Search

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 m2) and eGFR slope of 0.46 ± 0.07 ml/min/1.73 m2/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 m2/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. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Selection of resistant mutants was induced in broth by exposing pneumococci to serial sub-inhibitory concentrations of various β-lactam antibiotics. Aminopenicillins selected for resistance to themselves and to cephalosporins although cephalosporins tended to select for resistance to their own class, with the exception of cefixime which seems to select cross-resistant organisms. [ABSTRACT FROM PUBLISHER]

Monotherapy with macrolides for the treatment of disseminated Mycobacterium avium complex (MAC) bacteraemia leads to drug resistance and relapse of bacteraemia. Gastrointestinal intolerance is a common reason for treatment withdrawal of multidrug regimens. We have assessed the efficacy and safety of initial parenteral therapy together with a macrolide, for disseminated MAC infection, defined as two positive blood cultures, in AIDS patients. Patients received a daily infusion of amikacin 15 mg/kg + ethambutol 20 mg/kd + ciprofloxacin 400 mg/day, for 1 month, together with a macrolide by oral route. Fifteen patients were included and 13 (86%) achieved negative culture before the end of parenteral therapy. [ABSTRACT FROM PUBLISHER]

Visceral leishmaniasis is an anthropozoonosis endemic in the south of France. Its occurrence among patients infected with human immunodeficiency virus (HIV), in whom it presents with uncommon clinical, biological, and evolutionary signs, is being reported more and more often. We describe a case of leishmaniasis in an HIV-seropositive man that we believe is unique with respect to the cutaneous and then visceral location of the disease and the discovery at necropsy of an adrenal and myocardial leishmanial infiltrate. [ABSTRACT FROM PUBLISHER]

Abstract: The medical dashboard (DB) recording our clinical practices indicated on one hand the use of two different diagnosis terms, acute dermohypodermitis (ADH) or cellulitis, and on the other hand, an important antibiotic prescription heterogeneity. Our aim was to define these two diagnosis groups and to document compliance to our antibiotic therapy protocol. Method: ADH and cellulitis were selected in our medical DB that records all patient data. Our local antibiotic therapy protocol was designed in April 2009; the prescription of recommended antibiotic agents defined the compliance to recommendations. The patient files indicating non-consensual therapy were analyzed to determine the reasons for inappropriate prescription. Results: Three hundred and four cases of ADH and 82 of cellulitis were diagnosed over 6.5years. ADH was associated with older age (P =0.007), a higher frequency of venous insufficiency (P =0.015), a lower frequency of cancer (P =0.007), and was more often located on lower limbs (P <0.001), compared to cellulitis. The diagnosis of ADH was associated with higher compliance to our antibiotic therapy protocol, compared to cellulitis: 68% versus (vs.) 24%, P <0.001, and after April 2009: 53% vs. 64%, P =0.033. Among the 162 inappropriate antibiotic prescriptions (42%), 75 were deemed justified after analyzing the patient file, but less frequently for ADH compared to cellulitis: 49% vs. 11,5%, P <0.001. Conclusion: ADH presents different clinical characteristics compared to cellulitis. The antibiotic therapy protocol for ADH cannot be applied to cellulitis. [Copyright &y& Elsevier]

Background: COPD is a frequent and significant cause of respiratory morbidity in HIV-infected patients despite the control of HIV. We aimed to analyze the factors correlated with COPD in this population to evaluate the existence of specific indicators of vulnerability in this population., Methods and Findings: 623 HIV-infected outpatients were enrolled during one year. This population was characterised by a dedicated questionnaire and electronic patient records. COPD screening was performed according to recommended spirometric criteria. The prevalence of COPD was 9.0%. Age and smoking were independently correlated with COPD (OR, 1.61 per 10 years increase, P = 0.007; OR, 1.28 per 10 pack-year increase, P = 0.003, respectively). Body mass index (BMI) and CD4 cell-count were independently and negatively correlated with COPD (OR, 0.78, P < 0.001; 0R, 0.77 per 100 cell/mm3 increase, P < 0.001, respectively). Among COPD patients, 77% did not know their diagnosis. Five COPD-patients never smoked and 44.2% did not have any respiratory symptoms and so were not eligible to perform a spirometry according to the guidelines., Conclusions: In addition to known risk factors, immune defect through CD4 cell count was independently and strongly correlated with COPD. COPD is largely underdiagnosed and thus unmanaged. However, early management and urgent smoking cessation are essential to improve prognosis. Clinicians' awareness on the particular vulnerability for COPD in HIV-infected patients is crucial. Moreover, indications to perform conventional spirometry to diagnose COPD may include more parameters than tobacco-smoking and respiratory complaints with a particular concern toward patients with a profound CD4 cell count defect., Competing Interests: The authors have declared that no competing interests exist.

Cytomegalovirus (CMV) infection is common among HIV-infected patients but its repercussion on the course of CD4+ and CD8+ T cells after cART initiation remains elusive. The French Dat'AIDS cohort enrolled 5,688 patients on first-line cART, from which we selected patients who achieved HIV suppression for at least 12 months without modification of cART, and for whom CMV serostatus was available. Five hundred and three patients fulfilled the selection criteria (74% male, median age 43 yrs, 15.5% CDC stage C), of whom 444 (88.3%) were seropositive for CMV (CMV+). Multivariate analyses using mixed-linear models adjusted for the time from HIV suppression, sex, age, transmission risk group, duration of HIV follow-up, the interaction between time from HIV suppression and CMV+ serology, and the nadir CD4 count revealed a negative correlation between CMV+ and CD4:CD8 ratio (coeff. = -0.16; p = 0.001). This correlation was also observed among patients displaying optimal CD4 recovery (≥500 cells/mm3 at M12; coeff. = -0.24; p = 0.002). Hence, CMV+ serostatus antagonizes normalization of the CD4:CD8 ratio, although further analyses of the impact of co-morbidities that associate with CMV serostatus, like HCV infection, are needed to elucidate this antagonism formally. However, this might reflect a premature T cell senescence, thus advocating for a close monitoring of T cells in CMV co-infected patients. In addition, our results raise the question of the benefit of treatment for asymptomatic CMV co-infection in HIV-infected patients., Competing Interests: The authors have declared that no competing interests exist.

