Biomedical subjects
Publications and source records attributed to F Bricaire.
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The natural history of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patients has never been studied according to the concept of liver fibrosis progression. The aim of this work was to assess the fibrosis progression rate in HIV-HCV coinfected patients and in patients infected by HCV only. A cohort of 122 HIV-HCV coinfected patients was compared with a control group of 122 HIV-negative HCV-infected patients. Groups were matched according to age, sex, daily alcohol consumption, age at HCV infection, and duration and route of HCV infection. The fibrosis progression rate was defined as the ratio between fibrosis stage (METAVIR scoring system) and the HCV duration. The prevalence of extensive liver fibrosis (METAVIR fibrosis scores 2, 3, and 4) and moderate or severe activity were higher in HIV-infected patients (60% and 54%, respectively) than in control patients (47% and 30%, respectively; P <.05 and P <.001, respectively). The median fibrosis progression rate in coinfected patients and in control patients was 0.153 (95% confidence interval [CI], 0.117-0.181) and 0.106 (95% CI, 0.084-0.125) fibrosis units per year, respectively (P <.0001). HIV seropositivity (P <.0001), alcohol consumption (>50 g/d, P =.0002), age at HCV infection (<25 years old, P <.0001), and severe immunosuppression (CD4 count </=200 cells/microL, P <.0001) were associated with an increase in the fibrosis progression rate. In coinfected patients, alcohol consumption (>50 g/d), CD4 count (</=200 cells/microL), and age at HCV infection (<25 years old) (P <. 0001, respectively) were associated with a higher fibrosis progression rate. HIV seropositivity accelerates HCV-related liver fibrosis progression. In coinfected patients, a low CD4 count, alcohol consumption rate, and age at HCV infection are associated with a higher liver fibrosis progression rate.
Hepatitis B virus (HBV) resistance to lamivudine has not been extensively documented in human immunodeficiency virus (HIV)-infected patients. We studied the long-term incidence of HBV resistance to lamivudine in HIV-positive patients. Sixty-six HIV-HBV-coinfected patients were studied while receiving lamivudine (150 mg twice daily) as a part of antiretroviral therapy. All these patients had a detectable serum HBV DNA at the beginning of lamivudine therapy. Serum HBV DNA was quantified by molecular hybridization. Sequence analysis of the HBV polymerase was performed in patients who became resistant to lamivudine. After 2 months of lamivudine, HBV DNA became undetectable in 57 patients (86.4%, 95% CI: 75.7%-93.6%). After 2 years of lamivudine, 47% +/- 18.6% of the patients, had sustained HBV-DNA suppression. All the 22 tested patients with HBV resistance developed mutation at position 550 in the YMDD motif of the DNA polymerase. None of the following variables were associated with an increased risk of lamivudine resistance: age, associated protease inhibitor therapy, Center for Disease Control (CDC) stage C, known HIV-infection duration, serum HBV-DNA level at baseline, CD4 cell count and serum alanine transaminase levels at baseline and at HBV-replication suppression (2 months of lamivudine). Lamivudine (300 mg/d) is effective for the inhibition of HBV replication in HIV-infected patients. However, emergence of lamivudine-resistant HBV may occur in 20% of patients per year.
Cerebrospinal fluid (CSF) and plasma HIV-1 RNA levels were prospectively measured by the Roche Amplicor Monitor polymerase chain reaction assay in 30 HIV-1 infected patients without central nervous system opportunistic infections. All participants completed a global neuropsychological battery consisting of Mattis Dementia Rating Scale. Additional tests were used to better characterize the type of cognitive changes with a specific reference to frontal lobe function. The neuropsychological evaluation confirmed the subcortical pattern of cognitive dysfunction. CSF and plasma HIV-1 RNA levels were significantly correlated. No correlation was detected with either blood or CSF RNA levels and the global cognitive status, but when stratified in three cognitive subgroups, higher CSF HIV-1 RNA levels were observed in the more cognitively impaired subjects. Our results provide further evidence that plasma and CSF HIV-1 RNA level cannot be used as a reliable diagnostic marker for HIV-1 associated cognitive disorders. Only longitudinal studies will determine whether a high CSF HIV-1 level could be a risk factor for HIV-1 dementia.
