The Trivacan study.
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Antiretroviral Therapy, Highly Active↗
Biomedical subjects
Fredy Suter
Publications and source records attributed to Fredy Suter.
[Cardiovascular medicine unit: preliminary results of an in-hospital multidisciplinary intervention in heart failure].
BACKGROUND: In Italy the majority of patients with heart failure are admitted to Internal Medicine Divisions, where diagnostic and therapeutic procedures, suggested by guidelines, are less utilized than in Cardiology Divisions. In order to provide a better assistance to patients with heart failure, a Cardiovascular Medicine Unit was founded with interdepartmental valence (Cardiovascular and Internal Medicine) in the "Ospedali Riuniti" Hospital of Bergamo. The purpose of this study was to evaluate the preliminary results, concerning management of heart failure, in the first 6 months of activities carried out at the Cardiovascular Medicine Unit and to compare them with those of other structures that usually manage this disease. METHODS: Analysis of data concerning 150 admissions to the Cardiovascular Medicine Unit for heart failure in 147 patients during the first 6 months of 2003. Comparisons of admittance data for heart failure in the first semester 2001 deriving from the Internal Medicine Division of the "Ospedali Riuniti" Hospital of Bergamo, the TEMISTOCLE study and the Niguarda Ca' Granda Hospital of Milan. RESULTS: A higher prescription of beta-blockers and spironolactone was observed in the Cardiovascular Medicine Unit than in other structures (p < 0.001). Echocardiography and coronary angiography were performed more frequently (p < 0.001) and the number of rehospitalizations was lower for all cases (p < 0.05) as well as for heart failure (p < 0.001). The extensive use of diagnostic procedures and multidisciplinary evaluation of co-morbidities allowed to identify patients who could be managed successfully with surgical therapy; preliminary data suggest a net benefit in terms of NYHA functional class and reduction in rehospitalization in this subgroup of patients. CONCLUSIONS: These data demonstrate that the Cardiovascular Medicine model, based on integration of knowledge between cardiologists and internists, is effective with respect to organization and assistance and allows to optimize heart failure patient management.
Adrenergic beta-Antagonists↗
Exploratory analysis for the evaluation of lopinavir/ritonavir-versus efavirenz-based HAART regimens in antiretroviral-naive HIV-positive patients: results from the Italian MASTER Cohort.
OBJECTIVE: This retrospective longitudinal cohort study compared the virological and immunological responses to highly active antiretroviral therapy containing either efavirenz or lopinavir/ritonavir in previously antiretroviral-naive HIV-infected patients. PATIENTS AND METHODS: A total of 472 patients were selected (348 efavirenz and 124 lopinavir/ritonavir). The primary endpoint of this study was virological success (HIV RNA <50 copies/mL). The immunological response was assessed on the basis of either CD4+ T cell count variations (absolute and percentage) with respect to baseline values or categorical endpoints (defined as either a CD4+ T cell increase of > or =1;50 cells/mm(3) at week 24 or of > or =1;75 cells/mm(3) at week 48). RESULTS: At intention-to-treat (ITT) analysis, the adjusted odds ratio of virological success for patients who started lopinavir/ritonavir, compared with those who started efavirenz, was 0.54 (95% CI: 0.33-0.89, P = 0.016) at week 24 and 0.40 (95% CI: 0.33-0.89, P = 0.002) at week 48. However, patients receiving lopinavir/ritonavir had a more pronounced CD4+ T cell recovery, demonstrating both a mean absolute and percentage increase up to week 48 (MANOVA P < 0.0001). CONCLUSIONS: Although comparisons of drug efficacy in non-randomized studies should be viewed with caution, from a virological point of view efavirenz-containing regimens performed as well (on-treatment analysis) or better (ITT analysis) than those containing lopinavir/ritonavir. In contrast, immunological outcome appeared to favour lopinavir/ritonavir.
Adult↗
Switch strategies in patients on effective HAART.
