Metabolic acidosis in HIV-infected patients.
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Acidosis↗
Biomedical subjects
P Morlat
Publications and source records attributed to P Morlat.
Sarcoidosis-associated hepatitis C virus infection.
Although several reports of sarcoidosis have been reported in hepatitis C virus (HCV)-infected patients treated with interferon-alpha, this association has never been described in nontreated HCV patients. We report two cases of sarcoidosis associated with chronic hepatitis C infection. The patients developed multivisceral sarcoidosis (cutaneous, lungs, nodes) at two and at least six years after the presumed date of infection. One patient obtained remission of sarcoidosis with corticosteroid treatment but the other remained corticodependent. The levels of hepatic enzymes were not significantly modified throughout the course of corticosteroid therapy. In conclusion, these case reports suggest that HCV itself could induce a granulomatous reaction in chronic HCV-infected patients through the stimulation of the cellular immune system. It could be of interest to test for HCV infection all patients diagnosed with sarcoidosis and to watch over every treated or nontreated hepatitis C infected patient for the development of granulomatous lesions.
Adult↗
Causes of death among HIV-infected patients in the era of highly active antiretroviral therapy, Bordeaux, France, 1998-1999.
OBJECTIVES: To describe the causes of death in HIV-infected patients in the era of highly active antiretroviral therapy (HAART). METHOD: A retrospective survey conducted in Bordeaux, France. Medical records of all deaths that had occurred in 1998 and 1999 amongst patients followed within the Aquitaine cohort were reviewed by the same physician. Immediate and underlying causes of death were described, taking into account the morbidity at the time of death. RESULTS: Sixty-six deaths occurred in 1998, and 41 in 1999. Sixty-seven per cent of deceased patients were male. Median age at time of death was 43 years (range 25-71), median CD4 was 162 cells/microL (0-957); 28% of patients had a CD4 count > 200 cells/microL and 7% plasma viral load < 500 HIV-RNA copies/mL. Amongst morbidity present at the time of death, there were 23 bacterial infections, 16 non-Hodgkin's lymphomas, 16 cirrhoses, 15 non HIV-related malignancies, 13 central nervous system diseases and 10 myocardiopathies. The main immediate causes of death were: multiple organ failure (21%), coma (18%), septic shock (15%) and acute respiratory failure (14%). Underlying causes of death were AIDS-defining events (48%), non AIDS HIV-related infection (3%), hepatitis B- or C-associated cirrhosis (14%), non HIV-related malignancies (11%), cardiovascular events (10%), suicide and overdose (6%), treatment-related fatalities (4%), injury (2%) and unknown (2%). Patients dying from AIDS-related events were more often female, had a lower CD4 count, a higher level of HIV-RNA, a shorter history of HIV infection and were less often coinfected with hepatitis B and C viruses than those dying from other underlying causes. CONCLUSIONS: AIDS-related events are no longer the major causes of death of HIV-infected patients in the era of HAART. This evolving mortality pattern justifies an adaptation of both the epidemiological surveillance and the clinical monitoring of HIV-infected patients.
Adult↗
Prognostic factors of combined viral load and CD4+ cell count responses under triple antiretroviral therapy, Aquitaine cohort, 1996-1998.
OBJECTIVE: To describe the viroimmunologic response and its prognostic factors 6 months after initiating triple antiretroviral therapy in a cohort of HIV-1-infected patients. METHODS: Positive virologic response during follow-up (VL+) was defined as plasma HIV RNA level <500 copies/ml and positive immunologic response (CD4+) as an increase of CD4+ count of at least 50 cells/mm3. Four categories of response were defined: VL+/CD4+; VL+/CD4-; VL-/CD4+ and VL-/CD4-. Prognostic factors were studied through a polytomous logistic regression (VL-/CD4-, as reference). RESULTS: Baseline characteristics of the 478 studied patients were: 22% at AIDS stage, 77% pretreated, median CD4+ cell count 195/mm3 and HIV RNA level 4.42 log. At 6 months 37.5% were VL+/CD4+; 15.7% VL+/CD4-; 23.8% VL-/CD4+ and 23.0% VL-/CD4-. Baseline HIV RNA level was associated to a higher risk of VL-/CD4+ response. More advanced age was associated with a higher risk of isolated immunologic failure (VL+/CD4-), whereas pretreatment and saquinavir therapy were associated with a lower frequency of positive virologic response independently of immunologic response. CONCLUSION: HIV-RNA level, pretreatment, and saquinavir therapy were already known to be linked to therapeutic response. Based on our results, a high baseline HIV-RNA level is associated with isolated immunologic response; moreover, age should be of importance in treatment decision.
