Solid organ transplantations (SOT) are performed successfully in selected HIV‐infected patients. However, multiple and reciprocal drug–drug interactions are observed between antiretroviral (ARV) ...drugs and calcineurin inhibitors (CNIs) through CYP450 metabolization. Raltegravir (RAL), a novel HIV‐1 integrase inhibitor, is not a substrate of CYP450 enzymes. We retrospectively reviewed the outcomes of 13 HIV‐infected transplant patients treated by an RAL + two nucleosidic reverse transcriptase inhibitor (NRTI) regimen, in terms of tolerability, ARV efficacy (plasma viral load, CD4 cell count), drug interactions, RAL pharmacokinetics and transplant outcome. Thirteen patients with liver (n = 8) or kidney (n = 5) transplantation were included. RAL was initiated (400 mg BID) either at time of transplantation (n = 6), or after transplantation (n = 7). Median RAL trough concentration was 507 ng/mL (176–890), which is above the in vitro IC95 for wild type HIV‐1 strains (15 ng/mL). Target trough levels of CNIs were promptly obtained with standard dosages of tacrolimus or cyclosporine. RAL tolerability was excellent. There was no episode of acute rejection. HIV infection remained controlled. After a median follow‐up of 9 months (range: 6–14), all patients were alive with satisfactory graft function. The use of an RAL + two NRTI‐based regimen is a good alternative in HIV‐infected patients undergoing SOT.
Raltegravir use in solid organ transplantation represents a new option to reduce drug interactions in HIV‐infected patients.
Fatigue is a major component of quality of life (QOL) and is associated with depression in HIV–HCV co‐infected individuals. We investigated whether treating depressive symptoms (DS) could mitigate ...the impact of fatigue on daily functioning in co‐infected patients, even those at an advanced stage of disease. The analysis was conducted on enrolment data of 328 HIV–HCV co‐infected patients recruited in the French nationwide ANRS CO 13 HEPAVIH cohort. Data collection was based on medical records and self‐administered questionnaires which included items on socio‐behavioural data, the fatigue impact scale (FIS) in three domains (cognitive, physical and social functioning), depressive symptoms (CES‐D classification) and use of treatments for depressive symptoms (TDS). After multiple adjustment for gender and unemployment, CD4 cell count <200 per mm3 was associated with a negative impact of fatigue on the physical functioning dimension (P = 0.002). A higher number of symptoms causing discomfort significantly predicted a higher impact of fatigue on all three dimensions (P < 0.001). This was also true for patients with DS receiving TDS when compared with those with no DS but receiving TDS. A significant decreasing linear trend (P < 0.001) of the impact of fatigue was found across the categories ‘DS/TDS’, ‘DS/no TDS’, ‘no DS/TDS’ and ‘no DS/no TDS’. Despite limitations related to the cross‐sectional nature of this study, our results suggest that routine screening and treatment for DS can reduce the impact of fatigue on the daily functioning of HIV–HCV co‐infected patients and relieve the burden of their dual infection.
Bacterial spondylodiskitis—i.e., adjacent vertebral osteomyelitis and diskitis—was studied in 80 adult patients. The infection was due to Mycobacterium tuberculosis in 31 cases (39%) and to pyogenic ...bacteria in 49 cases (61%). The latter pathogens included gram-negative bacilli in 16 cases (20%), Staphylococcus species in 15 (19%), Streptococcus species in 9 (11%), and Corynebacterium species in 1 (1%); the pathogens in the 8 remaining cases (10%) were not identified. Of the patients with tuberculous spondylodiskitis, 55% came from countries where tuberculosis is endemic (P < .001). Cases due to staphylococci and those due to M. tuberculosis were associated with a high frequency of previous active infection with those respective organisms at any site (47% and 42%, respectively; P < .001) and with a high rate of neurological complications (33% and 32%, respectively; P < .001). Nine patients with pyogenic spondylodiskitis (18%) but only one patient with tuberculous spondylodiskitis (3%) had diabetes mellitus (P < .05). Blood cultures were positive in 23 (56%) of the 41 cases of pyogenic spondylodiskitis due to an identified bacterium. Discovertebral needle biopsy contributed to the bacteriologic diagnosis in 29 (74%) of 39 cases.
