Is there a need to widely prescribe antibiotics in patients hospitalized with COVID-19?

BACKGROUND: Debate continues regarding the usefulness and benefits of wide prescription of antibiotics in patients hospitalized with coronavirus disease 2019 (COVID-19). METHODS: All patients hospitalized in the Infectious Diseases Department, Dijon University Hospital, Dijon, France between 27 February and 30 April 2020 with confirmed COVID-19 were included in this study. Clinical, biological and radiological data were collected, as well as treatment and outcome data. An unfavourable outcome was defined as death or transfer to the intensive care unit. Patient characteristics and outcomes were compared between patients who did and did not receive antibiotic therapy using propensity score matching. FINDINGS: Among the 222 patients included, 174 (78%) received antibiotic therapy. The univariate analysis showed that patients who received antibiotic therapy were significantly older, frailer and had more severe presentation at admission compared with patients who did not receive antibiotic therapy. Unfavourable outcomes were more common in patients who received antibiotic therapy [hazard ratio (HR) 2.94, 95% confidence interval (CI) 1.07-8.11; P = 0.04]. Multi-variate analysis and propensity score matching indicated that antibiotic therapy was not significantly associated with outcome (HR 1.612, 95% CI 0.562-4.629; P = 0.37). CONCLUSION: Antibiotics were frequently prescribed in this study and this was associated with more severe presentation at admission. However, antibiotic therapy was not associated with outcome, even after adjustment. In line with recent publications, such data support the need to streamline antibiotic therapy in patients with COVID-19.

Comparative review of imipenem/cilastatin versus meropenem.

INTRODUCTION: Carbapenems are broad-spectrum antibacterial molecules. Imipenem-cilastatin and meropenem are the two main molecules used in French healthcare services. OBJECTIVE: We aimed to evaluate the relative strengths and weaknesses of these two molecules by considering their pharmacokinetic, pharmacodynamic, microbiological, and clinical properties. We demonstrated that imipenem-cilastatin and meropenem are not alike. METHOD: Review of the literature by querying the MEDLINE network. RESULTS: Imipenem-cilastatin is the first marketed molecule of the carbapenem class. It is more effective against Gram-positive cocci. Its stability does not allow for long infusions and its main adverse effect on the central nervous system limits its use. Meropenem is more effective against Gram-negative bacilli. Its stability and its milder adverse effects distinguish it from imipenem-cilastatin. CONCLUSION: Meropenem is preferred for daily use in healthcare services when carbapenems are to be used.

PICC management led by technicians: Establishment of a cooperation program with radiologists and evaluation of complications.

PURPOSE: The purpose of this study was to evaluate a cooperation program in order to compare incidence of complications after peripherally inserted central catheter (PICC) placement between radiologists and technicians. MATERIALS AND METHODS: PICC placement technique was standardized with ultrasound-guided puncture and fluoroscopic guidance. Numbers of PICC delegated to technicians, and PICC placement difficulties, were prospectively recorded for the whole study population whereas complications such as PICC infection, deep venous thrombosis and catheter occlusion were prospectively recorded until PICC removal for a subgroup of patients included during one month. RESULTS: A total of 722 patients had PICC placement. There were 382 men and 340 women with a mean age of 66.8±15.8 (SD) years (range: 18-94years); of these, 442/722 patients (61.22%) were included in the cooperation program with 433/722 patients (59.97%) who effectively had PICC placement by technicians and 289/722 (40.03%) by radiologists. Technicians needed radiologists' help for 23/442 patients (5.20%) including 6 failed PICC placement subsequently performed by radiologists. Twenty complications (20/77; 26%) were recorded in the subgroup of 77 patients studied for complications. No differences in complications rate were found between the 33 patients who underwent PICC placement by radiologists (6/33; 18%) and the 44 patients who underwent PICC placement by technicians (14/44; 32%) (P=0.296). Complications included 8 PICC-related infections (8/77; 10.4%), 3 deep venous thromboses (3/77; 3.9%) and 9 catheter occlusions (9/77; 11.7%). CONCLUSION: PICC placement led by technicians is feasible and safe without statistical difference in terms of complications compared to PICC placement made by radiologists.

Prolonged suppressive antibiotic therapy for prosthetic joint infection in the elderly: a national multicentre cohort study.