Adult↗
Increase of lipid plasma concentrations under protease inhibitor-containing regimens are not related to modifications of the tumour necrosis factor system.
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Adult↗
Prognostic value of plasma markers of immune activation in patients with advanced HIV disease treated by combination antiretroviral therapy.
We assessed the prognostic role of plasma levels of beta2-microglobulin, TNF-alpha, sTNFR-II, and IFN-gamma on the progression to AIDS in patients mostly treated with combination antiretroviral therapies. HIV-1-infected patients with advanced HIV disease (baseline CD4+ cell count between 50 and 250 x 10(6)/L) were included in a prospective cohort followed up for 36 months. In the 113 patients included, 22 first AIDS-defining events were reported. Cumulative probability of AIDS was 12% at M12, 18% at M24, and 20% at M36. Using a Cox model, the baseline level of sTNFR-II (hazard ratio of 3.75 for sTNFR-II > or =10 ng/ml vs < 10 ng/ml, P = 0.01) was associated with progression to AIDS. sTNFR-II remained a prognostic factor before and after the introduction of combinations of antiretrovirals. Whether or not this marker is of value in patients exclusively treated with highly active antiretroviral therapy needs to be assessed in specific studies.
Adult↗
[Sarcoidosis and comorbidity: retrospective study of 32 cases].
PURPOSE: A retrospective study was set up to investigate active pathologic processes associated with sarcoidosis diagnosed in 32 patients. METHODS: Eighteen patients had two identified granulomatous localizations (56%) and 14 patients had three localizations or more (27%). Comorbidity was noticed in nine patients (28% of cases). Sarcoidosis was associated with an infectious disease five times (hepatitis C virus [HCV] infection three times, including one case after recombinant interferon alpha therapy, and HIV and HCV co-infection two times). The association of sarcoidosis with a chronic immunologic inflammatory disease was noticed four times (lupus erythematosus two times, myasthenia and primary biliary cirrhosis). Finally, in two cases sarcoidosis was associated with a neoplasia (non-Hodgkin's lymphoma in a co-infected HIV-HCV patient, ovarian cystadenocarcinoma in another patient). Sarcoidosis preceded or revealed the comorbidity four times.
Adult↗
[Hemorrhagic accidents with low molecular weight heparin: 15 cases].
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Adult↗
Immunoblot profile as predictor of toxoplasmic encephalitis in patients infected with human immunodeficiency virus.
In order to define more accurately human immunodeficiency virus-infected patients at risk of developing toxoplasmic encephalitis (TE), we assessed the prognostic significance of the anti-Toxoplasma gondii immunoglobulin G (IgG) immunoblot profile, in addition to AIDS stage, a CD4(+) cell count <50/mm(3), and an antibody titer > or =150 IU/ml, in patients with CD4 cell counts <200/mm(3) and seropositive for T. gondii. Baseline serum samples from 152 patients included in the placebo arm of the ANRS 005-ACTG 154 trial (pyrimethamine versus placebo) were used. The IgG immunoblot profile was determined using a Toxoplasma lysate and read using the Kodak Digital Science 1D image analysis software. Mean follow-up was 15.1 months, and the 1-year incidence of TE was 15.9%. The cumulative probability of TE varied according to the type and number of anti-T. gondii IgG bands and reached 65% at 12 months for patients with IgG bands of 25 and 22 kDa. In a Cox model adjusted for age, gender, Centers for Disease Control and Prevention (CDC) clinical stage, and CD4 and CD8 cell counts, the incidence of TE was higher when the IgG 22-kDa band (hazard ratio [HR] = 5.4; P < 0.001), the IgG 25-kDa band (HR = 4.7; P < 0.001), or the IgG 69-kDa band (HR = 3.4; P < 0.001) was present and was higher for patients at CDC stage C (HR = 4.9; P < 0.001). T. gondii antibody titer and CD4 cell count were not predictive of TE. Thus, detection of IgG bands of 25, 22, and/or 69 kDa may be helpful for deciding when primary prophylaxis for TE should be started or discontinued, especially in the era of highly active antiretroviral therapy.
