saquinavir 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

In previous natural history studies and clinical trials, AIDS-related cytomegalovirus (CMV) retinitis has occurred primarily in patients with absolute CD4 counts of 50 cells/microL or less (0.05 x 10(9)/L) at the time of diagnosis.. We report five patients identified from our clinical practices who were diagnosed with CMV retinitis while their CD4 counts were above 195 cells/microL. We also analysed, based on CD4 counts, 76 AIDS patients with newly diagnosed CMV retinitis whose CD4 lymphocyte enumerations were done in laboratories that maintained certification in a common external quality control programme.. 5-24 weeks before retinitis was diagnosed, all five patients had had absolute CD4 lymphocyte counts of less than 85 cells/microL, and 4-7 weeks before diagnosis, all five patients had started taking highly active antiretroviral treatment (HAART) regimens. Only one (4%) of 27 patients enrolled in the trial between July, 1995, and February, 1996, had an absolute CD4 count of more than 50 cells/microL, and none of 27 had an absolute CD4 count of more than 100/microL on entry to the trial. However, from March, 1996 (when indinavir and ritonavir were approved by the FDA for marketing in the USA), to August, 1996, 14 (29%) of 49 patients had CD4 counts of more than 50/microL and seven (14%) of 49 had a CD4 count of more than 100 cells/microL on entry.. These findings suggest that the early immunological effects of HAART may not provide sufficient protection to prevent CMV retinitis in patients who have very low CD4 counts when therapy is started. Clinicians should note that CMV retinitis may now occur in patients who have CD4 counts of more than 100 cells/microL.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; CD4 Lymphocyte Count; Cytomegalovirus Retinitis; Drug Therapy, Combination; HIV Protease Inhibitors; Humans; Indinavir; Lamivudine; Male; Middle Aged; Prospective Studies; Saquinavir; Zidovudine

An HIV infected patient with cytomegalovirus retinitis with a CD4 lymphocyte count of 498 cells/mm3 after a good response to highly active antiretroviral therapy is described.. Some aspects of the immune system after highly active antiretroviral therapy remain unknown. CD4 T lymphocyte count might not be a good marker to identify some patients at risk of developing cytomegalovirus retinitis after this therapy.

Topics: Adult; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Antiviral Agents; CD4 Lymphocyte Count; Cytomegalovirus Retinitis; Didanosine; Ganciclovir; HIV Infections; HIV Protease Inhibitors; Humans; Lamivudine; Male; Retinal Hemorrhage; Reverse Transcriptase Inhibitors; Risk; Saquinavir; Stavudine; Substance Abuse, Intravenous; Zidovudine

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

To report on AIDS patients having combination antiretroviral therapy whose cytomegalovirus (CMV) retinitis remained inactive after discontinuation of anti-CMV maintenance therapy.. We describe the course of CMV-retinitis in 3 patients with AIDS after initiation of combination antiretroviral therapy.. After cessation of anti-CMV therapy no relapse of CMV-retinitis has been observed for up to 18 months. Two of the patients developed new CMV-retinitis in the first months after initiation of combination therapy, nevertheless after further improvement of immunological parameters retinitis remained stable without anti-CMV therapy.. The sustained immunological effects of combination therapy are possibly sufficient enough to provide protection against CMV-retinitis.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; CD4 Lymphocyte Count; Cytomegalovirus Retinitis; Drug Therapy, Combination; Follow-Up Studies; Ganciclovir; HIV; Humans; Indinavir; Male; Middle Aged; RNA, Viral; Saquinavir

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Cytomegalovirus Retinitis; Drug Therapy, Combination; HIV Protease Inhibitors; Humans; Lamivudine; Saquinavir; Stavudine; Zidovudine

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