Preliminary data from a trial conducted by the NIAID-supported Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) were presented on Jan. 18 during a meeting of CPCRA investigators. The study, known as CPCRA 007, assessed the safety and efficacy of combination therapy zidovudine (AZT) plus didanosine (ddI) or AZT plus zalcitabine (ddC) as compared to AZT monotherapy in HIV-infected people who previously had an AIDS-defining condition or had fewer than 200 CD4+ T cells per cubic millimeter (mm3) of blood.
The median CD4+ T cell count of patients at study entry was 119/mm3. All 1,113 participants received prophylaxis to prevent Pneumocystis carinii pneumonia (PCP), and about 77 percent had received prior AZT therapy for a median period of six months. The study opened in April 1992, and patients were followed until Nov. 30, 1995. All patients were followed for at least 17 months; the median follow-up was 35 months.
The patients were randomized into three treatment groups, and took the randomly assigned study drugs for a mean of 13 to 14 months. Overall, when compared to AZT alone, combination therapy (AZT plus ddI or AZT plus ddC) provided only modest benefits, which were not statistically significant in slowing progression of clinical disease and reducing the rate of death. However, in patients with no prior use of AZT, combination therapy was more effective than AZT alone for slowing clinical progression and improving survival. Use of combination therapy provided no additional benefit to patients who had previously used AZT.
The reported side effects in CPCRA 007 were similar to those reported in other studies involving the three study drugs. Patients who received AZT plus ddI reported higher rates of nausea/vomiting, diarrhea, abdominal pain and pancreatitis than those on AZT monotherapy. Those receiving AZT plus ddC had higher rates of neuropathy compared to those who received AZT alone.
The results of CPCRA 007 complement the findings of other recently completed studiesthe Delta trial (a European-Australian collaborative study) and another NIAID-supported trial known as the AIDS Clinical Trials Group (ACTG) 175 (see AIDS Agenda, December 1995). These studies addressed similar questions, but in populations with less advanced disease than the patients in CPCRA 007. NIAID investigators are collaborating with the sponsors of the Delta trial to further analyze the data from CPCRA 007, the Delta trial and ACTG 175. The CPCRA, a consortium of 16 clinical sites in 15 cities, conducts clinical trials in communities where HIV-infected people receive primary care. The drugs used in this study were provided by their manufacturers Glaxo-Wellcome Company (AZT), Bristol-Myers Squibb Inc. (ddI), and Hoffmann-LaRoche Inc. (ddC).