HIV-1 RNA response to antiretroviral treatment in 1280 participants in theDelta Trial: an extended virology study

Objective: To assess changes in HIV RNA and their relationship to disease p rogression. Design and setting: Delta was a randomized double-blind trial comparing zid ovudine (ZDV) monotherapy with ZDV plus didanosine (ddl) or ZDV plus zalcit abine (ddC). Participants had AIDS (with CD4 cell counts above 50 x 10(6)/l ), AIDS-related complex, or were asymptomatic with CD4 cell counts below 35 0 x 10(6)/l. The trial included both ZDV-naive and ZDV-experienced particip ants. Participants: A total of 1280 participants in the Delta trial whose serum s amples had been stored at -70 degrees C and who had a minimum of one sample taken before the start of treatment and at least one later sample. Methods: HIV-1 RNA quantification was performed using the nucleic acid sequ ence-based amplification HIV-1 RNA quantitative assay with a cut-off of 800 copies/ml. Results: Reductions in HIV RNA by treatment group were consistent with the clinical results; in ZDV-naive participants the maximum median fall occurre d at 4 weeks for all three groups (ZDV, 0.54 log(10) copies/ml; ZDV-ddl, 1. 38 log(10) copies/ml; ZDV-ddC, 1.31 log(10), copies/ml). On average the red uctions were smaller in ZDV-experienced participants but the difference bet ween the monotherapy and combination arms was very similar in ZDV-naive and experienced participants. Baseline HIV RNA levels, adjusted for CD4 cell c ounts were highly predictive of time to virological response (HIV RNA < 800 copies/ml); HIV RNA nadirs achieved were predictive of survival. Viral loa d rebound following response was independent of treatment group and previou s ZDV therapy. Conclusions: Virological changes in response to treatment are of Value in a ssessing prognosis and the activity of new therapies; in particular, there is a strong association between the minimum HIV RNA achieved in the first 1 6 weeks and subsequent clinical response. CD4 cell counts are independently predictive of response. (C) 1999 Lippincott Williams & Wilkins.