During prosthetic joint infection (PJI), optimal surgical management with exchange of the device is sometimes impossible, especially in the elderly population. Thus, prolonged suppressive antibiotic therapy (PSAT) is the only option to prevent acute sepsis, but little is known about this strategy. We aimed to describe the characteristics, outcome and tolerance of PSAT in elderly patients with PJI. We performed a national cross-sectional cohort study of patients >75 years old and treated with PSAT for PJI. We evaluated the occurrence of events, which were defined as: (i) local or systemic progression of the infection (failure), (ii) death and (iii) discontinuation or switch of PSAT. A total of 136 patients were included, with a median age of 83 years [interquartile range (IQR) 81-88]. The predominant pathogen involved was Staphylococcus (62.1%) (Staphylococcus aureus in 41.7%). A single antimicrobial drug was prescribed in 96 cases (70.6%). There were 46 (33.8%) patients with an event: 25 (18%) with an adverse drug reaction leading to definitive discontinuation or switch of PSAT, 8 (5.9%) with progression of sepsis and 13 died (9.6%). Among patients under follow-up, the survival rate without an event at 2 years was 61% [95% confidence interval (CI): 51;74]. In the multivariate Cox analysis, patients with higher World Health Organization (WHO) score had an increased risk of an event [hazard ratio (HR) = 1.5, p = 0.014], whereas patients treated with beta-lactams are associated with less risk of events occurring (HR = 0.5, p = 0.048). In our cohort, PSAT could be an effective and safe option for PJI in the elderly.

Efficacy and safety of DPP-4 inhibitors in patients with type 2 diabetes: Meta-analysis of placebo-controlled randomized clinical trials.

BACKGROUND: Guidelines for type 2 diabetes (T2D) recommend reducing HbA1c through lifestyle interventions and glucose-lowering drugs (metformin, then combination with dipeptidyl peptidase-4 inhibitors [DPP-4Is] among other glucose-lowering drugs). However, no double-blind randomized clinical trial (RCT) compared with placebo has so far demonstrated that DDP-4Is reduce micro- and macrovascular complications in T2D. Moreover, the safety of DPP-4Is (with increased heart failure and acute pancreatitis) remains controversial. METHODS: A systematic review of the literature (PubMed, Cochrane Library Central Register of Controlled Trials [CENTRAL] and https://clinicaltrials.gov), including all RCTs vs placebo published up to May 2015 and the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), published June 2015, was performed. Primary endpoints were all-cause mortality and death from cardiovascular causes; secondary endpoints were macrovascular and microvascular events. Safety endpoints were acute pancreatitis, pancreatic cancer, serious adverse events and severe hypoglycaemia. RESULTS: A total of 36 double-blind RCTs were included, allowing analyses of 54,664 patients. There were no significant differences in all-cause mortality (RR=1.03, 95% confidence interval [CI]=0.95-1.12), cardiovascular mortality (RR=1.02, 95% CI=0.92-1.12), myocardial infarction (RR=0.98, 95% CI=0.89-1.08), strokes (RR=1.02, 95% CI=0.88-1.17), renal failure (RR=1.06, 95% CI=0.88-1.27), severe hypoglycaemia (RR=1.14, 95% CI=0.95-1.36) and pancreatic cancer (RR=0.54, 95% CI=0.28-1.04) with the use of DPP-4Is. However, DDP-4Is were associated with an increased risk of heart failure (RR=1.13, 95% CI=1.01-1.26) and of acute pancreatitis (RR=1.57, 95% CI=1.03-2.39). CONCLUSION: There is no significant evidence of short-term efficacy of DPP-4Is on either morbidity/mortality or macro-/microvascular complications in T2D. However, there are warning signs concerning heart failure and acute pancreatitis. This suggests a great need for additional relevant studies in future.

On the collapse pressure of armored bubbles and drops.

