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Biomedical subjects

F Suter

Publications and source records attributed to F Suter.

At least 19 recordsLinked to original sources

Scedosporium apiospermum soft-tissue infection: a case report and review of kidney transplant literature.

Scedosporium apiospermum is an environmental mould. Human infections caused by this organism have been observed; however, only a few case reports show its role as a telluric contaminant to kidney recipients. We have reported here a case of a dramatic soft tissue infection by S. apiospermum in a kidney-transplanted man. Surgical drainage together with voriconazole systemic therapy was successful.

Antifungal Agents↗

Resolution of lymphocytic interstitial pneumonia in a human immunodeficiency virus-infected adult following the start of highly active antiretroviral therapy.

A case of human immunodeficiency virus (HIV)-associated lymphocytic interstitial pneumonia is described, in which improvement occurred soon after starting antiviral therapy. A 20-y-old black female with HIV infection (CD4+ count 228 x 10(6) cells and plasma viral load 379,670 copies/ml) showed radiological signs of reticulonodular infiltrates of the lungs and pulmonary functional tests indicative of a severe restrictive syndrome. Bronchoalveolar and blood cultures yielded no organism and transbronchial biopsy disclosed findings consistent with lymphocytic interstitial pneumonia. After 4 weeks on triple HIV combination therapy, she was well and respiratory tests had normalized. Six months later, a computed tomographic scan of the chest showed only residual alterations. Despite a good sirological response to treatment, no significant immune recovery occurred over a 2 y follow-up.

Adult↗

Gabapentin in painful HIV-related neuropathy: a report of 19 patients, preliminary observations.

The objective of this study was to assess the efficacy and safety of Gabapentin as the sole analgesic in patients with HIV-related painful neuropathy. Nineteen patients with HIV-related painful neuropathy were administered Gabapentin. Efficacy was evaluated with two 100-mm Visual Analogue Scales (VAS) (0: no symptom; 100: worst symptom), rating pain and interference of pain with sleep, performed at baseline and monthly intervals. Main Pain VAS score decreased from a baseline of 55.7 +/- 19.1 mm to a final 14.7 +/- 18.6 mm (ANOVA P = 0.0001) and mean Sleep Interference VAS score decreased from a baseline of 60.4 +/- 31.9 mm to a final 15.5 +/- 27.7 mm (ANOVA P = 0.0001). Gabapentin provided significant pain relief in our patients with HIV-associated painful sensory neuropathy.

Acetates↗

Guidelines of tuberculosis preventive therapy for HIV-infected persons: a prospective, multicentre study. GISTA (Gruppo Italiano di Studio Tubercolosi e AIDS).

The aim of this study was to assess the degree of implementation of national guidelines for isoniazid preventive therapy (IPT) among human immunodeficiency virus (HIV)-infected individuals and factors affecting the impact of the programme. Twenty-eight infectious disease hospital units in Italy participated in this observational, multicentre, prospective cohort study. A number of HIV-infected subjects, (n=1,705) seen for the first time as outpatients, were included in this analysis. Of the subjects considered, 1,215 out of the 1,705 completed purified protein derivative (PPD) screening. Variables independently associated with offering and completion of PPD screening included having acquired immune deficiency syndrome (AIDS), higher educational levels and currently receiving therapy. Overall, 103 subjects were identified as candidates for IPT. Of these subjects, five had tuberculosis and 15 had contraindications to IPT. Forty subjects agreed to start IPT, and 29 completed a full-course regimen. The incidence of tuberculosis among IPT candidates who either did not begin or discontinued IPT was 6.1 per 100 person-yrs, while no cases of tuberculosis were observed in subjects completing IPT. Several factors may limit the implementation of an isoniazid preventive therapy programme for human immunodeficiency virus-infected persons. Physicians fail to offer purified protein derivative screening to patients with high degrees of immunodeficiency, and those with a more intense workload seem to pay less attention to this test. The high number of contraindications among patients and their low level of acceptance further affects the impact of isoniazid preventive therapy.

