PubMed Health⌕ Search

Biomedical subjects

Andrea Patroni

Publications and source records attributed to Andrea Patroni.

17 recordsLinked to original sources
PubMed2006

Influence of viral chronic hepatitis co-infection on plasma drug concentrations and liver transaminase elevations upon therapy switch in HIV-positive patients.

It is still controversial whether viral hepatitis co-infection can influence antiretroviral plasma drug concentrations and whether drug concentrations are correlated with liver enzyme elevations during highly active antiretroviral therapy. An analysis of data from a cohort of 220 human immunodeficiency virus (HIV)-infected patients was conducted. Univariate and multivariate logistic analyses were performed to identify predictors of plasma drug concentrations. The association of transaminase elevation with higher plasma drug concentrations was explored following stratification of patients into HIV monoinfected and hepatitis C virus (HCV) and/or hepatitis B virus (HBV) co-infected groups. Hepatitis co-infections were independently correlated with drug concentrations above the therapeutic cut-offs at Week 1 (P=0.06), Week 4 (P=0.04) and Week 12 (P=0.005). The apparent effect was independent of the possible impact exerted by other variables such as demographics and medication adherence. The incidence of relevant hypertransaminasaemia was low. Patients with hepatitis co-infections had higher rates of transaminase elevation than monoinfected HIV patients; however, risk of transaminase elevation was not associated with drug concentrations. The presence of HCV and/or HBV co-infections correlated with higher plasma drug concentrations, although it did not appear to influence hepatotoxicity risk.

Adult↗
PubMed2006

Vaginal colonization with Candida spp. in human immunodeficiency virus-infected women: a cohort study.

We have conducted a longitudinal study on factors associated with candidal vaginal colonization, a precursor of vaginitis, in a cohort of HIV-infected women in Italy. All consecutive women attending a single, tertiary care clinical site were offered free screening for sexually transmitted infections and genital disorders every 6-12 months. Candidal vaginal colonization was defined as a positive culture for Candida spp. in an asymptomatic woman. From January 1998 to July 2002 we analysed 214 women. The baseline prevalence of candidal vaginal colonization was 16.8%. In the logistic regression analysis, the time since HIV infection > or =36 months (odds ratio [OR] = 0.18, 95% confidence interval [CI] 0.016-0.53, P = 0.002) and a plasma viral load > or =10,000 copies/mL (OR = 3.9, 95% CI 1.03-14.9, P = 0.045) were independently associated with candidal colonization. Among 130 women who were followed for a mean period of 24 months, the incidence of vaginal colonization was 10.7/100 women-years. In the Cox regression analysis, a CD4(+) T-lymphocytes count <100 cells/microL during the follow-up was associated with an increased risk of candidal vaginal colonization (OR = 4.45, C.I. = 1.20-16.81, P = 0.03). Risk of candidal vaginal colonization episodes in HIV-infected women significantly increase when CD4(+) T-lymphocytes are less than 100.

Adult↗
PubMed2005

Prediction of early and confirmed virological response by genotypic inhibitory quotients for lopinavir in patients naïve for lopinavir with limited exposure to previous protease inhibitors.

OBJECTIVE: To determine the impact of genotypic inhibitory quotient (GIQ) for lopinavir (LPV) in patients failing HAART with limited antiretroviral exposure. DESIGN: Retrospective analysis of a prospective trial. METHODS: Lopinavir GIQ was calculated as the ratio between the mean trough concentration (C(trough)) and the number of protease mutations using eight different HIV drug resistance mutation lists or algorithms. Early (by week 12) and confirmed (up to week 24) virological response (HIV-RNA< 400 copies/mL, ECVR) was used as dependent variable in logistic regression model. RESULTS: Seventy-one of 109 (65%) patients achieved ECVR. At multivariable logistic regression analysis, each mug/mL increase of GIQ was correlated with increasing probability of ECVR as far as the following mutations were computed: multi-protease inhibitor (PI) associated mutations listed by IAS (OR=1.17; 95% CI=0.99-1.39; P=0.058), mutations associated with LPV resistance by ANRS algorithm (OR=1.21; 95% CI=1.02-1.44; P=0.03), major mutations associated with LPV resistance by Stanford database (OR=1.16; 95% CI=1-1.35; P=0.05), and the whole set of mutations associated with LPV resistance in the same database (OR=1.22; 95% CI=1.02-1.46; P=0.03). Using ROC curve method, a specific threshold GIQ was assessed, above which this parameter could predict ECVR with the highest sensitivity (74.6% with GIQ obtained through Stanford LPV mutations) or specificity (89.5% with GIQ obtained through ANRS LPV mutations). CONCLUSIONS: Our results suggest that increasing GIQ can improve virological outcome even in patients with limited exposure to PIs. Further studies are necessary to understand what HIV protease mutations should be considered and whether such mutations should be weighted differently to improve LPV GIQ predictive value.

