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

OBJECTIVE: To assess changes in HIV RNA and their relationship to disease progression. DESIGN AND SETTING: Delta was a randomized double-blind trial comparing zidovudine (ZDV) monotherapy with ZDV plus didanosine (ddI) or ZDV plus zalcitabine (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 350 x 10(6)/l. The trial included both ZDV-naive and ZDV-experienced participants. PARTICIPANTS: A total of 1280 participants in the Delta trial whose serum samples 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 sequence-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 occurred at 4 weeks for all three groups (ZDV, 0.54 log10 copies/ml; ZDV-ddI, 1.38 log10 copies/ml; ZDV-ddC, 1.31 log10 copies/ml). On average the reductions were smaller in ZDV-experienced participants but the difference between the monotherapy and combination arms was very similar in ZDV-naive and experienced participants. Baseline HIV RNA levels, adjusted for CD4 cell counts were highly predictive of time to virological response (HIV RNA < 800 copies/ml); HIV RNA nadirs achieved were predictive of survival. Viral load rebound following response was independent of treatment group and previous ZDV therapy. CONCLUSIONS: Virological changes in response to treatment are of value in assessing prognosis and the activity of new therapies; in particular, there is a strong association between the minimum HIV RNA achieved in the first 16 weeks and subsequent clinical response. CD4 cell counts are independently predictive of response.