Drops and bubbles wrapped in dense monolayers of hydrophobic particles are known to sustain a significant decrease of their internal pressure. Through dedicated experiments we investigate the collapse behavior of such armored water drops as a function of the particle-to-drop size ratio in the range 0.02-0.2. We show that this parameter controls the behavior of the armor during the deflation: at small size ratios the drop shrinkage proceeds through the soft crumpling of the monolayer, at intermediate ratios the drop becomes faceted, and for the largest studied ratios the armor behaves like a granular arch. The results show that each of the three morphological regimes is characterized by an increasing magnitude of the collapse pressure. This increase is qualitatively modeled thanks to a mechanism involving out-of-plane deformations and particle disentanglement in the armor.

Informal consultation at a teaching hospital infectious diseases department.

INTRODUCTION: Informal consultations for advice in the infectious diseases department (IDD) induce a significant workload for physicians. Our aim was to retrospectively quantify and describe this activity in our institution. METHOD: The data was obtained from files documented and faxed by physicians from October 2009 to May 2012. One thousand nine hundred and seventy-two files were included. The file was faxed to the IDD specialist, analyzed, then a telephone conversation allowed making precisions, and the documented form was faxed back. RESULTS: The requests for advice concerned 39% of female and 61% of male patients with a mean age of 64±21 years. Twenty-nine percent of requests came from surgical departments and 71% from medical departments (P<0.01). The departments most frequently concerned were cardiology (10%), gastro-enterology (10%) and cardiovascular surgery (9.7%). The most frequent infections were urogenital (19%), osteoarticular (14%), and cardiovascular (11%). Forty-nine percent were considered as nosocomial and 25.3% were bacteremic. The requests concerned diagnostic aid in 16.2% of cases and therapeutic issues in 95.6%. The IDD specialist made therapeutic recommendation in 96.5% of cases and gave diagnostic advice in 43.7%. Treatment modification was suggested in 38.5% of cases. Twenty-two percent of consultations required a second one. CONCLUSION: This study documented the importance of antibiotic changes among medical and surgical units, the increasing need of these units to be helped, and also the complexity of the medical cases, all requiring the advice of an ID specialist. Our fax-phone-fax procedure seems to prevent the bias associated with informal consultations by phone, which is the most commonly used in other institutions.

Performance of two commercially available automated immunoassays for the determination of Epstein-Barr virus serological status.

This study evaluated the performance of two automated Vidas (V) and Liaison (L) immunoassays for Epstein-Barr virus (EBV) serology. The detection of the viral capsid antigen (VCA) IgM, the VCA/early antigen (VCA/EA) IgG, and the Epstein-Barr nuclear antigen (EBNA) IgG was assessed on 526 sera collected for routine EBV testing in immunocompetent subjects. The determination of expected EBV status (186 EBV primary infections, 183 past EBV infections, and 157 EBV-seronegative individuals) was based on results of routine laboratory enzyme immunoassays (EIAs) together with clinical data. The sensitivity and specificity of each individual marker were determined in comparison to the expected EBV status. The agreement between the V and L profiles and the expected EBV status was established through the interpretation of combinations of the different EBV markers. Statistically significant differences between the two tests were found for the specificity of the VCA IgM marker (96.2% for V versus 93.2% for L), the sensitivity of the VCA/EA IgG marker (89% for V versus 94% for L), and the specificity of the EBNA IgG marker (96.5% for V versus 74.2% for L). The results determined for the two assays with respect to overall agreement with the established expected EBV status were not significantly different (89.7% for V versus 88.2% for L), with discrepancies mainly observed in sera referenced as primary infections. These findings demonstrated the similar performances of the Vidas and the Liaison assays for the establishment of an EBV serological status using the VCA, EA, and EBNA markers.

[Recurrent atypical mycobacterial infections in the adult: think of autoantibodies against interferon-gamma !]. / Infections récurrentes à mycobactéries atypiques chez l'adulte : attention aux autoanticorps anti-interféron-gamma!

INTRODUCTION: Disseminated non-tuberculosis mycobacterial infections are associated with a defect of the cellular immune response. They have been mainly reported in AIDS patients. Cases related to the presence of anti-interferon-γ autoantibodies are rare. CASE REPORT: We report a non HIV-infected 45-year-old Thai woman, with a past medical history of Graves' disease. She presented with recurrent disseminated and severe non-tuberculous mycobacterial infections that were related to the production of anti-interferon-γ autoantibody. The diagnosis was suspected in the presence of a negative interferon-γ release assay (IGRA) including with the positive control, and evidenced by the identification of specific antibodies. CONCLUSION: Anti-interferon-γ autoantibody production is a rare cause of non tuberculous mycobacterial infection. Such a mechanism should be suspected in non HIV-infected patients and especially in those having an Asiatic ethnicity or an associated immune disorder. A negative IGRA (including with the positive control) is a reliable diagnostic tool and should be completed with the identification of specific autoantibodies.

