The effect of ß-carotene supplementation on the pharmacokinetics of nelfinavir and its active metabolite M8 in HIV-1-infected patients.

ß-Carotene supplements are often taken by individuals living with HIV-1. Contradictory results from in vitro studies suggest that ß-carotene may inhibit or induce cytochrome P450 enzymes and transporters. The study objective was to investigate the effect of ß-carotene on the steady-state pharmacokinetics of nelfinavir and its active metabolite M8 in HIV-1 infected individuals. Twelve hour nelfinavir pharmacokinetic analysis was conducted at baseline and after 28 days of ß-carotene supplementation (25,000 IU twice daily). Nelfinavir and M8 concentrations were measured with validated assays. Non-compartmental methods were used to calculate the pharmacokinetic parameters. Geometric mean ratios comparing day 28 to day 1 area under the plasma concentration-time curve (AUC(0-12 h)), maximum (C(max)) and minimum (C(min)) concentrations of nelfinavir and M8 are presented with 90% confidence intervals. Eleven subjects completed the study and were included in the analysis. There were no significant differences in nelfinavir AUC(0-12 h) and C(min) (-10%, +4%) after ß-carotene supplementation. The M8 C(min) was increased by 31% while the M8 AUC(0-12 h) and C(max) were unchanged. During the 28 day period, mean CD4+ % and CD4+:CD8+ ratio increased significantly (p < 0.01). ß-carotene supplementation increased serum carotene levels but did not cause any clinically significant difference in the nelfinavir and M8 exposure.

Viral pathogens including human metapneumovirus are the primary cause of febrile respiratory illness in HIV-infected adults receiving antiretroviral therapy.

To determine the spectrum of pathogens causing acute febrile respiratory illness in human immunodeficiency virus (HIV)-infected adults, we re-analyzed data from a prospective surveillance study involving 50 outpatients (90% of whom received highly active antiretroviral therapy). Nasopharyngeal samples were tested for 23 respiratory viruses by multiplex reverse-transcriptase polymerase chain reaction (PCR) and for atypical bacteria by PCR. Sputum cultures and serological testing were performed. Viruses accounted for 64% of infections. After influenza (22 cases), human metapneumovirus infection (6 cases) was most common and was associated with bronchospasm. Bacterial infections occurred in 6 patients (3 of whom had concurrent viral infection). Over 80% of patients received antibiotics. Rapid testing to identify specific viral pathogens could aid in patient management and reduce unnecessary antibiotic exposure.

Influenzavirus infection is a primary cause of febrile respiratory illness in HIV-infected adults, despite vaccination.

BACKGROUND: There are, to our knowledge, no prospective studies of respiratory tract infections in human immunodeficiency virus (HIV)-infected adults in the highly active antiretroviral therapy (HAART) era. We performed a surveillance study of outpatients who presented with fever and respiratory symptoms to examine the role of viral pathogens in these patients. METHODS: Consecutive patients with a temperature of >38.0 degrees C and respiratory symptoms were recruited from a tertiary care HIV clinic during the period 2003-2006. Nasal pharyngeal samples were tested for influenzavirus A and B, respiratory syncytial virus, and human metapneumovirus using real-time multiplex polymerase chain reaction assays. Paired acute- and convalescent-phase serum samples were tested for respiratory viruses by complement fixation. RESULTS: Fifty patients (90% of whom were receiving HAART) were included in the study (median CD4(+) T cell count, 325 cells/microL; median HIV RNA level, <50 copies/mL). A causative pathogen was identified in 25 patients (50%). Even though 76% of subjects had received influenza vaccine, viral infections were diagnosed in 21 patients (42%), as follows: influenza A, 10 patients; influenza B, 10; and parainfluenza virus type 3 infection, 1. Patients with and those without viral infection had similar demographic characteristics and HIV statuses. No patients with influenza and 23% of patients with other conditions had radiography-confirmed pneumonia (P=.07). Antibiotic prescriptions were common: 70% of patients received antibiotics. No patients with influenza required hospitalization, compared with 21% of other patients (P=.03). CONCLUSIONS: Although illness was mild, influenza accounted for a large proportion of unscheduled visits to a health care provider for respiratory illness and was associated with unnecessary antibiotic prescriptions that may contribute to antimicrobial resistance. Vaccination alone was insufficient to prevent infection. Thus, specific identification and management of influenza should be performed in HIV-infected outpatients who present with fever and respiratory symptoms.