To provide the best possible long-term outcomes for patients, a number of strategies have been proposed based on the possibility to switch from a successful protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) to another antiretroviral regimen. The available evidence from clinical trials in virologically controlled patients demonstrates that switching the PI-based HAART to a simplified regimen is safe. However, abacavir-based simplified therapies should be limited to patients with a known drug history who have not undergone prior mono or dual nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) therapy. Triple NRTI regimens that do not include a thymidine analogue have not been adequately tested so far and are not recommended. The switch strategy may enhance long-term adherence and induce a moderate reduction in cholesterol or amelioration of the total/high-density lipoprotein (HDL) cholesterol ratio that might be particularly relevant for patients presenting other risks for coronary heart disease. Simplified regimens are not associated with a clinically relevant improvement in the redistribution of body fat. Thus, if such a therapeutic strategy is considered, it should be preferably implemented to prevent or delay lipodystrophy. As the therapeutic scenario is significantly changing, in the future, convenience and metabolic alterations will be less of an issue in the decision to use a PI-switch strategy. Future switch strategies may involve NRTIs. Among NRTIs, thymidine analogues and particularly stavudine appear to be most associated with lipoatrophy. NRTI switches may also be beneficial in reducing the risk of lactate level elevation, mitochondrial toxicity, insufficient immunological response to HAART and of selecting class-inducing resistance mutations.
Antiretroviral Therapy, Highly Active↗
Clinical and laboratory features of acute rheumatic fever: a 18-year experience.
We present the retrospective analysis of clinical manifestations and laboratory findings observed in 30 patients (M/F 13/17; age range 9-66 yrs) affected by acute rheumatic fever observed within the Infectious Disease Department along a period of 18 years (1986-2004). Diagnosis of carditis was stated on clinical and echocardiographical bases and occurred in 50% of patients. Such patients presented mild to moderate heart disease (30%) and severe carditis (20%). Therefore, our data stand to confirm that rheumatic cardiac disease could determine permanent and/or severe heart damage. All patients were observed during a 48-month period of follow-up without exitus.
Acute Disease↗
Similar adherence rates favor different virologic outcomes for patients treated with nonnucleoside analogues or protease inhibitors.
BACKGROUND: This prospective study verified the effect of adherence on the risk of virologic failure. METHODS: At enrollment in the study, a total of 543 patients who were following a steady (duration, >or=6 months) and effective (viral load, <50 human immunodeficiency virus [HIV] RNA copies/mL) regimen of highly active antiretroviral therapy (HAART) completed a self-reported questionnaire derived from the Adult AIDS Clinical Trials Group Adherence Follow-up Questionnaire. Patients were followed up for the subsequent 6 months to document virologic failure, which was defined as 2 consecutive viral load measurements of >500 HIV RNA copies/mL. RESULTS: Only the type of treatment and the adherence rate at baseline were significantly associated with the virologic end point. Among patients who reported an adherence rate of 95%. When analysis was adjusted according to the type of regimen received, patients who were receiving protease inhibitor (PI)-based HAART and who had an adherence rate of up to 85% had a virologic failure rate of >20%, whereas, only for patients who were receiving nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based HAART and who had an adherence rate of 10%. For the comparison of NNRTI-treated patients and PI-treated patients with an adherence rate of 75%-95%, the odds ratio was 0.157 (95% confidence interval, 0.029-0.852). The number of pills and daily doses received correlated with the reported adherence rate. CONCLUSIONS: Patients receiving NNRTIs report a higher rate of adherence than do patients receiving PIs. Adherence is significantly influenced by the number of pills and daily doses received. Low adherence is a major determinant of virologic failure; however, different therapies have different cutoff values for adherence that determine a significant increment of risk.
Adult↗
New times for an old disease: intracranial mass lesions caused by Mycobacterium tuberculosis in 5 HIV-negative African immigrants.