[Vaccination coverage of healthcare professionals in an infectious diseases department]. / Couverture vaccinale des professionnels de santé dans un service d'infectiologie.

OBJECTIVES: The study's objective was to evaluate with a standardized questionnaire the knowledge of healthcare workers (HCWs) regarding occupational vaccinations and their vaccination coverage. POPULATION AND METHODS: This cross-sectional survey was conducted in the department of infectious diseases of a 1796 bed-teaching hospital in Dijon, France. RESULTS: Fifty-seven (93%) out of 61 HCPs completed the questionnaire. Vaccination against HVB was the most frequently mentioned vaccination (79%), followed by BCG (66%), and combine vaccine against diphtheria, tetanus, and polio (DTP) (66 %). Influenza was the most often quoted among recommended vaccinations (70%), followed by measles (61%), pertussis (39%), and varicella (14%). The number of correct answers was significantly correlated with age of participants, being a physician, and having had courses on vaccination. Almost all HCPs were up to date for mandatory vaccinations. In 2009 to 2010, vaccination rates against seasonal flu and H1N1 flu reached 88%. Only 52% of HCPs knew about their pertussis immunization and only a third of those born before 1980 had been tested for measles. CONCLUSIONS: HCPs knowledge of mandatory vaccinations is adequate but more limited for recommended vaccinations. Information on influenza vaccination has significantly improved its perception among HCPs resulting in a better adhesion to vaccination.

[Incidence, prevalence and risk factors for a first infectious complication on a totally implantable venous-access port]. / Incidence, prévalence et facteurs de risque de survenue d'une première complication infectieuse sur chambres à cathéter implantables.

BACKGROUND: Totally implantable venous-access ports (TIVAP) should present less risk of complications than central venous catheters over a long time period. AIMS: Firstly, the study's objective was to assess the prevalence and incidence of a first infectious complication on a TIVAP and secondly, to assess the risk factors associated with this first infection. METHODS: The authors made a longitudinal historical cohort study of patients with a TIVAP in 2003, in the Dijon University Hospital. RESULTS: Two hundred and nineteen patients (sex-ratio 1.9) were included, with a total follow-up of 92,773 patients-days. Ninety percent of the TIVAP were used for chemotherapy, 5% for antibiotic drug administration, 2% for parenteral nutrition and 3% for other reasons (recurrent blood transfusions, etc.). Overall, 34 (16.3%) out of 209patients presented with at least one infectious complication, with an incidence rate of 0.37infection/1,000patients-days. The 5-year cumulative probability to be free of infectious complication was only 62.8%. In multivariate analysis, only underlying hematological neoplasia (by contrast with solid tumors) was significantly associated to a higher risk of infectious complication. CONCLUSIONS: The infectious risk linked to the use of TIVAP is significant, higher in case of underlying hematological neoplasia and during the first months of use.

Limitation of exercise capacity in nucleoside-treated HIV-infected patients with hyperlactataemia.

