Safety and antiretroviral effects of combined didanosine and stavudine therapy in HIV-infected individuals with CD4 counts of 200 to 500 cells/mm(3)

The safety and antiretroviral effects of didanosine and stavudine in combin ation were evaluated in 86 people infected with HIV with CD4 counts between 200 and 500 cells/mm(3) who had received <7 days of prior nucleoside analo gue antiretroviral treatment. Patients were randomized to receive blinded t reatments with one of five weight-adjusted, twice-daily regimens of didanos ine and stavudine (100 + 10 mg, 100 + 20 mg, 100 + 40 mg, 200 + 20 mg, and 200 + 40 mg) for up to 1 year. Dosages were adjusted appropriately for pati ents weighing <60 kg and reduced in response to adverse effects. No clear d ose-related differences among treatment groups were detected with regard to suppression of plasma HIV RNA level or reduction in infectious titers in p eripheral blood mononuclear cells (PBMCs), improvement in CD4 count, or adv erse effects. However, trends toward greater decreases in viral load and in creases in CD4 count were detected when treatment groups containing the ful l recommended dosage of one or both agents (high-dose subgroup; arms 3, 4, and 5) were compared with the groups receiving lower dosages. At 28 weeks t he mean log 10 HIV RNA decrease was 1.12 (n = 52) and at 52 weeks it was 0. 97 (n = 32). Combination therapy was well tolerated, with no apparent dose- related adverse effects. Peripheral neuropathy occurred in 2 of 86 (2.3%) o f patients. Didanosine and stavudine together appear to be a good nucleosid e analogue foundation for aggressive triple- or quadruple-drug therapy. Ful l therapeutic doses of each of these two agents should be used to achieve o ptimal suppression of HIV replication.