[Valganciclovir maintenance therapy in AIDS: treatment failure due to the development of cytomegalovirus resistance to ganciclovir].
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Biomedical subjects
Publications and source records attributed to D Vittecoq.
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The prognosis of HIV infection has been modified by antiretroviral therapy. However, the morbidity and the mortality of HCV co-infection increase and may be a major problem of health service. Up to now co-infected patients are excluded of transplantation due to complexity, the ethical aspects, the immunodeficiency and the co-infection. This study tries to estimate the feasibility in this population. Between December 1999 and March 2002, seven patients were transplanted. The average of CD4 was 332/ml; the viral load was <50 copies/ml. Before transplantation, no patient had experienced opportunist infection and all patients received antiretroviral therapy adapted to their history. The average follow-up is of 14 months: one patient died 3 months after transplantation, the other one presented a candida in oesophagus, the average of CD4 was 280/ml, and viral load was <50 copies/ml in five patients. A relapse of HVC was observed in all patients. Interferon/rivabirine therapy was proposed for four patients. Every patient received tacrolimus and corticoids. HAART were modified four times for toxicity and one time for virological failure. We observed two cases of transient renal insufficiency, two cases of diabetes, two cases of pancreatitis, and abnormalities of the respiratory mitochondrial chain in four patients. Finally, liver transplantation in HIV-HCV co-infected patients seems to be feasible when strict criteria of selection are taken into account. This still experimental strategy requires a multidisciplinary partnership.
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INTRODUCTION: Cardiovascular complications occurring in patients infected by the human immunodeficient virus (HIV) have considerably changed since the appearance, in April 1996, of highly active antiretroviral tri-therapy (HAART), associating reverse transcriptase and protease HIV-1 inhibitors. The spectacular efficacy of anti-proteases has led to the almost complete disappearance of these opportunistic complications. However, in May 1998, acute coronary accidents were reported in the literature, thus questioning the possible responsibility of antiprotease treatment in the occurrence of accelerated atheroma. METHOD: We report a series of 8 seropositive patients in whom an acute coronary event had occurred between February 1997 and February 1999. RESULTS: The patients were young and all exhibited cardiovascular risk factors (smoking, dyslipidemia) and were treated with HIV-1 protease inhibitors. Six patients presented myocardial infarction, one patient unstable angina and one patient effort angina. COMMENTS: A rise in triglycerides was observed principally on ingestion of ritonavir and a rise in cholesterol and LDL-cholesterol with all the antiprotease agents. Glucose intolerance was observed with indinavir. The occurrence of acute coronary events appeared to be related to antiprotease treatment (at the origin of metabolic disorders, endothelial dysfunction...), although it was impossible to say whether the antiprotease agents were responsible for the early atheroma or whether they simply contributed to the event. The coronary lesions were characterized by their number (single artery) and their topography (proximal or median). Nelfinavir may carry less cardiovascular risks than the other antiproteases. Mean term prognosis was relatively good, after therapeutic adjustment (change in antiprotease, strategic measures against cardiovascular risk factors, introduction of anti-anginal treatment...). CONCLUSION: Larger and longer studies would help to specify the role of antiproteases in the occurrence of early coronary events. Rigorous monitoring (lipid and glucose measurements, tests to search for myocardial infarction,..) together with the development of new antiretroviral molecules would reduce the number of coronary events in this type of patient.
PURPOSE: Castleman's disease is a polyclonal lymphoplasmacytic and vascular proliferation prominant in lymphoid tissues. It is associated with lymph node enlargement, hepatosplenomegaly and fever. This manifestations could be secondary to hyperproduction of interleukin 6. The prognosis is poor. The opportunistic infections which are characteristic of severe HIV infection worsen the prognosis. Prolonged monochemotherapy with vinblastine or etoposide can control Castleman's disease. CURRENT KNOWLEDGE AND KEY POINTS: Recent advances in human herpesvirus 8 (HHV8) knowledge and its predominance in the forms which are linked to the HIV seropositivity have partly explained the clinical manifestations of Castleman's disease. Indeed, HHV8 produce an homologous interleukin 6, the vIL-6, responsible for lymphoplasmacytic proliferation. The presence of other homologues of human cytokines produced by HHV8 could contribute to lymphoplasmacytosis and to endothelial proliferation. FUTURE AND PROSPECTS: Taking into account this viral origin, alpha interferon could be an alternative in forms which are less progressive. However, antiviral therapy against HHV8 or HIV and the immunitary restoration do not have any influence on the evolution of Castleman's disease, contrary to opportunistic infections.