Adult↗
PubMed2005

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↗
PubMed2005

A randomized controlled trial to evaluate antiretroviral salvage therapy guided by rules-based or phenotype-driven HIV-1 genotypic drug-resistance interpretation with or without concentration-controlled intervention: the Resistance and Dosage Adapted Regimens (RADAR) study.

BACKGROUND: It is not well defined whether concentration-controlled intervention (CCI) and rules-based human immunodeficiency virus (HIV) type 1 genotype drug-resistance interpretation (GI) or virtual phenotype drug-resistance interpretation (VPI) may improve the outcome of HIV salvage therapy. METHODS: In a prospective, randomized, controlled trial, patients were randomized (on a factorial basis) to change treatment after either GI or VPI, and they then were further randomized to the control arm (no CCI) or the CCI arm. Protease inhibitor (PI) and nonnucleoside reverse-transcriptase inhibitor (NNRTI) trough concentration (Ctrough) values were determined at weeks 1, 4, 12, and 24 of the study. RESULTS: Among 230 patients, virological benefit (defined by an HIV RNA load of <400 copies/mL at week 24) was not statistically different, either between patients in the GI and VPI arms or between patients in the CCI and control arms. A virological benefit was found for patients in the CCI arm, compared with patients in the control arm, but this benefit was not statistically significant (56.8% vs. 64.3% at week 4 and 63.6% vs. 74% at week 12). Dosage adaptation was possible for only a fraction of patients, because of low rates of treatment adherence or patient refusal to increase dosages. In the logistic regression analysis, independent predictors of virological response at week 24 were a PI Ctrough value and/or an NNRTI Ctrough value in the higher quartiles (or above cutoff levels) and a low number of PIs previously received. Moreover, receipt of a regimen that contained PIs boosted with ritonavir was an independent predictor of virological response. CONCLUSIONS: The present study did not support the routine use of CCI for patients undergoing salvage treatment, probably as a result of existing difficulties associated with its clinical application. However, a higher Ctrough value appeared to be correlated with treatment response. No major differences were found between VPI or GI when they are used together with expert advice for the selection of salvage treatment combinations.

Adult↗
PubMed2005

Early virological failure after tenofovir + didanosine + efavirenz combination in HIV-positive patients upon starting antiretroviral therapy.

A prospective, randomized pilot trial was conducted in naive patients comparing three different combinations: zidovudine+lamivudine+lopinavir/ritonavir (arm A) versus tenofovir+lamivudine+efavirenz (arm B) versus tenofovir+didanosine+efavirenz (arm C). HIV-RNA slope (days 1, 3, 7, 14 and 28) was slower in arm C with respect to arm B (P < 0.0001). Seven out of eight patients (87.5%) reached undetectable HIV-RNA by week 28 in arm A, 10/10 (100%) in arm B and 6/10 (60%) in arm C. Among arm C patients who failed at week 4, one HIV isolate showed 67N and 219Q, and another one showed 210F and 215D substitutions in the HIV reverse transcriptase gene at baseline, respectively. Non-nucleoside reverse transcriptase inhibitor resistance-related mutations appeared first, followed by 65R mutations in all cases. Efavirenz AUC(0-24) values were lower in arm C with respect to arm B, especially in patients who failed early. A high virological failure rate after tenofovir+didanosine+efavirenz correlated with a slower HIV-RNA decrease and a peculiar accumulation of resistance mutations. A constellation of factors could be correlated with early failure events in patients receiving this combination such as resistance mutations or polymorphisms present at baseline, low CD4+ T-cell count or advanced disease and unexpectedly low efavirenz plasma levels.

Adult↗
PubMed2004

Drug resistance mutations and newly recognized treatment-related substitutions in the HIV-1 protease gene: prevalence and associations with drug exposure and real or virtual phenotypic resistance to protease inhibitors in two clinical cohorts of antiretroviral experienced patients.

This study aimed at identifying HIV-1 protease amino acid changes associated with protease inhibitor (PI) exposure and susceptibility. New amino acid substitutions were correlated with the number of experienced PIs, reaching statistical significance only for those at positions 3, 44, and 74. The correspondence multivariate model demonstrated that > or =3 experienced PIs and substitutions or mutations at positions 3, 46, 54, 73, 74, and 84 were correlated with PI cross-resistance, including resistance for lopinavir and amprenavir in this cohort of patients who were naive for these drugs.

Amino Acid Substitution↗
PubMed2004

Immune correlates of virological response in HIV-positive patients after highly active antiretroviral therapy (HAART).