The aim of the study was to investigate the impact of first-line combined antiretroviral therapy (cART) regimen on the course of CD8 T-cell counts in human immunodeficiency virus (HIV)-infected patients.A retrospective observational study conducted on the French DAT'AIDS Cohort of HIV-infected patients.We selected 605 patients initiating a first-line cART between 2002 and 2009, and which achieved a sustained undetectable HIV plasma viral load (pVL) for at least 12 months without cART modification. The evolution of CD8 T-cell counts according to cART regimen was assessed.CD8 T-cell counts were assessed in 572 patients treated with 2NRTIs+1PI/r (n= 297), 2NRTIs+1NNRTI (n= 207) and 3NRTIs (n= 68). In multivariate analysis, after 12 months of follow-up, the 3NRTIs regimen was associated with a significantly smaller decrease of CD8 T-cell count compared with NNRTI-containing regimens (-10.2 cells/μL in 3NRTIs vs -105.1 cells/μL; P=0.02) but not compared with PI-containing regimens (10.2 vs -60.9 cells/μL; P=0.21). After 24 months, the 3NRTIs regimen was associated with a smaller decrease of CD8 T-cell count and % compared with PI/r- and NNRTI-containing regimens (0.2 in 3NRTIs vs -9.9 with PI/r-regimens, P=0.001, and vs -11.1 with NNRTI-regimens, p < 0.0001). A focus analysis on 11 patients treated with an INSTI-containing cART regimen during the study period showed after 12 months of follow-up, a median decrease of CD8 T-cell count of -155 [inter quartile range: -302; -22] cells/μL.Our data highlight the fact that cART regimens have differential effects on CD8 pool down regulation., Competing Interests: The authors have no funding and conflicts of interest to disclose.

Objective: A recent consensus defines "late presentation" (LP) during the course of HIV infection as presentation with AIDS whatever the CD4 cell count or with CD4 <350 cells per cubic millimeter. Here, using this new definition, we examined the frequency and predictors of LP and its impact on mortality., Methods: In antiretroviral-naive patients enrolled in the French Hospital Database on HIV between 2003 and 2009, we studied risk factors for LP by multivariable logistic regression. The impact of LP on mortality was analyzed according to the level of immunodeficiency by using Cox multivariable models adjusted for potential confounders, with follow-up categorized into 0-6, 6-12, and 12-48 months., Results: There were 11,038 (53.9%) late presenters among the 20,496 patients included in the study. Compared with patients presenting for care with CD4 ≥350 cells per cubic millimeter, patients presenting with AIDS had a very high risk of death with crude hazard ratio ranging from 48.3 during the first 6 months of follow-up to 4.8 during months 12-48; the corresponding values among AIDS-free patients with CD4 ≤200 cells per cubic millimeter were 8.1 and 2.3. Importantly, patients presenting with CD4 between 200 and 350 cells per cubic millimeter also had a significantly increased risk of death beyond 6 months of follow-up (hazard ratio: 3.0 and 1.8 for months 6-12 and 12-48, respectively). Results were similar after adjustment., Conclusions: LP with HIV infection is still very frequent in France and is associated with higher mortality, even among patients with only moderate immunodeficiency. Encouraging early testing and access to care is still urgently needed.

We report the case of an HIV-infected patient who presented with acute renal failure due to visceral leishmaniasis (VL). Although renal failure is the leading cause of death in dogs, the natural reservoir of Leishmania infantum, renal involvement is usually absent in human VL. However, L. infantum can be considered a cause of renal failure in HIV-infected patients.

Selection of resistant mutants was induced in broth by exposing pneumococci to serial sub-inhibitory concentrations of various beta-lactam antibiotics. Aminopenicillins selected for resistance to themselves and to cephalosporins although cephalosporins tended to select for resistance to their own class, with the exception of cefixime which seems to select cross-resistant organisms.

In recent years, increasing numbers of Streptococcus pneumoniae strains displaying relative resistance to penicillin have been reported. Epidemiological studies have shown a correlation between aminopenicillin administration and resistance. We investigated the development of resistance in six strains (four sensitive and two intermediate-resistant to penicillin) by serial daily passages in subinhibitory concentrations of amoxicillin (AMX), amoxicillin + clavulanic acid (AMC), imipenem (IMP), cefixime (CFM), cefatrizine (CTZ), cefadroxil (CDX), and cefuroxime (CXM). MICs were determined by the macrodilution method in brain-heart broth for each daily passage. The number of daily passages needed to increase the MIC by a factor of 8 was achieved with AMX, AMC, and CFM for most of the strains after a mean of 24, 20, and 11 passages, respectively, and for one-third of the strains, with CDX, IMP, and CTZ after 11, 11, and 21 passages, respectively. Decreased susceptibility to breakpoints for intermediate-resistant S. pneumoniae populations was noted for all strains with CFM, AMX, and AMC after a mean of 10, 18, and 21 serial passages, respectively, and for four of five strains with IMP and CTZ after 12 and 13 passages. CTZ-, CDX-, and CXM-passaged variants had increased MIC values only for cephalosporins, while AMX-, AMC-, IMP-, and CFM-passaged variants exhibited increased MICs to all antibiotics tested. These in vitro data appear to be in agreement with epidemiological studies and warrant further exploration with respect to possible clinical implications.