Enterocytozoon bieneusi is an agent of intestinal microsporidiosis leading to malabsorption syndrome and diarrhea in AIDS patients. Respiratory tract microsporidiosis due to Encephalitozoon spp. has been reported. To date, however, only two cases of pulmonary involvement of E. bieneusi have been documented for patients with intestinal microsporidiosis. We report here another pulmonary localization of E. bieneusi in a human immunodeficiency virus-infected patient. Clinical features of these three cases are reviewed. E. bieneusi can colonize the respiratory tract but could be considered a simple carriage associated with an intestinal infection.
BACKGROUND: Since eradication of HIV is unlikely, long-term management of the disease necessitates careful evaluation of the combinations of currently available drugs to determine the most potent and useful rational sequencing of regimens. OBJECTIVE: To determine the antiretroviral efficacy and tolerability of saquinavir soft gelatin capsule (SQV-SGC) plus zalcitabine (ddC) and stavudine (d4T), as first-line treatment in HIV-infected patients. DESIGN: Multicentre, open-label, non-comparative study. PATIENTS AND METHODS: Thirty-five asymptomatic, HIV-infected adults with no prior antiretroviral treatment, a CD4 count > or =250 cells/microL and baseline > or = 5000 HIV RNA copies/mL were included in the study. Patients received SQV-SGC 1200 mg three times a day (tid), ddC 0.75 mg tid and d4T 30 or 40 mg twice a day (bid) for 24 weeks. Plasma HIV RNA, CD4 and CD8 cell counts, HIV reverse transcriptase and protease resistance genotypes, SQV plasma concentration and tolerability were evaluated. RESULTS: At baseline, median HIV RNA (interquartile range) was 4.99 (4.81-5.48) log10 copies/mL, and median CD4 count was 370 (318-504) cells/microL (n = 35). At week 24, the median decrease in HIV RNA was 3.05 (2.19-3.68) log10 copies/mL. A viral load below the level of quantification (200 copies/mL and 20 copies/mL) was achieved in 63% and 34% of patients, respectively (intent-to-treat analysis). The only mutations detected were L90M substitutions in two patients. At week 24, the median CD4 count increased (P < 0.0001), and CD8 cell counts decreased (P < 0.0001), relative to baseline. In total, there were five cases of peripheral neuropathy (14%). Mean triglyceride and cholesterol levels remained within normal ranges. CONCLUSIONS: Triple therapy with SQV-SGC plus ddC and d4T is a reasonably well tolerated regimen that markedly and rapidly reduces viral load with immunological improvement. This combination is an effective additional therapeutic option, with an efficacy that compares favourably to other triple regimens used in HIV treatment.
BACKGROUND: Given that several pathology-based studies reported some degree of coronary and arterial vasculopathy in HIV-infected patients, we investigated whether abnormal vascular reactivity may also be found in these patients. METHODS: Vascular reactivity was assessed noninvasively using finger-skin blood-flow monitoring by laser-Doppler flow measurement in 10 HIV-infected-patients (mean CD4 T-cell count, 350+/-84 cells/mm3) with cardiac symptoms (previous myocardial infarction or left-ventricular dysfunction) and/or HIV-related protease inhibitor-induced hyperlipemia (group 1, symptomatic), 19 HIV-infected patients free of cardiac disease, hyperlipemia, and previous opportunistic infections (mean CD4 T-cell count, 333+/-175 cells/mm3; group 2, asymptomatic), and 19 healthy control subjects (group 3). Laser-Doppler flow was measured at baseline, during postocclusive hyperemic response following transient interruption of brachial blood flow (reactive hyperemia), during transcutaneous delivery of acetylcholine (Ach) using iontophoresis (endothelium-dependent dilation) and after sublingual nitroglycerin administration (endothelium-independent dilation). RESULTS: During reactive hyperemia, the absolute increase in flow was found to be lower in asymptomatic HIV-infected patients than in controls (median values [25th-75th percentile]: asymptomatic: 300 [200-400]; versus controls: 600 [400-750] arbitrary units [AU]; p< or =.0001). This abnormality was more pronounced in symptomatic patients (100 [100-200]; p< or =.0001). There was also a reduced peak/baseline flow ratio (symptomatic: 1.14 [1.1-1.2]; asymptomatic: 1.40 [1.25-1.5]; versus controls: 1.83 [1.6-2.2]; p<.0001 for both comparisons) and a reduced hyperemic response, as assessed by the curve of area under the flow versus time from deflation to the end of the hyperemic response (symptomatic: 1850 [1100-2225]; asymptomatic: 6000 [2850-7950]; versus controls: 23,735 [16,000-31, 800] AU x sec; p<.0001 for both comparisons). Although there was no statistically significant difference in acetylcholine (Ach)-induced increases in flow between asymptomatic HIV patients and controls (peak/baseline flow ratio: 6 [4.4-10] versus 5.3 [4-8]; p =.47), a trend to lower values was seen in symptomatic patients (4.4 [1.2-5]; p =.06). Administration of 0.4 mg sublingual nitroglycerin resulted in increases in flow without statistically significant difference between patients and controls: peak/baseline flow ratio for symptomatic: 2.4 [1.9-2.7]; asymptomatic: 2.1 [1.75-2.34] versus controls: 1.97 [1.8-2.4]; p =.2 and.83, respectively). CONCLUSIONS: Postischemic reactive hyperemia is reduced in HIV-infected patients. In addition, there was is trend for a reduced response to Ach only in those with cardiac disease and/or hyperlipemia.
