TREATMENT HISTORY AND BASE-LINE VIRAL LOAD, BUT NOT VIRAL TROPISM OR CCR-5 GENOTYPE, INFLUENCE PROLONGED ANTIVIRAL EFFICACY OF HIGHLY-ACTIVE ANTIRETROVIRAL TREATMENT

Background: The efficacy of highly active antiretroviral treatment (HA ART) in HIV-1 disease may vary between nucleoside-naive and experience d patients as well as between patients with different viral phenotypes and in different stages of disease. Objective: To investigate variabl es of importance for successful long-term viral suppression by analysi ng virological, clinical and immunological characteristics at initiati on of protease inhibitor treatment on suppression of HIV RNA over 1 ye ar. Design: An open, non-randomized, observational clinical study. Set ting: Venhalsan, Department of Dermatovenereology, Soder Hospital, Sto ckholm, Sweden. Patients: A total of 147 unselected advanced patients with known HIV-1 infection For a mean of 7 years, of whom 37% had AIDS and who started treatment with a protease inhibitor during 1996. Inte rventions: All patients received HAART with at least two nucleoside an alogues in combination with either indinavir (81%) or ritonavir (19%). The majority (77%) had been previously treated with nucleoside analog ues for a mean of 39 months. Measurements: CD4+ lymphocyte count, plas ma HIV-1 RNA, viral phenotype and HIV-1 coreceptor CCR-5 genotype at b aseline. Viral load and CD4+ lymphocyte count were determined every 3 months. Results: Patients were analysed on an intention-to-treat basis . The mean CD4+ lymphocyte count at baseline was 170 x 10(6)/l and the median viral load was 68 600 copies/ml. Heterozygosity for the Delta 32 deletion of the CCR-5 gene (Delta 32/wt) was found in 27%. MT-2 pos itive virus (syncytium-inducing) was isolated in 46%. Logistic regress ion revealed that nucleoside analogue experience and baseline log,, HI V-1 RNA were the only factors independently related to plasma HIV-1 RN A levels below 500 copies/ml after 1 year of treatment, which was foun d in 69%. Conclusion: The virological outcome after 1 year of HAART wa s strongly correlated to prior treatment history and baseline viral lo ad, whereas CD-4+ lymphocyte count, CCR-5 genotype and viral biologica l phenotype had less influence. The long-term antiviral efficacy of HA ART was lowest in individuals with previous nucleoside analogue treatm ent and a high baseline viral load. In these individuals an even more aggressive treatment should be considered. (C) 1998 Lippincott William s & Wilkins