The prognostic significance of serum viral load, codon 215 reverse transcriptase mutation and CD4+ T cells on progression of HIV disease in a double-blind study of thymopentin.

OBJECTIVE

To determine in asymptomatic HIV-infected subjects the prognostic value of virion reverse transcriptase (RT) codon 215 mutation, serum HIV RNA level, CD4+ T-cell count and immune complex dissociated (ICD) p24 level. The retrospective evaluation of thymopentin treatment effect on subjects in high risk groups for progression was a secondary objective.

PARTICIPANTS

Zidovudine (ZDV)-experienced asymptomatic HIV-infected subjects (n = 352) who had been enrolled in a 48-week placebo-controlled double-blind trial of thymopentin treatment were studied.

METHODS

Post hoc analyses were conducted to determine which subjects at study entry were at greater risk for progression to AIDS-related complex (ARC), AIDS or death, and to determine the effect of treatment on these subjects. Four potential prognostic variables (virion RT codon 215 mutation, circulating HIV virion RNA copies, CD4+ T-cell count, and ICD p24) were evaluated by dichotomizing subjects for each variable based on the median of the observed values. CD4+ T-cell count was evaluated prospectively, whereas frozen samples were evaluated under blinded conditions for the other variables after the study was completed.

RESULTS

The presence of the codon 215 mutation [P = 0.044; relative hazard (RH), 2.6], > or = 20,000 HIV RNA copies/ml (P = 0.002; RH, 5.5), and < 350 CD4+ cells 10(6)/l (P = 0.042; RH, 2.2) were prognostic factors, and > or = 30 pg/ml ICD p24 level (P = 0.52; RH, 1.4) was not a prognostic factor in predicting progression. Subjects were prestratified by previous ZDV use (< or = 6 or > 6 months). Across both strata thymopentin delayed treatment progression to ARC, AIDS, or death (P = 0.015; RH, 3.0). This effect was magnified in the ZDV-experienced subjects at greater risk, where thymopentin delayed progression compared to placebo in the presence of the codon 215 mutation (P = 0.007; RH, 10.1), > or = 20,000 RNA copies/ml (P = 0.012; RH, 8.9), and CD4+ T-cell count < 350 x 10(6)/l (P = 0.005; RH, 10.4).

CONCLUSIONS

Codon 215 mutation, serum HIV RNA and CD4 T-cell count are independent predictors of progression in ZDV-experienced asymptomatic subjects. Furthermore, thymopentin delays HIV disease progression in the presence of a key ZDV resistance mutation as well as high viral load and low CD4+ T-cell counts.