Correlates of immune reconstitution after highly active antiretroviral therapy (HAART) are not completely understood, in particular as far as viro-immunological discordant responses are concerned. HIV-positive patients on stable HAART for > or = 1 year were recruited. Viro-immunological responses were categorized according to positive or negative area under the curve (AUC) variations for HIV plasma viral load (pVL) and CD4+ T-cell counts measured at least every 4 months. The following parameters were evaluated: lymphocyte spontaneous apoptosis (LSA), intracellular Bcl-2 expression in both CD4-CD45RA+ and CD4-CD45R0+, IL-7 and IL-15 plasma concentrations, and lymphocyte TRECs levels. Sixty-one patients were enrolled. A significant inverse correlation was found between CD4+ T-cell count and pVL AUC (r = 0.45; p = 0.0003). Patients with pVL response had higher levels of Bcl-2 in CD4-CD45R0+ (mean 65,409 MESF vs. 54,018 MESF; p = 0.089) and higher IL-15 (mean 1.34 pg/mL vs. 1.05 pg/mL; p = 0.069, respectively). Higher LSA and lower TRECs levels were found in viro-immunological non-responder patients with respect to those who had viro-immunological response (mean 24.84% vs. 14.89%; p = 0.01, and mean 17,796 copies/10(6) cells vs. 29,251 copies/10(6) cells; p = 0.68, respectively). Virological suppression may allow Bcl-2 and IL-15 hyperexpression during incomplete immune-reconstitution phase, while more complete immune reconstitution appeared to be marked by both high TRECs and low LSA levels, possibly indicating both central and peripheral CD4+ T-cell repopulations at this stage.

Adult↗
PubMed2003

HIV susceptibility to amprenavir: phenotype-based versus rules-based interpretations.

OBJECTIVES: The objective was to study genotypic correlates of discordant interpretations of amprenavir (APV) resistance between a rules-based algorithm and either recombinant phenotype or virtual phenotype. METHODS: HIV resistance mutations found in patients from the GenPheRex study were interpreted with VGI-TRUGENE (version 5.0; VGI) and compared with either recombinant-phenotype (Antivirogram, r-PHT) or virtual-phenotype (Virtual-Phenotype, v-PHT) interpreted through Virco biological cut-offs. RESULTS: Among 180 samples available, 56 (31.1%) were discordant with the observed genotype interpretation results, as a result of being judged as sensitive by r-PHT or v-PHT but resistant by VGI (S/R). Only the I84V mutation was almost invariably found in concordant resistant isolates compared with S/R isolates (60% versus 0%, respectively; P < 0.0001). Notwithstanding this, the number of multi-protease inhibitor-associated mutations (PAMs) was significantly higher in the concordant resistant isolates; the prevalence of >3 PAMs was 56.52% versus 33.93% in R/R and S/R isolates, respectively (P = 0.01). Correspondence analysis confirmed the relevance of PAMs, although additional mutations appeared to be correlated with APV resistance. CONCLUSIONS: The rate of discordance between rules-based and either r-PHT or v-PHT interpretations for APV was high. Mutation I84V and accumulation of >3 PAMs were found to be associated with resistance as interpreted with all systems tested. However, our results indicate that a number of mutations may have an impact on APV resistance, but that they are missed by current interpretation algorithms and this merits further investigations.

Algorithms↗
PubMed2003

Modifications of health resource-use in Italy after the introduction of highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV) infection. Pharmaco-economic implications in a population-based setting.

OBJECTIVE: To assess the impact of highly active antiretroviral therapy (HAART) on health resource utilisation (HRU) and to estimate associated direct costs in a population based setting. DESIGN: Retrospective study of all patients in the Institute of Infectious and Tropical Diseases (Brescia, Northern Italy) during a 4 years period related to the prescription of HAART has been performed: from 1997 (before HAART) to 2000 (after substantial period of HAART prescription). MAIN OUTCOME MEASURES AND RESULTS: HIV inpatient admissions (IA's) decreased from 506.8/1000 patients (pts) in 1997 to 246.3/1000 pts in the year 2000. Day care admissions (DCA's) also decreased from 1658.3/1000 pts to 942/1000 pts, while outpatient consultations (OC's) increased from 2046.9/1000 pts to 2590.6/1000 pts in the same years, respectively. By contrast, a relative increase of IA's and DCA's of patients whose serostatus was HIV-negative or unknown has been found. Cost of antiretroviral therapy increased by 2582 Euro (2272 US Dollars), while cost of HIV care (IA+DCA+OC) decreased by 1546 Euro (1360.4 US Dollars) per patient, resulting in a saving in direct cost equal to 60% of the increase in the expenditure for antiretroviral drugs. CONCLUSIONS: Our results demonstrate the shift of HIV care from inpatient to outpatient services that occurred after HAART had been introduced into clinical practice. Despite persisting clinical benefits, an increase in total direct cost for HIV pts has been seen for the first time during the HAART era in the year 2000, probably due to an over-prescription of HAART, according to actual Guideline for antiretroviral therapy use, to pts who were not at risk of clinical progression in the short term. Pharmacoeconomical surveillance of HAART is necessary while a favourable impact on the saving in cost is expected from the new treatment guidelines that suggest a relative delay in starting HAART.