BACKGROUND: The tuberculosis epidemic is still a global emergency, and its spread in the past 20 years has been fueled by the acquired immune deficiency syndrome pandemic and increasing drug resistance. International travel and migration may increase the incidence of tuberculosis in industrialized countries. METHODS: We reviewed the clinical charts of patients admitted to the infectious diseases unit of Ospedali Riuniti (Bergamo, Italy) to identify patients with intracranial mass lesions caused by Mycobacterium tuberculosis. RESULTS: During the past 6.5 years, 5 of 30 patients with a mass of infectious origin in the brain had tuberculous brain lesions diagnosed. All 5 were human immunodeficiency virus (HIV)-negative adults and African immigrants. No patient had concomitant meningitis, 1 had a concomitant pulmonary disease, and 3 subjects reported a past history of tuberculosis. At presentation, no patient had fever and 3 had seizures. Examination of cerebrospinal fluid revealed normal findings for 4 of 4 subjects, and neuroimaging showed multiple intracranial mass lesions in 4 of 5 patients. The diagnosis was definite for 2 subjects (based on analysis of brain specimens) and presumptive for 3 subjects (1 had concomitant pulmonary tuberculosis, and 2 had clinical response to therapy). Results of susceptibility tests for M. tuberculosis were available for 2 patients: both isolates were resistant to isoniazid, and 1 was also resistant to streptomycin. Duration of medical treatment ranged from 11 to 23 months, and 2 subjects underwent surgical procedures at the time of diagnosis. All 5 patients recovered. CONCLUSIONS: Clinicians in western countries should consider the possible role of tuberculosis in causing mass lesions in the brain, particularly in immigrants from regions where tuberculosis is endemic.
Adult↗
HIV-1 and hepatitis B virus: time for a re-think?
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Acute Disease↗
Effect of prolonged discontinuation of successful antiretroviral therapy on CD4 T cells: a controlled, prospective trial.
OBJECTIVE: To compare continuous highly active antiretroviral therapy with a CD4 cell count-driven structured treatment interruption (STI) strategy. The primary end-point was the proportion of subjects maintaining CD4 cell count > 400 x 10 cells/l. Secondary end-points were to identify the dynamic and predictive variables of CD4 cell loss. METHODS: The BASTA study is a randomized, controlled, prospective trial. Patients with CD4 cell counts > 800 x 10 cells/l were enrolled and the immunological threshold to resume therapy was set to the lower normal limit of CD4 cells for HIV-uninfected adults. RESULTS: Sixty-nine patients were randomized and followed for 64 weeks. At baseline, all had undetectable plasma HIV RNA and their mean CD4 cell count was 1077 x 10 cells/l. None of the patients showed a disease progression or any AIDS-defining event. At each time point, the proportion of subjects in the STI group that had a CD4 cell count < 400 x 10 cells/l was not statistically different from the control group. In all cases, the 95% confidence interval for this difference was smaller than +/-10%. However, 57% of patients with nadir CD4 cell count 200-350 x 10 cells/l reached a CD4 cell count < 400 x 10 cells/l. This was statistically different (P = 0.02) from the nearly 90% of patients with a nadir CD4 cell count 350-500 x 10 cells/l who maintained a CD4 cell count of > 400 x 10 cells/l. CONCLUSIONS: Prolonged STI in patients with fully suppressed virus and marked immune reconstitution is generally safe. The main predictor of CD4 cell decline is the nadir CD4 cell count. Pulse therapy warrants further careful prospective evaluation to investigate virological and clinical outcomes over a very long period.
Adult↗
Hepatitis C infection increases the risk of the modification of first highly active antiretroviral therapy in HIV-infected patients.
We assessed predictors of discontinuation or change of the first regimen of highly active antiretroviral therapy in 465 HIV-infected adults, in the first year. A total of 187 patients modified their regimen: 45 discontinuing and 142 changing because of clinical/virological failure, intolerance/toxicity or non-adherence. Predictors of modification of the regimen were hepatitis C seropositivity, liver cirrhosis, higher baseline viral load, sex (women had a lower risk) and calendar year (lower risk staring in 2000).