AIDS-Related Opportunistic Infections↗

Severe lactic acidosis and thiamine administration in an HIV-infected patient on HAART.

Severe lactic acidosis has been increasingly reported as a potentially fatal complication of HIV treatment. We report on an asymptomatic HIV-infected woman treated with stavudine, lamivudine and indinavir for one year. She was hospitalized because of progressive dispnoea, oedema, cyanosis and severe lactic acidosis. Arterial blood pH was 6.98, bicarbonate 4.4 mmol/l (normal value 22-26), blood lactate: 29.7 mmol/l (normal value <2.2). Hepatic function was normal. She had an impressively rapid response (within a few hours) to empirical treatment with thiamine (100 mg i.v.). No evidence of sepsis or malabsorption were identified and vitamin B1 level was not tested before thiamine infusion. Three months later she was re-started successfully on nelfinavir plus nevirapine. The rapid response to thiamine infusion deserves a careful attention and such an approach should be considered in similar cases as a support treatment of this potentially life-threatening complication of HIV therapy.

Acidosis, Lactic↗

Long-term clinical benefit after highly active antiretroviral therapy in advanced HIV-1 infection, even in patients without immune reconstitution.

Our objective was to assess, in the clinical setting, the predictors of immune reconstitution (IR) and its relation with long-term clinical benefit, in HIV patients with advanced disease after highly active antiretroviral therapy (HAART) through an observational study. A retrospective cohort study in a clinical setting of 383 consecutive adult patients with advanced HIV infection (CD4+ cells <200/mm(3) at baseline), starting their first protease inhibitor (PI)-containing regimen was observed. Immune reconstitution was defined as CD4 count >200 cells/mm(3) and an increase > or =100 cells from baseline, anytime since starting HAART. Clinical benefit was defined as decreased mortality and reduction in AIDS-defining events, AIDS-related complex (ARC) events, major infections and hospitalization (days spent in hospital). During a mean follow-up of 808 days, 261 patients (68.1%) achieved IR. About 50% of these patients reached this result within one year after starting HAART. In multivariate analysis, predictors of immune recovery were sex (female) and baseline CD4 count higher than 50 cells/mm(3). The group of patients with IR had greater clinical benefit with lower mortality, fewer AIDS-defining events, shorter lengths of stay in hospital, fewer ARC events and fewer major infections during all the follow-up (P < 0.0001, tests for trends). However, although they did less remarkably than the first group of patients, even those patients who did not achieve IR experienced a significant decrease in the incidence of all the above events, as compared with the first and sometimes the second trimester after starting their HIV therapy. About 70% of HIV patients with advanced disease achieved IR after starting HAART. Such a benefit is a time-dependent effect and may even take more than 2 years to occur. Predictors of IR were sex (female) and higher baseline CD4 count (>50 cells/mm(3)). The patients who achieved immune recovery performed clinically better than patients who did not. Also the patients who failed to gain such a strong immunological recovery experienced a long-term clinical benefit. This suggests that PI-containing regimens, in advanced HIV disease, may produce a significant clinical benefit, at least temporary, even for patients who do not achieve a substantial immune response.

AIDS-Related Complex↗

Virological and immunological responses to a once-a-day antiretroviral regimen with didanosine, lamivudine and efavirenz.

