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Biomedical subjects

Daniel Vittecoq

Publications and source records attributed to Daniel Vittecoq.

At least 19 recordsLinked to original sources
PubMed2005

Therapeutic immunization with a human immunodeficiency virus (HIV) type 1-recombinant canarypox vaccine in chronically HIV-infected patients: The Vacciter Study (ANRS 094).

This open single-arm study evaluated whether the administration of an HIV-recombinant canarypox vaccine (vCP1433) in highly active antiretroviral therapy (HAART)-treated patients chronically infected with HIV was safe, immunogenic and associated with prolongation of treatment discontinuation: 48 patients received four monthly vCP1433 injections and stopped HAART. Immunization was safe. HIV-p24-specific lymphoproliferative responses (LPR), significantly increased in the whole group after two injections but decreased thereafter, HIV-gag-specific CD8 T cells were boosted in 55% patients tested. Altogether, 11% patients with at least one HIV-specific LPR during immunization remained off therapy after 44 weeks of interruption. Detection of such LPR response at the time of treatment interruption was significantly associated with the probability of remaining off therapy. These results provide rationale for future randomized trials exploring this strategy.

AIDS Vaccines↗
PubMed2005

Repertoire, diversity, and differentiation of specific CD8 T cells are associated with immune protection against human cytomegalovirus disease.

To determine the correlates of immune recovery from active human CMV (HCMV) disease, we compared the antigenic repertoire, diversity, magnitude, and differentiation of HCMV-specific CD8+ T cells in HIV-HCMV coinfected subjects with no, cured, or active HCMV disease and in healthy HIV-negative HCMV-positive controls. ELISPOT-IFN-gamma assays using peptide pools spanning the pp65 and immediate early 1 (IE1) HCMV proteins showed that HCMV-specific CD8+ T cells had a significantly broader antigenic repertoire and greater diversity in HIV-positive patients controlling HCMV replication than in those with active HCMV disease, but the magnitude of the CD8 T cell response did not differ between the different groups. HCMV-specific T cells mainly were focused against IE1 during the short-term recovery from retinitis, and switched toward pp65 during long-term recovery. HCMV-specific T cells displaying an "early" (CD8+CD27+CD28+) and "intermediate" (CD8+CD27-CD28+) differentiation phenotype were increased significantly during long-term recovery compared with other HIV-positive patients and were nearly undetectable during active HCMV disease. HCMV-specific T cells with a "late" (CD8+CD27-28-) differentiation phenotype predominated in all cases. Therefore, restoration of immune protection against HCMV after active HCMV disease in immunodeficient individuals is associated with enlarged repertoire and diversity, and with early differentiation of virus-specific CD8+ T cells, thus defining immune correlates of protection against diseases caused by persistent viruses.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Long-term renal safety of tenofovir disoproxil fumarate in antiretroviral-naive HIV-1-infected patients. Data from a double-blind randomized active-controlled multicentre study.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) was developed for the treatment of human immunodeficiency virus (HIV) infection. However, controlled data are sparse on the long-term renal tolerability of TDF at the currently approved daily dose of 300 mg in treatment-naive HIV-infected patients. METHODS: Over 144 weeks, this 600 patient, multicentre randomized, placebo-controlled, double-blind trial compared stavudine (301 patients) and TDF (299 patients), both administered in combination with lamivudine and efavirenz, in antiretroviral-naive patients. TDF or placebo and stavudine or placebo were administered in an open-label fashion. All medications were taken orally. At screening, all patients had serum creatinines <1.5 mg/dl, calculated creatinine clearances > or =60 ml/min and a serum phosphorus > or =2.2 mg/dl. RESULTS: The incidences of grades 1 (> or =0.5 mg/dl increase from baseline), 2 (2.1-3.0 mg/dl) and 3 (3.1-6.0 mg/dl) serum creatinine elevations at week 144 were 4, <1 and 0%, respectively, in the TDF group and 2, 0 and <1% in the stavudine control group (P = NS). There were no grade 4 (>6 mg/dl) serum creatinine elevations. At week 144, there was no change from baseline in the mean (0.83 mg/dl) serum creatinine in the TDF group compared with a 0.1 mg/dl decrease from baseline (0.83 mg/dl) in the stavudine control group. The incidences of grades 1 (2.0-2.2 mg/dl), 2 (1.5-1.9 mg/dl) and 3 (1.0-1.4 mg/dl) hypophosphataemia at week 144 were 4, 3 and <1%, respectively, in the TDF group and 4, 2 and <1% in the control group (P = NS). No patient experienced grade 4 (<1.0 mg/dl) hypophosphataemia. At week 144, the decrease (Delta) of mean serum phosphorus levels from baseline in both groups was similar (Delta 0.2 from 3.6 mg/dl for the TDF group, and 0.1 from 3.5 mg/dl for the stavudine control group). No patient developed Fanconi's syndrome or proximal renal tubular dysfunction during the study. CONCLUSION: Through 144 weeks, TDF and stavudine, each administered in combination with efavirenz and lamivudine, had similar renal safety profiles in treatment-naive HIV-infected patients with normal renal function at baseline.