Septic arthritis due to Mycobacterium kansasii is rare; only 40 cases have been published. A French national inquiry revealed the occurrence of 10 new cases between 1992 and 1997 (8 men and 2 women: mean age, 37 years; range, 25-54 years). Seven had an underlying condition: AIDS (n=4), chronic skin psoriasis and AIDS (n=2), or a renal transplant (n=1). Trauma to the joint, use of intra-articular corticosteroid(s) 1 month to 2 years after the event, and chronic skin psoriasis were risk factors. The mean interval between appearance of the first symptoms of arthritis and the diagnosis was 5 months. Monarthritis was localized to the knee (n=4), wrist (n=3), finger (n=1), elbow (n=1), or ankle (n=1). The main diagnostic procedure was culture of a synovial biopsy specimen. In all cases, debridement was associated with antimycobacterial treatment. Three patients died of AIDS during treatment, and another is still undergoing treatment; the other 6 patients were cured. M. kansasii infection should be considered in all cases of indolent arthritis with any of the following risk factors: local trauma, local or systemic corticosteroid therapy, chronic skin psoriasis, and immunodepression, especially that due to human immunodeficiency virus infection.
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In order to analyze the impact of protease gene polymorphism on response to regimens containing a protease inhibitor, the entire protease coding domain from 58 human immunodeficiency virus type 1 (HIV-1)-infected patients who were protease inhibitor naive was sequenced before therapy was started. Plasma HIV-1 RNA levels were measured at baseline and at month 3 and month 6 after treatment. All patients were treated with a combination of two reverse transcriptase inhibitors and a protease inhibitor (saquinavir EOF [n = 28], ritonavir [n = 16], or indinavir [n = 14]). Before treatment, 30 different positions whose codons differed from the subtype B consensus sequence were observed. Major mutations associated with protease inhibitor resistance were not observed. No statistical correlation between the number of amino acid differences and the treatment efficacy at month 3 (-2.4 log) or month 6 (-2.7 log) was observed. At baseline, genotypic analysis of the HIV-1 protease gene of patients who have never received a protease inhibitor does not allow prediction of the efficacy of regimens containing a protease inhibitor.
Mutations associated with hepatitis B virus (HBV) resistance to lamivudine have not been extensively addressed in human immunodeficiency virus (HIV)-HBV coinfection. We have studied the HBV polymerase sequences from nine coinfected patients who experienced HBV recurrence while under lamivudine treatment. In seven of these nine patients, Met(550), belonging to the highly conserved YMDD motif, was mutated to Val and was associated with a substitution of Met for Leu(526) in each case. In the two remaining patients, we found a Met(550)-to-Ile change that was associated in only one case with a Leu(526)-to-Met mutation. No mutation was observed in three control patients not receiving lamivudine. This study demonstrates the emergence of particular genetic profiles in HBV-HIV-coinfected patients experiencing a loss of control of HBV infection despite high doses of lamivudine.
Protease inhibitors (PIs) are recently introduced drugs that have improved the survival of HIV-infected patients when given in combination with two reverse transcriptase inhibitors. The HIV-1 protease gene is naturally highly polymorphic. Selection pressure due to IP use can result in major or minor resistance-associated mutations (RAMs). This study investigated whether presence before IP therapy of minor RAMs on the protease gene predicts the virological response. Of the 58 PI-naive patients included in the study, 12 had received two nucleoside reverse transcriptor inhibitors, 14 had received indinavir, 16 ritonavir, and 28 saquinavir-SGC. Viral load was measured on D0 (prior to PI initiation) and at M3 and M6 (Roche Monitor 1.5 with 200 and 20 copies/ml as the thresholds). The protease gene was fully sequenced on D0 using the ABI 377 automatic sequencer after RNA amplification by nested RT-PCR. None of the viral strains exhibited major mutations, but 57 of 58 (98%) had at least one minor mutation (median number of substitutions, 4), 60% had 1 to 4 substitutions, and 40% had 5 to 9 substitutions. Substitutions seen with a prevalence > 20% were located at codons 15, 35, 37, 41, 63, and 77. Numbers of substitutions at M3 and M6 were not correlated with viral load or the nature of the PI used, and neither were they significantly different between patients with more or fewer than 20 copies/ml. These data suggest that the protease genotype at PI initiation does not predict the efficacy of a regimen including a PI and is of no assistance in deciding whether or not to include a PI in a triple combination regimen.
