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R Maserati

Publications and source records attributed to R Maserati.

At least 19 recordsLinked to original sources
PubMed2004

Markers of local immunity in cervico-vaginal secretions of HIV infected women: implications for HIV shedding.

OBJECTIVES: To link local proinflammatory cytokines with HIV related nucleic acids in cervico-vaginal secretions and the factors associated with them. METHODS: An observational study on 60 HIV positive women attending the department of obstetrics and gynaecology, University of Pavia, Italy. HIV-1 RNA in plasma, proviral HIV-1-DNA, cell associated and cell free HIV-1 RNA in cervico-vaginal secretions were evaluated by competitive polymerase chain reaction (c-PCR) and reverse transcriptase PCR (cRT-PCR). IL-1beta, IL-6, and TNF-alpha were measured by ELISA in cervico-vaginal lavages. Multiple regression analysis on ordinal categorical variables was used to test for the simultaneous associations of clinical and microbiological variables on quartiles of cytokine concentrations in lavage samples. RESULTS: Proviral HIV-1 DNA, cell associated and cell free HIV-1 RNA were detected in 76.7% (46/60), 70% (42/60), and 71.7% (43/60) of the patients, respectively. IL-1beta concentration was directly correlated with proviral HIV-DNA (Spearman rho = 0.35, p = 0.01) and cell associated HIV-RNA levels (Spearman rho = 0.263, p = 0.05). IL-1beta concentration (153.9 pg/ml) was higher (p<0.05) among women with cytological squamous intraepithelial lesion (SIL) than negative controls (73.4 pg/ml). In women with vaginal infection both IL-1beta (41.7 pg/ml) and IL-6 (10.2 pg/ml) were lower (p<0.05) in comparison to negative controls (144.9 pg/ml and 23.7 pg/ml, respectively). Women receiving stable antiretroviral therapy had significantly lower TNF-alpha (34.4 pg/ml versus 44.4 pg/ml, p = 0.04) and higher IL-6 (24.0 pg/ml versus 1.4 pg/ml, p = 0.004) levels in lavage samples compared to untreated women. The associations between the presence of SIL, antiretroviral treatment, vaginal infection and cytokine concentrations in cervico-vaginal secretions were confirmed in multiple regression analysis. CONCLUSIONS: Local immune activation may modulate HIV-1 shedding in cervico-vaginal secretion with possible influence on vaginal physiology and host defence. Pharmacological agents lowering HIV-1 replication cause a shift to a pattern of cytokine production which seems less favourable to the transmission of the disease.

Adult↗
PubMed2004

Diagnosis of visceral leishmaniasis: the sensitivities and specificities of traditional methods and a nested PCR assay.

In the present study, 67 patients suspected to be cases of visceral leishmaniasis (VL) were each checked for leishmanial infection by the microscopical evaluation of various biological specimens, in-vitro culture, serology and an assay based on nested PCR. Most (35) of the subjects were immunocompetent (IC) but 32 were immunodeficient (ID) as the result of HIV infection (18 cases), treatment to prevent transplanted organs being rejected (six) or haematological malignancies (eight). Forty-one (61.2%) of the subjects (19 IC subjects, 12 HIV-positive patients, four transplant patients and six patients with malignancies) were considered true cases of VL. For the IC subjects, only the production and microscopical examination of leucocytoconcentrates and cultures of Buffy coats gave sensitivities of <80%, the results of the other methods showing higher sensitivities and almost perfect agreement with the 'gold-standard' diagnoses. For the ID subjects, however, only the serological tests and the PCR gave reasonable sensitivities (of >80%). For the initial diagnosis of leishmaniasis in ID patients, IFAT and western blots may be useful, as, among the present ID patients, they gave sensitivities (of 80.9% and 88.2%, respectively) that were almost as high as that for the PCR, and specificities of 100%. In the diagnosis of VL in either IC or ID patients, the assay based on a nested PCR appeared to be particularly reliable, with sensitivities of 88.9% and 95.2%, respectively, and a specificity of 100% in both groups of patients. The testing of bone-marrow aspirates by PCR revealed very few VL cases who were not found positive when samples of their peripheral blood were checked in the same assay. For both IC and ID subjects therefore, the use of the PCR-based method to test samples of peripheral blood (which can be collected much more easily than bone-marrow aspirates and with much less pain for the subject) is recommended.

