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Background: Ritonavir is a potent inhibitor of cytochrome P4503A4 that strongly increases saquinavir bioavailability. In this study we assessed the safety and antiretroviral efficacy of the combination of these two compounds in patients pretreated and receiving continued treatment with zidovudine and lamivudine who were protease inhibitor naive and who had a CD4 cell counts below 200/mm3., Methods: In this 48-week pilot study, all patients received 600 mg ritonavir and 400 mg saquinavir twice daily. Administration of zidovudine and lamivudine was continued without a change in previous doses. Viral load, CD4 cell count, and the emergence of resistance to the two protease inhibitors were evaluated repeatedly up to week 48., Results: Sixteen patients were included in the study. Previous nucleoside analog treatment duration was 48+/-22 months (mean +/- SD). Two patients quit taking both protease inhibitors within 2 weeks. The ritonavir dose had to be reduced in 10 other patients because of side effects. Between inclusion and week 48, plasma viremia varied from 4.87+/-0.43 to 3.00+/-1.29 log10 copies/mL and CD4 cell counts ranged from 98+/-61 to 250+/-139/mm3. Ten patients (63%) had viral loads below 200 copies/mL and 7 (44%) had viral loads below 50 copies/mL. A single key mutation that conferred ritonavir resistance I84V and V82A/V developed in two patients. A mutation at codon 54 developed in another patient. These mutations were associated with repeated cessations of antiretroviral treatment. No lipodystrophy was observed., Conclusion: Ritonavir and saquinavir in combination are quite well tolerated and induce a high and sustained antiretroviral efficacy. A four-drug combination that includes these two protease inhibitors should be considered as a first line of treatment in patients with low CD4 cell counts.

Objective: To assess the clinical and economic consequences of the use of protease inhibitors in the treatment of HIV infection., Design: Multicentric, observational, retrospective cohort study., Setting: Ten AIDS reference centres in France., Patients: All patients followed in each centre from September 1995 through October 1996., Main Outcome Measures: AIDS-defining events, death, health-care resources use, administration of antiretroviral therapy., Results: Data from 7749 patients in 10 centres showed a drop in hospitalization days by 35%, new AIDS cases by 35%, and deaths by 46%. In the same period, the proportion of patients receiving antiretrovirals rose from 36 to 53% including highly active antiretroviral therapy (HAART), which rose from 0.3 to 18%. Overall cost evaluation showed a slight increase of monthly treatment cost of US$ 12 per patient. Comparison of the three centres that used HAART earliest to the three centres that used it latest showed a clear benefit to early HAART with a drop in hospitalization days by 41%, new AIDS cases by 41% and deaths by 69%. The proportion of patients with HAART rose to 27% and monthly health-care cost decreased by US$ 248852 (i.e., by US$ 101 per patient per month). Late prescribing centres experienced a less marked effect with a drop in hospitalization days by 22%, new AIDS cases by 31%, and deaths by 32.5%. Proportion of patients with HAART rose to 12% and monthly health-care costs increased by US$ 113578 (i.e., by US$ 38 per patient per month)., Conclusions: This study supports the extensive use of HAART in HIV-infected patients.

To determine the prognostic value of plasma viremia in long-term zidovudine (AZT)-treated HIV-infected patients, HIV-1 plasma viremia (PV) was quantified in 28 HIV-infected patients before and during AZT long-term treatment; the follow-up also included p24 antigenemia and CD4 cell counts. The variations of these markers during the follow-up period, the correlation with the clinical outcome (progressors versus nonprogressors), and the discrepancies between PV and surrogate markers were then analyzed. A significant and stable decrease in PV titer was observed in only nonprogressors (Friedman test, p < 0.005). At the end of follow-up, 11 (73%) of the 15 non-progressors were PV responders (patients who remained or became PV- long-term), whereas all the 13 progressors were PV nonresponders (patients who remained or became PV+). These results indicated a strong correlation between PV and clinical outcome (Fischer's exact test, p < 0.0001). The persistence, increase, or reappearance of viral replication appeared to be an important predictor of poor clinical outcome in HIV-infected patients under AZT treatment. This finding could provide a rational basis to help the clinician's decision in the clinical treatment of HIV-infected patients.

We report a patient with the acquired immunodeficiency syndrome (AIDS) in whom the acute onset of neurologic disorders and renal failure could be attributed to thrombotic microangiopathy. Clinical, biological, and pathological features were compatible with the diagnosis of thrombotic thrombocytopenic purpura (TTP). Such cases have been previously described, but histologically documented case reports are uncommon.