Current antiretroviral drugs cannot eradicate HIV infections, and persons living with HIV are often faced with very demanding daily therapeutic schedules that can induce poor adherence. More conveniently dosed and patient-friendly regimens are needed. We investigated, in this 48-week pilot study, a once-a-day highly active antiretroviral therapy regimen of didanosine, lamivudine and efavirenz. Seventy-five consecutive antiretroviral-naive subjects were enrolled. Over the 48-week period, plasma HIV-RNA levels declined sharply, with a median decrease at the end of the observation time >3.4 log copies/ml. The proportion of patients achieving a plasma HIV-RNA level below the limit of detection (50 copies/ml) was 77% (intention to treat analysis) at the end of the study period. The mean CD4 cell count increased steadily over time from 251 to 459 cells/microl. Antiviral efficacy was similar in patients with a baseline HIV-RNA level above or below 100,000 copies/ml. However, patients with a baseline CD4 cell count <200 cells/microl showed a significantly worse virological response than that observed in patients with higher baseline CD4 counts. Overall 15 patients interrupted therapy. In four cases treatment interruption was due to lack of treatment response; three additional patients were lost to follow-up or withdrew informed consent. Eight patients stopped therapy because of adverse events. The once-daily combination of didanosine, lamivudine and efavirenz resulted in sustained viral suppression and was well-accepted by patients. This regimen may offer advantages in selected difficult-to-treat populations, allows directly observed therapy and can be a safe and effective alternative in antiretroviral-naive patients. These encouraging pilot results need to be confirmed in a comparative clinical trial.

Adult↗

A randomized trial comparing the introduction of ritonavir or indinavir in 1251 nucleoside-experienced patients with advanced HIV infection.

ISS-IP1, a multicenter, randomized, 48-week open trial, was designed to compare the introduction of ritonavir or indinavir in patients with previous nucleoside experience and CD4+ cell counts below 50/mm3. Concomitant antiretroviral treatment with nucleoside analogs was allowed. Primary efficacy measures were survival and time to a new AIDS-defining event or death, analyzed through the whole period of observation by the intention-to-treat approach. Primary toxicity measures were time to treatment discontinuation and adverse events, grade at least 3/serious, analyzed by an on-treatment approach. Evaluation-of efficacy also included CD4+ cell and RNA response. The trial enrolled 1251 patients in 5 months. At baseline, mean CD4+ cell count was about 20 cells/mm3 and mean HIV RNA copy number was 4.9 log10/ml in both groups. Overall, 402 patients in the ritonavir group and 250 patients in the indinavir group permanently discontinued the assigned treatment (relative risk, 1.96; 95% CI, 1.68-2.30; p = 0.0001), with most of this difference dependent on a higher number of discontinuation for adverse events in the ritonavir group. After a mean follow-up of 307 days (ritonavir, 304; indinavir, 309), 124 deaths (ritonavir, 61; indinavir, 63; relative risk, 0.96; 95% CI, 0.67-1.36; p = 0.80) and 330 new AIDS-defining events (ritonavir, 170; indinavir, 160; relative risk, 1.05; 95% CI, 0.85-1.31; p = 0.60) were observed. CD4+ cell counts increased in both groups in patients still receiving treatment, with about 100 cells gained by week 24 and 150 cells gained by week 48. Body weight also increased over time in both groups. Analysis of RNA response showed a decrease of 1.5 log10 or higher in both treatment groups. Overall, 400 patients in the ritonavir group and 338 patients in the indinavir group developed at least one grade 3/serious new adverse event during follow-up (relative risk, 1.48; 95% CI, 1.28-1.72; p = 0.0001). Favorable CD4+ cell and RNA responses at 24 and 48 weeks were observed in both groups of patients remaining on treatment. Indinavir showed slightly better effects in sustaining RNA, CD4+ cell, and body weight responses. Ritonavir and indinavir results were comparable in terms of clinical outcome (survival and AIDS-defining events).

Adult↗

Duration of viral suppression in patients on stable therapy for HIV-1 infection is predicted by plasma HIV RNA level after 1 month of treatment.