AIDS-Related Opportunistic Infections↗
PubMed2002

Assessment of atherosclerosis using carotid ultrasonography in a cohort of HIV-positive patients treated with protease inhibitors.

OBJECTIVE: Lipid disorders associated with the use of protease inhibitors (PI) may be a risk factor for premature atherosclerosis development. The aim of this study is to evaluate the extent of carotid intima media thickness (IMT) among HIV-positive patients treated with PI containing regimens compared to PI-naïve and HIV-negative subjects. METHODS: We analysed plasma lipid levels and carotid IMT in 28 HIV-positive patients treated with protease inhibitors (PIs) for a mean of 28.7 months (range 18-43) and in two control groups constituted, respectively, by 15 HIV-positive naïve patients and 16 HIV-negative subjects, that were matched for age, risk factors for HIV infection, cigarette smoke use and CD4+ cell count. RESULTS: PI-treated patients had higher triglyceride, HDL and apo B levels than controls. Carotid IMT was significantly increased in PI-treated patients compared to naïve or HIV-negative subjects. A correlation between cholesterol HDL, triglyceride and ApoB levels and IMT was observed among the entire cohort. CONCLUSIONS: Plasma lipid alterations were associated with an increased IMT and intima media thickening was more pronounced in PI-treated patients than in the two control groups. Periodical evaluation of blood lipid profile and, if required, the use of lipid-lowering agents is advisable. Moreover, physicians should address concurrent risk factor for atherosclerosis that can be modified, including smoking, hypertension, obesity and sedentary life-style.

Adult↗
PubMed2001

Declining levels of rescued lymphoproliferative response to human cytomegalovirus (HCMV) in AIDS patients with or without HCMV disease following long-term HAART.

OBJECTIVE: To investigate the lymphoproliferative response (LPR) to human cytomegalovirus (HCMV) in two groups of AIDS patients undergoing long-term highly active antiretroviral therapy (HAART): group 1 ( n = 22) with nadir CD4(+) cell count <50/microl and no HCMV disease; group 2 ( n = 16) with <50/microl CD4(+) T-cell count and HCMV disease. All patients had previously undergone antiretroviral monotherapy or dual therapy before initiating HAART. STUDY DESIGN AND METHODS: The two groups of patients were tested prospectively for CD4(+) T cell count, HIV RNA load, HCMV viremia, and LPR to HCMV at baseline, and then after 3 and 4 years of HAART. A control group of 13 recently diagnosed treatment-naive AIDS patients with CD4(+) T-cell counts <100/microl was also investigated. RESULTS: No LPR to HCMV was found in any of the treatment-naive patients nor in any patient of the two groups examined at baseline, when HCMV viremia was 13.6% in the patient group without disease and 87.5% in the group with disease ( p <.0001). After 3 years of HAART, the frequency of patients who recovered an LPR to HCMV was not significantly different (81.8% in the group without HCMV disease, and 68.7% in the group with HCMV disease), whereas, compared with baseline, the HIV load decreased and the CD4(+) T-cell count increased significantly and to a comparable extent in the two groups of patients. In addition, the frequency of patients with HCMV viremia, although reduced, became comparable in both groups. After 4 years of HAART, the frequency of responders to HCMV without and with HCMV disease dropped to comparable levels (50.0 vs. 56.3%, respectively) in association with high median CD4(+) T-cell counts and low median HIV RNA plasma levels. In parallel, the frequency of patients with HCMV viremia did not change significantly. In addition, after between 3 and 4 years of HAART, although the frequency of stable responders and nonresponders remained unchanged (50%) in both groups, most of the remaining patients showed declining levels of responsiveness to HCMV. Although some patients from both groups were found to have CD4(+) T-cell counts >150/microl in the absence of LPR to HCMV, thus suggesting dissociation of specific and nonspecific immune reconstitution, a significant correlation was found between CD4(+) T-cell count and LPR to HCMV (r = 0.44; p <.001). From a clinical standpoint, anti-HCMV therapy could be safely discontinued in 8 patients with HCMV retinitis showing CD4(+) T-cell counts >150/microl, recovery of HCMV LPR, and no HCMV viremia. CONCLUSIONS: Declining levels of the previously recovered LPR to HCMV are often observed after long-term HAART. However, because the role of LPR in the evolution of HCMV infection and disease during HAART remains to be defined, the clinical impact of the declining LPR to HCMV must still be clarified in long-term prospective studies.