Sir Similarly to Alain Lafeuillade and colleagues,1 we saw three cases of mitochondrial toxic effects in patients co-infected by HIV-1 and hepatitis C virus (HCV) and treated by highly active ...antiretroviral therapy and interferon alfa and ribavirin for their HCV. In murine models, the efficacy of didanosine but also its toxic effects could be majored by ribavirin.3,4 In vivo, workers in a phase I and II trial done in 18 HIV-1-infected patients receiving didanosine alone (400 mg four times daily) for 4 weeks, then didanosine plus ribavirin for 8 weeks showed a significant decrease in HIV-1 viral load during the bitherapy period but also grade II-IV toxic effects in four (22%) patients during the first 12 weeks.5 Two of the 12 patients who followed their treatment for 20 weeks developed a biological pancreatitis that regressed when didanosine was stopped. If prospective studies confirm that the coadministration of didanosine and ribavirin leads to an increased risk of mitochondrial toxic effects, this could lead to new recommendations for the modalities of prescription of these two drugs, by reducing the dose of didanosine when coadministered with ribavirin or by avoiding their concomitant prescription.
Anti-tumour necrosis factor (TNF) therapy may be associated with opportunistic infections (OIs).
To describe the spectrum of non-tuberculosis OIs associated with anti-TNF therapy and identify their ...risk factors.
A 3-year national French registry (RATIO) collected all cases of OI in patients receiving anti-TNF treatment for any indication in France. A case-control study was performed with three controls treated with anti-TNF agents per case, matched for gender and underlying inflammatory disease.
45 cases were collected of non-TB OIs in 43 patients receiving infliximab (n=29), adalimumab (n=10) or etanercept (n=4) for rheumatoid arthritis (n=26), spondyloarthritides (n=3), inflammatory colitis (n=8), psoriasis (n=1) or other conditions (n=5). One-third (33%) of OIs were bacterial (4 listeriosis, 4 nocardiosis, 4 atypical mycobacteriosis, 3 non-typhoid salmonellosis), 40% were viral (8 severe herpes zoster, 3 varicella, 3 extensive herpes simplex, 4 disseminated cytomegalovirus infections), 22% were fungal (5 pneumocystosis, 3 invasive aspergillosis, 2 cryptococcosis) and 4% were parasitic (2 leishmaniasis). Ten patients (23%) required admission to the intensive care unit, and four patients (9%) died. Risk factors for OIs were treatment with infliximab (OR=17.6 (95% CI 4.3 - 72.9); p<0.0001)or adalimumab (OR=10.0 (2.3 to 44.4); p=0.002) versus etanercept, and oral steroid use >10 mg/day or intravenous boluses during the previous year (OR=6.3 (2.0 to 20.0); p=0.002).
Various and severe OIs, especially those with intracellular micro-organisms, may develop in patients receiving anti-TNF treatment. Monoclonal anti-TNF antibody rather than soluble TNF receptor therapy and steroid use >10 mg/day are independently associated with OI.
Background. Patients treated with tumor necrosis factor–α (TNF-α) antagonists have an increased risk of infection, but infection due to Legionella pneumophila has rarely been described in patients ...receiving such therapy. Methods. A registry involving 486 clinical departments in France was designed by a multidisciplinary group (Recherche Axée sur la Tolérance des Biothérapies RATIO) to collect data on opportunistic and severe infections occurring in patients treated with TNF-α antagonists. All cases are reported to RATIO in accordance with national health authorities and validated by infectious disease experts. The legionellosis rate among patients treated with TNF-α antagonists was compared with the rate in France overall. Results. We report a 1-year consecutive series of 10 cases of L. pneumophila pneumonia in France in 2004, including 6 cases treated with adalimumab, 2 treated with etanercept, and 2 treated with infliximab. The median patient age was 51 years (range, 40–69 years). Eight patients were treated for rheumatoid arthritis, 1 was treated for cutaneous psoriasis, and 1 was treated for pyoderma gangrenosum. The median duration of TNF-α antagonist treatment at onset of infection was 38.5 weeks (range, 3–73 weeks). Eight patients were receiving concomitant treatment with corticosteroids, and 6 were receiving treatment with methotrexate. The relative risk of legionellosis when receiving treatment with a TNF-α antagonist, compared with the relative risk in France overall, was estimated to be between 16.5 and 21.0. We also report a second episode of confirmed legionellosis following the reintroduction of infliximab therapy. Conclusions. L. pneumophila pneumonia is a potentially severe but curable infection that might complicate anti–TNF-α therapy. In patients receiving anti–TNF-α who develop pneumonia, legionellosis should be systematically investigated, and first-line antibiotic therapy should be efficient against L. pneumophila.
