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Biomedical subjects

F Raffi

Publications and source records attributed to F Raffi.

At least 19 recordsLinked to original sources
PubMed2001

Abacavir-lamivudine-zidovudine vs indinavir-lamivudine-zidovudine in antiretroviral-naive HIV-infected adults: A randomized equivalence trial.

CONTEXT: Abacavir, a nucleoside analogue, has demonstrated suppression of human immunodeficiency virus (HIV) replication alone and in combination therapy. However, the role of abacavir in a triple nucleoside combination regimen has not been evaluated against a standard protease inhibitor-containing regimen for initial antiretroviral treatment. OBJECTIVE: To evaluate antiretroviral equivalence and safety of an abacavir-lamivudine-zidovudine regimen compared with an indinavir-lamivudine-zidovudine regimen. DESIGN AND SETTING: A multicenter, phase 3, randomized, double-blind trial with an enrollment period from August 1997 to June 1998, with follow-up through 48 weeks at 73 clinical research units in the United States, Canada, Australia, and Europe. PATIENTS: Five hundred sixty-two antiretroviral-naive, HIV-infected adults with a plasma HIV RNA level of at least 10 000 copies/mL and a CD4 cell count of at least 100 x 10(6)/L. INTERVENTIONS: Patients were stratified by baseline HIV RNA level and randomly assigned to receive a combination tablet containing 150 mg of lamivudine and 300 mg of zidovudine twice daily plus either 300 mg of abacavir twice daily and indinavir placebo or 800 mg of indinavir every 8 hours daily plus abacavir placebo. After 16 weeks, patients with confirmed HIV RNA levels greater than 400 copies/mL were eligible to continue receiving randomized treatment or receive open-label therapy. MAIN OUTCOME MEASURE: Virologic suppression, defined as HIV RNA concentration of 400 copies/mL or less at week 48. RESULTS: The proportion of patients who met the end point of having an HIV RNA level of 400 copies/mL or less at week 48 was equivalent in the abacavir group (51% [133/262]) and in the indinavir group (51% [136/265]) with a treatment difference of -0.6% (95% confidence interval [CI], -9% to 8%). In patients with baseline HIV RNA levels greater than 100 000 copies/mL, the proportion of patients achieving less than 50 copies/mL was greater in the indinavir group than in the abacavir group with 45% (45/100) vs 31% (30/96) and a treatment diference of -14% (95% CI, -27% to 0%). The 2 treatments were comparable with respect to their effects on CD4 cell count. There was no difference between groups in the frequency of treatment-limiting adverse events or laboratory abnormalities. One death in the abacavir group was attributed to hypersensitivity reaction, which occurred following rechallenge with abacavir, approximately 3 weeks after initiating study treatment. CONCLUSIONS: In this study of antiretroviral-naive HIV-infected adults, the triple nucleoside regimen of abacavir-lamivudine-zidovudine was equivalent to the regimen of indinavir-lamivudine-zidovudine in achieving a plasma HIV RNA level of less than 400 copies/mL at 48 weeks.

Adult↗
PubMed2001

Evaluation of chronic hepatitis B virus (HBV) infection in coinfected patients receiving lamivudine as a component of anti-human immunodeficiency virus regimens.

The effect of lamivudine on chronic coinfection with hepatitis B virus (HBV) in human immunodeficiency virus (HIV)--infected patients was studied prospectively. Nineteen patients with HIV infection, who were receiving an anti-HIV regimen containing lamivudine (150 mg twice daily), and who had replicative chronic HBV infection, were followed for a median of 14 months. Twelve patients' regimens contained protease inhibitors. Serum HBV DNA became undetectable, by means of molecular hybridization, in 14. Seroconversion of hepatitis B e antigen to antibody occurred in 6 of 17 patients, and seroconversion of hepatitis B surface antigen to antibody occurred in 1 of 19. The median serum alanine aminotransferase concentration had decreased by the time of the final evaluation. The median CD4 cell count increased and plasma HIV RNA was undetectable in 10 of 19 patients. Five patients had recurrence of detectable serum HBV DNA despite good compliance with treatment, and 2 mutations related to the resistance of HBV were detected. These patients had a significantly longer duration of treatment (21 versus 13 months; P<.05). In conclusion, resistant strains of HBV emerge at high detectable levels while patients receive anti-HIV regimens containing lamivudine.

Adult↗
PubMed2000

Impact of fluoroquinolone administration on the emergence of fluoroquinolone-resistant gram-negative bacilli from gastrointestinal flora.

