ABSTRACT
Eighteen patients with symptomatic HIV disease were enrolled into a phase I/II study of a microsphere formulation of the HIV protease inhibitor KNI-272, with doses escalated up to a maximum dose of 60 mg/kg/day. One patient developed reversible elevation in hepatic transaminase. The plasma half-life of the drug was very short, varying between 0.25 and 1.1 h. No consistent effect on plasma HIV RNA levels or CD4(+) lymphocyte counts was seen.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV-1/drug effects , Oligopeptides/therapeutic use , Adult , Alanine Transaminase/drug effects , Alanine Transaminase/metabolism , Anti-HIV Agents/adverse effects , Anti-HIV Agents/pharmacokinetics , Area Under Curve , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/drug effects , Cohort Studies , Dose-Response Relationship, Drug , HIV-1/genetics , Humans , Male , Microspheres , Middle Aged , Oligopeptides/adverse effects , Oligopeptides/pharmacokinetics , Patient Dropouts , RNA, Viral/blood , RNA, Viral/drug effects , Treatment OutcomeABSTRACT
OBJECTIVES: although Mycobacterium kansasii infection has long been endemic in the U.K., the disease burden and characteristics of infection in the HIV-seropositive population has not been well documented. This study addresses these issues in an inner city population that comprises a quarter of all cases of acquired immunodeficiency syndrome (AIDS) reported in the U.K. METHODS: retrospective review of case notes from two inner London specialist HIV Units. RESULTS: twenty-nine cases of M. kansasii infection were identified, with case notes available for review in 26. Ten had pulmonary disease and nine had disseminated infection: a further seven patients appeared simply to be colonized (two respiratory and five gastrointestinal): M. kansasii was isolated from stool in over a third (nine of 26) of cases. Disseminated M. kansasii infection occurred in 0.44% of AIDS cases seen in our two units and all isolates were resistant to isoniazid ion vitro. A clinical response achieved in 11 of the 13 patients with M. kansasii-related disease who received anti-mycobacterial therapy. All four patients who relapsed following initial clinical response to therapy had received sub-optimal treatment. CONCLUSIONS: the incidence of disseminated M. kansasii infection in HIV-infected individuals in the U.K. is similar to that seen in those from high prevalence regions of the U.S.A., and anti-mycobacterial therapy leads to a clinical response in the majority of patients with HIV and M. kansasii co-infection. The frequent isolation of M. kansasii from the stool suggests that the gastrointestinal tract may be a significant source of disseminated infection.
