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Biomedical subjects

F Raffi

Publications and source records attributed to F Raffi.

At least 73 records · Page 4Linked to original sources
PubMed1999

["Buffalo neck": an unintended secondary effect of treatment with anti-HIV protease inhibitors].

BACKGROUND: Lipodystrophy and other fat distribution disorders have been reported in patients receiving protease inhibitor therapy for HIV infection. CASE REPORT: A 50-year-old HIV-positive patient was given protease inhibitor therapy (indinavir) for 6 months when he developed a lipomatous formation in the retrocervical area. Abdominal fat also increased in volume and the subcutaneous fat on the lower limbs decreased. DISCUSSION: We describe the main clinical features of these fat distribution disorders and discuss the pathogenic hypothesis of an interaction between antiprotease activity and hepatic lipoprotein receptor binding.

Abdomen↗
PubMed1999

[Experience with nevirapine taken once daily in 93 HIV-infected patients].

Due to its long half-life (25-30 hours) the once daily administration of nevirapine would appear logical but we do not have data regarding the tolerability and efficacy of this schedule. We have therefore tried to evaluate this schedule in 93 HIV-infected patients beginning a treatment containing nevirapine. The tolerability of once daily nevirapine was similar to the usual schedule with 15% of mucocutaneous allergy. The immunologic and virologic efficacy of once daily nevirapine was confirmed with a mean RNA HIV decrease of 1.4 log, 1.3 log, 1.1 log and 1.3 log at M1, M3, M6 and M9 respectively. The best results were observed in naïve patients. Residual plasma concentration of nevirapine was performed in 35 patients with a mean value of 3.8 mg/l.

Adult↗
PubMed1999

[Secondary prophylaxis for herpes zoster wi oral acyclovir in HIV patients].

We studied 39 AIDS patients from 1989 to 1996, with previous history of herpes zoster. Twelve of them received acyclovir (ACV) secondary prophylaxis. There were 31 males and 8 females, mean age 33.9 years (19-60) during first herpes zoster. Transmission was sexual in 71.8%. Among these 39 patients, 78 herpes zoster episodes occurred. Median CD4 lymphocytes was 18/mm3 (0-232) among the 12 patients with ACV prophylaxis. Mean posology of ACV was 2,400 mg (1,600-4,000) per day, during mean 10 months (median 4 months). ACV prophylaxis was used because of high frequence of herpes zoster (more than 4) (4 cases), neurologic complications in 4 cases (1 myelitis, 1 myeloradiculitis, 1 vascularitis and 1 meningo-encephalitis), disseminated herpes zoster in 4 cases and one hyperalgic zoster. Ten from these 12 patients occurred no zoster recurrence. Among patients without prophylaxis, zoster recurrences were more frequent at 12 months (68% versus 22% among patients with prophylaxis). This prophylaxis seems to be interesting, particularly in deep immunocompromised patients (CD4 < 50/mm3) with serious herpes zoster or frequent recurrences (more than 4). However, since protease inhibitors treatments, zoster incidence is decreasing in HIV+ patients. This prophylaxis will probably be less usefull than before.

AIDS-Related Opportunistic Infections↗
PubMed1999

Stavudine, didanosine and nevirapine in antiretroviral-naive HIV-1-infected patients.

In an ongoing, open-label, non-comparative study, the safety and efficacy of nevirapine/stavudine/didanosine were evaluated in 100 antiretroviral-naive adults with CD4 cell counts > or = 200 cells/mm3 and plasma HIV-1 RNA (pVL) > or = 5000 copies/ml. Sixty patients received nevirapine twice daily (VIRGO I) and 40 received nevirapine once daily (VIRGO II); all patients received didanosine once a day. After median follow-ups of 44 weeks in VIRGO I and 30 weeks in VIRGO II, the following virological results were observed (ongoing study): an intent-to-treat, non-completer equals failure analysis at week 24 showed the proportions of patients with pVL <500 copies/ml were 78% in VIRGO I (60% <50 copies/ml) and 75% in VIRGO II. An on-treatment analysis at week 52 showed 80% of patients with a pVL <500 copies/ml and 59% with <50 copies/ml in VIRGO I. The mean CD4 cell count increase was +171 cells/mm3 at week 24 and +218 cells/mm3 at week 52 in VIRGO I and +158 cells/mm3 at week 24 in VIRGO II. Cutaneous rash (grades 1 to 3) occurred in 24% of patients leading to nevirapine discontinuation in eight of 24 patients. Five other patients discontinued therapy during the first 24 weeks because of hepatic cytolysis, peripheral neuropathy or biological pancreatitis. The nevirapine/stavudine/didanosine combination is a convenient and safe regimen, with rapid and potent immunological and antiviral effects sustained over 12 months.

