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Biomedical subjects

L Ortona

Publications and source records attributed to L Ortona.

At least 19 recordsLinked to original sources
PubMed1999

Human herpesvirus 8 seropositivity and risk of Kaposi's sarcoma and other acquired immunodeficiency syndrome-related diseases.

BACKGROUND: The incidence of Kaposi's sarcoma (KS) is increased severalfold in individuals infected with human immunodeficiency virus-1 (HIV). Human herpesvirus 8 (HHV8) has also been implicated in KS. We investigated several factors that may determine the onset of KS, particularly HHV8 infection in individuals after becoming seropositive for HIV. METHODS: We studied 366 individuals belonging to different HIV-exposure categories (i.e., homosexual activity, intravenous drug use, and heterosexual contact) for whom a negative HIV serologic test and then a positive HIV serologic test were available within a 2-year period. HHV8 antibody testing was performed by use of an immunofluorescence assay on the first serum sample available after the first positive HIV test. Actuarial rates of progression of KS and of other acquired immunodeficiency syndrome (AIDS)-defining diseases were estimated by use of time-to-event statistical methods. All statistical tests were two-sided. RESULTS: Twenty-one of the 366 study participants developed AIDS-related KS, and 83 developed AIDS without KS. One hundred forty (38.3%) participants had detectable anti-HHV8 antibodies. The actuarial progression rate to KS among persons co-infected with HIV/HHV8 was nearly 30% by 10 years after HIV seroconversion. Increasing HHV8 antibody titers increased the risk of developing KS (for seronegative versus highest titer [1:125 serum dilution], adjusted relative hazard [RH] = 51.82; 95% confidence interval [CI] = 6.08-441.33) but not of other AIDS-defining diseases (adjusted RH = 1.14; 95% CI = 0.72-1.80). HHV8-seropositive homosexual men compared with HHV8-seropositive participants from other HIV-exposure categories showed an increased risk of KS that approached statistical significance (adjusted RH = 6.93; 95% CI = 0.88-54.84). CONCLUSIONS: Approximately one third of individuals co-infected with HIV/HHV8 developed KS within 10 years after HIV seroconversion. Progression to KS increased with time after HIV seroconversion. Higher antibody titers to HHV8 appear to be related to faster progression to KS but not to other AIDS-defining diseases.

AIDS-Related Opportunistic Infections↗
PubMed1999

A randomized, double-blind trial on the use of a triple combination including nevirapine, a nonnucleoside reverse transcriptase HIV inhibitor, in antiretroviral-naive patients with advanced disease.

The immunologic and virologic activity of nevirapine in combination with two nucleosides (zidovudine [ZDV] and didanosine [ddI]) was evaluated in antiretroviral-naive patients with a CD4 count <200/mm3 or clinical AIDS. In all, 68 patients were enrolled in a 48-week double-blind, placebo-controlled trial. A group of 32 patients received ZDV + ddI + nevirapine, and 36 patients received ZDV + ddI. Primary efficacy parameters were the activity on HIV-1 RNA and on peripheral blood CD4+ cells, with differences between groups analyzed by the Wilcoxon's nonparametric two-sample test. Baseline RNA was high in both treatment groups (median values, 5.8 and 5.7 log10). RNA and CD4 responses were significantly higher with the triple combination (median RNA reductions, 2.69 versus 1.05 log10 at 24 weeks and 1.97 versus 1.20 log10 at 48 weeks; median CD4 increases, 81 versus 64 cells/mm3 at 24 weeks and 101 versus 27 cells/mm3 at 48 weeks). This study demonstrates that a triple combination of ZDV + ddI + nevirapine used as first-line regimen in antiretroviral-naive patients can induce sustained virologic and immunologic response in patients with low CD4 count or a previous diagnosis of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Serum IgG antibodies to human herpesvirus-6 (HHV-6) do not predict the progression of HIV disease to AIDS. Italian Seroconversion Study group.