We retrospectively studied the epidemiological, clinical, histological and evolutive aspects of vertebral tuberculosis diagnosed in all consecutive patients recruited in 2 Parisian hospitals between January 1990 and July 1997. The diagnosis relied on a vertebral involvement associated with evidence of tuberculosis (culture of local puncture yielded Mycobacterium tuberculosis) or presumption of tuberculosis (evidence of other tuberculous focus, histological data, good outcome under specific treatment). Sixteen patients (mean age: 41 years; sex ratio: 1.29) have been included; thirteen were migrants. The main symptoms, which appeared within a mean period of 3 months were vertebral pain (13/16) and alteration of patient's general conditions (8/16). RMN imaging showed spondylitis (10/16), spondylodiscitis (4/16) and involvement of posterior arch (8/16). Inflammatory syndrome was present in 14 cases. The diagnosis of vertebral tuberculosis was confirmed in 12 cases according to the results of culture and/or histological grounds of local puncture. The diagnosis of vertebral tuberculosis was presumed in the 4 other cases according to the isolation of M. tuberculosis from an other site (2 cases), the characteristic histological pattern of a lymphadenopathy (1 case), and a favorable outcome upon specific treatment (1 case). All the patients were cured without complications with the exception of one patient who developed a spinal cord compression.
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A RECOGNIZED COMPLICATION: Ritonavir is an antiprotease used in the treatment of HIV-positive patients. Among the known side effects, nephrotoxicity can be severe. We have observed acute renal failure in 8 patients. CIRCUMSTANCES: Renal failure occurs early after introducing ritonavir (3-21 days). It is often severe with major creatinine elevation. One patient was dialyzed for 16 days. In these patients, saquinavir was usually associated with ritonavir. RITONAVIR ALONE: We retrospectively analyzed creatinine levels in 87 patients treated with ritonavir without saquinavir. Twelve of these 87 patients (13.7%) developed renal failure. Creatinine clearance (Cockcroft) was reduced 116 to 71 ml/min in 12 patients. Finally, it was demonstrated in 6 patients that ritonavir can reduce creatinine clearance by 25% after only 3 days of treatment. VIGILANCE: Ritonavir has a known nephrotoxic potential. Acute renal failure may be severe and can occur with ritonavir alone or in combination with saquinavir. The pathogenic mechanism has not been demonstrated from renal biopsies or experimental studies. Renal function should be followed in these patients and risk factors controlled.
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OBJECTIVE: To describe the epidemiological characteristics of toxoplasmic encephalitis in HIV-infected patients with a more than 12-year follow-up. METHODS: From a data base of 1,628 AIDS subjects hospitalized from 1983 to 1994, we studied the epidemiological characteristics of 399 patients with toxoplasmic encephalitis. Diagnosis of toxoplasmic encephalitis was based on the association of central neurological disorders, typical lesions on CT scan or MRI, and favorable outcome under appropriate toxoplasmosis therapy. RESULTS: Four hundred sixty-four cases of toxoplasmic encephalitis were reported in 399 patients (24.5% of the patients with AIDS). The overall incidence was 20.5 per 100 patients-year. Toxoplasmic encephalitis was the first AIDS defining event in 51% of the cases and revealed HIV infection in 13% of the cases. In the remaining 49%, the mean delay from AIDS diagnosis to toxoplasmic encephalitis was 13 months (range: 1-71 months). At the time of diagnosis, mean CD4 count was 44/mm3 (range: 0-408/mm3). Antibodies to Toxoplasma gondii were found in 97% of the cases. Before the first episode of toxoplasmic encephalitis, 58% of the patients were given antiretroviral therapy (mean: 17.8 months; range: 1-64 months). Of the 399 patients with toxoplasmic encephalitis, 366 (92%) did not receive any primary toxoplasmosis prophylaxis. Among them, 205 (56%) did not receive any drug prophylaxis, and 161 (44%) had Pneumocystis carinii pneumonia prophylaxis alone (aerosolized pentamidine). Thirty-three failures were observed (8%) with cotrimoxazole: 14 cases (3%) were considered to have irregular compliance. Sixty-five relapses were observed in 52 patients. At the end of the study 334 patients had died (84%). The median survival was 11.4 months (95% confidence interval, range: 10.4-12.4 months). CONCLUSIONS: Toxoplasmic encephalitis incidence has decreased since the introduction of appropriate drug prophylaxis.