saquinavir and AIDS-Related-Opportunistic-Infections

To assess the drug concentrations, efficacy and safety of concomitant use of rifampicin and regimens containing ritonavir/saquinavir (400mg/400mg twice daily) in tuberculosis-HIV treatment-naive patients.. This was an open-label, non-randomised, multiple-dose study. On study day (D)1, tuberculosis treatment (rifampicin 600mg/isoniazid 400mg per day fasting plus pyrazinamide 2 g/day) was introduced in 30 patients. On D31, highly active antiretroviral therapy (HAART) consisting of two nucleoside analogues plus ritonavir/saquinavir 400mg/400mg twice daily was initiated (n = 20). The pharmacokinetics were assayed with a validated reversed-phase HPLC method before the introduction of HAART on D30 (for rifampicin), after 30 days of HAART at D60 (for rifampicin plus ritonavir/saquinavir), and at the end of the study (without rifampicin) on D210 (for ritonavir/saquinavir). Clinical evaluations were performed on a monthly basis. CD4 counts and viral load were collected on D30, D60 and D180. Genotyping test for HIV was collected at baseline and at D180. Primary endpoints were drug concentration and viral load at D180 (<80 copies/mL). Secondary endpoints were presence of grade 3 and serious adverse events, clinical improvement, CD4 count and genotypic resistance to ritonavir/saquinavir.. Ten patients dropped out of the study during tuberculosis therapy alone. Mean (+/- SD) baseline CD4 count (on D30) was 151.89 (+/- 146.77) cells/mm(3) and viral load was 5.34 (+/- 0.4) log. During the antiretroviral therapy, 15 patients dropped out, 14 because of adverse events. One patient (of five) presented a viral load of <80 copies/mL at D180. All but one patient increased CD4 counts from baseline. No genotypic resistance was detected. Clinical improvement was evident in all five patients who tolerated the therapy. Serum concentrations of ritonavir/saquinavir and rifampicin remained within the therapeutic range.. Therapeutic concentrations of the studied drugs and reduction of viral load were achieved; adverse events are the main limitation of use of a ritonavir/saquinavir regimen in treatment-naive patients, but its clinical benefits were evident.

Topics: Adult; AIDS-Related Opportunistic Infections; Antibiotics, Antitubercular; Antiretroviral Therapy, Highly Active; Area Under Curve; Bisexuality; CD4 Lymphocyte Count; Drug Administration Schedule; Female; Half-Life; HIV Infections; HIV Protease Inhibitors; Homosexuality; Humans; Karnofsky Performance Status; Male; Metabolic Clearance Rate; Rifampin; Ritonavir; Saquinavir; Time Factors; Treatment Outcome; Tuberculosis; Viral Load

Our primary aim was to evaluate the plasma exposures and safety of rifabutin and its active 25-O-desacetyl metabolite during concomitant therapy of intermittent rifabutin dosing regimens with a combination of ritonavir and saquinavir.. Twenty-four patients without mycobacterial infection who were human immunodeficiency virus seropositive and who were receiving 400 mg each of ritonavir and saquinavir twice daily participated in a 3-period, 2-group longitudinal pharmacokinetic study. Patients were equally randomized to receive 300 mg of rifabutin every 7 days (group 1) or 150 mg of rifabutin every 3 days (group 2) for 8 weeks. Blood samples were collected over the dosing intervals of the protease inhibitors at baseline (period 1) and of the 3 drugs after 4 weeks (period 2) and 8 weeks (period 3) for HPLC measurement of plasma concentrations of the 3 drugs and 25-O-desacetylrifabutin.. Nineteen patients (group 1, n = 10; group 2, n = 9) completed the study. Five individuals withdrew from the study; 3 of them experienced side effects, and 2 were lost to follow-up. For combined groups, mean saquinavir and ritonavir overall (area under the concentration-time curve [AUC]) and peak (C(max)) plasma exposures averaged over periods 2 and 3 did not change significantly (8% to 19%; P > .05) compared with those in period 1 (90% confidence intervals, -7% to 26% for ritonavir and -2% to 38% for saquinavir). Rifabutin and metabolite AUC and C(max) exposures were stable over the 8 weeks, with intraindividual coefficients of variation of 12% to 19%. Oral clearance of rifabutin was similar in both groups (321 mL/min in group 2 versus 372 mL/min in group 1; P = .34). Rifabutin C(max) values were significantly lower in group 2 (310 ng/mL versus 496 ng/mL in group 1; P = .004). Rifabutin and metabolite predose levels were significantly higher in group 2 (rifabutin: 54 ng/mL versus 17 ng/mL; desacetyl rifabutin: 55 ng/mL versus 28 ng/mL; P < .002).. Rifabutin exposures were similar at 4 and 8 weeks and had minimal effect on ritonavir and saquinavir exposures. Intermittent rifabutin dosing over 8 weeks provided a safe and manageable regimen for concurrent therapy with a combination of ritonavir and saquinavir.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Analysis of Variance; Antibiotics, Antitubercular; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV Protease Inhibitors; Humans; Male; Mycobacterium Infections; Rifabutin; Ritonavir; Saquinavir