AIDS-Related Opportunistic Infections↗
PubMed2001

Viral excretion in cervicovaginal secretions of HIV-1-infected women receiving antiretroviral therapy.

A longitudinal study was conducted to evaluate the viral shedding present in cervicovaginal secretions of HIV-1-seropositive women receiving antiretroviral therapy. A total of 128 paired cervicovaginal and blood samples was obtained from 37 women during a median follow-up period of 21 months. A sensitive, competitive, polymerase chain reaction and a reverse transcription polymerase chain reaction were used for the simultaneous quantitation of HIV-1 proviral DNA and RNA in cervicovaginal cells and cell-free RNA in cervicovaginal secretions, as well as HIV-1 RNA in peripheral blood. The cumulative probability of detecting proviral DNA in genital secretions was significantly higher over time in women with detectable viremia than in women in whom HIV-1 RNA was persistently undetectable in plasma (< 50 copies/ml) (P = 0.028 by log-rank test). The presence and amount of proviral DNA, cell-associated RNA and cell-free RNA in the cervicovaginal secretions were positively correlated with the presence of detectable viremia or the number of HIV-1 RNA copies in plasma (Spearman rank correlation, 0.290, 0.279, and 0.305, respectively; all P < 0.01), but no correlation was found with the CD4+ cell count. In addition, vaginal infections were positively correlated with the detection of proviral DNA in cervicovaginal secretions (odds ratio, 2.60; 95% confidence interval, 1.07-5.70). However, the positive correlation between the presence and amount of HIV in cervicovaginal secretions and the viral load in plasma provides no assurance that HIV shedding does not occur in the genital tract of women with undetectable HIV-RNA in plasma.

Adult↗
PubMed2001

Higher levels of HIV DNA in memory and naive CD4(+) T cell subsets of viremic compared to non-viremic patients after 18 and 24 months of HAART.

The degree of infection of memory and naive CD4(+) T cells in patients treated with HAART and with durable undetectable or detectable viral load in plasma was evaluated. The following two groups of patients were analyzed cross-sectionally: (i) patients with undetectable HIV RNA plasma levels during follow-up (responders); (ii) patients with no reduction or with rebound in HIV RNA levels during treatment (non-responders). Patients were examined following 6, 12, 18 and 24 months of HAART, respectively, by quantifying: (i) plasma HIV RNA load; (ii) CD4(+) T cells; (iii) memory and naive CD4(+) T cells; (iv) HIV DNA levels in memory and naive CD4(+) T cells. HIV RNA plasma levels were significantly higher in non-responders vs responders at each time point (P<0.02), while CD4(+) T cell counts as well as memory and naive CD4(+) T cell levels were comparable in both viremic and non-viremic patients. However, higher HIV DNA values were observed in both memory and naive CD4(+) T cells of non-responders vs responders after 18 and 24 months of HAART (P<0.02), suggesting an increased amount of HIV-infected naive CD4(+) T cells and a sustained high degree of infection of memory CD4(+) T cells. Immunological reconstitution following HAART might potentially be hampered in viremic patients despite the absolute increase in CD4(+) T cell counts.

