Purpose: To determine factors associated with virological failure during long-term treatment with the triple combination of saquinavir soft gel capsule, zalcitabine and zidovudine.
Method: Open-label, prospective, multicentre study undertaken in private practices and the outpatient department of the Auguste-Viktoria-Hospital. A total of 95 patients with plasma HIV RNA > 5000 copies/ml who had received no more than 6 months pre-treatment with NRTIs and no prior PI therapy received saquinavir soft gel, zalcitabine and zidovudine for 52 weeks, before being randomly assigned to either remain on therapy or switch to nelfinavir, lamivudine and zidovudine for further 52 weeks.
Results: Combination therapy with saquinavir, zalcitabine and zidovudine was found to be effective and well tolerated, with virological response to therapy maintained for up to 2 years. In patients responding to therapy, switching to a novel triple regimen did not result in a virological or immunological worsening, but it did not confer an additional clinical benefit. Factors predictive of early treatment failure (virological failure within 16 weeks of treatment initiation) included high viral load and presence of RT mutations at baseline (OR: 0.30, 95% CI 0.11 0.83 and OR 0.13, 95% CI 0.03 0.52, respectively), with baseline viral load and the development of genotypic mutations on therapy being predictive of late treatment failure (16 52 weeks; OR: 0.15, 95% 0.05 0.46 and OR: 0.26, 95% CI < 0.001 1.16, respectively). Plasma saquinavir concentration < 50 mg/ml at 4 weeks was also found to be an independent risk factor for both early and late treatment failure (OR: 1.80, 95% CI 1.23 2.64 and OR: 1.16, 95% CI 0.84 1.60, respectively).
Conclusions: While antiretroviral drug resistance appears to be a principal cause of treatment failure, other factors such as inadequate drug plasma concentrations also play a role.