To investigate the pharmacokinetics of liposomal daunorubicin (DaunoXome) administered alone or in combination with antiviral therapy including protease inhibitors (PI) to HIV-positive patients affected by Kaposi's sarcoma (KS).. A group of 18 patients with extensive or rapidly progressing AIDS-related KS received DaunoXome at a dose of 40 mg/m2 alone or in association with a triple combination therapy consisting of one PI plus two nucleoside reverse transcriptase inhibitors (NRTI). Daunorubicin pharmacokinetics were determined in a total of 23 cycles, 6 with DaunoXome alone, 9 in combination with indinavir, 6 with ritonavir and 2 with saquinavir. Plasma samples were obtained at different times during the 72 h after DaunoXome administration. Daunorubicin and daunorubicinol plasma levels were determined by high-performance liquid chromatography.. After the DaunoXome infusion, daunorubicin was rapidly cleared from the body following, in most cases, a one-compartment open kinetic model. The daunorubicin peak concentrations, clearances and elimination half-lives were (means +/- SD): 16.3 +/- 2.8 microg/ml, 0.3 +/- 0.1 l/h per m2 and 5.6 +/- 2.6 h after DaunoXome alone; 15.1 +/- 4.9 microg/ml, 0.5 +/- 0.3 l/ h per m2 and 5.8 +/- 2.1 h after the combination with indinavir; and 14.5 +/- 2.8 microg/ml, 0.4 +/- 0.2 l/h per m2 and 6.5 +/- 3.9 h after the combination with ritonavir. In all groups, daunorubicinol plasma levels were approximately 25-30 times lower than those of the parent drug.. Our data show that there are no significant differences in the pharmacokinetic parameters of daunorubicin in patients receiving DaunoXome in combination with indinavir and ritonavir compared with those in patients not receiving PIs. Therefore in patients affected by AIDS-related KS treated with Highly Active AntiRetroviral Therapy (HAART) there is no pharmacokinetic justification for reducing the doses of DaunoXome.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antibiotics, Antineoplastic; Daunorubicin; Drug Interactions; Drug Therapy, Combination; Female; HIV Protease Inhibitors; Humans; Indinavir; Liposomes; Male; Middle Aged; Ritonavir; Saquinavir; Sarcoma, Kaposi

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 study the relationship between the CD4+ cell response after initiation of protease inhibitors and the occurrence of opportunistic infections and survival.. Prospective observational cohort study.. HIV-1-seropositive subjects followed-up in HIV centres of Bordeaux University Hospital, Southwest France who were prescribed at least one available protease inhibitor between January and December 1996 were included in this analysis. A Cox model estimated the independent effect of baseline covariates and CD4+ cell response, considered as a time-dependent covariate, on the occurrence of new AIDS-defining opportunistic infection, new AIDS-defining events, new AIDS-defining opportunistic infection or death.. A total of 556 HIV-positive patients were prescribed at least one protease inhibitor: 34% saquinavir, 52% indinavir, and 14% ritonavir. Median CD4+ cell count at baseline was 95 x 10(6)/l and mean plasma HIV RNA was 5.0 log10 copies/ml. After a median follow-up of 230 days, 65 patients experienced a new episode of opportunistic infection, 79 patients experienced at least one AIDS-defining event, and 24 had died. On average, the increase in CD4+ cell count was 42 x 10(6)/l (SD, 74) after a median of 49 days. In the multivariate analysis of opportunistic infection or death, each 50% higher CD4+ cell count at baseline was associated with a 23% reduction [95% confidence interval (CI), 14-30] of risk. Each 50% increase in CD4+ cell count during follow-up was associated with a 9% reduction (95% CI, 2-15) of risk, adjusted for the presence of AIDS prior to protease inhibitor therapy (hazard ratio, 3.76 versus absence of AIDS; P < 0.01) and haemoglobin level (hazard ratio, 0.48 if > 11 g/dl versus <11 g/dl; P < 0.01).. Our results show, at least indirectly, how protease inhibitors might produce clinical stabilization. This result may be due to improved functionality of CD4+ cells in patients started on protease inhibitors.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; CD4 Lymphocyte Count; Cohort Studies; Disease Progression; Female; Follow-Up Studies; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Male; Predictive Value of Tests; Prospective Studies; Risk Factors; 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