OBJECTIVES: To evaluate if different levels of human herpesvirus 6 (HHV-6) antibodies can predict HIV disease progression. DESIGN: Longitudinal study of individuals with a documented date of HIV seroconversion. SETTING: Clinical centers located throughout Italy. PATIENTS: Individuals who serconverted for HIV between 1983 and 1995 in Italy. METHODS: Sera were tested for IgG antibodies to HHV-6 using a commercial enzyme immunoassay. A serum sample with an optical density (OD) > or =242 (i.e. the mean value of 10 negative controls +4x standard deviation) was considered as HHV-6 positive; the progression of HIV disease was evaluated estimating the relative hazards (RH) of AIDS (by Cox models) for individuals with higher levels vs. lower levels of HHV-6 antibodies or considering levels of antibodies based on 10% increase of the distribution (deciles). Rates of CD4 decline fitting linear regression were also estimated. RESULTS: A total of 381 persons were followed for a median time of 4 years (range: 0.15-9 years) following the date of collection of the serum sample. The median OD value of HHV-6 antibodies was 306, with an interquartile range of 241-440 and a range of 48-2330. A slight inverse correlation was found between HHV-6 antibody levels and age of the individual at the time of serum collection (Spearman rank correlation coefficient, -0.16; p = 0.0013). No association was found between HHV-6 and CD4 level or between HHV-6 and CD8 level at the date of serum collection. The unadjusted RH of progression to AIDS was 0.63 (95% CI: 0.42-0.96) for HHV-6 positive individuals vs. HHV-6 negative; when adjusting for possible confounders (CD4, age, pre-AIDS HIV-related pathologies at the date of sera collection, and previous anti-herpes treatment), the RH of AIDS increased to 0.80 (95% CI: 0.51-1.23). No particular association with HIV disease progression was found when using the deciles of the distribution of HHV-6 antibodies. The median CD4 cell loss was 5.0x10(6) cells/l per month among HHV-6 positive individuals and 5.7x10(6) cells/l per month among the others. CONCLUSIONS: The presence of high levels of HHV-6 antibodies does not seem to predict the clinical or immunologic progression of HIV disease.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Application of molecular methods for detection and transmission analysis of mycobacterium tuberculosis drug resistance in patients attending a reference hospital in Italy.

A molecular analysis of drug-resistant isolates of Mycobacterium tuberculosis was done in a population with a high prevalence of human immunodeficiency virus infection. Seventy-one consecutive isolates were tested for genotypic resistance to isoniazid, rifampicin, streptomycin, and ethambutol by polymerase chain reaction-single strand conformation polymorphism analysis and automated sequencing of target regions. Phenotypic and genotypic resistance to isoniazid, rifampicin, streptomycin, and ethambutol were detected in 23.4%, 11.2%, 7%, and 5.6% of isolates and in 87%, 88%, 40%, and 100% of resistant isolates, respectively. Specificity was 100% for all target regions. When rpoB, katG, and ahpC mutation analysis were combined, 86% of resistant isolates to any drug were identified. No mutations in inhA were found in isoniazid-resistant isolates. Molecular detection of drug resistance, particularly for isoniazid and rifampicin, may represent a sensitive and very specific technique. The strategy of selecting rpoB, katG, and ahpC to quickly identify most resistant isolates, with a relevant saving of resources, is warranted.

