Antiretroviral therapy and improving AIDS survival.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
L Ortona
Publications and source records attributed to L Ortona.
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↗
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↗
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↗
Defining and measuring quality of life in medicine.
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Culture↗
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↗
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↗
Highly active antiretroviral therapy decreases the incidence of bacteremia in human immunodeficiency virus-infected individuals.
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AIDS-Related Opportunistic Infections↗
Routine use of PCR-reverse cross-blot hybridization assay for rapid identification of Mycobacterium species growing in liquid media.
A PCR-reverse cross-blot hybridization assay procedure that is able to rapidly identify 13 species of clinically relevant mycobacteria was evaluated for routine use in the identification of acid-fast isolates growing in BACTEC 460 TB (12B and 13A) and BACTEC 9000 MB (Myco/F) liquid media. Eight of the probes used were already described by Kox et al. (L. F. F. Kox et al., J. Clin. Microbiol. 33:3225-3233, 1995). In addition, we used six other probes specific for M. chelonae, M. malmoense or M. szulgai, M. genavense, M. gordonae, M. terrae, and M. marinum/M. ulcerans that we designed ourselves. This procedure allowed us to identify 459 mycobacterial species directly from broth cultures of 5,466 clinical samples collected over 1 year and processed with the radiometric or nonradiometric BACTEC system. Our results were in agreement with those obtained by conventional identification methods and also with those obtained by mycolic acid analysis by high-performance liquid chromatography. This assay seems to be a reliable procedure for the routine identification of mycobacteria, providing an accurate identification of mycobacterial isolates more rapidly than conventional tests, with remarkable implications for an efficacious specific antimycobacterial therapy.
Chromatography, High Pressure Liquid↗
Meningoencephalomyelitis caused by herpes simplex virus-1 in a patient with idiopathic T CD4+ lymphocytopenia.
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Adult↗
90K (Mac-2 BP) predicts CD4 decline in human immunodeficiency virus-infected patients with CD4 counts above 200 x 10(6) cells/L.
OBJECTIVE: To evaluate the ability of serum levels of 90K, previously reported as a progression marker of human immunodeficiency virus infection, to predict the future rate of CD4 lymphocyte decline. DESIGN: Retrospective analysis of data from outpatients enrolled in a multi-institutional study. PATIENTS: One hundred five human immunodeficiency virus-positive intravenous drug users who had at least six serial CD4 lymphocyte measurements and starting CD4 levels of 200 x 10(6) cells/L or higher. MAIN OUTCOME MEASURE: Rate of CD4 lymphocyte decline. RESULTS: During a median follow-up of 28 months (range, 20-36 months), the estimated loss of CD4 cells in the whole patient population was 3.4 x 106 cells/L per month (P = .0045). Subjects who were on zidovudine treatment at study entry showed an average loss of 3.8 x 10(6) cells/L per month, significantly higher than in untreated subjects (P = .02), but similar to the loss observed for those requiring initiation of treatment during the course of the study. At baseline, 56 subjects had 90K levels of 10 microg/mL or less, and 49 had more than 10 microg/mL. The rate of CD4 decline in the high-90K group was approximately 5 x 10(6) cells/L per month (P < .0015), whereas in the low-90K group it was not different from zero (P = ns). No difference emerged in the rate of CD4 decline when subjects were stratified according to baseline 90K levels and zidovudine treatment, beta2-microglobulin, or neopterin serum levels. CONCLUSION: 90K serum levels are predictive of CD4 decline.
Antigens, Neoplasm↗
Intracellular expression of P-170 glycoprotein in peripheral blood mononuclear cell subsets from healthy donors and HIV-infected patients.