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OBJECTIVES: To compare the efficacy and safety of saquinavir soft gelatin capsules (SQV-SGC) and nelfinavir (NFV), with or without two concomitant nucleoside reverse transcriptase inhibitors (NRTIs), in an exploratory objective to identify populations most likely to benefit from quadruple therapy. DESIGN: Phase II/III, open-label, randomized, parallel-arm, multicenter trial. PARTICIPANTS: Enrollment included 157 protease inhibitor-naive adults (> or = 13 years) with HIV-1 RNA > or = 10,000 copies/ml; 132 participants completed 48 weeks of therapy. INTERVENTIONS: SQV-SGC 1200 mg, NFV 750 mg, SQV-SGC 800 mg plus NFV 750 mg, all with two NRTIs, and SQV-SGC 800 mg plus NFV 750 mg alone, all three times daily for 48 weeks. MAIN OUTCOME MEASURES: Proportion of participants with HIV-1 RNA <50 copies/ ml (16 and 48 weeks); time to virologic relapse (48 weeks). RESULTS: Proportions of patients with HIV RNA <50 copies/ml were not statistically significantly different between arms at 16 or 48 weeks, although trends favored the quadruple-therapy arm. In patients experiencing virologic relapse, time to relapse was statistically significantly longer in the quadruple-therapy arm than in the other three arms (p = .007). Quadruple therapy provided benefit in NRTI-experienced patients and those with viral loads above the median value at baseline. Adverse events were mainly mild gastrointestinal disorders in all treatment arms. CONCLUSIONS: Quadruple therapy, including SQV-SGC and NFV, gave a more durable response than triple therapy with either single protease inhibitor. Quadruple therapy might particularly benefit NRTI-experienced patients and those with high baseline viral loads.
This phase IIa, randomised, single-blind, placebo-controlled study was conducted to determine the dose of recombinant human granulocyte colony-stimulating factor (lenograstim) suitable for use in AIDS patients. The study was conducted at 27 European AIDS/HIV centres, and recruited 69 AIDS patients with an initial episode or relapse of cytomegalovirus infection (neurological site excluded) and an absolute neutrophil count (ANC) < or = 1.0 x 10(9)/L upon diagnosis or between days 1 and 12 of ganciclovir (GCV) treatment. The patients were randomised to placebo (n = 14) or one of four lenograstim arms: 150 microg/m2/d (the standard onco-haematology dose, n = 13) or 100 (n = 13), 50 (n = 15), or 25 microg/m2/d (n = 14). In all groups, the planned dose of GCV was 10 mg/kg/d for 21 d. Median ANC at weeks 2 and 3 was significantly higher in each lenograstim group than in the placebo group (p = 0.05). At week 3, median ANC (x 10(9)/L) was 0.7 in the placebo group, compared with 6.0, 7.4, 4.5, and 2.0 in the 150, 100, 50, and 25 microg2/d lenograstim groups, respectively. Median ANC was not significantly different between the 150, 100, and 50 microg/m2/d lenograstim groups at any time point, but significantly higher in the 50 than in the 25 microg/m2/d group at weeks 2 (p = 0.05) and 3 (p = 0.02). Lenograstim was generally well tolerated, leading to no severe adverse events. In conclusion, lenograstim 50 microg/m2/d is suitable for the treatment of ganciclovir-induced neutropenia and is safe. These results should help the physician choose an optimal and cost-efficient regimen for patients with AIDS-related neutropenia when rHuG-CSF support is indicated.