Drug Resistance, Microbial↗
PubMed1999

HHV-8/KSHV is not associated with AIDS-related primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) is a major complication of the late stages of human immunodeficiency virus (HIV) disease. Epstein Barr virus (EBV) infection is the only genetic lesion consistently associated with this neoplasia. Recently, it has been proposed that the pathogenesis of AIDS-related PCNSL (AIDS-PCNSL) may be associated with infection by human herpesvirus-8/Kaposi's sarcoma associated herpesvirus (HHV-8/KSHV), although at present such association remains controversial. In order to conclusively assess the link between HHV-8/KSHV infection and AIDS-PCNSL, we performed a comprehensive study based on multiple molecular assays on cerebral tissues and cerebrospinal fluid (CSF) as well as specific immunologic assays on patients' sera. A well characterized panel of 33 Italian patients with AIDS-PCNSL and 13 controls with other HIV-related brain focal diseases from the same geographical area was analyzed. No signs of HHV-8/KSHV infection were detected in cerebral tissues by single-step PCR. Cerebral tissues of all AIDS-PCNSL scored negative for HHV-8/KSHV DNA sequences also by nested PCR, with the exception of one single patient who was simultaneously affected by Kaposi's sarcoma. All CSF samples analyzed were consistently devoid of HHV-8/KSHV sequences by molecular assays. By serologic assays, detecting both latent and lytic HHV-8/KSHV antigens, a specific immunoreactivity was observed in 16/33 (48%) AIDS-PCNSL and in 6/13 (46%) controls (P = 0.88). A significant correlation with HHV-8/KSHV serum reactivity was seen with a homosexual route of HIV transmission (P = 0.018), but not with the presence of AIDS-PCNSL. The results of our analysis conclusively assess that HHV-8/KSHV infection is not a feature of AIDS-PCNSL.

Antibodies, Viral↗
PubMed1999

Value of combined approach with thallium-201 single-photon emission computed tomography and Epstein-Barr virus DNA polymerase chain reaction in CSF for the diagnosis of AIDS-related primary CNS lymphoma.

PURPOSE: To determine the diagnostic capability of thallium-201 (201Tl) single-photon emission computed tomography (SPECT) combined with Epstein-Barr virus DNA (EBV-DNA) in CSF for the diagnosis of AIDS-related primary CNS lymphoma (PCNSL). PATIENTS AND METHODS: All human immunodeficiency virus (HIV)-infected patients with focal brain lesions observed between June 1996 and March 1998 underwent lumbar puncture and 201Tl SPECT. Each CSF sample was tested with polymerase chain reaction (PCR) for EBV-DNA. RESULTS: Thirty-one patients were included, 13 with PCNSL and 18 with nontumor disorders. In 11 PCNSL patients, EBV-DNA was positive. Thallium-201 uptake ranged from 1.90 to 4.07 in PCNSL cases (mean, 2.77; 95% confidence interval [CI], 2.35 to 3.19) and from 0.91 to 3.38 in nontumor patients (mean, 1.62; 95% CI, 1.30 to 1.94) (P<.0002). Using a lesion/background ratio of 1.95 as cutoff, a negative SPECT was found in one PCNSL case and 16 nonneoplastic cases. A cryptococcoma and a tuberculoma showed highly increased 201Tl uptake. Epstein-Barr virus DNA was never detected in nonneoplastic patients. For PCNSL diagnosis, hyperactive lesions showed 92% sensitivity and 94% negative predictive value (NPV), whereas positive EBV-DNA had 100% specificity and 100% positive predictive value. The presence of increased uptake and/or positive EBV-DNA had 100% sensitivity and 100% NPV. CONCLUSION: Combined SPECT and EBV-DNA showed a very high diagnostic accuracy for AIDS-related PCNSL. Because PCNSL likelihood is extremely high in patients with hyperactive lesions and positive EBV-DNA, brain biopsy could be avoided, and patients could promptly undergo radiotherapy or multimodal therapy. On the contrary, in patients showing hypoactive lesions with negative EBV-DNA, empiric anti-Toxoplasma therapy is indicated. In patients with discordant SPECT/PCR results, brain biopsy seems to be advisable.

Adult↗
PubMed1999

Epstein-Barr virus in monitoring the response to therapy of acquired immunodeficiency syndrome-related primary central nervous system lymphoma.

