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Biomedical subjects

F Raffi

Publications and source records attributed to F Raffi.

At least 55 records · Page 3Linked to original sources
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↗
PubMed2000

[Mycobacterium avium complex disease in HIV seropositive patients: incidence and risk factors before and after the introduction of highly active antiretroviral treatments. Clinical Epidemiology Group of the Information and Care Center for Human Immunodeficiency].

The objective of this study was to determine the risk factors of the first occurrence of Mycobacterium avium complex disease (MAC) infection among human immunodeficiency virus (HIV)-infected subjects during two different time periods: before and after the introduction of protease inhibitor (respectively, period 1: 1 January 1992 to 31 December 1995, and period 2: 1 January 1996 to 30 June 1998). This study was performed using the French Hospital Database on HIV (FHDH). Subjects were included when their CD4+ cell count was less than 100/mm3. If they did not die or develop MAC within the first 6 months after the inclusion, their follow-up had to be longer than 6 months to be included. Cox's model was used to calculated the relative hazards (RH) of MAC occurrence according to the age and time-dependent variables, such as CD4+ below 50/mm3, previous occurrence of tuberculosis, cytomegalovirus (CMV) infection and other acquired immunodeficiency syndrome (AIDS)-defining disease, nature of antiretroviral treatment and MAC prophylaxis. Among the 14,779 subjects followed during period 1, 1,710 (11.6%) had a diagnosis of MAC infection during their follow-up (incidence: 8.4 +/- 0.2 for 100 persons per year), while only 453 (4.4%) among 10,239 subjects presented this infection during period 2 (2.8 +/- 0.1 for 100 persons per year). Rifabutin regular prescription was a protective factor of MAC occurrence during period 1 (RH = 0.51 95% confidence interval (CI) = [0.37-0.69]), whereas this protective effect was not observed during period 2 (RH = 1.05 CI = [0.63-1.67]). Thus, during the HAART period, the results that we present do not indicate an interest into continuing MAC prophylaxis.

Adult↗
PubMed2000

The VIRGO study: nevirapine, didanosine and stavudine combination therapy in antiretroviral-naive HIV-1-infected adults.

The virological and immunological efficacy of the triple regimen containing nevirapine (once or twice daily), didanosine (once daily) and stavudine, in antiretroviral-naive patients infected with HIV-1, was evaluated in an open-label, prospective, non-randomized, multi-centre, 52-week study. The first 60 patients (VIRGO I) received nevirapine as the standard dose, 200 mg twice daily; the subsequent 40 patients (VIRGO II) received nevirapine at a dose of 400 mg once daily. All patients received 400 mg of didanosine once daily and 40 mg of stavudine twice daily, adjusted for body weight. At baseline, the median CD4 cell count and plasma viral load (pVL) were 414 cells/mm3 and 4.59 log10 copies/ml in VIRGO I, and 412 cells/mm3 and 4.87 log10 copies/ml in VIRGO II. Using an intent-to-treat, 'non-completer equals failure', analysis, 78% (95% CI, 68-88%) of patients in VIRGO I and 68% (95% CI, 53-83%) of those in VIRGO II had a pVL <500 copies/ml at 24 weeks; the proportions achieving a pVL of <50 copies/ml were 62% (95% CI, 50-74%) and 50% (95% CI, 35-65%), respectively. The week 24 median CD4 cell count increase was 168 cells/mm3 (VIRGO I) and 139 cells/mm3 (VIRGO II). At week 52, 39/45 (87%) of VIRGO I patients had pVL <500 copies/ml and 30/45 (67%) <50 copies/ml. Of the 100 patients, 44 experienced grade 2 to 4 adverse events; 20 permanently discontinued study medication because of an adverse event. Combination therapy with the three reverse transcriptase (RT) inhibitors stavudine, once-daily didanosine and either once- or twice-daily nevirapine could be considered as an alternative option for first-line antiretroviral therapy.

Adult↗
PubMed1999

[Abiotrophia related endocarditis: contribution of molecular biology].

BACKGROUND: Former nutritionally-deficient (variant) streptococci were recently separated from other streptococci viridans to constitute a new Abiotrophia genus, subdivided into two species, Abiotrophia defectiva (ex-Streptococcus defectivus) and Abiotrophia adjacens (ex-Streptococcus adjacens). CASE REPORT: A woman was admitted to the hospital because of purpura and fever. Vegetations were shown by trans-esophageal echocardiography. Although blood samples were positive within 24 hours, accurate identification of the morphologically and biochemically streptococcus-like bacteria that had grown remained impossible. Molecular biology technicals permitted to identify Abiotrophia defectiva, ex-Streptococcus defectivus. DISCUSSION: This new genus is important to be identified in clinical practice, because of the increased virulence of these bacteria, when compared with Streptococci viridans. They are also frequently penicillin-resistant. Molecular biology technicals allow precocious diagnosis, and make possible the improvement of the prognosis.

Endocarditis, Bacterial↗
PubMed1999

[Anti-HIV drugs].

Anti-HIV drugs act by blocking intracellular replication of the virus by inhibiting viral enzyme either reverse transcriptase or protease. Reverse transcriptase inhibitors belong to 3 different categories: nucleoside analogues, which active forms are the triphosphorylated intracellular compound, non nucleoside inhibitors and the more recent nucleotide analogues. Protease inhibitors are very active in vitro but besides their digestive side effects, have numerous drug interactions because they are metabolised through P450 liver cytochromes, and are associated with long-term toxicity.

