ABSTRACT
A significant percentage of human immunodeficiency virus type 1 (HIV-1)-infected persons treated with highly active antiretroviral therapy (HAART) will develop plasma HIV-1-specific virion RNA levels <50 copies/mL. HIV-1-infected persons receiving virally suppressive HAART were studied with a viral outgrowth assay of the patients' peripheral blood mononuclear cells (PBMC), and a quantitative polymerase chain reaction assay was used to analyze HIV-1 2-long terminal repeat (2-LTR) circular DNA in PBMC, which indicates new HIV-1 infections of cells in vivo. Viral outgrowth in vitro correlated inversely with the level of peripheral blood CD4(+) T lymphocytes. Detection and quantitation of 2-LTR circular DNA correlated strongly with viral outgrowth patterns and inversely with CD4(+) T lymphocyte counts. Relevant subgroups of HIV-1-infected subjects on suppressive HAART with residual viral disease and reservoirs can now be stratified.
Subject(s)
DNA, Viral/analysis , HIV Infections/virology , HIV-1/genetics , Proviruses/genetics , Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/virology , Cohort Studies , DNA, Complementary/analysis , Female , HIV Infections/drug therapy , HIV Infections/immunology , HIV Long Terminal Repeat/genetics , HIV-1/pathogenicity , Humans , Male , Time Factors , Virus ReplicationABSTRACT
Ceftazidime is a beta-lactam antibiotic highly effective against Pseudomonas aeruginosa infection. Using a rabbit model of Pseudomonas keratitis, 10(3) bacteria (in 20 microliters) were injected unilaterally into the corneal stroma of albino rabbits. Twenty-six hours after inoculation, topical Ceftazidime (50 mg/ml) drops were administered for 48 h, following which the corneal tissue was cultured. Eighteen of 20 corneal cultures (90%) from rabbits treated with Ceftazidime drops were negative. In comparison, all untreated control group cultures showed florid bacterial growth. These results suggest that topical Ceftazidime may be a useful agent in the treatment of P. aeruginosa keratitis.
Subject(s)
Ceftazidime/therapeutic use , Eye Infections, Bacterial/drug therapy , Keratitis/drug therapy , Pseudomonas Infections/drug therapy , Administration, Topical , Animals , Ceftazidime/administration & dosage , Colony Count, Microbial , Disease Models, Animal , Keratitis/microbiology , Ophthalmic Solutions , Pseudomonas aeruginosa/isolation & purification , RabbitsABSTRACT
OBJECTIVE: Cryptococcus neoformans infections of the central nervous system affect up to ten percent of AIDS patients. Standard therapy with amphotericin B with or without 5-flucytosine has a high rate of failure, relapse, and toxicity. Fluconazole is a new triazole antifungal agent available in both oral and intravenous forms that has shown efficacy in the primary and maintenance treatment of cryptococcal meningitis in AIDS patients. In this open, noncomparative trial, we evaluated the safety and efficacy of intravenous fluconazole followed by oral fluconazole in the treatment of acute cryptococcal meningitis in AIDS patients. METHODS: Thirteen AIDS patients with acute cryptococcal meningitis, or relapse after successful primary therapy, received 400 mg of intravenous fluconazole daily for 12-16 days followed by oral fluconazole 400 mg/d for the duration of primary therapy. If cerebrospinal fluid (CSF) cultures converted to negative within 32 weeks of treatment, the fluconazole dose was decreased to 200 mg/d as maintenance therapy. RESULTS: Fluconazole therapy was successful in six patients (46 percent) and unsuccessful in seven (54 percent). Of the seven patients considered unsuccessful, one demonstrated clinical improvement but remained CSF-culture positive, five were clinical failure and were switched to amphotericin B therapy, and one died after two weeks secondary to cryptococcal meningitis. No patient experienced any adverse reactions necessitating discontinuation of therapy. CONCLUSIONS: In this small group of patients, moderate doses of parenteral and oral fluconazole for acute cryptococcal meningitis in AIDS patients demonstrated failure rates similar to those reported in other studies with fluconazole and with amphotericin B. As there was no difference in initial Karnofsky scores or the severity of disease in treatment successes versus failures, it is difficult to determine who might respond to fluconazole as initial therapy or who should be treated initially with another agent. Further studies and clinical experience are needed.