To evaluate the value of Epstein-Barr virus DNA (EBV-DNA) assay in cerebrospinal fluid (CSF) for monitoring the response to treatment in acquired immunodeficiency syndrome-related primary central nervous system lymphoma (AIDS-PCNSL), 9 human immunodeficiency virus-infected patients with biopsy-proven AIDS-PCNSL who underwent multimodal therapy were investigated for EBV-DNA detection in CSF by semiquantitative nested polymerase chain reaction (PCR). Tumoral tissue expression of bcl-6 oncogene protein and of EBV-encoded latent membrane protein (LMP-1) was also investigated. The 2 patients who had a response to chemotherapy showed a reduction of mean EBV-DNA concentration values after chemotherapy and displayed a large noncleaved morphology and a BCL-6+/LMP-1- phenotype. Conversely, the 4 patients with progressive disease after chemotherapy showed increasing mean values of EBV-DNA and displayed an immunoblastic morphology and a BCL-6-/LMP-1+ phenotype. No significant changes were observed for patients with stable disease. EBV-DNA burden reduction was significantly associated with prolonged survival. These results suggest that EBV-DNA monitoring might be helpful in predicting response to chemotherapy and in segregating distinct biological and prognostic categories of AIDS-PCNSL.

Analysis of Variance↗
PubMed1998

Nosocomial bloodstream infections in HIV-infected patients: attributable mortality and extension of hospital stay.

A 3-year prospective matched case-control study was performed to investigate the potential risk factors, prognostic indicators, extension of hospital stay, and attributable mortality of nosocomial bloodstream infections in HIV-infected patients. Matching variables were: age, gender, number of circulating CD4+ T lymphocytes, cause of hospital admission, hospitalization in the same ward within the 6 weeks of diagnosis of the case, and length of stay before the day of infection in the case. Eighty-four cases and 168 matched controls were studied. Nosocomial bloodstream infections complicated about 3 of 1000 hospital days per patient in the study period. With step-wise logistic regression analysis, the most important predictors for developing nosocomial bloodstream infections were: increasing value of Acute Physiology and Chronic Health Evaluation (APACHE II) score (p = .001) and use of central venous catheter (CVC) (p = .002). The excess of hospital stay attributable to nosocomial bloodstream infections was 17 days. The crude mortality rate was 43%. The attributable mortality rate was estimated to be 27% (95% confidence interval [CI] = 13%-48%). The estimated risk ratio for death was 3.91 (95% CI = 2.06-7.44). Multivariate analysis identified two prognostic indicators that were significantly associated with unfavorable outcome of bloodstream infections: number of circulating CD4+ T cells <100/mm3 (p = .002) and APACHE II score >15 (p = .01). Nosocomial bloodstream infections are more common in patients with advanced HIV disease. Important cofactors are high APACHE II score and use of CVC. These infections can cause an excess mortality and significantly prolong the hospital stay of HIV-infected patients.

Adult↗
PubMed1998

Changing disease patterns in focal brain lesion-causing disorders in AIDS.

OBJECTIVES: To assess temporal trends of the different disorders causing focal brain lesions (FBL) in HIV-infected patients and to examine the reliability of the U.S. Centers for Disease Control and Prevention (CDC) criteria for presumptive diagnosis of toxoplasmic encephalitis (TE) for the years 1991 to 1996. DESIGN/METHODS: A prospective, monocenter study. Percentages of occurrence of the different FBL-causing disorders for each year were calculated. Temporal trends were analyzed by chi2 test for linear trend and multivariate polytomous nonordinal logistic regression. The positive predictive value (PPV) of the CDC's presumptive criteria for the diagnosis of TE (recent onset of a focal neurologic abnormality consistent in intracranial disease or a reduced level of consciousness, evidence on brain imaging of a lesion having mass effect or the radiographic appearance of which is enhanced by injection of contrast medium, and serum antibody to toxoplasmosis) was calculated using contingency tables for each calendar year. RESULTS: A highly significant decline of the risk of TE and an increase of the probability of patients to take anti-Toxoplasma prophylaxis were observed. A threefold but statistically not significant augmented risk of diagnosing both primary central nervous system lymphoma (PCNSL) and progressive multifocal leucoencephalopathy (PML) has been registered for 1996 compared with 1991. Among FBL showing contrast enhancement, the increased finding of PCNSL over the years studied was significant. The probability of other FBL-causing disorders, such as focal viral encephalitis sustained by cytomegalovirus or herpes simplex virus, increased significantly over the years studied. Multivariate analysis confirmed that the year of diagnosis of FBL had a significant effect on the risk reduction of TE. The PPV of the CDC's criteria for the presumptive diagnosis of TE dropped from 100% for the year 1991 to 39% in the year 1996. A similar result was obtained in calculating the PPV of presumptive criteria only among patients without previous primary prophylaxis. CONCLUSIONS: Because of the significant decrease of TE and the increase of PCNSL empiric anti-Toxoplasma therapy no longer seems appropriate as a first-line approach to all HIV-positive patients with FBL. Especially in the case of a finding of FBL by contrast enhancement, new diagnostic strategies should be employed to identify the underlying disorder rapidly and accurately.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Bacterial pneumonia in HIV-infected patients: analysis of risk factors and prognostic indicators.

