Predictors of optimal virological response to potent antiretroviral therapy

Background: Current potent antiretroviral therapy (using a protease inhibit or and two nucleoside reverse transcriptase inhibitors) produces a durable suppression of HIV replication in less than 75% of treated patients. Identi fication of predictors of successful therapy might allow the development of improved strategies to increase response rates. Methods: We analyzed retrospectively the results from a multicenter, random ized, double-blind Phase III study of combination anti-HIV therapy with nel finavir, zidovudine, and lamivudine to evaluate the relationship between vi rological response over 48 weeks of treatment to variables which could pote ntially serve as early predictors of long-term response. The goal was to pr oduce long-term suppression of viral load to sensitive (< 400 copies HIV RN A/ml) and ultrasensitive (< 50 copies HIV RNA/ml) limits of quantification with the Amplicor PCR assay. Findings: Baseline viral load, the change in viral load over the first 4 we eks of treatment, the 2 h post-dose nelfinavir levels and the time to respo nd to HIV RNA levels of < 400 copies/ml and < 50 copies/ml have the best pr edictive value in determining response and response duration. Patients who achieved very low viral nadirs (< 50 copies HIV RNA/ml) had significantly l onger responses than those who achieved nadirs of 50-400 copies HIV RNA/ml. Interpretation: Parameters that can be measured easily at baseline or early after therapy is started can identify patients at high risk of failure wit h standard treatment. Such patients may be candidates for more aggressive t herapy or for alternative strategies designed to improve outcome. In additi on, these results support the use of ultra-sensitive HIV RNA assays to pred ict long-term outcome of anti-HIV therapy. (C) 1999 Lippincott Williams & W ilkins.