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F Raffi

Publications and source records attributed to F Raffi.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1999

Specific anti-toxoplasmic IgG antibody immunoblot profiles in patients with AIDS-associated Toxoplasma encephalitis.

Among 186 suspected cases of Toxoplasma encephalitis (TE) in HIV-infected patients, 113 were classified as TE and 73 as non-TE. Serum Toxoplasma gondii (T.g.) antibodies were detected by ELISA in 97% of TE vs 71% of non-TE cases (p < 0.001). In the 164 patients positive for T. g. antibodies, the IgG 27 and 32 bands were more frequently present in TE than in non-TE (p = 0.003, p = 0.002, respectively). Among patients with positive T.g. serology, multivariate analysis showed that the presence of an IgG 32 (OR 3.1) or IgG 27 band (OR 2.7) on Western blot was highly indicative of TE independently of each other. Positive T.g. serology, but not anti-T.g. IgG antibody titres, was predictive. Thus, the positivity of IgG 27 and 32 bands on Western blot analysis provides useful data for improving the diagnosis of presumptive TE in HIV-infected patients with suspected TE and positive Toxoplasma serology.

AIDS-Related Opportunistic Infections↗
PubMed1999

Highly active antiretroviral treatment initiated early in the course of symptomatic primary HIV-1 infection: results of the ANRS 053 trial.

Highly active antiretroviral treatment (HAART) was given early to 64 patients with symptomatic primary human immunodeficiency virus (HIV)-1 infection. At the time of analysis, patients had been followed up for 9-21 months. No patient had died or developed an AIDS-defining event. Survival analysis showed that by month 21 the proportion of patients with plasma HIV-1 RNA <50 copies/mL was 72% (95% confidence interval, 58%-95%) in intention-to-treat analysis. After 18 months of treatment, 50% of the patients with undetectable plasma HIV-1 RNA also had undetectable HIV-1 RNA in peripheral blood mononuclear cells (PBMC). Only 1 of 3 patients had undetectable HIV-1 RNA in lymphoid tissue, while all patients had quantifiable HIV-1 DNA both in PBMC and lymphoid tissue. The median CD4 lymphocyte increase from baseline was 230 cells/microL. These preliminary results support the use of HAART in patients with primary HIV-1 infection.

Anti-HIV Agents↗
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↗
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↗