ritonavir and Cytomegalovirus-Retinitis

We prospectively studied the incidence of cytomegalovirus (CMV) retinitis in 93 patients treated with highly active antiretroviral therapy (HAART) containing a protease inhibitor (PI), during a median follow-up period of 24 months. The median initial CD4+ count was 22 cells/microl (range, 1-311 cells/microl), and the median plasma HIV viral load was 5.1 log10 copies/ml (range, 2.4-6.4 log10 copies/ml). The fundus was examined monthly in patients with a history of CMV retinitis or an initial CD4+ count <50 cells/microl and every 3 months in the other patients. Of patients with previously controlled CMV retinitis, 1 of 7 relapsed. In addition, 6 of 59 patients with a CD4+ count <50 cells/microl and no history of CMV retinitis before starting PI therapy developed CMV retinitis. Of them, 3 had at least one relapse during follow-up. CD4+ counts were <40 cells/microl at the time of primary or recurrent CMV retinitis, except in two cases (147 cells/microl and 203 cells/microl). In conclusion, the incidence of CMV retinitis was 0.091 per patient-year among study subjects with advanced HIV infection who were receiving HAART (95% confidence interval [CI], 0.037-0.145). The time to progression of CMV retinitis (mean, 215 days; 95% CI, 113-317 days) was longer than reported before widespread use of PIs.

Topics: Adult; AIDS-Related Opportunistic Infections; CD4 Lymphocyte Count; Cytomegalovirus Retinitis; Drug Therapy, Combination; Foscarnet; Ganciclovir; HIV Protease Inhibitors; Humans; Incidence; Indinavir; Nelfinavir; Outcome Assessment, Health Care; Prospective Studies; Reverse Transcriptase Inhibitors; Ritonavir; Saquinavir

To assess the impact of highly active antiretroviral therapy (HAART) on the prevalence and progression of CMV retinitis (CMVR) among AIDS patients with baseline CD4 cell counts <100 cells x 10(6)/l.. A longitudinal cohort study of 1292 patients. CD4 cell counts and HIV viral load measurements were obtained before commencing therapy, at 3 months, 1 year, 2 years, and at last follow up. The CMVR prevalence rate was measured for the subgroup with baseline CD4 cell counts <100 cells x 10(6)/l. CMVR adverse event (AE) rates per 100 person days at risk were calculated for the subgroup with CMVR and baseline CD4 cell counts <100 cells x 10(6)/l.. 1292 patients were started on HAART. 8% of patients had CD4 counts <50 cells x 10(6)/l and 40% had detectable HIV viral load at last follow up. The prevalence of CMVR for the subgroup with baseline CD4 <100 cells x 10(6)/l was 10%. For those with baseline CD4 <100 cells x 10(6)/l, the mean CMVR AE rate was greatest during the first 6 months of follow up after HAART commencement (p <0.003). The mean AE rate per 100 person days at risk was 0.36 (95% CI 0.167 to 0.551) before starting HAART, and 0.14 (95% CI 0.085 to 0.199) after starting HAART (p = 0.03).. HAART significantly prolongs the disease-free intervals in patients with pre-existing disease but recurrences persist within the first 6 months of starting therapy. AE were absent beyond 18 months of follow up in all patients including those with persistently low CD4 counts and detectable HIV viral load indicating clinical immunorestoration. New methods for monitoring the response to therapy are needed to identify those at risk.

Topics: Adult; Aged; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Cytomegalovirus Retinitis; Follow-Up Studies; HIV Infections; Humans; Indinavir; Longitudinal Studies; Middle Aged; Nelfinavir; Prevalence; Protease Inhibitors; Ritonavir; Saquinavir; Viral Load

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Bacterial Agents; Antiviral Agents; Cidofovir; Clinical Trials as Topic; Cytomegalovirus Retinitis; Cytosine; HIV Infections; Humans; Isoquinolines; Nelfinavir; Nevirapine; Organophosphonates; Organophosphorus Compounds; Protease Inhibitors; Pyridines; Ritonavir; Sulfonic Acids

Cytomegalovirus (CMV) retinitis is the most common opportunistic viral infection in acquired immunodeficiency syndrome (AIDS) patients with a low CD4+ count. Without specific treatment, the disease is an important cause of blindness. We report two cases of AIDS with nonprogressive CMV retinitis after undergoing a combined antiHIV treatment schedule including at least one protease inhibitor. The treatment was associated with an increase in circulating CD4+ lymphocytes. This newly available antiviral combination may well prevent the recurrence of CMV disease and decrease the morbidity of CMV retinitis.

Topics: Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; CD4 Lymphocyte Count; Cytomegalovirus Retinitis; Drug Therapy, Combination; Fundus Oculi; Ganciclovir; HIV Protease Inhibitors; Humans; Lamivudine; Male; Ritonavir; Saquinavir

Many treatments highlighted at the ICAAC conference were designed to suppress the replication of HIV completely, but growing numbers of people are reporting rebound increases after initial decreases in viral load. However, new drugs are being developed which may be more effective, better tolerated, and less likely to lead to resistance. Agouron Pharmaceuticals has opened an expanded access program for its new protease inhibitor, Viracept; the program is open to people who cannot tolerate the other approved drugs. Gilead Sciences is warning physicians and patients that cidofovir should not be used with other kidney-toxic drugs.

Topics: AIDS-Related Opportunistic Infections; Antiviral Agents; CD4 Lymphocyte Count; Cidofovir; Cytomegalovirus Retinitis; Cytosine; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Isoquinolines; Kidney; Mutation; Nelfinavir; Organophosphonates; Organophosphorus Compounds; Reverse Transcriptase Inhibitors; Ritonavir; Saquinavir; Sulfonic Acids; Treatment Failure; Viral Load