Benoit Martha

Epidemiology, diagnosis and treatment of chronic hepatitis B in HIV-infected patients (EPIB 2005 STUDY).

Objective:To describe the characteristics of hepatitis B (HBV) infection in HIV-infected patients and the impact of anti-HBV treatments. Patients and methods:All the patients with past or present chronic HBV infection seen in October 2005 in 17 French hospitals were included. Data were retrospectively collected from their first visit in a time-dependent manner, through a detailed standardized questionnaire. Results:Among 477 HBV-infected patients, 261 (55%) were co-infected with HIV. The HBV–HIV co-infected patients underwent fewer serological, virological and histological evaluations. Initial positive HBe antigenemia (HBe Ag) was more frequent in these patients (57.9 versus 28.6%; P < 10−4), as was cirrhosis on the initial liver biopsy (17.9 versus 7.6%; P = 0.05). Throughout the mean 5-year follow-up, HBe Ag loss was less frequent (P = 0.04), as was HBe seroconversion (incidence rate 2.6 versus 10/100 patient-years; P < 10−3). HBe Ag loss was associated with fibrosis improvement (METAVIR score −0.5 ± 0.4 versus +0.2 ± 0.6 if persistent positive HBe Ag, P = 0.01). In co-infected patients on tenofovir, adefovir or interferon, HBe seroconversions were seen in patients on combined HBV treatment, the use of which is increasing (58% in 2005). Nevertheless, no significant difference in virological, immunological or biochemical evolution was observed between these different treatments. Conclusions:In HBV–HIV co-infected patients, the assessment of HBV infection still needs to be improved, the HBV wild-type remains predominant, and HBe Ag loss is rare and associated with a better histological evolution. There is insufficient evidence of the superiority of combined HBV treatment, and this still needs be demonstrated in long term studies.

Concentration of Circulating Oxidized LDL in HIV-Infected Patients Treated with Antiretroviral Agents: Relation to HIV-Related Lipodystrophy

Abstract Background: Circulating oxidized LDL (ox-LDL) is associated with clinical manifestations of atherosclerosis. The aim of the study was to investigate the concentrations of ox-LDL in HIV-infected patients under antiretroviral therapy with (HIV-LD) or without (HIV-nLD) HIV-related lipodystrophy. Method: A total of 44 HIV-infected men were enrolled in the study. Half of them had HIV-LD. The control group included 12 age- and body mass index (BMI)-matched HIV-uninfected men. Ox-LDL concentration and C-reactive protein level were determined. Insulin sensitivity was measured using the homeostasis model assessment (HOMA-IR). LD was assessed by using a validated score calculated from clinical and biological data. Results: HIV-infected patients had significantly higher ox-LDL concentrations when compared to HIV-negative controls (0.8 ±0.3 mg/dL vs. 0.60 ±0.1 mg/dL; p = .007). HIV-LD patients had significantly higher ox-LDL concentrations than HIV-nLD patients (0.91 ±0.38 and 0.69 ±0.16; p = .04). In HIV-LD patients, current therapy with protease inhibitors (PIs); duration of PI therapy; HOMA-IR; and time exposure to stavudine, efavirenz, ritonavir, saquinavir, and amprenavir were significantly higher than in HIV-nLD patients. In multivariate analysis, time exposures to stavudine and ox-LDL concentration were independently related to lipodystrophy. Conclusion: The high concentration of ox-LDL was found in HIV-infected patients under antiretroviral therapy, especially in those with lipodystrophy.

Low Trough Plasma Concentrations of Nevirapine Associated with Virologic Rebounds in HIV-Infected Patients Who Switched from Protease Inhibitors

BACKGROUND: The substitution of a nonnucleoside reverse-transcriptase inhibitor (NNRTI) for protease inhibitors (PIs) has demonstrated its suitability to maintain virologic response. However, the switch from PIs to an NNRTI could fail for a number of reasons, including NNRTI-associated toxicity and emergence of NNRTI-resistant variants. OBJECTIVE: To describe the virologic failures among 74 HIV-infected patients who switched from PIs to nevirapine. METHODS: Virologic failure was defined as any rebound of the plasma HIV-RNA (pVL) levels >1000 copies/mL on one occasion or 2 consecutive intermittent viremia episodes defined as increases of the pVL >20 copies/mL but <1000 copies/mL. Virologic failures were investigated retrospectively by determining nevirapine trough concentrations and performing genotypic resistance analysis. RESULTS: The mean nevirapine concentration was significantly lower in patients with virologic failure in comparison with patients with virologic response (2572 ± 1642 vs 4550 ± 2084 ng/mL, respectively; p = 0.003). In multivariate analysis, the mean duration of undetectable pVL before the switch and the mean plasma concentration of nevirapine were significantly associated with virologic success with relative rates of 1.39 (95% CI 1.10 to 1.76, p = 0.006) and 2.7 (95% CI 1.37 to 5.41, p = 0.01), respectively. In patients with pVL >1000 copies/mL, nevirapine mutations and nucleoside reverse-transcriptase inhibitor mutations were found in 80% of the cases. CONCLUSIONS: The risk of virologic failure after the switch from PI to nevirapine is higher in cases of inadequate nevirapine plasma concentrations. Our data support prospective monitoring of nevirapine plasma concentrations to detect low concentrations prior to the emergence of resistance mutations.

