The HYDILE trial: efficacy and tolerance of a quadruple combination of reverse transcriptase inhibitors versus the same regimen plus hydroxyurea or hydroxyurea and interleukin-2 in HIV-infected patients failing protease inhibitor-based combinations.

PURPOSE: To compare the efficacy and tolerance of a stavudine (d4T), didanosine (ddI), efavirenz (EFV), and abacavir (ABC) combination regimen with an identical regimen plus hydroxyurea (HU), or plus HU and interleukin-2 (IL-2), in patients failing protease inhibitor-based combinations and naive of EFV and ABC. METHOD: This was a randomized prospective trial in 69 HIV-infected patients recruited in one clinical center. Antiretroviral drugs were administered at standard doses according to weight. HU was added at week 6 at 500 mg twice daily. Three courses of IL-2 were given subcutaneously at 4.5 MU twice daily for 5 consecutive days, between weeks 24 and 40. The proportion of patients reaching plasma HIV-1 RNA <200 and <50 copies/mL was compared in the three trial groups at weeks 6, 24, and 48 using intent-to-treat and as-treated analyses. CD4+ T-cell count changes from baseline were also assessed at the same time points, along with anthropometric and metabolic measurements. RESULTS: After 48 weeks, only 25% of patients receiving antiretrovirals had plasma HIV-1 RNA <200 copies/mL versus 59.1% in the group receiving HU and 56.5% in the group receiving HU and IL-2 (intent-to-treat; p <.01). At the 50 copies/mL cutoff, the results were 20.8%, 54.5%, and 47.8%, respectively. Most treatment discontinuations were due to failure in the first group and adverse events in the two others. A median decline of 27 CD4+ cells was observed in patients receiving antiretrovirals plus HU, against a gain of 78-118 cells at week 48 in patients receiving antiretrovirals alone or in combination with HU and IL-2. More patients were affected by clinical fat atrophy symptoms at week 48 than at baseline. Additionally, a trend toward increased cholesterol levels was observed throughout the study. CONCLUSION: During this trial, virologic response in patients failing previous regimens was clearly enhanced by the addition of HU, despite d4T and ddI recycling. Although adverse events were more frequent in the HU-containing arms, no unexpected toxicity was observed and the blunted CD4 response prompted by HU was corrected by the addition of IL-2. The combination of HU with reverse transcriptase inhibitors can therefore be regarded as a valuable alternative for patients with few remaining therapeutic options.