW OF INTERSTUDY CONSISTENCIES, Journal of acquired immune deficiency syndromes, 7, 1994, pp. 190000012-190000023
A number of clinical trials have explored the optimal dosage for antir
etroviral therapy and, in various ways, the optimal time, in terms of
stage of human immunodeficiency virus (HIV) disease, at which treatmen
t should begin. Some studies have shown that treatment with zidovudine
results in a delay in progression to more advanced stages of HIV dise
ase, and that the benefits are more durable among persons who started
zidovudine with higher CD4(+) cell counts. Efficacy is preserved and t
oxicity is reduced when zidovudine is used at dosages lower than those
originally recommended. The Concorde study found that administration
of zidovudine to asymptomatic persons was associated with increases in
CD4(+) cell counts and improvement in delaying disease progression at
55 weeks, but found no correlation between time of initiation of ther
apy and either longer-term delay in onset of symptomatic disease or ul
timate survival. The analysis of these results, however, is complicate
d because of premature crossover of study participants from deferred t
reatment to immediate treatment. The consensus of the discussants of t
hese studies is that antiretroviral treatment should be initiated by t
he time the CD4(+) cell count has fallen to 200-500 cells/mm(3). Altho
ugh recognizing that, in general, viral infections call for treatment,
the panelists were divided in their opinions about treatment of asymp
tomatic patients with CD4(+) cell counts >500/mm(3).