Prevalence and impact of GBV-C, SEN-V and HBV occult infections in HIV–HCV co-infected patients on HCV therapy

BACKGROUND/AIMS It has been suggested that, in HIV-HCV co-infected patients, co-infections with other viruses may affect the response to HCV therapy. We aimed to assess the prevalence of GBV-C, SEN-V and occult HBV infections, their impact on HCV and HIV infections and on the response to HCV therapy in HIV-HCV co-infected patients. METHODS Three-hundred and sixty eight patients were tested before starting interferon-ribavirin for the presence of occult hepatitis B DNA, GBV-C RNA and SEN-V DNA by using real time PCR. Clinical, immunological, virological, histological characteristics and response to HCV therapy were compared according to the presence or not of each viral co-infection. RESULTS HBV DNA, GBV-C RNA and SEN-V DNA were found in 5 (1.4%, CI95%: 0.2-2.4%), 104 (29.9%, CI95%: 25.1-34.7%) and 209 patients (57.9%, CI95%: 52.8-63.0%), respectively. GBV-C positive patients had significantly higher CD4 count at baseline, during and after HCV therapy, even after stratification on antiretroviral treatment. No other significant difference was observed according to the presence or not of GBV-C or SEN-V co-infection, in particular regarding virological responses to HCV combination therapy. CONCLUSIONS There is no reason to withhold HCV therapy in HIV infected patients who have access to HAART, because of occult HBV, GBV-C or SEN-V co-infections.

Treatment of chronic hepatitis C in HIV-infected patients: From clinical trials to field practice

In a prospective cohort of 87 HIV coinfected patients with chronic hepatitis C, 63% had been treated for HCV, with global success rate (47%, 95% CI 34–61) close to or higher than that reported in therapeutic trials. These results argue for earlier, more frequent and improved HCV treatment in HIV-infected patients.

In vivo efficacy of humanised intermittent versus continuous ceftazidime in combination with tobramycin in an experimental model of pseudomonal pneumonia.

In this study, we compared the efficacy of ceftazidime (CAZ) intermittent versus continuous infusion with or without tobramycin (TOB) for the treatment of pneumonia caused by Pseudomonas aeruginosa in rabbits. Treatments were humanised and mimicked intermittent CAZ (iCAZ) (2g three times daily), continuous CAZ (cCAZ) (4g once daily (qd)) and TOB (10mg/kg qd). Minimum inhibitory concentrations (MICs) were 1mg/L and 4mg/L for TOB and CAZ, respectively. Bacterial efficacy in lungs was as follows: control, 9+/-0.6 colony-forming units (CFU)/g; TOB monotherapy, 8+/-0.5CFU/g; iCAZ monotherapy, 7.8+/-1.4CFU/g; cCAZ monotherapy, 8+/-0.4CFU/g (P = 0.005); and iCAZ+TOB, 8+/-0.5CFU/g; cCAZ+TOB, 7.2+/-0.3CFU/g (P < 0.05). Bacterial efficacy in the spleen was as follows (% sterile): control, 4+/-1.6CFU/g (0%); TOB monotherapy, 1.7+/-1.2CFU/g (60%); iCAZ monotherapy, 3.5+/-0.5CFU/g (17%); cCAZ monotherapy, 1.5+/-0.6CFU/g (75%) (P = 0.02); and iCAZ+TOB, 2.1+/-0.6CFU/g (50%); cCAZ+TOB, 1.2+/-0.3CFU/g (82%) (P < 0.05). The time the drug concentration was above the MIC (T > MIC) was 62% and 99% for iCAZ and cCAZ, respectively. We conclude that CAZ is more effective when administered continuously, especially for the sterilisation of septicaemia. A synergistic therapeutic effect of the association CAZ+TOB was observed in vivo, which can be explained by the longer T > MIC of cCAZ. These findings suggest that continuous treatment with 4g CAZ could be appropriate in patients with P. aeruginosa infections.

Histological and molecular biology diagnosis of neurocysticercosis in a patient without history of travel to endemic areas: case report.

Background: in endemic areas, neurocysticercosis appears mainly as a single, large, spherical and non-enhancing intracranial cyst. Case presentation: an atypical case of neurocysticercosis (NCC) in a French Caucasian, without history of travel to endemic areas, was confirmed by histology and molecular speciation. Imaging was atypical, showing several hook-bearing scolices visible in the cyst, while the serology employed was non-contributary. Conclusions: NCC should be considered when multiple taeniid scolices are observed within the same cystic lesion.