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We describe a case of recurrent Scopulariopsis brevicaulis subcutaneous infection, which occurred 6 years after the patient underwent liver transplantation. Combined surgery and long-term oral therapy with terbinafine resulted in a favorable outcome, although this is not the rule in the previously reported S. brevicaulis infections in immunocompromised patients.
Both nature and prognosis of cardiac complications occurring in patients infected by the Human Immunodeficiency Virus-1 (HIV-1) have changed considerably since the introduction of highly acive and anti-retroviral triple therapy ("HART"). Opportunist cardiac infections have thus been displaced and side effects of drugs now occupy the primary aetiological role. Torsades de pointe may be exceptionally triggered by anti-infectious agents such as pentacarinat or trimethoprime-sulfamethoxazole, as are those induced by the association of ketoconazole and terfenadine or cisapride, the dangers of which are well known and the prevention more effective, especially with the association with HIV antiproteases which inhibit the cytochrome P450. The diagnosis of iatrogenic myocardial dysfunction is more difficult, except when it occurs acutely as with phosphonoformate (Foscarnet), or interleukine-2. Progressive cardiomyopathy caused by -interferon and dideoxynucleosides (zidovudine, didanosine and zalcitabine), reversible on withdrawal of the drug responsible in half the cases, should be distinguished from those due to the HIV itself (therapeutic relay) or to another associated cause (alcohol, coronary artery disease). The coronary complications of diseases treated by antiproteases usually occur in smokers whose cholesterol and triglyceride levels are rapidly increased with HAART. In a series of 9 patients (amongst 700 treated with the antiproteases), after the acute phase of myocardial infarction during which the interventional approach is often preferred, the medium-term prognosis is relatively good, on condition that the patients correct the hyperlipidaemia and give up smoking.
Although cardiac and vascular complications have been recognized among patients infected with the Human Immunodeficiency Virus-1 (HIV-1), their vascular biology and rheology have not been studied. Rheology of red blood cells (RBC) was assessed with an erythroaggregometer in 22 HIV-1 infected asymptomatic patients (pts) and 17 healthy HIV negative controls (C). All participants were normotensive, nondiabetics, had normal lipid levels and had an hematocrit ranging from 37 to 44% and hemoglobin levels > or = 12 g/100 ml. Patients had a shorter RBC aggregation characteristic time than controls (1.49 +/- 0.17 vs. 2.04 +/- 0.41 s, p = 0.001) and an increased disaggregation shear rate (166 +/- 34.9 vs. 122 +/- 25.4 s(-1), p = 0.001). This hyperaggregation tendancy was associated with increased gamma-globulin (18.3 +/- 3.3 vs. 13.7 +/- 1.9 g/l, p = 0.01) and fibrinogen (3.52 +/- 0.57 vs 3.03 +/- 0.48 g/l, p = 0.003) levels and with an increased erythrocyte sedimentation rate (ESR) (25 +/- 14.3 vs. 12.3 +/- 7.5 mm, p = 0.02). Even in patients with ESRs ranging within normal values (< or = 20 mm), the aggregation characteristic time was found lower in patients than in controls (p = 0.004). There was no correlation between these rheological changes and the CD4+ T-cell count. The 17 patients receiving an antiviral therapy had lower CD4+ T-cell counts than their 5 untreated counterparts (244.7 +/- 167 vs. 410 +/- 106/mm3, p = 0.025), and a higher disaggregation shear rate (177.4 +/- 38.2 vs. 127 +/- 25.4, p = 0.01). Thus, an impairment of rheological characteristics is observed in asymptomatic HIV-I infected patients in association with changes in plasma proteins.
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BACKGROUND: Impaired intestinal function could account for diarrhoea and weight loss, which are common features of advanced human immunodeficiency virus (HIV) infection. METHODS: We assessed intestinal permeability to lactulose and mannitol and absorption of D-xylose in 96 HIV-infected patients (group I: asymptomatic subjects (CDC-A); group II: symptomatic subjects (CDC-B or C) without body weight loss and/or diarrhoea; group III: 25 acquired immunodeficiency syndrome (AIDS) patients (CDC-C) with severe body weight loss and/or diarrhoea) and 10 healthy subjects as controls. RESULTS: An incremental decrease in urinary D-xylose recoveries was observed, with all groups statistically different from each other. Impaired intestinal permeability was only found in patients of group III (statistically different from all other groups). CONCLUSIONS: These findings suggest a loss of intestinal functional absorptive surface as HIV disease progresses. This process may be present at the early stage of infection. Impaired intestinal permeability is observed later in AIDS patients when digestive signs are present, particularly diarrhoea.