AIDS-Related Opportunistic Infections↗
A randomized, controlled trial of triple antiviral therapy as initial treatment of chronic hepatitis C in HIV-infected patients.
BACKGROUND/AIMS: Interferon and ribavirin combination therapy for chronic hepatitis C induces a low response rate in human immunodeficiency virus (HIV) infected patients. To assess the impact of intensification of interferon administration and of the addition of amantadine on the efficacy and safety of standard anti-hepatitis C virus (HCV) treatment in HIV-infected patients. METHODS: Multicentre, prospective, open-label, randomized, phase III clinical trial. Eighty co-infected patients were randomized to receive ribavirin 800-1,000 mg/day in combination with, group A: interferon alpha 2a 3MIU thrice weekly; group B: IFN alpha 2a 3MIU daily, plus amantadine 200 mg/day; treatment duration was 24-48 weeks according to HCV genotype. RESULTS: Forty-one patients were randomized in group A and 39 in group B. Intention-to-treat analysis showed a sustained virological response, defined as HCV-RNA negativization, 6 months after stopping treatment in 22% of patients from group A and 13% from group B (P>0.05). The lack of a 2-log drop in HCV-RNA levels after 12 weeks of treatment showed a 100% predictive value of lack of sustained response. CONCLUSIONS: Amantadine addition and interferon intensification do not improve the low efficacy of combination of interferon alfa plus ribavirin in HIV/HCV co-infected patients. Patients with no early virologic response did not have any probability of sustained response.
Adult↗
Outcome of 2 simplification strategies for the treatment of human immunodeficiency virus type 1 infection.
In a prospective, open-label, 104-week study, patients who were infected with human immunodeficiency virus type 1 (virus load, <50 copies/mL) and who were receiving protease inhibitor-based therapy were randomly assigned to continue treatment with a protease inhibitor or to replace it with abacavir or efavirenz. Treatment failure, defined as virological failure (virus load, >500 copies/microL) or any clinical or biochemical adverse event with a grade of >or=3 (on the basis of the World Health Organization [WHO] or American Heart Association [AHA] scales), was the primary outcome measurement. Failure rates were more frequent in the group treated with protease inhibitors (P<.01), and there were no significant differences in the rate of treatment failure between the group treated with efavirenz and the group treated with abacavir. Tolerability was better in the groups treated with abacavir or with efavirenz versus those treated with protease inhibitors. Fewer patients who received efavirenz experienced viral rebound. Among all groups, the mean increase in the CD4 cell count was 131 cells/microL (P<.001), with no significant difference between groups. This switching strategy maintains optimal levels of virological suppression and may improve lipid profiles in most patients.
Adult↗
Salvage therapy with abacavir in HIV-1-infected patients with previously documented M184V mutation: a possibility of NRTI recycling.