We assessed the risk factors for acquisition of fluoroquinolone-resistant, gram-negative organisms in the gastrointestinal tract of hospitalized patients. We analyzed stool samples from 204 patients and recovered fluoroquinolone-resistant, gram-negative organisms from 63. Receipt of fluoroquinolone during the month preceding admission was the only risk factor identified, whereas female sex, duration of hospitalization, exposure to indwelling devices, admission from another hospital, and history of infection were risk factors for fecal colonization after day 4.

Acinetobacter↗
PubMed2000

[Resistance to protease inhibitors: the role of the MDR gene].

MDR GENES: Overexpression of MDR genes leads to the production of glycoprotein P (PGP) that can use protease inhibitors as a substrate. This overexpression of MDR genes appears to be the cause, at least partially, of resistance to protease inhibitors by induction of very low intracellular inhibitor concentrations. IN VITRO: New compounds capable of inhibiting GPG have been tested. Ritonavir and verapamil reduce the impact of PGP efflux. Compared with verapamil, ritovavir appears to be more effective with a concentration-dependent action. IN VIVO: In vitro studies demonstrated that ritonavir can inverse the effect resulting from the expression of the MDR gene and the production of PGP, with restoration of significant intracellular levels of protease inhibitors, at least higher than obtained in the absence of ritonavir. Likewise, in vivo, it has been demonstrated that the more the gene is expressed, the less elevated is the intracellular concentration of the protease inhibitor.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

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↗
PubMed2000

Phase II placebo-controlled trial of fozivudine tidoxil for HIV infection: pharmacokinetics, tolerability, and efficacy.

Fozivudine tidoxil (FZD) is a thioether lipid-zidovudine (ZDV) conjugate with anti-HIV activity demonstrated in vitro and in pilot phase I studies. To assess its safety, efficacy and pharmacokinetics, we conducted a multicenter, randomized, double-blind, placebo-controlled trial of FZD monotherapy in 72 HIV-infected patients who had not previously received antiretroviral therapy. In each dosage group (200 mg daily, 400 mg daily, 200 mg twice daily, 800 mg daily, 400 mg twice daily, and 600 mg twice daily), 12 patients were randomized to receive in a 10:2 ratio either FZD or a placebo for 4 weeks. Overall, FZD was well tolerated in all dosage groups; only 1 patient discontinued the drug, because of a moderate rise in aminotransaminase activity. HIV viral load fell in all the patients who were receiving FZD, except in the 200 mg daily group. The largest decrease (-0.67 log10) was observed in the 600 mg twice daily group. The plasma half-life was significantly longer (approximately 3.8 hours) than that of the parent drug ZDV. Exposure to ZDV, as reflected by the area under the time-concentration curve, was much lower after FZD than after ZDV administration. FZD thus appears to be as effective as and potentially better tolerated than ZDV during short-term administration and has the advantage of once daily intake.

Adult↗
PubMed2000

[Skin and osteoarticular bacterial infections of the diabetic foot. Ulcers of the diabetic foot: epidemiology and physiopathology].

EPIDEMIOLOGY: There are more than 2 million diabetics in France. Fifteen percent have suffered at one time or another from a foot ulcer. This condition accounts for 20% of all admissions of diabetic patients and for 50% of corresponding hospitalization stays. Fifteen to 25% of diabetic foot ulcers lead to an amputation, the patients being in the 45-65 year age range. Fifty percent of the amputated patients will have a contralateral amputation within the next 5 years. PATHOPHYSIOLOGY: Diabetic foot ulcers result from damage caused by diabetic neuropathy and micro- or macroangiopathy. Ulceration is favored by usually minimal trauma and secondary infection. The neuropathy causes deformations and sensorial disorders. Repair is hindered by the often precarious vascular supply. Reduced antibacterial defense related to high serum glucose levels and impaired diapedesis favor superinfection. MANAGEMENT: Careful physical examination and appropriate explorations are required for proper care giving the patient the best chances for cure.

Aged↗
PubMed2000

[Skin and osteoarticular infections of the diabetic foot. Role of infection].