AIDS-Related Opportunistic Infections↗
Prognostic score of short-term survival in HIV-infected patients admitted to medical intensive care units.
A retrospective cohort was set up to identify prognostic factors associated with in-hospital survival in HIV-infected patients admitted to medical intensive care units (MICUs), from 1991 to 1994. Survival from MICU admission to hospital discharge (or in-hospital fatal issue) was estimated and a prognostic score at MICU admission was developed. One hundred and thirty patients were recruited of whom 20% were AIDS-free prior to admission. In-hospital mortality rate was 65%. Median survival was 20 days. The following variables were predictive of mortality: Simplified Acute Physioloy Score II (SAPS II): (hazard ratio [HR]=1.5 for 10 points higher, P<10(-3)), time between HIV diagnosis and admission >5 years (HR=2.7, P<10(-4)), hypoalbuminaemia (HR=1.2 per 5 g/l lower, P=0.03). The prognostic score developed was: SAPS II+25 (if time between HIV diagnosis and MICU admission >5 years) albuminaemia (g/l). A new prognostic score including SAPS II, prior HIV history and albuminaemia better reflected the in-hospital mortality than SAPS II alone. Our findings may still be useful to better evaluate the immediate prognosis of current HIV-infected patients admitted to MICU, particularly those naive to antiretroviral therapy or in treatment failure.
APACHE↗
The absence of hyperbilirubinaemia is highly predictive of treatment failure in advanced HIV-infected patients treated with indinavir.
In order to determine prognostic factors associated with treatment failure (TF) in advanced HIV-infected patients treated with a regimen including indinavir, a prospective cohort study of 80 patients was set up between 1 March and 31 December 1996. TF time was calculated using the Kaplan-Meier method, from treatment induction to the first of the following events: treatment modification for adverse event or lack of significant virological and/or immunological response, AIDS-defining diagnosis or death. Date of point was 31 December 1998. Multivariate analysis was performed using a Cox model. At baseline, 60% of the patients were AIDS-free, median viral load and CD4+ count were respectively 4.8 log/ml and 79/microl. After a median follow-up of 26 months, 70% of the patients experienced a TF in a median time of 8 months. Seventy-two per cent presented an hyperbilirubinaemia (>2 mg/dl). In multivariate analysis, initial AIDS stage (hazard ratios [HR]=1.94, P=0.04) and digestive intolerance (HR=2.32, P=0.003) were predictive of TF. Conversely, hyperbilirubinaemia was associated with a better outcome (HR=0.35, P<0.0001). These 2 latter parameters very likely reflected patients' treatment compliance.
Adult↗
Clinical and laboratory findings of cytomegalovirus infection in 115 hospitalized non-immunocompromised adults.
We report a retrospective study of 115 hospitalized non-immunocompromised adults with proved or presumed diagnosis of cytomegalovirus infection. Clinical symptoms were fever (95%), constitutive symptoms (80%), joint and muscle pain (41%), shivering (32%), abdominal pain (26%), non-productive cough (20%), cutaneous eruption (20%), and diarrhea (10%). Examination found hepatomegaly (25%), splenomegaly (23%), cutaneous rash (20%), adenopathy (19%), pharyngitis (9%), jaundice (3%) or signs of meningeal irritation (1%). Seventeen patients had a gastrointestinal form (hepatitis, jaundice, colitis, antral gastritis or cholecystitis), eight had a pattern of hemopathy, two interstitial pneumonitis, two pericarditis, two immune thrombocytopenic purpura, two a polymyalgia rheumatica-like pattern, one thrombotic thrombocytopenic purpura, one cutaneous vasculitis and one meningoencephalitis. Sixty-four percent of the patients had atypical lymphocytosis. Hepatocellular injury occurred in 90% of the patients. Nineteen of the patients had biological immune abnormalities. Cytomegalovirus infection should be mainly suspected in any patient with persistent fever, isolated or associated with signs of poor specificity, or in some patients with visceral manifestations of initially unknown origin.