Anti-HIV Agents↗
PubMed2001

Increased frequency of JC virus type 2 and of dual infection with JC virus type 1 and 2 in Italian progressive multifocal leukoencephalopathy patients.

To verify the possibility of different role of JC virus genotypes in the etiology of progressive multifocal leukoencephalopathy, we analysed several JC virus isolates amplified from AIDS patients with and without progressive multifocal leukoencephalopathy and healthy controls by nucleotide sequencing. Cerebrospinal fluid (CSF), peripheral blood mononuclear cells (PBMCs) and urine from 52 AIDS patients suffering from various neurological diseases including 21 cases of progressive multifocal leukoencephalopathy, and PBMCs and urine from healthy subjects were evaluated by nested polymerase chain reaction (PCR) for the presence of DNA belonging to the highly conserved large T antigen (LT) of JC virus. The different JC virus subtypes were identified by nucleotide sequence analysis of the virion protein (VP1) genomic region. JC virus DNA was detected in all the CSF samples from the progressive multifocal leukoencephalopathy patients, but not in the CSF from non-progressive multifocal leukoencephalopathy cases, while the frequency of JC virus DNA detection in the PBMCs and urine did not differ among the three groups studied. JC virus type 2 was detected only in progressive multifocal leukoencephalopathy patients, and in particular in 52.4% of their CSF samples. Moreover, in the CSF of 19.0% of the progressive multifocal leukoencephalopathy cases, dual infection with both JC virus types 1 and 2 was found. The data obtained in this study indicate that the unexpected involvement of JC virus type 2, a strain not common in Italy, and the high frequency of dual infection with both JC virus types 1 and 2 in progressive multifocal leukoencephalopathy CSF, can be indications of risk factors for progressive multifocal leukoencephalopathy development.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Antiretrovirals: simultaneous determination of five protease inhibitors and three nonnucleoside transcriptase inhibitors in human plasma by a rapid high-performance liquid chromatography--mass spectrometry assay.

An analytical technique using liquid chromatography (LC) coupled with electrospray-mass spectrometry (ESI--MS) has been developed for the simultaneous determination of five protease inhibitors (PIs): saquinavir, indinavir, ritonavir, nelfinavir, and amprenavir; and three non-nucleoside reverse transcriptase inhibitors (NNRTIs): nevirapine, delavirdine, and efavirenz, in human plasma. This assay allows the elution and identification of these drugs in a single run (10 minutes) using a linear gradient with water and acetonitrile. The procedure involves liquid--liquid extraction. High-performance liquid chromatography (HPLC) separation was achieved on a C18 reversed-phase column, with a linear gradient elution followed by mass spectrometry detection. The calibration curves, obtained by automatic process peak area integration, show a good linearity in a range of concentrations between 20 and 10,000 ng/mL (40--10,000 ng/mL for efavirenz). The limit of detection was approximately 10 ng/mL for seven drugs (25 ng/mL for efavirenz). The coefficients of variation (CV) were always less than 15% for both intraday and interday precision for each compound. The recovery of the eight drugs ranged from 88.5% to 100%. This novel LC/ESI--MS assay provides an excellent method for simultaneous quantitative monitoring of different components of the highly active antiretroviral treatments (HAARTs) in patients treated simultaneously with PIs and NNRTIs, and it has been successfully applied to therapeutic drug monitoring and pharmacokinetic studies.

Alkynes↗
PubMed2001

Factors associated with nucleic acids related to human immunodeficiency virus type 1 in cervico-vaginal secretions.