We evaluated in an open-label, randomized, controlled, pilot trial if the re-emergence of previously selected resistant strains, harbouring M184V mutation, could be modulated by the use of different drug associations as components of the new antiretroviral regimens. In addition, we assessed the clinical relevance of this mutation on the management of heavily pretreated HIV-infected patients. The primary end-point of the study was the reselection of M184V mutation. Secondary end-points were the variation over time of HIV RNA plasma levels and CD4 cell counts and the progression of HIV disease. The primary population for efficacy analysis was the intention-to-treat exposed population. After a run-in phase consisting in a new treatment regimen excluding either lamivudine (3TC) or abacavir (ABC) so as to clear the previously documented M184V mutation, 18 patients with an HIV RNA plasma level greater than 10000 copies/ml were randomized to receive an antiretroviral drug regimen (at least three drugs) including either ABC or the association of ABC+3TC. All patients were naive to ABC. The M184V mutation reappeared in 1/9 patients in the ABC group and in 8/9 patients in the ABC+3TC group (P<0.003, 95% CI: 0.5-1). In the ABC group we observed a rapid decrement of viral load that was maintained throughout all the study period (P<0.05). On the contrary, in the ABC+3TC group, after a transient decrement at 2 months, a progressive increment towards baseline values was observed. The proportion of patients with a viral load reduction of at least 0.5 logs at 12 months was significantly higher in the ABC group: 8/9 patients vs 3/9 (P=0.05, 95% CI: 0.2-0.92). Similarly, from an immunological point-of-view, the increase at all time points (since randomization) in CD4 cell count was statistically significant in the ABC group (P<0.01), while no difference was observed in the ABC+3TC group. The possibility of a successful use of ABC in salvage regimens opens alternative therapeutic options for heavily pretreated patients with previously documented M184V mutation. Further studies should clarify whether this is true for other drugs of the nucleoside analogues class.
Adult↗
Once-a-day therapy for HIV infection: a controlled, randomized study in antiretroviral-naive HIV-1-infected patients.
BACKGROUND: Complex antiretroviral regimens require optimal adherence to maintain long-lasting effectiveness. Simpler regimens, possibly with easy schedule and low pill burden, are needed for the long-term treatment of HIV infection. OBJECTIVE: To assess the efficacy and tolerability of a once-a-day highly active antiretroviral therapy (HAART) compared with two other conventional twice-a-day regimens. METHODS: In a prospective and randomized study, antiretroviral-naive patients received either EFV+ddl+3TC (once-a-day regimen; OD), or EFV+Combivir (twice-a-day and low-pill burden regimen; BID-low) or NFV+Combivir (twice-a-day and high-pill burden regimen; BID-high). Primary outcome was the proportion of patients with viral load <50 copies/ml at week 52 of follow-up. Results were evaluated according to intention-to-treat and on-treatment analysis. RESULTS: Thirty-four patients in each arm were enrolled. Baseline characteristics were similar in the three groups. The proportion of patients with viral load <50 copies/ml at week 52 were 74.4, 74.4 and 50.0% for OD group, BID-low group and BID-high group, respectively (P=0.02, ITT analysis). According to on-treatment analysis, the same figures were 88.9, 85.7 and 60% (P<0.02). Overall, 26 (25.5%) patients discontinued treatment for different reasons and immune recovery was similar in all study arms. CONCLUSIONS: Once-a-day HAART with ddl+3TC+EFV is a safe and effective alternative to twice-a-day regimens. Once-a-day therapy, with its simple daily schedule, may be proposed as one of the first choice treatments in HIV infection.
Adult↗
Genotypic resistance tests for the management of patients at simplification of highly active antiretroviral therapy.
Witness for the prosecution: There is a growing interest in exploring simpler protease inhibitor (PI)-sparing regimens that could improve patients' quality of life and adherence, provide relief from adverse events and, at the same time, preserve virological and immunological success. Simplified maintenance studies have used switch regimens with equivalent antiretroviral efficacy to PI-containing highly active antiretroviral therapy (HAART), replacing the PI with non-nucleoside reverse transcriptase inhibitors (NNRTI) such as efavirenz and nevirapine or with a 3 nucleoside-based maintenance regimen. As simplification strategies apply to patients with undetectable viral load, the conventional methods to measure viral resistance on plasma RNA cannot be applied. The only possibility relies on the determination of mutations within the integrated HIV-DNA in peripheral blood mononuclear cells. A careful anamnestic examination is therefore the only tool the caregiver has to direct his choices. In this respect and in our opinion it would be wise not to simplify treatment with abacavir in those patients who underwent a previous suboptimal therapy with lamivudine or thymidine analogues. Witness for the defence: The antiretroviral therapy that includes PI and 2 nucleoside analogue reverse transcriptase inhibitors (NRTI) was the first HAART in HIV infection: this combination results in a reduction of the risk of progression to AIDS and death, but it shows many problems caused by high tablet volume, dietary restrictions, multiple daily dosing and development of toxicity. Simplifying antiretroviral treatment regimens would increase patients' adherence and minimize toxicity.
