ddI + d4T Combination Therapy Proves Effective

Two French studies presented at the 4th National Conference on Retroviruses and Opportunistic infections confirmed the benefit of combination therapy with ddI and d4T. One group from Nice led by Durant treated 25 patients with mean entry CD4 counts of 116 cells/mm3 and plasma RNA levels of 199,792 with the combination of ddI and d4T at standard doses. patients were either not eligible for AZT therapy due to hematological, digestive or muscular intolerance or had evidence of clinical or CD4 failure on AZT therapy. After an average follow-up of 12 weeks a one log reduction in HIV RNA was observed and 33% had undetectable levels of virus in addition to a substantial increase in CD4 cells (mean 45 cells). Tolerance was good with only 4 patients having adverse effects which required discontinuation of therapy (3 neuropathies and one hyperamylasemia). No AIDS defining events were noted during the follow-up period although minor clinical endpoints such as oral thrush (1), herpes zoster (1) and oral hairy leukoplakia occurred in a few patients.

Another pilot French trial conducted by Raffi and colleagues included 60 patients with extensive prior antiretroviral experience (median duration of AZT therapy was 25 months and ddC was 11 months) but no prior ddI or d4T, with CD4 counts > 100 cells/mm3 and RNA levels > 10,000 copies/ml. The median duration of ddI + d4T therapy was 24 weeks, yet the results were not as encouraging. Undetectable viremia was evident in only 15% of patients although a 1 log viral load reduction and a > 50 CD4 cell increase were sustained for 24 weeks. Over a third (37%) of patients had side effects including neuropathy (3), paraesthesias (4), digestive symptoms (10), transaminase elevations (3) and pancreatitis (2).