Anti-HIV Agents↗
PubMed1998

A randomized trial of three maintenance regimens given after three months of induction therapy with zidovudine, lamivudine, and indinavir in previously untreated HIV-1-infected patients. Trilège (Agence Nationale de Recherches sur le SIDA 072) Study Team.

BACKGROUND: The long-term effectiveness of potent three-drug antiretroviral regimens for the treatment of human immunodeficiency virus type 1 (HIV-1) infection is limited by problems related to compliance and tolerability. We investigated whether two-drug maintenance therapy would suppress viral replication after a three-month period of aggressive triple-drug induction therapy. METHODS: A total of 378 HIV-1-infected adults who had not received previous antiretroviral treatment received three months of induction therapy consisting of 300 mg of zidovudine every 12 hours, 150 mg of lamivudine every 12 hours, and 800 mg of indinavir every 8 hours. The 279 patients in whom the plasma HIV-1 RNA titer fell below 500 copies per milliliter after two months of triple-drug therapy, and who completed the induction phase, were randomly assigned at month 3 to one of the following three open-label maintenance regimens: zidovudine, lamivudine, and indinavir; zidovudine and lamivudine; or zidovudine and indinavir. The primary end point was an increase in HIV-1 RNA levels to 500 copies or more per milliliter during the maintenance phase. RESULTS: The proportion of patients who reached the primary end point was significantly higher among patients receiving zidovudine plus lamivudine (29 of 93 patients, P<0.001) or zidovudine plus indinavir (21 of 94, P=0.01) than among patients receiving continued triple-drug therapy (8 of 92). This higher failure rate in the groups treated with the two-drug maintenance regimens was also observed in the subgroup of patients with maximally suppressed HIV-1 RNA (below 50 copies per milliliter) at the time of randomization to maintenance therapy. CONCLUSIONS: In HIV-1-infected adults not previously treated with antiretroviral drugs whose plasma HIV-1 RNA levels fell below 500 copies per milliliter after three months of induction therapy with zidovudine, lamivudine, and indinavir, two-drug maintenance therapy was less effective in sustaining a reduced viral load than continued three-drug therapy.

Adult↗
PubMed1998

Efficacy and safety of stavudine and didanosine combination therapy in antiretroviral-experienced patients.

OBJECTIVES: To assess the efficacy, tolerance, and safety of combination antiretroviral therapy with didanosine and stavudine in HIV-infected patients with CD4+ cell counts > 100 x 10(6)/l and HIV plasma RNA > 10(4) copies/ml previously treated with other antiretroviral agents for at least 3 months. DESIGN: In this open, multicentre, non-randomized, Phase II pilot study, adult patients were administered didanosine (200 mg twice daily) plus stavudine (40 mg twice daily) for 6 months. Patients for whom the first regimen had led to undetectable HIV RNA levels were offered a second 6-month course of treatment; those who had achieved insufficient immunological and virological gains in the first 6 months were given a new combination. METHODS: Primary evaluation of efficacy was based on viral load measured by branched DNA second-generation testing (lower limit of detection, 500 copies/ml) and CD4+ cell counts; secondary evaluations included AIDS-defining events and clinical side-effects. RESULTS: Sixty-five patients with median prior antiretroviral therapy of 24 months (65 with zidovudine, 29 with zalcitabine) were included in the study. At baseline, median CD4+ cell count was 198 x 10(6)/l and median plasma HIV RNA was 80000 copies/ml (4.9 log10 copies/ml). In this heavily pretreated population, an increase in the mean CD4+ cell count was observed (+70 x 10(6)/l at 24 weeks). In addition, rapid and prolonged antiviral activity was seen, with a mean maximal decrease of 1.1 log10 copies/ml at week 4, a mean decrease of 0.89 log10 copies/ml at week 24, and a plasma RNA viraemia < 500 copies/ml achieved in 14% of patients at week 24. CONCLUSIONS: Combination therapy with stavudine and didanosine is safe and leads to a sustained antiviral effect, even in patients with prolonged prior antiretroviral exposure and low CD4+ cell counts.

