saquinavir and Chronic-Disease

When to start highly active antiretroviral therapy (HAART) in asymptomatic chronically HIV-1-infected subjects with CD4 cell counts of 300 x 10(6)-500 x 10(6)/l is debated extensively. Retrospective analyses of virological and immunological responses following HAART have been evaluated in both blood and lymph nodes according to pre-treatment levels of CD4 cells either above or below 500 x 10(6)/l.. Open-label, observational, non-randomized, prospective study.. Outpatients attending the Centre of Clinical Investigation in Infectious Diseases, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland.. Fifty-four HIV-1-infected antiretroviral-naive subjects with CD4 cell count > or = 250 x 10(6)/l and plasma viraemia > or = 5000 copies/ml who had been treated with HAART for at least 48 weeks. Controls were 49 HIV-negative subjects.. All patients received abacavir, nelfinavir, saquinavir soft gel capsules, and amprenavir in varying combinations for 72 weeks.. The extent of immune reconstitution following HAART in 43 and 11 subjects with either more or fewer than 500 x 10(6) CD4 cells/l at baseline was evaluated in blood and lymph node, and compared with immunological measures observed in 49 HIV-negative controls.. After 48 weeks of therapy, plasma viraemia was suppressed effectively in both groups of patients. Normalization of both CD4 cell count in blood, divided equally between memory and naive cells, and percentage of CD4 cells in lymph nodes occurred in the two groups. Consistently, the net increase over baseline in CD4 cell count and in memory and naive CD4 subsets was greater in patients with fewer than 500 x 10(6) CD4 cells/l at baseline. Recovery of HIV-specific responses was similar in the two groups.. This study suggests that virological and immunological responses are comparable in asymptomatic therapy-naive HIV-1-infected subjects with CD4 cell counts above or below 500 x 10(6)/l.

Topics: Adult; Anti-HIV Agents; Antigens, Fungal; Antigens, Viral; Antiretroviral Therapy, Highly Active; Candida albicans; Carbamates; CD4 Lymphocyte Count; Chronic Disease; Cytomegalovirus; Dideoxynucleosides; Drug Therapy, Combination; Furans; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Nelfinavir; Prospective Studies; Reverse Transcriptase Inhibitors; RNA, Viral; Saquinavir; Simplexvirus; Sulfonamides; T-Lymphocyte Subsets

Topics: Adolescent; Adult; Antibodies, Viral; Antiviral Agents; Chronic Disease; Dose-Response Relationship, Drug; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Female; Hepatitis C, Chronic; HIV Protease Inhibitors; Humans; Interferon-alpha; Lamivudine; Male; Middle Aged; Reverse Transcriptase Inhibitors; Saquinavir

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

Modified, human immunodeficiency virus (HIV)-inoculated thy/liv-SCID-hu mice were used to evaluate the in vivo efficacy of antiretroviral drugs. Ritonavir treatment alone initially suppressed plasma viremia, but the viremia recurred with the appearance of ritonavir-resistant HIV isolates. Multidrug therapy suppressed plasma HIV RNA to undetectable levels; however, plasma viremia returned after therapy was stopped, showing that the therapy did not completely suppress HIV infection in the thymic implant. When thy/liv-SCID-hu mice were treated with a combination of zidovudine, lamivudine, and ritonavir immediately after inoculation with HIV, cocultures of the thymic implants remained negative for HIV even 1 month after therapy was discontinued, suggesting that acute treatment can prevent the establishment of HIV infection. Thus, these modified thy/liv-SCID-hu mice should prove to be a useful system for evaluating the effectiveness of different antiretroviral therapies on acute and chronic HIV infection.

Topics: Animals; Anti-HIV Agents; Chronic Disease; Drug Resistance, Microbial; Drug Therapy, Combination; Fetal Tissue Transplantation; Flow Cytometry; HIV Infections; HIV-1; Lamivudine; Leukocytes, Mononuclear; Liver Transplantation; Mice; Mice, SCID; Recurrence; Ritonavir; RNA, Viral; Saquinavir; Thymus Gland; Viremia; Zidovudine