UNLABELLED: The aim of this study was to assess the predictive value of HIV RNA levels after 1 month of therapy on the long-term virologic outcome in an unselected general population of HIV-infected patients. DESIGN: Analysis was conducted retrospectively on an ongoing clinical cohort of HIV-positive patients who were receiving antiretroviral treatment. Data on 575 patients were analyzed. RESULTS: The HIV RNA value at 1 month was significantly correlated with the virologic outcome after 12 and 24 months of therapy (R = 0.258 and R = 0.44, respectively). The predictive value of the 1-month viral load was also statistically significant after stratification for baseline CD4 T-cell counts. Prediction was similar in highly compromised patients (CD4 < or = 100 cells/microl; R = 0.426; p = .001) or in patients with a better immunologic status (R = 0.419; p < .0001). It retained validity in patients who were naive or experienced for antiretroviral therapy. CONCLUSION: HIV RNA level after 1 month of therapy is a useful prognostic marker in HIV-infected patients. It predicts long-term virologic and immunologic outcome. A cutoff level of 5000 copies/ml identifies patients most likely to fail current therapy. In these patients, a more aggressive strategy or specific diagnostic interventions to clarify the relative influence of viral resistance and/or subtherapeutic regimens is advised.

Anti-HIV Agents↗

Different immunologic profiles characterize HIV infection in highly active antiretroviral therapy-treated and antiretroviral-naïve patients with undetectable viraemia. The Master Group.

BACKGROUND: Suppression of human immunodeficiency virus (HIV) replication can be obtained in chronically infected individuals by highly active antiretroviral therapy (HAART) and can also be observed in antiretroviral-naïve patients. The immunological correlates of these two situations were examined. DESIGN AND METHODS: Cross-sectional study involving 32 HIV-infected patients with undetectable HIV plasma viraemia (< 500 copies/ml) and either antiretroviral-naive (n = 14) or undergoing HAART therapy with two nucleoside reverse transcriptase inhibitors (NRTI) plus one (n = 13) or two (n = 5) protease inhibitors (PI). CD4 counts, disease duration, and CDC clinical stage were comparable between the two groups of individuals. Immune parameters (antigen- and mitogen-stimulated proliferation and cytokine production; cytokine mRNA; beta chemokine production; HIV coreceptors mRNA) were analysed in all patients. RESULTS: Results showed immune profiles to be profoundly different in antiretroviral-naive in comparison with HAART-treated patients. Thus: (1) T-cell proliferation to HIV-specific and HIV-unrelated antigens is potent in antiretroviral-naive but suppressed in HAART-treated individuals; (2) interleukin-(IL)2, IL-12 and interferon gamma (IFNgamma) production is robust in naive patients; and (3) a high CCR5/low CXCR4 pattern of HIV coreceptors-specific mRNA is observed in naive but not in HAART-treated patients. In contrast with these observations, no clear differences were detected when beta chemokine production by either peripheral blood mononuclear cells or purified CD8+ T-cells was analysed. Results from HAART-treated patients undergoing therapy with one PI and two NRTI or two PI and two NRTI were in very close agreement. CONCLUSIONS: These data suggest that control over HIV replication can be independently achieved by pharmacological or immunologic means. HAART is associated with weaker HIV-specific and -non-specific immune responses.

CD8-Positive T-Lymphocytes↗

Quantification of the impact of HIV-1 reverse transcriptase and protease mutations on the efficacy of rescue HAART.

The reduction in the efficacy of rescue treatment (administered on a clinical basis) due to drug resistance was retrospectively quantified in 55 human immunodeficiency virus type 1 (HIV-1)-infected patients failing highly active antiretroviral therapy (HAART) by using a novel score calculation system based upon HIV-1 reverse transcriptase (RT) and protease (PR) mutations. Patients were all naive for nelfinavir (NFV) and efavirenz (EFV) and were assigned to one of the following rescue therapy schedules: (i) 17 patients received NFV + EFV + stavudine (d4T) (group A); (ii) 14 patients received NFV + saquinavir (SQV) + lamivudine (3TC) + d4T/zidovudine (AZT) (group B); (iii) 19 patients received NFV + d4T + didanosine (ddI)/3TC/zalcitabine (ddC) (group C); (iv) five patients received miscellaneous treatments including NFV (group D). Responders were considered patients showing a drop in HIV-1 RNA level > 0.5 log10 after 3 months of therapy. Forty-eight (28 responders and 20 non-responders) out of 55 patients completed the first 3 months of rescue therapy and reduction in HIV-1 viral load was found to be significantly higher in group A compared to groups B and C (81.2% responders vs. 38.5 and 40.0%, respectively). At baseline, no patient carried EFV- or d4T-resistant HIV-1 strains, despite prolonged administration of d4T, while 41/48 (87.2%) patients had mutations conferring resistance to NFV in the absence of previous treatment with this drug. A significant inverse correlation between reduction in viral load and reduction in therapy efficacy due to drug resistance, as determined by the score calculation system, was found (r = 0.62). A cut-off value of 36% reduction in therapy efficacy showed a positive predictive value (capacity to detect failure of rescue treatment) of 81.2% and a negative predictive value (ability to detect successful treatment) of 75.8%. In addition, 45 out of 48 patients completed also the 9-12 month period of rescue therapy and 10/28 responders had a rebound in HIV-1 viral load level detected after the first 3 months of rescue therapy. Of these, 5/7 (71.4%) showed a further reduction in rescue therapy efficacy due to the emergence of new mutations.