Adult↗
PubMed1998

Opportunistic infections occurring during highly active antiretroviral treatment.

OBJECTIVE: To analyse the characteristics of opportunistic infections in patients receiving highly active antiretroviral treatment (HAART). DESIGN AND METHODS: A retrospective study performed in seven hospitals, included all patients starting treatment by ritonavir or indinavir between 26 March and 31 December 1996. Patients were evaluated for the development of AIDS-defining events. Clinical evaluation, plasma HIV-1 RNA quantification, CD4 cell count were recorded at baseline and at the onset of the event. RESULTS: Four hundred and eighty-six patients were included: 44.2% had a CD4 cell count below 50 x 10(6) cells/l. Fifty clinical events were recorded in 46 patients with a mean follow-up of 6.1 months, of which 34 events (68%) were observed during the first 2 months of HAART. Eighteen of these occurred despite a reduction of viral load by at least 1.5 log10) and a 100% increase of the CD4 cell count compared with that at the onset of the event, corresponding to 11 cytomegalovirus infections, five mycobacterial infections, one case of cryptococcosis, and one case of Varicella-Zoster virus-related acute retinal necrosis. Among the 16 events observed after the second month, six occurred despite a marked biological improvement, corresponding to a recurrence in five of six patients who had stopped their maintenance therapy. Events were one cytomegalovirus infection, two mycobacterial infections, one episode of oesophageal candidiasis and one cryptococcal meningitis. CONCLUSION: In patients at high risk of developing an opportunistic infection prior to the institution of a HAART regimen, prophylaxis should not be discontinued during the first 2 months of treatment, and maintenance therapy should be carried on despite a significant increase in the CD4 cell count.

AIDS-Related Opportunistic Infections↗
PubMed1998

[Extrapulmonary tuberculosis in the central western region. Retrospective study of 217 cases (Gericco 1991-1993)].

OBJECTIVES: To analyze the epidemiological, clinical and diagnostic characteristics of extrapulmonary tuberculosis in western France observed from 1991 to 1993 in different patients populations (HIV+ infected patients, immunosuppressed non-HIV infected patients, non-immunosuppressed patients) and according to various localizations (lymph nodes, bone and joints, genital organs, nervous system and meninges, miliary disease). METHODS: This retrospective study included 217 cases of extrapulmonary tuberculosis diagnosed from 1991 to 1993 in western France by GERICCO (Groupe d'Epidémiologie et de Recherche en Infectiologie Clinique du Centre-Ouest). Demographic, clinical, biological, microbiological and radiographic characteristics as well as clinical course on specific therapy were assessed. RESULTS: Extrapulmonary tuberculosis generally occurred most often in immunosuppressed patients but 34% of cases were observed in people without any underlying disease or risk factors. Delay to diagnosis was especially long in the non-immunosuppressed patients (mean = 96 days) but shorter in the HIV-infected patients (mean = 59 days). It was shorter in case of nervous system involvement (mean = 52 days) or military disease (mean = 80 days) than in bone and joints (mean = 120 days) and lymph nodes (mean = 102 days). Microbiologically proven tuberculosis represented only 75% of cases despite numerous investigations. Overall prognosis was good except in nervous system and meninges localizations. Failures were mainly due to death in immunosuppressed patients. CONCLUSION: Extrapulmonary tuberculosis remains frequent even in patients lacking risk factors. In 50% of cases, confirmation of diagnosis takes more than one month. In case of doubt, clinicians should not wait for laboratory results before implementing empirical specific therapy.

AIDS-Related Opportunistic Infections↗
PubMed1998

Stavudine plus didanosine and nevirapine in antiretroviral-naive HIV-infected adults: preliminary safety and efficacy results. VIRGO Study Team.