OBJECTIVE: To assess HIV-related nucleic acids in cervico-vaginal secretions and the factors associated with them. DESIGN: Observational study. SETTING: Department of Obstetrics and Gynaecology, University of Pavia, Italy. POPULATION: HIV-positive patients attending a cytology service. METHODS: Paired blood and cervico-vaginal lavage samples were obtained from 122 known HIV-seropositive patients during periodic visits for cytologic screening for lower genital tract neoplasia. Vaginal specimens for the diagnosis of bacterial vaginosis, trichomonas vaginalis and candida infection were also obtained. HIV-1-RNA in plasma, proviral HIV-1-DNA, cell associated and cell-free HIV-1 RNA in cervico-vaginal secretions were quantitatively evaluated by competitive polymerase chain reaction (c-PCR) and reverse transcriptase PCR (cRT-PCR). MAIN OUTCOME MEASURE: Prevalences of HIV related nucleic acids in cervico-vaginal secretions and their univariate and multivariate associations with clinical variables. RESULTS: Proviral HIV-1 DNA, cell-associated and cell-free HIV-1 RNA were detected in 50% (61/122), 37.7% (46/122) and 32.8% (40/122) of the patients, respectively. In logistic regression analysis, the presence of HIV-1 RNA in blood was the factor which correlated best with the detection of HIV-1 DNA (OR = 5.48, 95% CI = 2.28-13.20), cell-associated (OR = 4.85; 95% CI = 1.89-12.45) and cell-free HIV-1 RNA (OR = 4.63, 95% CI = 1.74-12.33) in cervico-vaginal samples. However, between 20% and to 35% of patients who tested negative for blood HIV-1 RNA were positive for either HIV-1 DNA or HIV-1 RNA detection in cervico-vaginal lavages. Bacterial vaginosis was associated with an increased prevalence of cell-associated (OR = 3.58, 95% CI = 1.22-10.54) and cell-free HIV-1 RNA (OR = 2.94, 95% CI = 1.0-8.7) detection in cervico-vaginal secretions. Additional factors associated with increased prevalence of HIV-1 RNA detection were advanced stage of HIV disease and vulvovaginal candidiasis. CONCLUSIONS: Although the presence of HIV-1 RNA in blood is the factor which correlates best with the detection of HIV-related nucleic acids in cervico-vaginal secretions, the shedding of HIV in the genital tract can occur in 20-30% of non-viremic subjects. Bacterial vaginosis and candida infection could have a facilitating role in local HIV viral replication and shedding.

Adult↗
PubMed2001

Nelfinavir suspension obtained from nelfinavir tablets has equivalent pharmacokinetic profile.

The pharmacokinetics of nelfinavir tablets (A) and an oral simplified nelfinavir suspension (B) were studied. Twelve healthy volunteers randomly received either five 250-mg nelfinavir tablets or a simplified oral suspension obtained from tablets dissolved in water (nelfinavir 1250 mg in 100 mL of water) in a single dose before being crossed over to the second treatment after a one-week washout period. Blood samples were drawn up to 24 h after drug administration. Nelfinavir concentrations in plasma were analyzed by a specific and validated reverse-phase high-performance liquid chromatography assay (HPLC) with UV detection, and pharmacokinetic values were determined. For the AUC(0-infinity) with means+/-SD of 31.71+/-7.85, 30.88+/-10.28 (microg/L) respectively for treatments B and A, the ratio (F(B/A)) was of 1.1 with a C.I. of 0.90-1.24. For Cmax with means+/-SD of 3.1+/-0.6 (treatment B) and 3.2+/-0.8 mg/mL (treatment A), the ratio was 1.0. with C.I. of 0.92-1.08. The two treatments evidenced no significant differences in AUC(0-inifnity) and Cmax values and the two-one sided t-test showed that the two preparations are bioequivalent. There was no significant difference in Tmax between the liquid and tablets. Nelfinavir suspension might be a option for treating HIV-infected patients with swallowing disturbances or compliance problems.

Administration, Oral↗
PubMed2001

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↗
PubMed2001

[Pathogenic protozoans in man: differential characterization of Entamoeba histolytica/Entamoeba dispar complex, Acanthamoeba spp., Microsporidia].