Anti-HIV Agents↗

Sexual behaviour of women living with HIV/AIDS naïve for antiretroviral therapy: the ICONA-BEHEPI Study.

This study describes the sexual behaviours of women living with HIV, and assesses differences by history of drug use. Its general aim is to contribute in the design of programmes to help people with HIV/AIDS (PWH/A) adopt and maintain safe sexual behaviours. A self-administered questionnaire on sexual and drug use behaviours was distributed to study participants. Between 1997 and 1999, 573 women with HIV infection naive to antiretroviral therapies completed the questionnaire (of whom 234 reported a history of injection drug use (IDU) and were enrolled in the study. Non-IDU women reported fewer sexual partners, both in their lifetime and in the preceding month, than IDU women: 19% of IDU and 4% of non-IDU women reported more than 25 lifetime sexual partners (p < 0.001). Interestingly, 83% of non-IDU women were infected by their regular partners: these women reported the lowest number of sexual partners. No difference emerged between IDU and non-IDU women in terms of number of sexual intercourse in the two weeks preceding the interview or in terms of condom use in the last intercourse (reported, overall, by 54% of these 573 women). Among women who had sex partners at the time of interview, more non-IDU (65%) than IDU (43%) women reported HIV-positive partners (p < 0.001). Overall, these findings stress a marked heterogeneity in the levels of past and recent sexual promiscuity according to history of drug use. It suggests the need to differentiate and individualize messages about self-protection and behaviours that may prevent further spread of HIV infection.

Adult↗

Effects of subinhibitory concentrations of moxifloxacin in an in-vitro dynamic model.

The postantibiotic effect (PAE), sub-MIC effect (SME) and postantibiotic sub-MIC effect (PASME) of moxifloxacin were investigated in an in-vitro dynamic model reproducing in-vivo elimination kinetics of the antibiotic. The PAE was induced by exposing strains of Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli and Klebsiella pneumoniae to 5 x MIC of the antibiotic for 1.5 hours. After induction, cultures were washed to eliminate the antibiotic and resuspended into the dynamic model either in the presence or absence of a subinhibitory concentration of the antibacterial agent of 0.5 x MIC. Unexposed controls were treated similarly. PASMEs were constantly longer than corresponding SMEs, but differences between them were not statistically significant. Both PASMEs (mean 11:17 hours, range from 8:17 to 14:57) and SMEs (mean 9:23 hours, range from 6:03 to 12:34) had an initial bactericidal effect and were significantly longer than PAEs (mean 1:31 hours, range from 0:21 to 2:14). The primary effect of moxifloxacin sub-MICs appears to be prevalent in PAE. The possibility of once-daily dosing of the drug is strengthened.

Anti-Infective Agents↗

In-vitro activity of moxifloxacin combined with other antibacterials against methicillin-resistant Staphylococcus aureus.

