Date: Thu, 11 Jul 1996 08:11:12 -0400 From: Lloyd Grosse Subject: Vancouver News Update 8 Jul 96 Monday 8th July 1996 Continuing our coverage of the X1th International Conference on AIDS, updating you on new information for Roche's HIV and CMV products presented on Monday 8th July. The first clinical sessions of the XIth International Conference on AIDS began with long term information from the three studies ACTG 175, Delta and NuCombo (CPCRA 007). These studies confirmed the clinical benefit for combination therapy of ZDV with zalcitabine or didanosine over ZDV monotherapy. ACTG 175 also confirmed viral load as a predictor of clinical outcome. Exciting new surrogate marker data was presented for triple combinations of agents which included a proteinase inhibitor, heralding the next major advance in HIV therapy. Combinations of ZDV and lamivudine with either saquinavir or indinavir showed similar viral load reductions of around 99% (2 logs). Similar sustained reductions were achieved with ZDV in combinatio= n with zalcitabine and ritonavir. The most exciting aspect for the day was the presentation of clinical endpoint data for the proteinase inhibitors saquinavir and ritonavir. The benefit seen for saquinavir combined with only one nucleoside analogue (zalcitabine), is the largest clinical benefit seen to data especially in ZDV-pretreated patients. Viral load as a marker of disease progression... Dr D. Katzenstein (Stanford, U.S.A.) presented data from the ACTG175 trial investigating the effects on viral markers of therapy with either zidovudin= e alone, zidovudine plus didanosine or zidovudine plus zalcitabine. The plasm= a HIV RNA level at study entry and syncytia virus phenotype were found to be significant, independent factors contributing to the risk of AIDS and death in subjects treated with reverse transcriptase inhibitors. Decreased plasma RNA following therapy was associated with significantly lower risk of CD4+ cell count decline, AIDS and death. Thus the reduction of virus load by reverse transcriptase inhibitors is of particular significance in the therapeutic action of these agents. ...the impact of combination therapy Data comparing the ability of zidovudine monotherapy, zidovudine plus didanosine and zidovudine plus zalcitabine to reduce viral load was presented by Dr F. Brun-V=E9zipet. In a subset of the Delta trial, a total = of 230 patients were recruited in 22 centres in France, the UK and the Netherlands for virological assessment. Quantitative cellular and plasma cultures were performed at regular intervals over a 96-week period. At baseline, patients had a mean CD4+ cell count of 210 cells/mm3 and cellular viremia was detected in 91% of patients. Viral load decreased in all treatment groups with mean reductions at week 4 of 0.47 log10, 1.53 log10 and 1.22 log10 in zidovudine, zidovudine plus didanosine and zidovudine plu= s zalcitabine groups, respectively. At week 48, mean viral RNA levels had returned to baseline in the zidovudine monotherapy group, while a reduction was maintained in both combination therapy groups. At week 80, a decrease o= f around 0.9 log10 persisted in the zalcitabine combination therapy group, compared with 0.6 in the didanosine combination group. These results demonstrated a more sustained reduction in viral load for combination therapy over zidovudine monotherapy. In concurrence with the Delta trial, Dr D. Mayers (Bethesda, U.S.A) presented data from CPCRA-007 which showed that at 6 months, combination therapy with zidovudine and either didanosine or zalcitabine produced a significantly greater reduction in virus titre than zidovudine monotherapy. However, in contrast with Delta, virus titres were not significantly different between groups after 1 year. Evaluating virus titre in relation t= o disease progression indicated that a 1.0 log unit decrease in virus titre a= t 6 months was associated with a significantly lower risk of disease progression. However, changes in virus titre at 1 year were found not to be predictive of disease progression. Similarly, the relative risk of disease progression was independent of CD4+ cell count as the risk continued to increase when CD4+ cell count increased. Quality of life is not impaired The effect of treatment on quality of life indices in a subgroup of patient= s in the Delta trial was presented by Dr M. Hooker (London, UK). Visual analogue scales were used to assess global quality of life and a medical outcome survey was used to rate overall health, pain, energy and fatigue. I= n almost all assessments over the periods 0-8 and 0-24 weeks, the median change in score from baseline was zero or close to zero. Thus, there was no evidence for a beneficial or adverse effect of any treatment group. Disease progression - advantage with earlier treatment Data from the CPCRA-007 trial on the ability of the three treatment regimen= s to alter disease progression and death rates in patients with AIDS was presented by Dr L. Saravolarz (Bethseda, U.S.A.). Patients were already at an advanced stage of disease at study entry, having a median CD4+ cell coun= t of 92 cells/mm3 and a median duration of prior zidovudine usage of 7 months=