The review summarizes the results in the main parasitological topics of our Lab: amoebic infections due to Entamoeba histolytica/Entamoeba dispar complex and to Acanthamoeba spp. respectively, and human infections caused by microsporidia. Different rapid and advanced techniques have been included in the standardized diagnostic protocols for each topic, and a critical comparison among them was made, in order to define the gold standard diagnostic method: a) E. histolytica/E. dispar: in vitro culture, zymodeme typization, biomolecular identification (PCR), immunoenzymatic assay (ELISA) for direct detection in stools of specific surface antigenic lectins; b) Acanthamoeba spp.: in vitro culture, light and ultrastructural characterization, species identification by immunofluorescence method with monoclonal antibodies, in vitro pharmacological studies; c) Microsporidia: ultrastructural (TEM), biomolecular (PCR), biochemical and immunological (SDS-PAGE, Immunoblotting) studies for species identification, use of advanced ultrastructural techniques ("freeze-etching", "deep-etching") in order to deepen the spore wall structure, to study the cytoskeletal function of actin and to define the mode of infection, in vitro pharmacological assays on some inhibitors of chitin-synthases.

Acanthamoeba↗
PubMed2000

Role of brain biopsy in the management of focal brain lesions in HIV-infected patients. Gruppo Italiano Cooperativo AIDS & Tumori.

In this multicenter, retrospective study of 160 brain biopsies in the assessment of HIV-related focal brain lesions, diagnostic sensitivity was acceptable (87%), but the procedure carried considerable morbidity (7.5%) and mortality (3.1%). Moreover, it is not always possible to initiate the changes in therapy indicated by the results, and overall survival remains poor, with a median of 2 months. Criteria for brain biopsy for the diagnosis of focal brain lesions should be redefined to include selected patients for whom a less invasive approach does not yield a definitive diagnosis.

Adult↗
PubMed2000

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↗
PubMed2000

Higher short-term virologic efficacy of three-class versus two-class highly active antiretroviral salvage therapy in HIV-infected patients.

The efficacy of two-class versus three-class antiretroviral salvage treatment was analyzed retrospectively in 63 HIV-infected patients in whom highly active antiretroviral therapy failed. Twenty-eight patients (group A) received two-class therapy, and 35 patients (group B) received three-class therapy. After 3 months of treatment, a significantly greater proportion of patients in group B (23/35, 65.7%) than in group A (8/28, 28.5%) showed a > or = 1 log10 decrease in the plasma HIV RNA level (P = 0.0034). However, after 9-12 months, 12 of 23 (52.1%) group B responders showed viral load rebound. The results were partially explained by the finding that, at baseline, the great majority (21/27, 77.7%) of group A patients showed mutations conferring resistance to all drugs administered, whereas in group B patients' susceptibility to at least two drug classes was retained. However, after 9-12 months of therapy, most (18/20, 90%) of the short-term responders in group B showed emergence of additional mutations that hampered long-term response.

Anti-HIV Agents↗
PubMed2000

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↗
PubMed2000

MRSA carriage: the relationship between community and healthcare setting. A study in an Italian hospital.

From May 1997 to June 1998, all patients admitted to the study institution were screened at entry for MRSA carriage (both colonization and infection). Eighty-six MRSA carriers were identified; of these, 85 were nasal carriers. Risk factors were compared to those of 86 controls. Although the vast majority of both carriers and controls had at least one previous hospital stay, carriers were less likely than controls to be referred from a community setting, and had resided within the community for a shorter time before the current admission. The number of underlying conditions was comparable in the two groups, but those infected were more likely to have cancer than the controls. While community-acquired MRSA carriage is rare, exposure to a health care setting (particularly if repeated) within six months from the current admission, is a risk factor for MRSA carriage and introduction of the organism into an institution.

Aged↗