Topics: AIDS-Related Opportunistic Infections; Antibiotics, Antitubercular; Developing Countries; Drug Therapy, Combination; HIV Protease Inhibitors; Humans; Rifampin; Ritonavir; Saquinavir; Tuberculosis

To describe the incidence and risk factors of bacterial pneumonia occurring in patients treated with antiretrovirals.. In the ongoing APROCO (Anti-proteases) cohort, 1281 patients at the initiation of a protease inhibitor (PI)-containing antiretroviral regimen were enrolled from 1997-1999. All events requiring hospitalization during follow up are recorded. Of these, bacterial pneumonia was defined as the occurrence of a new pulmonary infiltrate with fever and either evidence of a bacteriological cause (definite cases) or favourable outcome with antimicrobial therapy (presumptive cases). Risk factors of bacterial pneumonia were studied using survival analyses.. During a median follow up of 43 months, 29 patients had at least one episode of bacterial pneumonia, giving an incidence of 0.8/100 patient years. The 11 definite cases were attributable to Streptococcus pneumoniae (n=9), Legionella pneumophila (n=1) and Haemophilus influenzae (n=1). In multivariate analysis, bacterial pneumonia was significantly more frequent in older patients, injecting drug users, patients having a CD4 cell count>500 cells/microL at baseline and patients who initiated PI therapy with nonboosted saquinavir. It was significantly less frequent in nonsmokers. The occurrence of bacterial pneumonia was also associated with lower self-reported adherence to antiretroviral therapy and to higher plasma HIV-1 RNA levels during follow-up.. Bacterial pneumonia occurs rarely in patients treated with a PI-containing regimen and may be associated with virological failure.

Topics: Age Factors; AIDS-Related Opportunistic Infections; CD4 Lymphocyte Count; Drug Therapy, Combination; Female; Haemophilus influenzae; HIV Protease Inhibitors; HIV-1; Hospitalization; Humans; Legionella pneumophila; Male; Patient Compliance; Pneumonia, Bacterial; Prospective Studies; Risk Factors; RNA, Viral; Saquinavir; Smoking; Streptococcus pneumoniae; Substance Abuse, Intravenous

Cryptococcus neoformans is an opportunistic pathogen that can manifest in immunocompromised patients with acquired immune deficiency syndrome. Prevention of cryptococcosis and other opportunistic diseases is an objective in the management of human immunodeficiency virus (HIV)-infected patients. The goal of highly active antiretroviral therapy (HAART) is to reduce the viral loads and enhance CD4 counts in HIV-infected patients. These 2 mechanisms keep HIV-infected patients healthier and enhance their immune systems, thus reducing and often preventing opportunistic infections such as ocular cryptococcal infections. Discontinuation of HAART can lead to ocular opportunistic infections such as cryptococcal choroiditis.. Presented here is a case of a patient who was treated successfully with HAART of stavudine (D4T), abacavir (Ziagen), ritonavir (Norvir), and saquinavir (Invirase). His last CD4 count before HAART was discontinued was 131 cells/mm(3), and viral load was less than 50 copies/mL. He discontinued his HAART regimen for 2 years and presented to the emergency room with complaints of a severe headache with neck pain, lightheadedness, nausea, disorientation, and unsteady gait. Lumbar puncture results showed cryptococcal infection, and the patient was admitted for the treatment of cryptococcal meningitis with amphotericin B and 5-flucytosine. Cryptococcal choroiditis was diagnosed after treatment of the meningitis. After resolution, his resultant visual acuities were 10/350 in the right eye and 10/600 in the left eye. He is on a maintenance dose of antifungal therapy and has been reinitiated on HAART of abacavir/zidovudine/lamivudine (Trizivir) and lopinavir/ritonavir (Kaletra).. This case exemplifies the importance of HAART in the prevention of opportunistic infections, cryptococcal meningitis/choroiditis in particular. Eye care professionals can play a role in encouraging patients to comply with their HAART regimens.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Choroiditis; Cryptococcus neoformans; Dideoxynucleosides; Eye Infections, Fungal; Follow-Up Studies; Humans; Male; Meningitis, Cryptococcal; Middle Aged; Ritonavir; Saquinavir; Stavudine