BACKGROUND: Inhibition of DNA polymerase gamma by nucleoside reverse transcriptase inhibitors (NRTIs) can cause mitochondrial dysfunction and cellular toxicity. Hyperlactataemia, which is a consequence of a shift in the metabolism of pyruvate, is an indicator of nucleoside-related mitochondrial toxicity. METHODS: We evaluated exercise and oxidative capacities as well as circulatory and ventilatory responses to exercise in 24 HIV-infected patients on NRTIs presenting hyperlactataemia [mean (+/-standard deviation) fasted lactate=3.5+/-1.1 mmol/L]; 27 NRTI-treated patients with normal baseline lactate concentrations were used as controls (mean fasted lactate=1.6+/-0.3 mmol/L). RESULTS: In the patients with hyperlactataemia, the average peak work capacity (1.7+/-0.6 W/kg) and peak oxygen consumption (VO(2)) (21+/-4 mL/kg/min) were significantly lower (P<0.01) than in control subjects (work, 2.1+/-0.4 W/kg; VO(2), 25+/-4 mL/kg/min). The capacity to increase oxygen extraction during exercise was significantly diminished in the hyperlactataemia group, as shown by a low peak systemic arteriovenous oxygen difference (a-vO(2)) difference compared with controls (11+/-3 vs 14+/-3 mL/dL; P=0.008), and as indicated by a linear correlation between VO(2) and systemic a-vO(2) difference (r(2)=0.76). During exercise, the increases in cardiac output relative to VO(2) (mean Delta cardiac output (Q)/DeltaVO(2)=8+/-3.6) and ventilation (mean Delta ventilation (VE)/DeltaVO(2)=48.6+/-13.2) were significantly higher in hyperlactataemia patients compared with controls (mean cardiac output Delta(Q)/DeltaVO(2)=6+/-2; mean DeltaVE/DeltaVO(2)=42+/-12.7; P=0.03). CONCLUSIONS: The degree of exercise limitation in patients with nucleoside-related mitochondrial toxicity correlates directly with the severity of impaired muscle oxidative phosphorylation, as indicated by the capacity for muscle oxygen extraction. Exaggerated circulatory and ventilatory responses to exercise are direct consequences of the level of impaired muscle oxidative phosphorylation.

[Pyogenic psoas abscess: six cases and review of the literature]. / Les abcès pyogènes secondaires du psoas: à propos de six cas et revue de la littérature.

PURPOSE: Psoas abscess is a rare disease in developed countries. Its diagnosis is difficult and any delay could lead to a worsen prognosis. The aim of this study is to determine the best diagnostic and therapeutic practices. METHODS: A retrospective study of psoas abscess that occurred during six months was performed. RESULTS: Six cases of secondary psoas abscess are reported. They were associated with spondylodiscitis in three cases, arthritis and gynaecologic infection in the three remaining cases. Anatomic diagnosis was performed by tomodensitometry. Microbiologic diagnosis was obtained by blood culture or direct puncture of the abscess. Antibiotics were associated with percutaneous drainage in two cases, with simple puncture in one case, and with surgery in one case. A local improvement w observed in all cases. The oldest patients presented the worst complications which were not directly caused by the abscess. CONCLUSION: Physicians must be aware of psoas abscess because of their increasing incidence. Despite the fact that digestive pathologies are the main cause of secondary psoas abscess, bone infections, particularly spine infections, should be taken into consideration. Tomodensitometry guided puncture or percutaneous drainage are of diagnostic and therapeutic interest. Infectious samples must be taken before starting antibiotics, which have to be efficient against Gram negative bacillus, anaerobes and Staphylococcus aureus. Surgery must be quickly performed when the primary infection localisation need it, in case of voluminous abscess or when antibiotics and drainage are inefficient.

Serum adiponectin and metabolic parameters in HIV-1-infected patients after substitution of nevirapine for protease inhibitors.