A MAJOR PROBLEM: Two-thirds of all amputations involve infection. Infection is favored by dysfunction of the antibacterial defense systems due to high blood glucose and vascular disorders. DIAGNOSIS: General signs of infection are usually not found. A careful exploration is required to rule out or confirm osteitis in order to guide surgery and plan the antibiotic regimen. A history of chronic and/or recurrent ulceration or direct signs at inspection may be suggestive of osteitis. Radiographic signs are late and nonspecific. Scintigraphy scans are difficult to interpret. Magnetic resonance imaging can be quite helpful in difficult cases. BACTERIOLOGICAL PROOF: Staphylococcus aureus and to a lesser extent streptococci account for almost all of the superficial infections in the diabetic foot. In case of deep ulceration, it is important to obtain deep specimens at surgical cleansing as more superficial samples are easily contaminated. Nevertheless, if Staphylococcus aureus is isolated from pus coming from a deep zone fistulizing to the skin, it is likely the causal agent since 80% of all bone infections involve S. aureus. Other germs besides staphylococci and streptococci include enterobacteria (40%), enterococci (26%) and pseudomonas (7%). Several germs are involved in about 70% of cases with a probable synergetic effect between the different bacterial colonies within the infected tissues.

Amputation, Surgical↗
PubMed2000

[Skin and osteoarticular bacterial infections of the diabetic foot. Treatment].

MULTIDISCIPLINARY CARE: A multidisciplinary approach is essential. General measures include immobilization of the focus, controlling blood glucose, anticoagulation, and anti-tetanus vaccination. Topical application of growth factors is currently under evaluation. ANTIBIOTIC THERAPY: The antibiotics chosen should diffuse well into bone tissue. Combinations with synergetic or additive effects against Staphylococcus aureus are best. Treatment duration depends on the depth of the ulceration. Two weeks is generally advised for superficial ulcers. For deep ulcers, treatment duration depends on the presence or not of osteitis and the quality of surgical debridement. In case of osteitis, after amputation with a healthy margin, antibiotics can generally be discontinued 2 weeks after surgery. Six weeks are required if the amputation margins do not lie in healthy zones. Finally, if no surgery is attempted, the antibiotic regimen should be continued for 3 months, or even longer, with a risk of failure greater than 50%. The best criterion for successful treatment is the absence of late recurrence. SURGERY: Surgery is an indispensable element in the overall treatment of deep infections and/or osteitis. The operation should be performed as early as possible to improve prognosis. Well-conducted early surgical debridement can prevent the infection from spreading and avoid the need for much more mutilating "salvage" procedures. Vascular surgery can help maintain sufficient blood supply for wound healing and antibacterial defense. Plastic surgery can be very helpful. PREVENTION: A certain number of simple measures help reduce the risk of diabetic foot ulcers. However, many patients, and practitioners, are insufficiently aware of their effectiveness. Prevention and treatment can best be accomplished by a multidisciplinary approach calling upon the endocrinologist and the vascular and orthopedic surgery teams. A carefully planned rehabilitation program using adapted soles, orthesis, orthopedic shoes or prostheses as needed can considerably reduce the frequency of recurrence. The risk of recurrence in a patient wearing adapted footwear is only 26% at 5 years compared with 83% in other cases.

Anti-Bacterial Agents↗
PubMed2000

Mechanisms of virologic failure in previously untreated HIV-infected patients from a trial of induction-maintenance therapy. Trilège (Agence Nationale de Recherches sur le SIDA 072) Study Team).

CONTEXT: In the Trilège trial, following induction with a zidovudine, lamivudine, and indinavir regimen, human immunodeficiency virus (HIV) replication was less suppressed by 2-drug maintenance therapy than by triple-drug therapy. OBJECTIVE: To identify mechanisms of virologic failure in the 3 arms of the Trilège trial. DESIGN: Case-control study conducted from February to October 1998. SETTING: Three urban hospitals in Paris, France. PATIENTS: Fifty-eight case patients with virologic failure (HIV RNA rebound to >500 copies/mL in 2 consecutive samples) randomized to 3 therapy groups: triple drug (zidovudine, lamivudine, and indinavir), 8; zidovudine-lamivudine, 29; and zidovudine-indinavir, 21; the case patients were randomly matched with 58 control patients with sustained viral suppression. MAIN OUTCOME MEASURES: At virologic failure (S1 sample) and 6 weeks later (S2 sample), assessment of protease and reverse transcriptase gene mutations, plasma indinavir level, and degree of viral load rebound; pill count during induction and maintenance periods. RESULTS: Only 1 primary resistance mutation, M184V, was detected in S1 plasma samples from 4 of 6 patients in the triple-drug and in all 22 in the zidovudine-lamivudine therapy groups and in S2 plasma samples from 3 of 6 in the triple-drug and 20 of 21 in the zidovudine-lamivudine groups. Of controls, M184V was detected in 11 of 13 S1 plasma samples and in 10 of 11 S2 plasma samples. Indinavir levels were undetectable in all S1 samples but 2 in 7 triple-drug cases tested and in the expected range in 11 of 18 S1 and 5 of 12 S2 zidovudine-indinavir case plasma samples tested. Maintenance adherence rates were lower for cases vs controls for zidovudine (P = .05) and indinavir (P = .05). Low indinavir levels, lower adherence rates for zidovudine (P = .04) and lamivudine (P = .03), and rebound to near-baseline values suggested adherence as cause of early failure for 4 of 8 triple-drug cases. In the zidovudine-lamivudine arm, for which case and control adherence rates did not differ significantly (P = .96), most failures occurred late with low rebound, suggesting suboptimal drug potency. In the zidovudine-indinavir arm, virologic failures may be related to both mechanisms. CONCLUSIONS: During the maintenance phase early and late virologic failures appeared to be related more to problems of adherence and antiretroviral treatment potency, respectively, than to selection of resistant mutant viruses.