Topics: AIDS-Related Opportunistic Infections; Antifungal Agents; Antiretroviral Therapy, Highly Active; Bronchoalveolar Lavage Fluid; Bronchoscopy; HIV Infections; HIV Protease Inhibitors; Humans; Nelfinavir; Pneumocystis carinii; Pneumocystis Infections; Pyridines; Pyrones; Ritonavir; Saquinavir; Sulfonamides

To determine the incidence of significant liver enzyme elevations following the initiation of protease inhibitor (PI)-based antiretroviral therapy (ART) with or without pharmacokinetic boosting with ritonavir (RTV), and to define the role of chronic viral hepatitis in its development.. Prospective, cohort analysis of 1161 PI-naive, HIV-infected patients receiving RTV-boosted (lopinavir, indinavir and saquinavir) and unboosted PI-based ART (indinavir, nelfinavir) that had at least one liver enzyme measurement before and during therapy.. The incidence of grade 3 and 4 liver enzyme elevations among persons with and without hepatitis B and/or C co-infection treated with PI-based ART were compared. Severe hepatotoxicity was defined as an increase in serum liver enzyme >/= 5-times the upper limit of the normal range or 3.5-times an elevated baseline level.. The incidence of grade 3 or 4 elevations among PI-naive patients was: nelfinavir, 11%; lopinavir/RTV (200 mg/day), 9%; indinavir, 13%; indinavir/RTV (200-400 mg/day), 12.8%; and saquinavir/RTV (800 mg/day), 17.2%. The risk was significantly greater among persons with chronic viral hepatitis (63% of cases); however, the majority of hepatitis C virus (HCV)-infected patients treated with nelfinavir (84%), saquinavir/RTV (74%), indinavir, 86%, indinavir/RTV (90%) or lopinavir/RTV (87%) did not develop hepatotoxicity.. Our data suggest that the lopinavir/RTV is not associated with a significantly increased risk of hepatotoxity among HCV-infected and uninfected patients compared with an alternative PI-based regimen, nelfinavir. Accordingly, other medication-related factors (e.g, efficacy and non-hepatic toxicity) should guide individual treatment decisions.

Topics: Adult; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Chronic Disease; Drug Therapy, Combination; Female; Hepatitis; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Liver; Lopinavir; Male; Nelfinavir; Prospective Studies; Pyrimidinones; Reverse Transcriptase Inhibitors; Risk Factors; Ritonavir; Saquinavir; Treatment Outcome

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

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Drug Administration Schedule; HIV Protease Inhibitors; Humans; Indinavir; Odds Ratio; Ritonavir; Saquinavir; Spain; Survival Analysis; Treatment Failure; Treatment Outcome

A 30-year-old man with a known HIV infection for 7 years presented for treatment with antiretroviral drugs. He was known to have had herpes zoster, oral hairy leukoplakia and recurrent Candida stomatitis, but was otherwise without symptoms.. The CD4 lymphocyte count was 19 cells/mm3 and there were 41,000 HIV-RNA copies/ml.. The HIV infection was in CDC stage B3, indicating the need for combined antiretroviral treatment. A week after starting stavudine, saquinavir and ritonavir he had to be admitted because of nausea and vomiting, colicky abdominal pain, diarrhea, fever up to 39 degrees C and a rise of C-reactive protein to 207 mg/dl. Bacteriological examination of feces and biopsy of an enlarged retroperitoneal lymph node revealed atypical mycobacteria. Antituberculosis treatment was started. The CD4 cell count rose to 56/mm3 and the viral count fell to 11,000/ml. Each time after initiating a different antiviral regimen the symptoms recurred.. This case illustrates an atypical manifestation of on opportunistic infection: during combined antiviral treatment the CD4 cell count rose and thus precipitated an heretofore subclinical mycobacterial infection with focal lymphadenitis. If, on starting antiretroviral treatment at a late HIV stage, new symptoms develop within 1-3 weeks, one should consider drug-induced side effects or the onset of an opportunistic infection that has become manifest as the result of an improved immunological state.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antitubercular Agents; Diagnosis, Differential; Drug Therapy, Combination; Follow-Up Studies; HIV Infections; HIV Protease Inhibitors; Humans; Lymphadenitis; Male; Mesenteric Lymphadenitis; Mycobacterium avium-intracellulare Infection; Reverse Transcriptase Inhibitors; Ritonavir; Saquinavir; Stavudine; Time Factors; Tuberculosis