Adolescent↗
Clinical prediction of lower limb deep vein thrombosis in symptomatic hospitalized patients.
We evaluated two clinical scores for the prediction of deep venous thrombosis (DVT) in hospitalized patients (Wells' and Kahn's). We included 273 patients referred to the vascular exploration unit for the suspicion of DVT. A clinical questionnaire was tilled in by the practitioner and the scores were calculated from this form. 66 of the 273 patients had a DVT. When Wells' score was 3, a DVT was found by duplex echography in 51% patients; when the score was 0, a DVT was found in 9%. Kahn's score was not adapted to this population. We then developed a new simple score (cancer, palsy or plaster immobilization, warmth, superficial venous dilation, unilateral pitting edema, other diagnosis). A DVT was found in 76% patients with a score of 3 and in 11% in those with a score of 0. We therefore propose a 6-item score whose main advantages are simplicity and usefulness in routine practice.
Female↗
Lipodystrophy, metabolic disorders, and human immunodeficiency virus infection: Aquitaine Cohort, France, 1999. Groupe d'Epidémiologie Clinique du Syndrome d'Immunodéficience Acquise en Aquitaine.
The objective of this study was to estimate the prevalence of and risk factors for clinical lipodystrophy (LD) and metabolic disorders in human immunodeficiency virus (HIV) type 1-infected patients. A cross-sectional survey of the Aquitaine Cohort was performed in January 1999. The clinical diagnosis of LD was categorized as fat wasting (FW), peripheral fat accumulation (FA), and mixed syndromes (MS). Of the 581 patients studied, 61% were treated with protease inhibitors. The overall prevalence of LD was 38% (95% confidence interval [CI], 32-42): prevalence of FW was 16% (95% CI, 13-18); of FA, 12% (95% CI, 10-15); and of MS, 10% (95% CI, 8-13). The prevalences of metabolic abnormalities were 49% (95% CI, 44-53) for lipid disorders and 20% (95% CI, 17-23), for glucose disorders. Factors associated with LD were age (for FW and MS), male sex (for FW), AIDS stage (for MS), body mass index (for FW and FA), waist-to-hip ratio (for FA and MS), and duration of antiretroviral treatment (for FW).
Adult↗
Increase of atherogenic plasma profile in HIV-infected patients treated with protease inhibitor-containing regimens.
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Adult↗
Once-daily combination therapy with emtricitabine, didanosine, and efavirenz in human immunodeficiency virus-infected patients.
The safety and efficacy of a once-daily regimen that combines emtricitabine, didanosine, and efavirenz was studied among 40 previously untreated human immunodeficiency virus (HIV)-infected patients. The median plasma HIV RNA level was 4.77 log(10) copies/mL at baseline and decreased by a median of 3.5 log(10) copies/mL at 24 weeks, with 98% and 93% of patients achieving plasma HIV RNA levels <400 and <50 copies/mL, respectively. The median CD4 cell count was 373 cells/microL at baseline and increased by a median of 159 cells/microL at week 24. The most common treatment-related adverse events were mild to moderate central nervous system symptoms (73% of patients), diarrhea (33%), rashes (10%), and biochemical abnormalities. Adverse reactions led to permanent drug discontinuation in only 1 patient. The once-daily combination therapy of emtricitabine, didanosine, and efavirenz was safe and demonstrated strong antiviral and immunologic effects that lasted for the 24-week period of the study.
Adult↗
Clinical progression of HIV-1 infection according to the viral response during the first year of antiretroviral treatment. Groupe d'Epidémiologie du SIDA en Aquitaine (GECSA).