The objective of this open-label trial is to evaluate the virological and immunological effects of triple therapy with stavudine (40 mg twice daily if > or = 60 kg, 30 mg twice daily if < 60 kg)/didanosine (400 mg once daily if > or = 60 kg, 300 mg once daily if < 60 kg)/nevirapine (200 mg daily from day 1 to 14, then 200 mg twice daily) in 60 antiretroviral-naive HIV-infected adults with CD4 cell counts > or = 200 cells/mm3 and plasma HIV RNA > or = 5000 copies/ml. At present, 59 patients have begun receiving the trial regimen. Characteristics of patients at baseline were as follows: 46 men/13 women, CDC stage A, 75%; mean CD4 cell count, 429 cells/mm3; mean HIV RNA, 4.6 log10 copies/ml). Mean decrease of viral load was -1.9 log10 at week 4 (n = 39), -1.9 log10 at week 16 (n = 20), with HIV RNA below the detectable level (< 500 copies/ml) in 62% of patients at week 4 and 85% at week 16. Mean CD4 cell count increase was +118 cells/mm3 at week 4. Cutaneous intolerance occurred within the first 4 weeks in 11/59 (19%) patients after a mean of 14 days (range, 3-24 days) and led to nevirapine discontinuation in 3/11 patients. Preliminary results of this ongoing trial show that combination therapy with stavudine/didanosine/nevirapine is a convenient (seven pills in two daily intakes) triple-therapy regimen with rapid immunological and antiviral effects. Rash, frequent in the first weeks of therapy, usually can be managed without stopping nevirapine. Long-term suppression of plasma HIV RNA with this combination needs to be confirmed but may support use of nevirapine as a component of first-line anti-HIV therapy along with two nucleosides.

Adult↗
PubMed1998

[Multifocal tuberculosis. Apropos of 49 cases in the midwest region. GERICCO (Group for Epidemiology and Research in Clinical Infections of the Central West of France), 1991-1993].

Diffuse or multifocal tuberculosis (TB) accounts for 9% to 10% of cases of extrapulmonary TB and carries a poor prognosis with a mortality rate of 16% to 25%. Forty-nine cases of multifocal TB defined as involvement of two extrapulmonary sites with or without pulmonary TB were reviewed. Mean patient age (+/- SD) was 50 +/- 18 years. Twenty-three per cent of patients were immigrants. A history of TB and contact with a TB patient were found in 23% and 18% of cases, respectively. Of the 52% of immunocompromised patients, 38% were HIV-positive. The skin tuberculin test was positive in 67% of cases. Mean time from symptom onset to admission was 80 +/- 77 days (median, 58 days). The 49 patients had a total of 128 TB foci. Six patients had positive blood cultures. The tubercle bacillus was recovered from the extrapulmonary sites in 88% of cases. Mean treatment duration was nine months. Recovery from the TB was achieved in 64% of cases. The overall mortality rate was 47%, and 33% of patients died as the direct result of TB. Most deaths occurred in immunocompromised patients. A high index of suspicion for multifocal TB should be maintained in immunocompromised patients, even those who test negative for the HIV.

AIDS-Related Opportunistic Infections↗
PubMed1998

[Unusual lung mycosis: Penicillium++ marneffei infection].

We report an uncommon radiographic finding which led to the diagnosis of Penicillium marneffei pulmonary mycosis in an HIV positive woman. The patient who lived in France had travelled several times to her native country. Thailand, prior to the development of fever, weight loss, skin lesions with a macular aspect around the umbilicus. The chest x-ray demonstrated non-excavated round opacities. Penicillium marneffei was isolated from alveolar lavage fluid and blood samples. This rare fungus is usually found in immunodepressed subjects, especially HIV+ patients (CD4 < 50) should be suspected in subjects who have travelled to endemic zones (Southeast Asia). Penicillium marneffei is considered as a criteria for AIDS. P. marneffei is the only dimorphic member of the Penicillium genus and has a particular affinity for the reticuloendothelial system. Clinical manifestations vary, usually with skin lesions. Mycology diagnosis is usually made on blood samples as well as alveolar lavage or pleural fluids. Antifungals (amphotericin B. itraconazole, ketoconazole) are generally effective but the risk of relapse underlines the importance of secondary prophylaxis in immunodepressed subjects.

Female↗
PubMed1997

[Limitations of the protein profile for diagnostic orientation in initial internal medicine consultation. Prospective study on 76 patients].