Ambulatory Care↗
PubMedDate not supplied

Effect of highly active antiretroviral therapy (HAART) and hepatitis C Co-infection on hyperlipidemia in HIV-infected patients: a retrospective longitudinal study.

BACKGROUND: Lipid abnormalities are among the most frequent treatment-limiting adverse events during HAART in HIV-infected individuals. Lipid disturbances have also been associated with hepatitis C virus (HCV) chronic infection in HIV-uninfected participants. HAART-induced lipid abnormalities may then have peculiar features in HIV-HCV co-infected individuals. PURPOSE: To estimate the prevalence and incidence rates of hypertriglyceridemia and hypercholesterolemia and to identify associated factors in a large clinic population of HIV patients after HAART has been initiated. DESIGN: We performed a retrospective longitudinal follow-up study in a large cohort of HIV patients on their first HAART. PATIENTS AND METHOD: The clinical databases of two major clinical centers in Italy participating in the MASTER study were merged. Treatment-emerging metabolic disorders in patients on their first HAART regimen (PI-based or NNRTI-based) who were stable for at least 4 months were prospectively analyzed by baseline parameters, drug regimens, and viroimmunological outcome of therapy. Follow-up was continued for 24 months or until drug discontinuation, whichever came first. RESULTS: Two hundred and eighty two (282) HIV-infected patients undergoing HAART (203 PI + 79 NNRTI; 65 including stavudine [d4T]) met inclusion criteria and were enrolled in the study from 1997 to 2001. Mean follow-up was 18.5 +/- 6.7 months. After HAART had been initiated, a statistically significant mean increase in total cholesterol over time was observed in comparison to baseline (p <.0001), without difference between treatment groups (PI vs. NNRTI, with or without d4T). In the univariate analysis, predictive factors for HAART-induced hypercholesterolemia were baseline total plasma cholesterol and triglycerides values and CD4+ cell count differential increase over time, while a negative correlation was found with zalcitabine-including regimens and baseline HCV seropositivity. At multivariate analysis, only high baseline total plasma cholesterol and triglycerides values retained their predictive value and baseline HCV seropositivity was significantly associated with lower increase in total cholesterol values under HAART, regardless of treatment groups (p <.001). CONCLUSION: HCV co-infection is an independent factor preventing the emergence of treatment-limiting total cholesterol increase under any HAART regimen, possibly reflecting impaired total cholesterol synthesis in the liver or total cholesterol hypercatabolism. On the contrary, no HCV influence on triglycerides plasma levels was noted. Our data do not suggest any favoring role of specific treatment or drugs (PI and/or d4T) on total cholesterol and triglycerides increase under HAART.

Adult↗
PubMedDate not supplied

Hepatitis B virus co-infection in human immunodeficiency virus-infected subjects.

Shared epidemiological risks have resulted in HIV-infected populations having a high prevalence of hepatitis B virus (HBV) co-infection. Several prospective studies have investigated the impact of HBV co-infection on HIV disease progression; most of them were negative. On the contrary, there is evidence that HIV may modify the natural history of HBV infection. HIV positive subjects have higher rates of HBV chronification, higher HBV replication, lower ALT levels and lower rates of seroconversion to anti-HBe and anti-HBs. The impact of HIV co-infection on the outcome of HBV infection is still controversial, even if some studies have shown an accelerated progression towards decompensated cirrhosis in HIV co-infected subjects. HBV co-infection is a risk factor for severe hepatotoxicity during HAART. Vaccination for HBV is mandatory in nonimmune HIV subjects, however its efficacy in immunosuppressed patients is still controversial. HIV co-infection decreases the effectiveness of Interferon in the treatment of HBV infection. Because of its activity against both HBV and HIV, lamivudine is used in HIV-HBV co-infected patients at doses of 300 mg/daily and as part of an antiretroviral regimen, but the rate of sustained response is poor and HBV strains with mutations associated with lamivudine resistance occur at a rate of 20% per year. Trials of new drugs with activity against HBV, some of them with activity also against HIV, and some of them without cross-resistance with lamivudine, are now underway. Highly Active Anti-Hepatitis B Therapy will probably soon come of age.

Adult↗