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antineoplastic Agents, Phytogenic; Delavirdine; Drug Interactions; Female; HIV Protease Inhibitors; Humans; Male; Paclitaxel; Reverse Transcriptase Inhibitors; Saquinavir; Sarcoma, Kaposi

Topics: Adult; AIDS-Related Opportunistic Infections; Chemical and Drug Induced Liver Injury; Drug Therapy, Combination; Female; HIV Protease Inhibitors; HIV-1; Humans; Portal Vein; Saquinavir; Venous Thrombosis

The effects of therapeutically relevant concentrations of the human immunodeficiency virus (HIV) proteinase inhibitors saquinavir and indinavir on the in vitro proteinase activity of Candida albicans were investigated with isolates from HIV-infected and uninfected patients with oral candidiasis. After exposure to the HIV proteinase inhibitors, proteinase activity was significantly reduced in a dose-dependent manner. These inhibitory effects, which were similar to that of pepstatin A, and the reduced virulence phenotype in experimental candidiasis after application of saquinavir indicate the usefulness of these HIV proteinase inhibitors as potential anticandidal agents.

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Aspartic Acid Endopeptidases; Candida albicans; Candidiasis, Oral; Dose-Response Relationship, Drug; Fungal Proteins; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Pepstatins; Saquinavir

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; Hepacivirus; Hepatitis C; HIV Protease Inhibitors; Humans; Immunity; Indinavir; Retrospective Studies; Ritonavir; Saquinavir

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

To evaluate the clinical and biological impact of protease inhibitors on HIV-associated Kaposi's sarcoma.. A cohort of 10 patients included prospectively from April 1996 to June 1997 were studied in one institutional centre after initiation of protease inhibitors.. All patients but one (stable disease) had progressive Kaposi's sarcoma. Three out of 10 patients had stopped specific chemotherapy for Kaposi's sarcoma for more than 4 weeks, three were still under chemotherapy, and four had never received specific treatment of Kaposi's sarcoma. Plasma HIV viral load, human herpesvirus (HHV)-8 viraemia in peripheral blood mononuclear cells (PBMC), and CD4 cell count were sequentially assessed from the beginning of therapy. For six patients, a semiquantitative evaluation of HHV-8 viral load in the Kaposi's sarcoma lesions was performed during treatment using polymerase chain reaction.. After initiation of HIV triple therapy with protease inhibitors, we observed six complete responses, two partial responses, and two patients with progressive disease. All patients had undetectable plasma HIV viral load within 2 months of treatment. Undetectable HHV-8 viraemia in PBMC occurred in seven out of eight patients with partial or complete response and in none of the progressive patients. A decrease or negation of HHV-8 viral load in Kaposi's sarcoma lesions was observed in two complete responders.. Our results suggest that antiviral therapy with protease inhibitors are clinically efficient in HIV-associated Kaposi's sarcoma and that there exists a correlation between clinical response and negation of HHV-8 viraemia.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Didanosine; Dideoxynucleosides; Drug Therapy, Combination; Female; Herpesvirus 8, Human; HIV Protease Inhibitors; Humans; Indinavir; Lamivudine; Male; Middle Aged; Prospective Studies; Reverse Transcriptase Inhibitors; Ritonavir; Saquinavir; Sarcoma, Kaposi; Stavudine; Treatment Outcome; Viral Load; Viremia; Zalcitabine; Zidovudine