Determination of the protein profile of orientation (PPO) is now considered by some authors as a means of improving the diagnosis in internal medicine. The feasibility of systematizing this practice was investigated in 76 outpatients (79 included, three excluded secondarily) seen for pathology of undetermined diagnosis. The 79 patients (mean age: 52 years) underwent the classical biological explorations plus PPO. The physicians were divided into two groups (seniors and assistants). Two complete clinical files were established for each patient, with one difference concerning inflammatory and immunologic data: one file included the minimum number of tests considered necessary by the physician and the other the complete PPO (nine proteins). Each file (with or without PPO) was randomly distributed to one of two physicians in the same group. Each physician filled in a diagnostic evaluation sheet indicating whether there was organic pathology or not, the main diagnosis (inflammatory, neoplastic, infectious or other), the secondary diagnosis and the hypothesis of probability. The relevance of the clinical opinion was analyzed by an internal medicine specialist from outside the department with 40 years of clinical experience. The duration of symptoms before the medical visit was from 3 weeks to 5 years (mean 6 months). A diagnosis of organic pathology was reached for three out of four patients. Sixty-seven patients were seen again after a minimum of 6 months, and nine were lost to follow-up. Diagnostic efficiency was no greater for cases with PPO, which appears to be a biological examination of second intention. We suggest that the term "protein profile of orientation" be replaced by "broad protein profile."

Adult↗
PubMed1997

A prospective study of criteria for the diagnosis of toxoplasmic encephalitis in 186 AIDS patients. The BIOTOXO Study Group.

OBJECTIVE: To define the factors associated with diagnosis of toxoplasmic encephalitis (TE) in AIDS patients; and to establish a rational procedure for the clinician faced with a decision concerning empiric antitoxoplasma therapy. DESIGN: A 15-month prospective multicentre cohort study in France. METHODS: One hundred and eighty-six consecutive HIV-positive inpatients undergoing empiric antitoxoplasma therapy for a first episode of presumed TE were monitored. The clinician's initial estimation of the probability of response to antitoxoplasma therapy was recorded. In addition, a validation committee classified cases as TE or non-TE. RESULTS: Among the 186 patients, the following variables were significantly more frequent in TE (n = 113) than non-TE (n = 73) patients: fever (59% versus 40%). headache (55% versus 33%), seizures (22% versus 11%), suggestive lesions on the brain scan (98% versus 76%), positive Toxoplasma serology (97% versus 71%). Median CD4+ lymphocyte count was significantly higher in TE than in non-TE (27 x 10(6)/l versus 11 x 10(6)/l). The rate of TE in patients on systemic antiprotozoal prophylaxis at entry was 43% as compared with 75% in patients without previous prophylaxis. Pre-therapy estimation of response to empiric therapy was highly correlated with final diagnosis. Multivariate logistic regression analysis showed that the following variables contributed independently to the diagnosis of TE: clinician's estimation of response to treatment at entry > 75%; absence of systemic antiprotozoal prophylaxis; seizures; headache; suggestive lesions on CT or MRI brain scan; and positive Toxoplasma serology. CONCLUSIONS: A linear logistic model is proposed which uses significant variables, which are readily available. This model gives good accuracy to classify suspected cases of TE.

AIDS-Related Opportunistic Infections↗
PubMed1997

Potential efficacy of fumagillin in intestinal microsporidiosis due to Enterocytozoon bieneusi in patients with HIV infection: results of a drug screening study. The French Microsporidiosis Study Group.

OBJECTIVE: Intestinal microsporidiosis due to Enterocytozoon bieneusi is a frequent cause of chronic diarrhoea in patients with HIV infection for which there is no available therapy. This study was designed to search for a drug with activity against this organism. DESIGN: Prospective open-labelled Phase II multicentre study. SETTING: University hospitals. PATIENTS: Sixty HIV-infected men with intestinal E. bieneusi infection. INTERVENTIONS: Ten drug regimens were consecutively tested orally for 3 weeks: albendazole plus metronidazole, sulphadiazine plus pyrimethamine, atovaquone, doxycycline plus nifuroxazide, itraconazole, flubendazole, chloroquine, paromomycin, sparfloxacin and fumagillin. Nine evaluable patients per regimen were required, but each patient could be enrolled up to three times in the study. OUTCOME MEASURE: Efficacy was assessed primarily by the clearance of E. bieneusi from stools and intestinal biopsies. The safety of each regimen was also assessed. RESULTS: Only purified fumagillin was able to clear E. bieneusi from stools as well as intestinal biopsies, whereas all other regimens failed to show antiparasitic efficacy. However, only four patients received fumagillin because of drug-induced thrombocytopenia. The four patients who received fumagillin remained free of E. bieneusi infection after a mean follow-up of 10 months. CONCLUSION: Eradication of E. bieneusi from the intestinal tract of patients with HIV infection and persistent immunosuppression is an achievable goal. Our study allowed the identification of oral fumagillin as a potential treatment for intestinal microsporidiosis due to E. bieneusi.

AIDS-Related Opportunistic Infections↗