BACKGROUND AND OBJECTIVE: P-glycoprotein (P-gp) is a transmembrane efflux pump that actively extrude a variety of unrelated drugs from cancer cells, leading to the so-called multidrug resistance (MDR) phenomenon. However, P-gp has also been found in normal bone marrow and peripheral blood mononuclear cells (PBMC). Recently, the presence of P-glycoprotein in PBMC from human immunodeficiency virus (HIV)-infected patients has also been investigated and a phenotype-associated P-gp expression has been detected. DESIGN AND METHODS: A total of thirty-eight HIV-1 positive patients with a mean age of 34 years (range, 24-41 years) were studied after an informed consent. Peripheral blood mononuclear cells (PBMC) were isolated by centrifugation on a Ficoll/Hypaque and P-glycoprotein expression was investigated on lymphocyte population by single and double-color immunofluorescence techniques. We investigated: i) both surface and intracellular expression of the P-gp molecule in different PBMC subsets, ii) P-gp expression modifications occurring during HIV infection, and iii) the effect of HIV-gp120 on the expression of P-gp by T lymphocyte subsets from healthy donors. RESULTS: Our experimental findings indicate that: a) P-gp glycoprotein can be detected on an intracellular level in different PBMC subpopulations (mainly CD8+ T lymphocytes, CD16+ NK cells and CD14+ monocytes); b) this intracellular expression is decreased in specific PBMC subsets (i.e. T-CD8+ and NK-CD16+) from HIV-infected patients and c) a rearrangement was obtained when CD4+ and CD8+ lymphocytes from healthy donors were exposed in vitro to the HIV-binding glycoprotein gp120. INTERPRETATION AND CONCLUSIONS: Our results indicate that P-gp glycoprotein can also be expressed intracellularly and can be rearranged in PBMC subsets from HIV-infected patients.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Evaluation of the Abbott LCx Mycobacterium tuberculosis assay in comparison with culture methods in selected Italian patients.
A ligase chain reaction (LCR) DNA amplification method for the molecular diagnosis of Mycobacterium tuberculosis (Abbott LCx MTB) was evaluated in comparison with solid and liquid phase culture on 622 selected samples collected in two large Italian hospitals, of which 310 obtained from HIV-1 positive patients and 312 from HIV-negative individuals. The overall prevalence of mycobacteria by culture was 22% (137/622), and the apparent sensitivity and specificity of LCx vs. culture were 87.6% and 98.2%. Of the 26 culture positive/LCx negative samples, 22 were positive for MOTT and 4 for M. tuberculosis. All 9 samples positive by LCx and negative by culture were classified as true positive by clinical criteria. The final values of sensitivity, specificity, positive predictive value and negative predictive value for LCx rose to 96.8%, 100%, 100% and 99.2%, respectively. The adjusted sensitivity of culture methods was 89.5% for solid phase and 92.7% for Bactec. In view of the high sensitivity on both smear-positive (100%) and smear-negative (92.4%) samples and of the high negative predictive value, the LCR-based amplification method appears suitable as a routine screening method for the rapid diagnosis of M. tuberculosis in high-risk patients.
DNA, Bacterial↗
Risk factors, nutritional status, and quality of life in HIV-infected patients with enteric salmonellosis.
AIMS: To define the potential risk factors, prognostic indicators, and quality of life of HIV-infected patients with enteric salmonellosis. METHODS: A five-year matched (1:2) case-control study was performed. Thirty cases and 60 matched controls were studied. RESULTS: Univariate analysis (p < 0.05) identified six risk factors for enteric salmonellosis: 1) increasing value of APACHE II score, 2) altered nutritional status, 3) previous antibiotic therapy, 4) ingestion of "risk" foods, 5) multiple (> or = 2) previous opportunistic infections, 6) stage C of HIV infection. Using the multivariate analysis, the most powerful predictors for developing an enteric salmonellosis were: increasing value of APACHE II score and altered nutritional status. The response to therapy was favourable in all episodes. Five (17%) patients suffered from one or more relapses. Multivariate analysis identified that a low number of circulating CD4+ (< 100/mm3) and a high APACHE II score (> 15) predict an increased risk of relapses. CONCLUSIONS: HIV-associated enteric salmonellosis occurs more frequently in patients with advanced stage of HIV infection and with impaired nutritional status. We stress the need for a prompt and accurate diagnosis and treatment since the possible haematogenous spread and relapses appear reduced under early and prolonged antibiotic therapy.
AIDS-Related Opportunistic Infections↗
Central venous catheter-related sepsis in a cohort of 366 hospitalised patients.