BACKGROUND: In the context of HIV infection and antiretroviral therapy, adiponectin concentrations have been shown to be related to lipodystrophy, metabolic alterations and HIV-protease inhibitor (PI) use. The replacement of PI by nevirapine has improved the lipid profile of patients under antiretroviral therapy. The aim of the present study was to examine whether adiponectin concentration or insulin sensitivity level correlate with the modifications of lipid parameters after the switch of PI by nevirapine. MATERIAL AND METHODS: The evolution of metabolic parameters before and after 6 months of substitution of nevirapine for protease inhibitors was evaluated in a cohort of 55 HIV-1 infected patients. Adiponectin concentration, insulin sensitivity, lipid profile, cholesterol ester transfer protein (CETP) mass concentration and triglyceride enrichment of HDL were determined before and after the replacement of PI by nevirapine. Insulin sensitivity was evaluated by the HOMA model assessment. RESULTS: Twenty-four weeks of treatment with nevirapine improved significantly the lipid profile with a significant reduction of apoB (from 0.98 to 0.92 g L(-1); P = 0.005) and triglyceride (from 2.02 to 1.66 mmol L(-1); P = 0.02). HDL cholesterol and apoA1 increased significantly (from 0.99 to 1.19 mmol L(-1); P = 0.001 and from 1.40 to 1.57 g L(-1); P < 0.001, respectively). The triglyceride enrichment of HDL significantly decreased after the replacement of PI by nevirapine (from 0.248 +/- 0.092 to 0.213 +/- 0.093; P = 0.003). At baseline, and after 24 weeks of nevirapine treatment, we observed significant correlations between adiponectin level and lipid parameters [(HDL-cholesterol (r = 0.66, P = 0.001 and r = 0.69, P = 0.001); triglycerides (r = -0.42, P = 0.002 and r = -0.57, P = 0.001), and triglyceride enrichment of HDL (r = -0.43, P = 0.005 and r = -0.53, P = 0.005)]. Twenty-four weeks of treatment with nevirapine did not significantly change adiponectin concentrations (from 984 to 1086 micro g L(-1), P = 0.22), CETP mass and insulin sensitivity. CONCLUSION: This study shows that even though a strong correlation was found between adiponectin and some metabolic parameters at baseline and after 24 weeks of treatment by nevirapine, the improvement of lipid profile observed after the replacement of PI by nevirapine was not in relation to the change of plasma adiponectin concentration. The significant decrease of triglyceride enrichment of HDL after the replacement of PI by nevirapine probably leads to a decreased catabolism of HDL lipoprotein, and consequently explains the increase of plasma HDL concentration observed in this study.

A prospective study of Epstein-Barr virus load in 85 hematopoietic stem cell transplants.

EBV viral load (EBV-VL) in PBMC was prospectively determined by semi-quantitative PCR in 85 stem cell transplants (40 genoidentical, 45 non-genoidentical) in order to characterize the kinetics of EBV-VL and to assess the ability of this measure to predict the development of EBV-induced lymphoproliferative disease (EBV-LPD). PCR was performed prior to and after transplantation. An EBV-VL >300 copies/microg DNA was chosen as the threshold for risk of developing an EBV-LPD. Two hundred and fifty-eight EBV-VL measures were evaluable. Five patients (5.9%) developed an EBV-LPD. All had an elevated EBV DNA peak level before EBV-LPD. Fifteen out of 80 recipients (18.7%) without EBV-LPD had EBV levels over 300 copies/microg DNA at least once during the follow-up. Overall, the manifestation of at least one EBV-VL over 300 copies/microg DNA during the entire follow-up demonstrated a sensitivity, specificity, positive and negative predictive value for the diagnosis of EBV-LPD of 100%, 81%, 25% and 100%, respectively. In patients without EBV-LPD, HLA incompatibility, grade > or = II acute GVHD and use of an unmanipulated graft were significantly associated with an EBV-VL >300 copies/microg DNA. This strategy appears sensitive for the diagnosis of EBV-LPD but its positive predictive value has to be improved in order to guide pre-emptive therapy.

Exercise stress testing for detection of silent myocardial ischemia in human immunodeficiency virus-infected patients receiving antiretroviral therapy.

The prevalence of silent myocardial ischemia (SMI) and the factors associated with SMI were evaluated in patients infected with human immunodeficiency virus (HIV) who had been receiving highly active antiretroviral therapy (HAART) for > or =12 months and did not have known coronary artery disease or cardiac symptoms. Patients prospectively underwent exercise stress testing. The prevalence of SMI was 11% (11 of 99 patients). Patients who had SMI were significantly older than were patients who did not (mean+/-SD, 51+/-8 years vs. 42+/-9 years; P=0.001) and were more likely to have trunk obesity (54% of patients vs. 17%; P=.004). A significant correlation was found between a positive exercise test result and obesity (correlation,.006), waist-to-hip ratio (.007), and glucose and cholesterol levels (.04; P=.03). In multivariate analysis, age, central fat accumulation, and cholesterol level were independent variables associated with the detection of SMI. Exercise testing might be recommended for patients with HIV who have central fat accumulation and hypercholesterolemia.

Randomized salvage therapy with saquinavir-ritonavir versus saquinavir-nelfinavir for highly protease inhibitor-experienced HIV-infected patients.