Antiretroviral Therapy, Highly Active↗
Early and late effects of highly active antiretroviral therapy: a 2 year follow-up of antiviral-treated and antiviral-naive chronically HIV-infected patients.
BACKGROUND: Control of HIV replication can be observed in highly active antiretroviral therapy (HAART)-treated and, occasionally, in HAART-naive patients. The immunological correlates of these situations were examined in a longitudinal study. DESIGN: A prospective study. Immunovirological analyses in 16 chronically HIV-infected, HAART-naive patients (time 0) who started HAART. Fifteen patients (short-term HAART) were re-evaluated after 24 months (time 1). Results were compared with those of 30 patients who received HAART for more than 12 months before the study period (long-term HAART) and were analysed at the same timepoints. Fifteen patients who were antiviral therapy naive (naive) at both timepoints were also studied. RESULTS: Over a 24-month period CD4 and CD8 cell counts and viraemia remained unchanged in naive and long-term HAART patients; CD4 cell counts increased and viraemia diminished in short-term HAART individuals. Antigen-stimulated proliferation was unmodified in naive and short-term HAART patients, but improved in long-term HAART individuals. Gp160-stimulated IL-2 and IFN-gamma production was augmented in long-term HAART patients and marginally modified in other patients. IL-7 production was unmodified in naive individuals, augmented in short-term HAART patients, and diminished in long-term HAART patients. Chemokine production was similar in all patients. Naive patients showed the highest CD8 cell counts at both timepoints. CONCLUSION: HAART has a major impact on the outcome of HIV infection, even if functional immune modulation in HAART-treated patients is evident only after long periods of therapy. Low but detectable HIV replication in HAART-naive patients with preserved immune functions might not be associated with CD4 cell reduction, functional immune defects, or changes in viraemia.
Antiretroviral Therapy, Highly Active↗
Age at infection affects the long-term outcome of transfusion-associated chronic hepatitis C.
Before the introduction of hepatitis C virus (HCV) screening for blood donors, the risk of acquiring HCV infection as a result of a transfusion was about 10%. The aim of this study was to assess the frequency and rate of progression to cirrhosis in patients with transfusion-associated chronic HCV infection and identify possibly negative prognostic factors. Of 2477 consecutive patients with clinical or laboratory evidence of liver disease, 392 (16%) were anti-HCV- and HCV-RNA-positive, had anamnestic evidence of a single and precisely dated transfusion event, and showed no other causes of chronic liver disease; 268 (68%) underwent ultrasound-guided liver biopsy and were enrolled in the study. After a mean interval of 18.4 years, 54 patients (20.1%) had cirrhosis, which multivariate analysis showed to be independently associated with the duration of follow-up, age at infection and at the time of liver biopsy, and serum alanine aminotransferase levels at biopsy. The time necessary to have a 50% probability of developing cirrhosis in patients aged 21-30, 31-40, and more than 40 years was 33, 23, and 16 years, respectively. In comparison with those aged 20 years or less at infection, the risk ratio of developing cirrhosis over a period of 30 years for patients aged 21-30 and at least 31 years at infection was, respectively, 4.51 (95% confidence interval, 1.03-19.76) and 12.29 (95% confidence interval, 3.06-49.40). In patients with transfusion-associated chronic hepatitis C, the risk of cirrhosis is related to age at infection and disease activity. Our findings suggest that an aggressive therapeutic approach should be adopted in patients infected by HCV at an older age to prevent the progression to end-stage liver disease.
Adolescent↗
Strategic selective treatment in highly pre-treated HIV patients harbouring multiply resistant viruses.
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Adult↗