Anti-HIV Agents↗
PubMed1999

[Varicella zoster virus infection area in 39 HIV-infected patients. Therapeutic management].

OBJECTIVES: The main goal of this study was to assess therapeutic strategies in HIV-infected patients with varicella-zoster virus infection. PATIENTS AND METHODS: This retrospective study conducted between 1989 and 1996 concerned 39 HIV-infected patients who had reached the AIDS stage and had at least one episode of varcella-zoster infection. Epidemiological, clinical and therapeutic data were recorded. Chi-squared test was used for comparisons. RESULTS: A total of 78 episodes of varicella-zoster infection occurred including 39 primary episodes and 39 recurrences. Aciclovir (ACV) 200 mg per os was given in 27 cases as first intention therapy (mean dose 4000 mg/day for a mean 10 days), ACV 800 mg per os in 10 cases (mean dose 4000 mg per day for a mean 10 days), and intravenous ACV in 23 cases (mean dose 30 mg/kg/day for a mean 7 days). Foscarnet was used 5 times, 90-100 mg per day for 8 to 21 days. We did not observe any difference in efficacy between the three ACV formulations, probably because of the small number of patients in the series and the retrospective nature of the study. All of the failures of the oral treatments occurred in patients with CD4 counts below 100/mm3. CONCLUSION: Aciclovir (800 mg) can be given in HIV-infected patients who develop non-complicated varicella-zoster virus infection. Intravenous aciclovir should be reserved for severe disseminated and/or neurological forms and for highly immunodepressed patients (for example those with a CD4 count below 200/mm3). These findings should be confirmed by prospective studies.

AIDS-Related Opportunistic Infections↗
PubMed1999

[Community-acquired bacterial meningitis in the Loire-Atlantic region: evolution of pneumococcal and meningococcal sensitivity to penicillin].

OBJECTIVES: An epidemiological study of community-acquired bacterial meningitis was conducted in Loire-Atlantique in subjects aged over 1 month. Risk factors and changes in pneumococcal and meningococcal susceptibility to betalactams were analyzed. PATIENTS AND METHODS: All cases of proven or presumed bacterial meningitis registered by Loire-Atlantic bacteriology laboratories between May 1995 and April 1998 were analyzed. RESULTS: One hundred two cases were registered (annual incidence: 3.12 cases per 100,000 inhabitants). In children (33 cases) the main germs were meningococci (51%), pneumococci (24%) and Haemophilus influenzae (6%). In adults (69 cases), pneumococci (49%), meningococci (14%) and Listeria (4%) predominated. An underlying disease was noted 44% of the cases. Mortality was 17.6%. Sequellae were observed in 9.5%. Some degree of penicillin resistance was observed in 45% of the pneumococcal strains and in 50% of the meningococcal strains. Half of the pneumococcal strains were also resistant to third generation cephalosporins (C3G). No risk factor was significantly related to resistant strains. Susceptibility to antibiotics was not correlated with mortality for either pneumococcal or meningococcal strains, but sequellae were more frequent after meningitis caused by resistant pneumococci. CONCLUSION: For cases of community-acquired meningococcal meningitis diagnosed in 1999, it would be advisable to prescribe a combination C3G-vancomycin regimen as the first line empirical treatment while waiting for results of susceptibility tests. Certain guidelines proposed by the February 1996 consensus conference on community-acquired purulent meningitis would thus need to be amended.

Adult↗
PubMed1999

Safety and efficacy of ritonavir and saquinavir in combination with zidovudine and lamivudine.

BACKGROUND: Ritonavir is a potent inhibitor of cytochrome P4503A4 that strongly increases saquinavir bioavailability. In this study we assessed the safety and antiretroviral efficacy of the combination of these two compounds in patients pretreated and receiving continued treatment with zidovudine and lamivudine who were protease inhibitor naive and who had a CD4 cell counts below 200/mm3. METHODS: In this 48-week pilot study, all patients received 600 mg ritonavir and 400 mg saquinavir twice daily. Administration of zidovudine and lamivudine was continued without a change in previous doses. Viral load, CD4 cell count, and the emergence of resistance to the two protease inhibitors were evaluated repeatedly up to week 48. RESULTS: Sixteen patients were included in the study. Previous nucleoside analog treatment duration was 48+/-22 months (mean +/- SD). Two patients quit taking both protease inhibitors within 2 weeks. The ritonavir dose had to be reduced in 10 other patients because of side effects. Between inclusion and week 48, plasma viremia varied from 4.87+/-0.43 to 3.00+/-1.29 log10 copies/mL and CD4 cell counts ranged from 98+/-61 to 250+/-139/mm3. Ten patients (63%) had viral loads below 200 copies/mL and 7 (44%) had viral loads below 50 copies/mL. A single key mutation that conferred ritonavir resistance I84V and V82A/V developed in two patients. A mutation at codon 54 developed in another patient. These mutations were associated with repeated cessations of antiretroviral treatment. No lipodystrophy was observed. CONCLUSION: Ritonavir and saquinavir in combination are quite well tolerated and induce a high and sustained antiretroviral efficacy. A four-drug combination that includes these two protease inhibitors should be considered as a first line of treatment in patients with low CD4 cell counts.

Acquired Immunodeficiency Syndrome↗