A pilot case-control study of zidovudine compared with zidovudine plus didanosine in patients with advanced HIV-1 disease and no previous experience with antiretrovirals.

Although zidovudine (ZDV) is effective in HIV-1-infected patients, the duration of its efficacy may be short when treatment is started in advanced HIV disease. This pilot prospective case-control study was designed to evaluate the combination of ZDV plus didanosine [ddI] compared with ZDV monotherapy as an initial therapeutic strategy. 'Control' patients (ZDV monotherapy) were matched with 'case' patients (ZDV plus ddI combination therapy) according to the presence or absence of AIDS-defining criteria at entry and CD4 cell count. The case patient group consisted of 35 consecutive HIV-1-infected individuals with < or = 300 CD4 cells/mm3, no previous experience of antiretroviral therapy and who accepted treatment with a combination of ZDV plus ddI. The control patient group consisted of 35 consecutive patients with similar characteristics, but who preferred to start treatment with ZDV alone. Control patients received 250 mg ZDV bid and case patients received ZDV at the same dose plus ddI (200 mg bid). Primary study endpoints were virological (serum HIV-1 RNA) and immunological (CD4 cell count) responses. Viral phenotype (syncytium-inducing (SI) or non-syncytium-inducing (NSI)), development of mutations at codons 215, 41 and 74 and clinical progression (new AIDS-defining event or death) were also assessed. Virological and CD4 cell count responses were significantly greater and more sustained in the group treated with ZDV plus ddI than in the control group, with peak responses of -1.2 +/- 0.7 log10 versus -0.3 +/- 0.4 log10 at 1 month (P = 0.0003) and 61 +/- 52 cells/mm3 versus 19 +/- 25 cells/mm3 at 2 months (P = 0.001), respectively. In both groups the percentage of patients developing a mutation at codon 215 was around 80 per cent at 12 months. A mutation at codon 74 was detected in 30 per cent of case patients at 12 months. Five case patients (14 per cent) versus 12 control patients (34 per cent) showed signs of clinical progression (P = 0.09). In a multivariate model, clinical progression was significantly associated with a baseline