Adenine↗
PubMed2005

Hepatitis C virus viral recurrence and liver mitochondrial damage after liver transplantation in HIV-HCV co-infected patients.

BACKGROUND/AIMS: As life expectancy in HIV-HCV co-infected patients improves, end stage liver disease requiring liver transplantation (LT) may become an emerging problem. We report the Paul Brousse Hospital experience of transplantation for end stage cirrhosis in HIV-HCV co-infected patients. METHODS: Seven consecutive HIV-HCV co-infected patients were transplanted between December 1999 and December 2002 for end stage liver disease due to HCV. All patients were treated by highly active antiretroviral therapy (HAART), HIV plasma viral load was <400 copies/ml and median CD4 lymphocyte count was 306 cells/mm3 (range, 103-510) before LT. At the time of evaluation (March 2003), the median follow-up was 21 months (range, 4-40). RESULTS: Two patients died, 4 and 22 months, respectively after LT. At the last biopsy, METAVIR score was staged F4 in two patients, F3 in two, and F1 in one. Microvesicular steatosis was noted in nearly all patients. The ratio of mitochondrial to nuclear DNA was low in three of four patients examined as compared with the amount of liver mtDNA found in eight HIV-negative, HCV-infected controls (P=0.01). CONCLUSIONS: A significant defect in the activity of the respiratory chain complex IV was noted in all five patients studied. Mitochondrial hepatotoxicity and severe HCV recurrence occur in HIV-HCV co-infected patients after LT.

Adult↗
PubMed2004

Renal safety of tenofovir in HIV treatment-experienced patients.

The safety of tenovir disoproxil fumarate (TDF) was assessed in two double-blind, placebo-controlled studies. Furthermore, we retrospectively collected 19 cases of TDF-associated tubular dysfunction. The incidence of renal events was similar among the active TDF groups and the placebo group in the two double-blind, placebo-controlled studies. Proximal tubulopathy was diagnosed 6.89 +/- 5.51 months after TDF therapy started. All abnormalities normalized within 4.7 +/- 2.94 weeks after drug discontinuation.

Adenine↗
PubMed2004

Prospective evaluation of blood concentration of mitochondrial DNA as a marker of toxicity in 157 consecutively recruited untreated or HAART-treated HIV-positive patients.

Highly active antiretroviral therapy (HAART) can cause mitochondrial toxicity. The concentration of mitochondrial DNA (mtDNA) in peripheral blood cells has been reported to be a marker of this toxicity. However, these observations are controversial and were drawn from small series. Thus, we analysed the value of blood mtDNA as a marker of mitochondrial toxicity in a large cohort of human immunodeficiency virus (HIV)-infected out-patients during routine clinical evaluations. Real-time quantitative PCR was used to determine the mtDNA to nuclear DNA (nDNA) ratio in peripheral blood mononuclear cells from 157 consecutive HIV-1-infected patients (13 naive, 144 receiving HAART) and 30 HIV-1-uninfected patients. The mtDNA to nDNA ratio was significantly lower in both groups of HIV-infected patients than in the control group. No significant difference was observed between treated and naive HIV-infected patients. Lactataemia was significantly lower in controls than in the group of HIV-treated patients. None of the treated patients had lactataemia >5 mmol/l or bicarbonates <20 mmol/l. Triglyceride levels were significantly higher in the HAART-treated patients than in the nontreated patients. Clinical symptoms of lipodystrophy were observed in 62 HAART-treated patients. These symptoms were not associated with an abnormal mtDNA to nDNA ratio or plasma triglyceride concentration. The mtDNA to nDNA ratio was lower in DDI/D4T-treated patients than in AZT/3TC-treated patients. In conclusion, there are no obvious links between the mtDNA to nDNA ratio in peripheral mononuclear cells and any clinical symptoms or lactate level. Thus, the mtDNA to nDNA ratio in leukocytes does not seem to be an accurate marker of mild and/or long-term mitochondrial toxicity.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Enhanced saquinavir exposure in human immunodeficiency virus type 1-infected patients with diarrhea and/or wasting syndrome.