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Drug Interactions; HIV Infections; HIV Protease Inhibitors; Humans; Pneumonia, Pneumocystis; Saquinavir; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Cohort Studies; Drug Therapy, Combination; Hemophilia A; Hepacivirus; Hepatitis C; HIV; HIV Protease Inhibitors; Humans; Indinavir; Lamivudine; Reverse Transcriptase Inhibitors; RNA, Viral; Saquinavir; Stavudine; Treatment Outcome; Viral Load; Zidovudine

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Bisexuality; Didanosine; Drug Therapy, Combination; Herpesvirus 8, Human; HIV Seroprevalence; HIV-1; Homosexuality, Male; Humans; Indinavir; Male; Middle Aged; Saquinavir; Sarcoma, Kaposi; Stavudine; Viral Load

Uveitis is an ocular manifestation rarely observed in HIV-infected patients. We observed three cases of anterior uveitis without progressive retinitis in HIV patients receiving antiprotease treatment.. The first patient developed a first episode of uveitis during ritonavir therapy. Two other episodes occurred with indinavir. The second patient developed uveitis when treated with indinavir. In the third patient, the first episode developed with indinavir and a second with a ritonavir-saquinavir combination. Uveitis was unilateral in 4 episodes. Clinical manifestations were red irritable eyes and, in 2 episodes, reduced visual acuity. The antiprotease was interrupted in 4 of the 6 episodes and clinical course was rapidly favorable.. Pure anterior uveitis should suggest drug induction in HIV infected patients; rifabutin is often the cause. Infectious causes predominate in case of total uveitis associating choroid and retinal involvement. Cytomegalovirus, herpes zoster, syphilis, and toxoplasmosis have been incriminated. Antiproteases would appear to be a new cause of anterior uveitis in HIV-infected patients.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Drug Combinations; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Male; Middle Aged; Rifabutin; Ritonavir; Saquinavir; Uveitis; Uveitis, Anterior; Visual Acuity

Diarrhea due to infection with Microsporidium (M) or Cryptosporidium (C) raises significant therapeutic challenges in HIV-infected patients. The usefulness of protease inhibitor therapy was evaluated in 20 HIV-positive patients with positive tests for M and/or C. There were 17 men and three women with a mean age of 42.5 years (range, 26-64 years). Two patients had category B disease and 18 category C disease according to the 1993 CDC classification scheme (CD4 count before therapy, 72/mm3; mean viral burden, 4.6 log). Seventeen patients had chronic diarrhea (due to M in 12 cases and to C in five), and the remaining three patients were asymptomatic M carriers. Clinical symptoms resolved after addition to the antiretroviral regimen of indinavir (n = 17) or saquinavir (n = 3). Mean weight gain was 10.5 kg. Karnofsky's index improved. Twelve patients, including one of the three who were asymptomatic at baseline, had negative follow-up stool cultures. The mean CD4 count increase was 125/mm3, and the mean viral burden decrease was 1.285 log. These data suggest that protease inhibitors may be capable of eradicating M and/or C infection refractory to other treatments. The reason for this effect may involve partial restoration of immune function due to inhibition of HIV replication.

Topics: Adult; AIDS-Related Opportunistic Infections; Animals; Anti-HIV Agents; Cryptosporidiosis; Diarrhea; Drug Therapy, Combination; Feces; Female; HIV Infections; HIV Protease Inhibitors; Humans; Immunocompetence; Indinavir; Male; Microsporida; Microsporidiosis; Middle Aged; Reverse Transcriptase Inhibitors; Saquinavir; Treatment Outcome

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Drug Therapy, Combination; Humans; Lamivudine; Male; Molluscum Contagiosum; Saquinavir; Zidovudine

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Delavirdine; Diarrhea; Didanosine; Drug Interactions; Drug Therapy, Combination; HIV Infections; Humans; Indinavir; Lamivudine; Nelfinavir; Nevirapine; Protease Inhibitors; Reverse Transcriptase Inhibitors; Ritonavir; Saquinavir; Virus Replication; Zalcitabine; Zidovudine

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; HIV Protease Inhibitors; Humans; Male; Mouth Mucosa; Mouth Neoplasms; Ritonavir; Saquinavir; Sarcoma, Kaposi

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

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Antiviral Agents; Candidiasis, Oral; Didanosine; Fluconazole; HIV Protease Inhibitors; Humans; Isoquinolines; Male; Quinolines; 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