Increased time exposure to tenofovir is associated with a greater decrease in estimated glomerular filtration rate in HIV patients with kidney function of less than 60 ml/min/1.73 m2.

Tenofovir (TDF), atazanovir (ATAZ) and indinavir (IND) have been reported as possible risk factors for incident chronic kidney disease (CKD) in HIV-infected patients. We investigated the relationship between the duration of antiretroviral exposure and estimated glomerular filtration rate (eGFR) evolution in CKD patients. In a cohort of 1,750 HIV-infected patients, we identified 121 CKD patients with a mean follow-up of 44 ± 35 months. The relationship between mean eGFR at baseline, eGFR slope and time exposure to antiretroviral treatment as well as confounding factors were investigated using a joint modeling procedure. Seventy (58%), 30 (25%) and 33 patients (27%), with a mean age of 50.3 ± 11.7 years, mean eGFR at baseline of 53.0 ± 0.8 (ml/min/1.73 m(2)) and eGFR slope of 0.46 ± 0.07 ml/min/1.73 m(2)/year, were exposed to TDF, ATAZ and IND, respectively. In univariate analysis, hepatitis C virus infection, decreased nadir of log CD4 count, high blood pressure at baseline, angiotensin-converting enzyme inhibitor treatment and greater time exposure to TDF during follow-up were associated with a higher slope, whereas greater time exposure to IND was associated with a lower slope. In multivariate analysis, higher TDF time exposure was still significantly associated with eGFR decline, with a dose-effect relationship (slope ± standard error of the mean: 1.1 ± 0.1, 0.5 ± 0.1, -0.07 ± 0.08 and -0.87 ± 0.06 ml/min/1.73 m(2)/year for no time exposure, <34, 34-67 and ≥67%, respectively; trend test: p < 0.001), whereas the IND time exposure association was abolished. In HIV patients with CKD, a greater TDF time exposure was independently associated, in a graded manner, with a greater eGFR decline.

In the era of highly active antiretroviral therapy, why are HIV-infected patients still admitted to hospital for an inaugural opportunistic infection?

OBJECTIVES: To identify factors related to delayed testing, and delayed or interrupted care-seeking or treatment uptake, among HIV-infected patients. DESIGN: HIV-infected patients hospitalized for an opportunistic infection (OI) cases were included in a prospective study and compared with controls matched by age and sex who had regular follow-up and treatment. Patients were asked to complete a questionnaire about their therapeutic itinerary and their socioeconomic, psychological and medical characteristics. RESULTS: Seventy patients were matched with 140 controls. According to their therapeutic itinerary prior to admission, cases were subdivided into four groups among which three will be more particularly studied: nontested patients (NT) (24%; n=17), known HIV-infected patients with no medical follow-up (NF) (30%; n=21); and noncompliant patients (NC) (36%, n=25). Characteristics of NT and NF patients included a predominantly sexual mode of contamination (P=0.01), continuing occupational activity (P=0.01) despite a low mean Karnofsky index (P=0.001) and unfavourable virological and immunological parameters. NT patients displayed a low degree of anxiety, and lacked awareness concerning risk of contamination and HIV-related symptoms. HIV-status announcement (P=0.04) and the benefits of medical follow-up (P=0.05) were less favourably perceived by NF patients than by controls, and were associated with a high degree of anxiety in NF patients. NC patients had a weaker commitment to follow-up and treatment, and more frequent treatment discontinuation associated with a higher rate of interruption of follow-up in a context of social difficulties. CONCLUSIONS: Patients ignorant of their HIV status, patients NF and NC have very specific characteristics. More appropriate approaches are needed regarding screening and access to care in order to reduce the incidence of delayed care-seeking.

Efficacy and safety of vancomycin constant-rate infusion in the treatment of chronic Gram-positive bone and joint infections.

OBJECTIVE: To evaluate the efficacy and safety of vancomycin constant-rate infusion over 24 h in the treatment of Gram-positive bone infections, METHODS: Vancomycin (40 mg/kg/day) was administered without a loading dose to 15 patients (12 male, three female) aged 23--90 years, weighing 46--85 kg, with postoperative chronic bone and joint infections. The 24-h dose was adjusted to maintain plasma levels between 25 and 35 mg/L. Mean duration of therapy was 6.2 months (4--8.5) via a portable infusion pump. Sites of infection included hip and femur (10), tibia (three), patella (one) and vertebrae (one). Sequestrectomy (two), removal of material (7/8 prosthetic hips, 1/5 metal implants) and debridement (two) were performed at the beginning of the treatment. Involved bacteria included Staphylococcus aureus (eight, six methicillin resistant), S. epidermidis (four methicillin-resistant), Enterococcus faecalis (one), Enterococcus avium (one) and Streptococcus bovis (one). RESULTS: MIC of vancomycin ranged from 1 to 4 mg/L. The mean vancomycin bone concentration when available was 67.7plus minus38.9 microg/L. Based on a mean post-treatment follow-up of 14plus minus4 months (6--20.6), cure was achieved in 10 patients (66.6%). Failures were related to the inability to remove the infected prosthesis (one) or implants (three) and to the persistence of a deep wound abcess (one). Adverse events included pruritus (four cases), tinnitus (two), mild transient elevation of creatinine level (three) and transient neutropenia (two). Vancomycin was maintained in all the patients. CONCLUSIONS: Prolonged treatment with vancomycin constant-rate infusion is effective and safe for treatment of Gram-positive chronic bone and joint infections, providing that complete surgical débridement and prosthetic material removal are performed.