The protease inhibitor saquinavir was administered to 100 human immunodeficiency virus type 1 (HIV-1)-infected patients as a single 600-mg oral dose (hard gelatin capsules) with a standard breakfast, including 200 ml of grapefruit juice, during an open-label trial to assess whether diarrhea and/or wasting syndrome has consequences on its pharmacokinetics. Three groups of patients were enrolled: group 1, asymptomatic patients (n = 30); group 2, AIDS symptomatic patients without body weight loss or diarrhea (n = 37); and group 3, AIDS symptomatic patients with severe body weight loss and/or diarrhea (n = 33). Clinical and biological data (covariates) were collected. A population approach was performed with three blood samples per patient to estimate the mean population pharmacokinetic parameters (clearance [CL]/oral bioavailability [F], V/F, k(a), and lag time) and the derived ones (k(el), C(max), T(max), and area under the curve [AUC]). The relationships between groups, exposure (i.e., estimated individual post hoc AUCs), and covariates were explored by using multiple linear regressions. A significant increase in median AUCs (165, 349, and 705 ng. h. ml(-1) for groups 1, 2, and 3, respectively [P < 0.0001]) was observed. The enhancement in saquinavir exposure could be due to the destruction of the transporters in enterocytes and/or to the enlargement of their tight junctions, allowing a paracellular crossing of saquinavir as the illness spreads. Because of grapefruit juice intake by every patient, no implication of CYP3A4 could be assessed. These results strongly suggest that, despite its low intrinsic oral bioavailability, saquinavir can be considered as a relevant treatment for HIV-1-infected patients with diarrhea and/or wasting syndrome. This must be evaluated in a long-term period.

Adult↗
PubMed2003

Coronary artery disease in HIV infected patients.

OBJECTIVE: To assess the incidence, clinical features, treatment, and follow-up of coronary events in HIV-infected patients over a period of 5 years. PATIENTS AND PARTICIPANTS: A cohort of 840 patients. MEASUREMENTS AND RESULTS: A coronary event occurred in 17 patients (5.9/1000 persons-years). Sixteen of them were exposed to highly active antiretroviral therapy (HAART). Patients with coronary events differed in age (48.3 vs. 43 years), CD4 T-cell count (284 vs. 486/mm(3)), total cholesterol (6.2 vs. 5.3 mmol/l), HDL cholesterol (0.72 vs. 1.16 mmol/l), and LDL cholesterol (4.95 vs. 3.391.61 mmol/l). No difference was observed regarding duration of HAART, weight, glucose level, or smoking status between the two groups. Acute coronary syndrome was the first manifestation in 14 patients. Coronary angiography showed 2.56 stenosis per patient, with a single vessel involvement in one-half. Percutaneous angioplasty was performed in all cases, with stenting in 11. After a mean follow-up of 36 months, 14 patients remain alive. Restenosis ( n=4) occurred in 3 patients (PTCA 3; stenting 4). All 14 patients are free of heart failure symptoms. Their mean left ventricular ejection fraction is 61%. CONCLUSIONS: A higher coronary-event rate is observed among HIV-infected patients, associated with drug-induced metabolic disturbances and a high prevalence of tobacco smoking. However, treatment and prognosis of acute myocardial infarction has no specificity.

Adult↗
PubMed2003

Brief report: carotid intima-media thickness in heavily pretreated HIV-infected patients.