Anti-HIV Agents↗
PubMed2000

Localized Mycobacterium genavense soft tissue infection in an immunodeficient HIV-negative patient.

An HIV-negative woman with chronic lymphopenia related to past sarcoidosis situated in the bone marrow presented with an inflammatory lesion in the iliac region due to a localized Mycobacterium genavense soft tissue infection. The lesion resolved after 12 months of antibiotic therapy with clarithromycin, ethambutol and ciprofloxacin. The patient had no recurrence of the subcutaneous abscess during a follow-up period of 14 months after the end of the treatment.

Adult↗
PubMed2000

Hepatitis C virus co-infection is a negative prognostic factor for clinical evolution in human immunodeficiency virus-positive patients.

A longitudinal study of human immunodeficiency virus (HIV)-infected individuals followed-up in 13 centres was performed to assess the influence of hepatitis C virus (HCV) on the clinical and immunological evolution of HIV-infected patients. Eight-hundred and twelve HIV-infected patients with known HIV acquisition date, 89 co-infected with HCV, were included in the cohort. Clinical progression was defined as: 30% decrease of Karnofsky's index; and/or 20% body weight loss; and/or acquired immune deficiency syndrome (AIDS)-defining illness; and/or death (except by accident, suicide, or overdose). Immunological progression was defined as a decrease of initial CD4 count to below 200 mm(-3). If immunological progression was not statistically different between groups (P=0.25), clinical progression was significantly faster in HCV-HIV co-infected patients in univariate (P=0.02) and multivariable survival analysis (hazard ratio=1.63, P=0.03). This argues for active management of hepatitis C chronic infection among HCV-HIV co-infected patients.

Adult↗
PubMed2000

Substitution of a nonnucleoside reverse transcriptase inhibitor for a protease inhibitor in the treatment of patients with undetectable plasma human immunodeficiency virus type 1 RNA.

Seventy-three patients infected with human immunodeficiency virus type 1 (HIV-1) were enrolled in a prospective observational study to investigate the efficacy and tolerance of substituting a nonnucleoside reverse transcriptase inhibitor (NNRTI) for a protease inhibitor (PI) in patients whose plasma viral load (pVL) was controlled by a PI regimen. After a median follow-up of 52 weeks, 63 patients (86.3%) had undetectable pVLs. The incidence of virological breakthrough at 12 months of follow-up was 6.5% (95% confidence interval [CI], 1-20) among patients who had been antiretroviral naive before receiving HAART and 19.2% (95% CI, 6-34) among patients who had been treated with antiretroviral drugs before receiving the PI regimen (P=.10).

CD4 Lymphocyte Count↗
PubMed2000

Hepatitis B or hepatitis C virus infection is a risk factor for severe hepatic cytolysis after initiation of a protease inhibitor-containing antiretroviral regimen in human immunodeficiency virus-infected patients. The APROCO Study Group.

In a cohort of 1,047 human immunodeficiency virus type 1-infected patients started on protease inhibitors (PIs), the incidence of severe hepatic cytolysis (alanine aminotransferase concentration five times or more above the upper limit of the normal level >/= 5N) was 5% patient-years after a mean follow-up of 5 months. Only positivity for hepatitis C virus antibodies (hazard ratio [HR], 7. 95; P < 10(-3)) or hepatitis B virus surface antigen (HR, 6.67; P < 10(-3)) was associated with severe cytolysis. Before starting patients on PIs, assessment of liver enzyme levels and viral coinfections is necessary.

AIDS-Related Opportunistic Infections↗