Two small studies presented at the National Conference on Retroviruses and Opportunistic Infections in Washington,D.C. examined the effect of the combination of ritonavir and saquinavir in advanced HIV positive patients. Prior to these studies, the combination of ritonavir and saquinavir had been reported to exert a very potent antiretroviral effect in protease inhibitor naive patients, with over 3 log reductions in HIV RNA viral load and over 150 CD4 cell increases after 20 weeks of therapy.

In the first study conducted by Steinhart and colleagues form Miami, Florida 10 antiretroviral experienced patients with a mean CD4 count of 60 cells/mm3 not responding to combination therapy with nucleoside analogues and intolerant to the recommended doses of ritonavir (600 mg twice daily) were continued on their nucleoside regimen and given saquinavir (800 mg twice daily) and ritonavir (400 mg twice daily). After a mean length of follow-up of 5.2 months CD4 counts increased in 9 of the 10 patients with a mean percentage increase of 275% and HIV RNA became undetectable (< 500 copies/ml) in 5 of 10 patients. No opportunistic infections occurred and there were no adverse effects or laboratory effects of treatment.

In a second study presented by Barbour and others from the Desert AIDS Project in Palms Springs, California 32 HIV positive patients with CD4 counts < 250 cells/mm3 were treated with ritonavir (600 mg twice daily) and saquinavir (400 mg twice daily) and two nucleoside reverse transcriptase inhibitors. All had baseline HIV viral loads > 5,000 copies of RNA/ml or evidence of disease progression despite 4 months of triple therapy (2 nucleoside analogues and one protease inhibitor). Baseline CD4 count on average was 79 cells and HIV RNA viral load was 4.86 logs. After 4 weeks of therapy with the four drug combination 53% of patients had achieved a reduction in viral load below the level of detection at 400 copies/ml, which persisted for 8 subsequent weeks. The mean increase in CD4 count was 72 cells at 12 weeks. Two patients withdrew because of side effects

These two studies suggest that the combination of ritonavir and saquinavir (using lower doses of either one) may be effective in patients with either intolerance to higher doses or evidence of virologic or clinical failure on triple protease inhibitor containing combinations. Further studies of this combination in protease-experienced patients are urgently needed.