Effects of treatment intensification with hydroxyurea in HIV-infected patients with virologic suppression

Background: Virologic rebound can result from suboptimal antiviral potency in combination antiretroviral therapy. Design: Multicenter, partially blinded, prospective, randomized study of 20 2 HIV-infected subjects to determine whether therapy intensification improv es long-term rates of virologic suppression. Methods: Subjects had plasma HIV RNA < 200 copies/ml, CD4 cell count of > 2 00 x 10(6) cells/l, and treatment with indinavir (IDV) + izidovudine (ZDV) + lamivudine (3TC) for at least 6 months before randomization to stay on th is regimen or to receive IDV + didanosine (ddl) + stavudine (d4T) plus or m inus hydroxyurea (HU) (600 mg twice daily). Treatment failure was defined a s either confirmed rebound of HIV RNA level to > 200 copies/ml or a drug to xicity necessitating treatment discontinuation. Results: Treatment failure occurred more frequently in subjects randomized to the HU-containing arm (32.4%), than in those taking IDV + ddl + d4T (17. 6%) or IDV + ZDV + 3TC (7.6%). The time to treatment failure was shorter fo r the HU-containing arm compared with the IDV + ZDV + 3TC (P < 0.0001) or I DV + ddl + d4T arms (P = 0.032). Dose-limiting toxicities rather than virol ogic rebound accounted for the differences between treatment failure among the study arms. Pancreatitis led to treatment discontinuation in 4% of subj ects in treatment arms containing ddl + d4T. Three subjects with pancreatit is died, all randomized to the HU-containing arm. Conclusions: Switching to IDV + ddl + d4T + HU in patients treated with IDV + ZDV + 3TC was associated with a worse outcome, principally because of dr ug toxicity. (C) 2001 Lippincott Williams & Wilkins.