This case control study assessed risk factors and prognostic indicators of 350 episodes of bacterial pneumonia in 285 HIV-infected patients. On univariate analysis, intravenous drug abuse (i.v.DA; p < .001 versus controls), regular cigarette smoking (p < .001), cirrhosis (p = .04), and history of a previous episode of pneumonia (p = .04) were risk factors for community-acquired episodes of bacterial pneumonia, whereas length of hospitalization (p = .01) was a risk factor only for nosocomial bacterial pneumonia. The small amount of circulating T CD4+ cells (<100/ mm3) was a risk factor in both groups of pneumonia (p < .05). Stepwise logistic regression analysis revealed that i.v.DA in community-acquired episodes and low levels of circulating T CD4+ cells, both in community-acquired and hospital-acquired episodes, were independent risk factors for the development of bacterial pneumonia. The case-fatality rate observed in our study was 27%. On stepwise logistic regression analysis, T CD4+ cell counts < or = 100/mm3 (p = .02), neutropenia (p = .04), PO2 arterial level < or = 70 mm Hg (p = .01), and Karnofsky score < or = 50 (p = .04) were independent indicators of mortality. According to a personally developed prognostic score, 211 episodes of pneumonia (60%) were classified as mild, 63 (18%) as moderate, and 76 (22%) as severe. Clinicians must carefully evaluate those variables that can influence the prognosis of bacterial pneumonia to make early identification of affected patients and to promptly establish the most appropriate therapeutic strategy in each case.

AIDS-Related Opportunistic Infections↗
PubMed1998

Phase II controlled trial of post-exposure immunization with recombinant gp160 versus antiretroviral therapy in asymptomatic HIV-1-infected adults. VaxSyn Protocol Team.

OBJECTIVE: To alter the natural course of HIV-1 infection by inducing or potentiating immune responses to HIV-1 envelope glycoprotein. DESIGN: Multicentre, double-blind, three-arm, placebo-controlled study. SETTING: Outpatients attending clinics in two University Hospitals. PATIENTS: Ninety-nine asymptomatic HIV-1-infected adults with CD4+ T-cell counts > 400 and < 600 x 10(6)/l and no previous antiretroviral therapy were included. INTERVENTIONS: Patients were randomly assigned to three groups treated with: (i) gp160 in alum over a 2-year period in combination with placebo for the full study duration (n = 32); (ii) gp160 in alum over a 2-year period in combination with zidovudine for the full study duration (n = 34); and (iii) alum over a 2-year period in combination with zidovudine for the full study duration (n = 33). RESULTS: Immunotherapy was well tolerated and no significant differences in disease progression were seen in the treatment groups. The majority of patients (85%) receiving gp160 showed persistent lymphoproliferative responses to the immunogen and to a different Env antigen preparation. CD4+ cell count changes in patients receiving zidovudine alone were significantly higher than those seen in patients receiving immunotherapy alone after 1 year of treatment. Zidovudine administration was associated with initial transient reduction of plasma viraemia. CONCLUSIONS: Prolonged immunization with a soluble HIV-1 subunit provided no benefit to asymptomatic HIV-1-infected patients and was inferior to zidovudine monotherapy. Furthermore, immunization with gp160 shortened the duration of the transient viral load reduction induced by zidovudine.

