Hydroxyurea plus didanosine as maintenance therapy for HIV-infected patients on long-term successful highly active antiretroviral therapy.

BACKGROUND: Toxicity and quality of life issues have moved to delay the initiation of highly active antiretroviral therapy (HAART) and to explore novel treatment strategies for HIV infection. The switch to simpler regimens or treatment discontinuation has been attempted with limited success. The combination of hydroxyurea (HU) plus didanosine (ddI) is a simple regimen that might be able to restrain virus replication for long periods of time and could be an acceptable option as maintenance therapy in patients on prolonged successful HAART. METHOD: The combination of HU (500 mg bid) plus ddI (400 mg qd) was offered to participants with viral load (VL) <50 HIV RNA copies/mL and CD4 counts >350 cells/microL for more than 6 months under HAART. The prior HAART regimen was resumed if VL rose to >5,000 copies/mL and/or the CD4 count fell to <200 cells/microL after being on HU + ddI maintenance therapy. RESULTS: A total of 187 participants replaced HAART with HU + ddI. In an intent-to-treat analysis at 48 weeks, 109 (58%) and 77 (41%) patients had VL below 5,000 and 500 HIV RNA copies/mL, respectively. The mean CD4 count dropped from 809 +/- 283 to 573 +/- 270 cells/microL, while 77% of patients remained above 350 cells/microL. The proportion of participants with hypercholesterolemia declined from 70% to 46% (p <.001), while those with hypertriglyceridemia fell from 36% to 21% (p <.05). Significant improvements in lipohypertrophy and lipoatrophy were observed in 52% and 64% of participants, respectively. Grade 3-4 toxicities appeared in 20 patients (11%), including 3 cases of pancreatitis and 1 of peripheral neuropathy. Prior history of VL >5 log, CD4 counts <200 cells/microL, and ddI experience were independently associated with lower response to HU + ddI maintenance therapy. CONCLUSION: The combination of HU + ddI may be a satisfactory maintenance therapy for more than half of patients on successful HAART who want to alleviate drug-related toxicities and/or pill burden. Patients with metabolic and/or body-shape abnormalities might particularly benefit from switching to this simple regimen.