Dirks et al. 1 's recent study provides greater insight into the neu-ropsychiatric symptoms experienced by HCV-infected patients and questions how these symptoms are associated with HCV clearance. ...The authors show that in HCV-infected patients with mild liver disease , none of the following outcomes depend on HCV clearance: cognitive function, mood alteration, health-related quality of life (HRQL) and fatigue (FIS scores). However, these results may not be generalizable to HIV-HCV co-infected patients and cirrhotic patients , who were excluded from the study and who are generally more concerned by fatigue and neuropsychiatric symptoms. This restriction avoids possible interferences of specific clinical conditions with neuropsychiatric symptoms but reduces external validity. The HIV-HCV co-infected population includes a non-negligible proportion of individuals with a history of injection of opioids. Exposure to opioids tends to amplify neuropsychiatric and painful symptoms. Cirrhotic patients also have more numerous and more acute symptoms related to their disease, treatment experience and poor quality of life. The results from two studies we conducted in these specific patient subpopulations 2,3 were similar to those of Dirks et al. 1 The first of these studies was based on data collected on HIV-HCV-co-infected patients in the French cohort ANRS CO13-HEPAVIH. In that study, changes in FIS scores before/ after pegylated interferon (PegIFN)-based treatment were not significantly associated with HCV clearance. 2 Moreover, functional fatigue-related limitations persisted two years in median after the end of treatment. It is interesting to note that the characteristics of the 107 patients analysed in that study were quite different from those in Dirks et al's study. More specifically, time since HCV diagnosis was shorter in the former (10 years in median vs 26 years) and the percentage of HCV-cleared patients higher (53% vs 23%). Our second study analysed HRQL in 47 HCV-infected patients with compensated cirrhosis who switched from PegIFN-based to PegIFN-free therapy. Results showed no major improvement in physical HRQL after the end of therapy, despite HCV clearance and improved physical and mental HRQL being observed during PegIFN-free treatment. 3 However, just as for Dirks et al.'s study, 1 our results were obtained in patients treated with PegIFN-based therapies and may not be repeatable in the era of direct-acting antivirals (DAA). Data from DAA clinical trials show major improvements in patient-reported outcomes (including better HRQL, less fatigue and fewer symptoms) for HCV-treated patients. 4 However, real-world, long-term, post-HCV clearance changes in patient-reported outcomes of DAA-treated patients still require further evaluation. 5 ORCID F. Marcellin orcid.org/0000-0001-8853-3829 D. Salmon-Ceron orcid.org/0000-0002-6817-8951 M. P. Carrieri
We compared IgG and IgA distribution in serum, three different salivary samples, two different rectal secretion samples, cervicovaginal secretions, and seminal secretions from asymptomatic CDC stage ...II/III HIV-1-infected subjects (n = 44) and from HIV-1-seronegative volunteers (n = 52). In-house ELISAs were used to measure total IgG and total IgA levels, as well as HIV-specific anti-gp120 MN and anti-p24 LAI IgG and IgA. Human serum albumin was titrated in parallel to calculate the relative coefficient of excretion (RCE). In spite of substantial interindividual variability, total IgG concentrations in all fluids were found to be significantly greater in the HIV-1-infected group than in the seronegative subjects. Calculation of RCE values revealed three different types of mucosal secretion: secretions with no local Ig production, such as sperm; secretions with local production of IgA and transudative origin of IgG, such as salivary and rectal samples; and secretions with local production of both IgG and IgA, such as in cervicovaginal secretions. For all mucosal specimens from HIV-1-infected subjects, the response to HIV-1 was predominantly IgG, with highest titers observed in cervicovaginal secretions (although these were lower than serum levels). In contrast, the specific IgA response appeared weaker in the mucosa than in serum.
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