PURPOSE: To compare saquinavir + ritonavir and saquinavir + nelfinavir with nucleoside recycling in patients with multiple failures of highly active antiretroviral therapy (HAART). METHOD: This was a prospective, multicenter, randomized open trial. Inclusion criteria were the following: consent, age > 18, previous protease inhibitor (PI) exposure > 6 months, unchanged HAART > 3 months, and viral load > 3 log. The treatments compared were ritonavir 200 mg bid + saquinavir 600 mg bid (Rito-Saq), and nelfinavir 1,000 mg bid + saquinavir 600 mg bid (Nelf-Saq). Nucleoside analogues were recycled, and nonnucleoside inhibitors were not permitted. Trough levels of the three drugs were measured by high-performance liquid chromatography at the month 3 visit. After the study had been completed, genotyping analysis was done on the first serum at entry. RESULTS: The study was interrupted due to the availability of new anti-HIV drugs. A random sample of 31 (16 Rito-Saq and 15 Nelf-Saq) patients was divided into two groups, which were comparable in terms of demographic data and previous history of HIV infection. Mean CD4 cell count and plasma viral load (pVL) were 316 +/- 169 and 3.89 +/- 0.87 for Rito-Saq and 448 +/- 238 and 3.85 +/- 0.32 for Nelf-Saq. Previous duration of PI exposure was 31 months for both groups. The mean number of protease gene mutations was 3.8 (range, 2-7) and 4.4 (range, 2-9), respectively. On intention-to-treat (ITT) analysis at month 6, pVL stabilization or decrease >/= 0.5 log was observed in 18 patients (58%): 10 for Rito-Saq and 8 for Nelf-Saq. In a multivariate logistic regression analysis, virological success at month 3 was inversely correlated to baseline viral load (R = 0.14; 95% CI 0.03-2.9; p =.01); and at month 6, virological success was inversely associated to the number of mutations in the protease gene (R = 2.2; 95% CI 0.73-6.53; p =.06). CONCLUSION: Nelf-Saq and Rito-Saq combinations can be proposed in case of multiple HAART failures. The fact that the virological response was inversely correlated to baseline viral load makes the case for an early switch after a HAART failure.

Coronary heart disease associated with the use of human immunodeficiency virus (HIV)-1 protease inhibitors: report of four cases and review.

Four cases of human immunodeficiency virus (HIV)-infected patients who developed coronary heart disease (CHD) while under treatment with a protease inhibitor (PI) are described, and the epidemiologic and clinical features of 18 cases reported in the literature are analyzed. Cardiac manifestations mostly included myocardial infarctions. Smoking and hyperlipidemia were the most common risk factors for CHD, reported in 72 and 81% of the patients, respectively. Hypercholesterolemia was observed in 75% of the cases at the time of the cardiovascular event. Ninety percent of the patients with pretreatment normal lipid values experienced a rise in the plasma lipid levels during PI therapy. Although a definite relationship between the development of CHD and HIV PIs can not be made, this analysis suggests that PI-induced hyperlipidemia may play a role in accelerating coronary atherosclerosis in patients with concomitant risk factors. Evaluation and control of risk factors for CHD should be performed in each patient for whom treatment with a PI is indicated.

Therapeutic trials in HIV infection: which benefits for which patients?

PURPOSE: The purpose of our study was to make an assessment of the HIV patients' overall opinion of therapeutic trials, to analyze the motivations and the reasons linked to this perception, and to determine if their involvement in a therapeutic trial is a help or a hindrance to their treatment. METHOD: All the inpatients and outpatients attending the Dijon University Hospital AIDS day care unit during the first 4 months of 1999 were given an anonymous questionnaire designed to record the patients' attitudes toward therapeutic trials, their motivations, and the perceived risks. The questionnaire was often completed in consultation with a psychoanalyst. RESULTS: Two hundred and seven (207) patients were surveyed; 194 of them had a favorable opinion of therapeutic trials. The main motivations to take part in a therapeutic trial were altruistic. In contrast, individualistic considerations and relational motivations (such as to modify the relationship between the caregiver and the patient) were more closely associated with a negative perception. CONCLUSION: Most of the patients will benefit or at least will not be harmed by being involved in a trial. However, the patients' attitudes toward the principle of therapeutic trials have to be determined before these patients are included in a given therapeutic trial. This is necessary to avoid the risk of subsequent medical care being altered because participation was either induced or compelled.