OBJECTIVE: To compare HIV-disease progression according to changes of plasma HIV RNA observed in the year following initiation of a new antiretroviral treatment. DESIGN: Prospective cohort treated with two nucleoside analogues or a triple combination including a protease inhibitor. METHODS: A Cox model was used to estimate the effect of viral response during the first year after initiation of treatment on the subsequent occurrence of new AIDS-defining events or death. Viral response was fitted either as HIV RNA reduction during the initial 4-12 months of treatment or reduction during the first month. RESULTS: Among 773 patients (47% with triple drug combination) followed for a median period of 27 months, 62 patients experienced a clinical event. Poor viral responders (at least two measurements > 3.7 log10 copies/ml during 4-12 months of treatment) had a higher risk of disease progression than good responders (RNA < 2.7 log10 copies/ml) after adjustment [hazard ratio (HR), 2.24; 95% confidence interval (CI), 1.1 7-4.29]. Intermediate responders (2.7 < or = RNA < or = 3.7 log10 copies/ml) had a risk of progression comparable with that of good responders (HR, 1.43; 95% CI, 0.64-3.22). A large initial viral reduction was also a protective factor for clinical progression (HR, 0.51 for 1 log10 copies/ml increase of the reduction; 95% CI, 0.31-0.85) and was associated with the viral response during the subsequent 4-12 month period. No patient with a reduction < 0.5 log10 copies/ml in the first month was classified as a good responder in the subsequent 4-12 month period (P < 0.01). CONCLUSIONS: A sustained HIV RNA > 3.7 log10 copies/ml should suggest a prompt change of treatment. When the reduction in HIV RNA is < 0.5 log10 after 1 month of treatment, this action should be anticipated. A sustained HIV RNA level between 2.7 and 3.7 log10 copies/ml may permit the deferral of a change of drug regimen according to the patient's history and therapeutic options.
Adult↗
Prognostic factors after non-Hodgkin lymphoma in patients infected with the human immunodeficiency virus: Aquitaine Cohort, France, 1986-1997. Groupe d'Epidémiologie Clinique du SIDA en Aquitaine (GECSA).
BACKGROUND: The prognosis for survival of patients infected with the human immunodeficiency virus (HIV) who develop non-Hodgkin lymphoma (NHL) usually is considered to be poor. To the authors' knowledge the impact of highly active antiretroviral therapy, recently introduced in HIV disease case management, has not yet been studied in such circumstances. METHODS: All cases of NHL prospectively diagnosed between January 1986 and December 1997 among patients followed in the Aquitaine Cohort were reviewed. The Kaplan-Meier method and the proportional hazards model were used for statistical analysis. RESULTS: One hundred one NHL diagnoses were validated during the 12-year study period. The median proportional hazards cell count at the time of diagnosis of NHL was 112/mm(3). Histologic findings (Working Formulation classification) were: intermediate grade (N = 23), high grade (N = 61), other (N = 7), and undetermined (N = 10). In 56% of cases, staging classification was Ann Arbor Stage IV. Approximately 73% of patients received a specific NHL chemotherapy. During follow-up, 44% were treated with nucleoside reverse transcriptase inhibitors (NRTIs) alone and 18% with triple therapy including a protease inhibitor (PI). The median survival was 6.0 months. In multivariate analysis, after adjusting for age, year of NHL diagnosis, histologic type, medical center, and transmission category, the following factors recorded at the time of diagnosis of NHL were indicative of an increasing risk of death: CD4+ count </= 50/mm(3) (relative hazard [RH: 2.4, 95% confidence interval [95% CI], 1.2-4.7), hemoglobin </= 10 g/dL (RH: 2.1, 95% CI, 1.1-4.0), and Ann Arbor Stage IV (RH: 2.0, 95% CI, 1.2-3.6). Antiretroviral therapy after the diagnosis of NHL was associated with survival: NRTIs (RH: 0.27, 95% CI, 0.13-0.53) and NRTIs plus PI (RH: 0.08, 95% CI, 0.03-0.21). CONCLUSIONS: Although recently introduced and prescribed, antiretroviral therapy including PIs already has improved the survival of HIV-infected patients with NHL significantly.
Adult↗