Killing kinetic experiments were performed with moxifloxacin, a novel fluoroquinolone, vancomycin, clarithromycin, cotrimoxazole, gentamicin, rifampicin and with moxifloxacin in combination with each of the above drugs against six methicillin-resistant Staphylococcus aureus clinical isolates. Half of the strains were ciprofloxacin-resistant. The early bactericidal effect of moxifloxacin alone was substantially greater than that of the other tested drugs. No antagonism was observed between moxifloxacin and each of the other drugs. For each combination the mean decrease in the number of organisms (after 6 hours) was comparable to that achieved with moxifloxacin alone, however, when moxifloxacin was tested with gentamicin, a slight increase in the bactericidal effect was observed.

Anti-Infective Agents↗

Efavirenz, nelfinavir, and stavudine rescue combination therapy in HIV-1-positive patients heavily pretreated with nucleoside analogues and protease inhibitors.

Tolerability, activity, and pharmacokinetic parameters of a combination therapy with efavirenz (EFV), nelfinavir (NFV), and stavudine (d4T) were evaluated in this study. Forty-seven HIV-1-infected study subjects, naive to NFV and nonnucleoside reverse transcriptase inhibitors (NNRTIs), who had experienced virologic failure while being treated with combination antiretroviral therapies including protease inhibitors (PIs), were enrolled. At baseline, HIV-1 viral load in plasma was 4.8 log10, CD4+ count was 204 cells/microl (both mean values); patients had received a mean of 3.1 different treatments (range, 2-5 treatments). Study medications were generally well tolerated; 7 of 47 patients (14.8%) were dropped from the study because of related drug toxicity. At week 24, mean plasma viral load (pVL) was reduced by 1.9 log10, with mean CD4+ count increased to 324 cells/microl (+/-59% from baseline); pVL was below the limit of detection (500 copies/ml) in 46.1% of patients. An extended follow-up study was performed at 12 months. Results showed a reduction of 1.7 log10 in pVL from basal values that was consistent with values observed at months 3 and 6. A history of previous use of PIs represented a negative prognostic marker. Sequencing analysis, performed in a subset of patients, showed the presence of multiple point mutations associated with PI resistance. Pharmacokinetic analysis demonstrated a marked interindividual variability in NFV plasma concentrations, producing in 4 of 18 patients (22%) trough concentrations lower than minimum effective concentration. In pretreated patients, further studies are needed to characterize the pharmacokinetic factors that affect response to therapy and the association of these results with the 95% inhibitory concentration (IC95) determined by phenotyping.

Adult↗

Intravenous drug use, relationship with providers, and stage of HIV disease influence the prescription rates of protease inhibitors.

OBJECTIVE: To assess rates of prescriptions of protease inhibitors (PI) and determinants of not being prescribed PIs in a cohort of HIV-infected people eligible (according to published guidelines) for highly active antiretroviral therapy (HAART). DESIGN: Cross-sectional survey. METHODS: A total of 684 patients with CD4+ counts <500 cells/microl were enrolled from seven Italian HIV treatment centers from October 1997 to April 1998. A questionnaire on health-related quality of life (MOS-HIV) and patient ratings of the quality of care was administered. Sociodemographic variables, HIV disease-related factors, and prescribed antiretroviral therapy were also recorded. RESULTS: 61% of those enrolled were prescribed PI (median, 7.5 months). In addition, 75% of patients had previously received antiretroviral therapy. Fewer than 1% were prescribed nonnucleoside reverse transcriptase inhibitors (NNRTIs). Using multivariable logistic regression considering those with CD4+ counts <500 cells/microl, patients reporting the least information received (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.23-2.58), injecting drug users (IDUs; OR, 1.73; 95% CI, 1.18-2.54), people with CD4+ counts >200 cells/microl (OR, 1.76; 95% CI, 1.19-2.61), and patients with early stage disease (OR, 2.24; 95% CI, 1.73-2.90) were less likely to have be prescribed PIs. CONCLUSIONS: Of patients eligible for HAART, only 61% were prescribed PIs. People who wanted more information, IDUs, and patients in earlier disease stages are significantly less likely to be prescribed PIs. Access to HAART remains a critical issue in the management of HIV disease.

Adult↗