ANTIRETROVIRAL EFFECT AND SAFETY OF ABACAVIR ALONE AND IN COMBINATIONWITH ZIDOVUDINE IN HIV-INFECTED ADULTS

Objectives: To evaluate, over 12 weeks, the antiretroviral activity an d safety of abacavir, used alone and in combination with zidovudine (Z DV), as treatment for HIV-1-infected subjects who had limited or no an tiretroviral treatment. Design: Seventy-nine HIV-1 infected subjects, with CD4 cell counts 200-500 x 10(6)/l and <12 weeks of previous treat ment with ZDV were enrolled in a multicenter study. Subjects were rand omly assigned to one of four cohorts receiving abacavir monotherapy fo r the first 4 weeks (200, 400, or 600 mg every 8 h daily, or 300 mg ev ery 12 h daily) and, thereafter, combination therapy of abacavir with 600 mg ZDV or ZDV placebo, administered in a double-blind manner for a n additional 8 weeks. Methods: Antiretroviral activity was assessed by measuring changes in plasma HIV-1 RNA levels and CD4+ cell counts. Sa fety was assessed by monitoring clinical adverse events and laboratory abnormalities during the 12-week period and for 4 weeks post-treatmen t. Results: Treatment with abacavir, alone or in combination with ZDV, produced marked decreases in plasma HIV-1 RNA loads and increases in CD4+ cell counts in all groups. At week 4, median plasma HIV-1 RNA loa ds decreased by 1.11-1.77 log(10) copies/ml and median CD4+ cell count s increased by 63-111 x 10(6)/l in all groups. At week 12, median HIV- 1 RNA loads decreased by 1.02-2.24 log(10) copies/ml (abacavir monothe rapy) and by 1.81-2.01 log(10) copies/ml (abacavir-ZDV); median CD4+ c ell counts increased by 79-195 x 10(6)/l (abacavir monotherapy) and by 93-142 x 10(6)/l (abacavir-ZDV). At week 12, the percentage of subjec ts who had plasma HIV-1 RNA levels below 400 and 40 copies/ml were 28 and 11%, respectively (abacavir monotherapy) and 69 and 22%, respectiv ely (abacavir-ZDV). Eight subjects (10%) discontinued the study premat urely because of adverse events; nausea (n = 4) and hypersensitivity ( n = 3) were the most common reasons for withdrawal. There were no deat hs among the study subjects. Conclusions: In HIV-infected subjects who have received little or no prior antiretroviral therapy, treatment wi th abacavir alone or in combination with ZDV is