The authors used ultrasonography to measure carotid artery intima-media thickness (IMT) in 36 HIV-infected patients taking highly active antiretroviral therapy (cases) and in two control groups without (control group 1) or with (control group 2) blood lipid and glucose disturbances similar to those of the patients. Case IMT values were 8% higher than control group 1 IMT values (p <.05) but not different from control group 2 IMT values. Positive independent associations of IMT with the total-to-HDL cholesterol ratio and waist circumference existed for cases (p <.05) but not for controls. Case IMT did not correlate with parameters of HIV infection and antiretroviral treatment. This case-control study suggests that lipid disturbances, mainly hypoHDLemia, may be involved in the early atherosclerotic process in HIV-infected patients.

Adult↗
PubMed2003

Coronary heart disease in HIV-infected patients in the highly active antiretroviral treatment era.

OBJECTIVES: To assess the incidence and the clinical features of coronary heart disease in HIV-infected patients. To assess atherosclerosis risk factors in this population. METHODS: A review of our experience consisting of 16 patients with acute myocardial infarction (AMI) was the basis of our retrospective analysis of two cohorts in France. Incidence was compared with the national database on the incidence of AMI in the general population. RESULTS: Incidence appears to be between 5 and 5.5 per 1000 person-years among HIV-infected patients. This accounts for at least a threefold increase in incidence (1.52 per 1000 person-years reported in the Monica database registry in France). Age of onset of AMI in HIV-infected patients (younger than 50 years in most cases) is a point of major concern and is an indirect way to confirm the increased incidence. AMI was typically of sudden onset without prior history of angina pectoris. Treatment and prognosis of AMI in this population has no specificity. Patients with coronary heart disease present several risk factors such as tobacco smoking, hypertension, diabetes mellitus and low high-density lipoprotein level. The links between AMI and protease inhibitor exposure is still a matter of debate, and longer duration of follow-up is needed in order to reach any conclusion. CONCLUSIONS: Coronary heart disease is of a higher than expected incidence in HIV-infected patients. The limitation of risk factors (mainly tobacco smoking) is a new challenge. An adaptation of the Framingham score is necessary to state the individual risk. Prospective, controlled studies are necessary to assess new strategies such as the role of statins and switching therapeutic regimens.

Adult↗
PubMed2002

Mitochondrial damage associated with long-term antiretroviral treatment: associated alteration or causal disorder?

Combination of antiretroviral drugs has dramatically improved the prognosis of human HIV infection but is also associated with many adverse effects, the mitochondrial origin of which is discussed. In this study using extensive diagnostic procedures set up for inherited mitochondrial disorders, we analyzed HIV patients under active antiretroviral therapy who complained of severe adverse symptoms unexplained by HIV. All these patients had been treated for at least 5 years. They all had significant mitochondrial damage as evidenced by the diverse combination of lactate accumulation in blood or cerebrospinal fluid, mitochondrial morphologic alterations in muscle, and biochemical defects in muscle and liver, which designated mitochondrial DNA (mtDNA) as the main target of the toxic mechanisms. Southern blot and/or polymerase chain reaction -based analyses disclosed multiple deletions of the muscle mtDNA and reduction of the muscle and/or liver mtDNA copy number in a majority of the patients. In opposition to muscle and liver, blood mononuclear cells were devoid of significant biochemical or genetic alterations. Whether the mitochondrial toxicity is directly responsible for the patients' adverse symptoms remains disputable, because the investigations were transversal. Its severity argues for its clinical relevance, however. The skewed tissue distribution of mitochondrial alterations indicates potential pitfalls in the needed future prospective studies.

Adult↗
PubMed2002

[Anti-Jo1 antibodies syndrome in an HIV-infected patient].

An HIV-infected man developed primary polymyositis (fever, myalgia, elevated serum muscle enzymes, and signs of inflammation) associated with serum anti-Jo1 antibodies and pulmonary fibrosis. Anti-Jo1 antibodies are exceptional in HIV-infected patients. We discuss the role of infection in polymyositis. HAART and corticosteroids led to rapid clinical and radiological improvement.

Adrenal Cortex Hormones↗