AIDS Vaccines↗
PubMed1998

Minimally invasive diagnosis of acquired immunodeficiency syndrome-related primary central nervous system lymphoma.

BACKGROUND: The detection of Epstein-Barr virus (EBV)-DNA in cerebrospinal fluid (CSF) by means of the polymerase chain reaction (PCR) has been revealed, in retrospective studies, to be a good marker of primary central nervous system lymphoma (PCNSL) related to acquired immunodeficiency syndrome (AIDS); however, the technique's usefulness in the management of AIDS patients with focal brain lesions is still unknown. We studied the clinical usefulness of testing CSF obtained by lumbar puncture for the presence of EBV-DNA as a minimally invasive approach to the diagnosis of AIDS-PCNSL in patients with focal brain lesions. METHODS: Human immunodeficiency virus (HIV)-infected patients with focal brain lesions, observed prospectively during a 30-month period, underwent lumbar puncture if not contraindicated; otherwise, ventricular CSF was obtained at brain biopsy. The presence of EBV-DNA was determined by means of PCR. RESULTS: We evaluated 122 patients: 42 diagnosed with brain lymphoma and the remaining 80 diagnosed with other brain disorders. Cerebrospinal fluid was collected from 101 patients--by lumbar puncture in 95, including 40 patients with AIDS-PCNSL. The sensitivity and specificity of PCR for EBV-DNA detection in lumbar CSF were 80% (95% confidence interval [CI] = 60.9%-91.6%) and 100% (95% CI = 92.6%-100%), respectively. Lumbar puncture and subsequent assessment of EBV-DNA would have allowed a correct diagnosis in 63.2% (95% CI = 46.0%-77.7%) of patients with AIDS-PCNSL and excluded this diagnosis in 76.3% (95% CI = 65.2%-84.8%) of patients without lymphoma (because EBV-DNA was not detected). CONCLUSIONS: The presence of EBV-DNA in lumbar CSF is a sensitive and highly specific diagnostic marker of AIDS-PCNSL, and EBV-DNA detection in this fluid may allow a minimally invasive diagnosis in a large percentage of patients with brain lymphomas.

Adult↗
PubMed1998

Major liver resection for non-Hodgkin's lymphoma in an HIV-positive patient: report of a case.

A very unusual clinical presentation of non-Hodgkin's lymphoma (NHL) of the liver is reported herein. The patient was a 35-year-old male who had been HIV-positive since 1987. Following an episode of acute pain in the right upper abdominal quadrant, ultrasonography (US) and computed tomography (CT) were performed, revealing a nodular lesion, 2.5 cm in diameter, localized in the eighth segment of the liver. Despite the fact that the lesion became significantly enlarged over a 6-month period, three repeated percutaneous biopsies proved negative. Finally, his increasing pain and the lack of a definitive diagnosis prompted us to perform a right hepatectomy. The patient had an uneventful postoperative course and is well 1 year after his operation. Establishing a diagnosis of extranodal lymphoma can be difficult, especially in HIV-positive or AIDS patients. Thus, performing a laparotomy is justified to confirm a diagnosis and decide upon the most appropriate treatment. However, in about 10% of these patients, only surgical resection allows for the diagnosis. In accordance with other reports, our experience confirms that, in contrast with AIDS patients, HIV-positive patients have a similar prognosis as non-HIV patients, and are suitable candidates for even major surgical procedures.

Adult↗
PubMed1998

A new, striking morphological alteration of P-glycoprotein expression in NK cells from AIDS patients.

Natural killer cells from healthy donors express P-glycoprotein on their surface. This molecule is rearranged during the process of cell-mediated cytotoxicity and it appears to be clustered in the cell-to-cell contact regions. By contrast, in HIV-infected subjects this rearrangement is hindered. These results seem to be associated with cytoskeleton network alterations of the cell-mediated killing process occurring in AIDS patients and can contribute to the comprehension of the mechanisms of the natural killer cell deficiency found in these patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