Five hundred two central venous catheters inserted in 366 patients were evaluated prospectively over a one-year period to determine the frequency and risk factors associated with catheter-related sepsis. For study purposes, in cases in which catheter infection was suspected but the initial blood cultures were negative, the catheters were replaced by guidewire technique; otherwise, the catheters were routinely changed after 21 days by guidewire technique. A catheter-related infection was suspected in 190 cases (190/502, 38%). A diagnosis of catheter-related sepsis was established in 50 patients, which represents 10% of the total number of lines (502). Over a total of 6428 days of catheter use, the infection rate was 0.8 cases of sepsis per 100 catheter-days. Staphylococcus epidermidis, Staphylococcus aureus, and Candida spp. were the most frequently isolated aetiological agents of sepsis. On univariate analysis, six variables affecting the rate of catheter-related sepsis were identified: neutropenia for more than eight days (p < 0.001); AIDS (p < 0.001); haematological malignancy (p < 0.001); administration of total parenteral nutrition (p = 0.001); duration of site use (p = 0.04); and high APACHE II score (p = 0.04). The logistic regression analysis revealed that AIDS and haematological malignancies were independent risk factors of catheter-related sepsis. Catheter replacement over a guidewire was no more likely to be associated with sepsis than was percutaneous catheter insertion. In conclusion, although the incidence of established catheter infection is much lower than the incidence of suspected infection, in most cases of suspected infection it is wise to change the catheter with the guidewire technique and wait for culture of the tip, rather than to remove the catheter immediately. Such a policy may help reduce the number of unnecessary catheter removals.
APACHE↗
Comparative analysis of prognostic indicators of aspergillosis in haematological malignancies and HIV infection.
The objective of this study was to identify the prognostic factors influencing the outcome of aspergillosis in two models of immunodeficiency, namely haematological malignancies and HIV infection. The study is based on a 5 year prospective logistic regression analysis of risk factors, clinical features, radiological findings and therapy affecting the prognosis of aspergillosis in 43 patients, i.e. 27 haematological neoplastic patients (group A) and 16 HIV infected patients (group B). Univariate analysis indicated that neutropenia (P = 0.02), haemoptysis (P = 0.03) and concomitant AIDS (P = 0.02), negatively influenced the prognosis of aspergillosis. Comparing the two groups of patients, significant differences emerged in the prognostic indicators. In particular respiratory failure (P = 0.02) and radiological bilateral involvement of the lungs were associated with a poor prognosis in group A (P = 0.04) and low (2100/mm3) T CD4+ cell count in group B (P = 0.02). At variance, a better prognosis was documented in patients treated with sequential therapy (amphotericin B and itraconazole) only within the group of haematological patients (P = 0.003). On multivariate analysis sequential therapy (P = 0.01) and AIDS (P = 0.03) were independent prognostic indicators of aspergillosis. In conclusion, our prospective study indicates that aspergillosis, although an uncommon event in patients with HIV infection, has a more severe prognosis in comparison to haematological patients. Future prospective clinical trials are necessary to confirm the real importance of the sequential therapy, with amphotericin B and itraconazole, in patients with aspergillosis.
Adult↗
Fluconazole resistant oral candidiasis in HIV-infected patients.
OBJECTIVE: To evaluate the risk factors associated with the emergence of fluconazole resistant Candida spp. in HIV-infected patients with oral candidiasis. METHODS: Candida spp. were isolated from oral swabs and tested in vitro for resistance to fluconazole. The factors potentially correlated with vazole-resistent Candida spp. infections were investigated. RESULTS: Fifty-one out of 118 patients (43%) with oral candidiasis had fluconazole resistant Candida spp. The following factors were significantly associated with the development of fluconazole resistance: (1) more than five episodes of oral candidiasis in the previous year (P < 0.001); (2) fluconazole therapy in the previous 6 months (P < 0.001); (3) C3 category of HIV infection (P < 0.001); and (4) low number of TCD4+ cells (< 50 mm3, P = 0.002). According to multivariate analysis, previous therapy with fluconazole was the only risk factor that independently influenced the development of Candida spp. resistance (P = 0.003). CONCLUSIONS: The prophylaxis and therapy of mild fungal infections in HIV-infected patients, which may lead to azole resistance, should be carefully considered.
AIDS-Related Opportunistic Infections↗
Pneumothorax in HIV-infected patients: role of Pneumocystis carinii pneumonia and pulmonary tuberculosis.
Patients with acquired immune deficiency syndrome (AIDS) are at increased risk for pneumothorax, which usually occurs in the setting of Pneumocystis carinii pneumonia. The rationale of the present study was based on the hypothesis that the increased incidence of pulmonary tuberculosis in human immunodeficiency virus (HIV)-infected patients could favour the development of pneumothorax in such patients. A case-control study was performed comprising 140 HIV-infected patients grouped as follows: 35 patients with pneumothorax and 105 matched controls without pneumothorax. Univariate analysis identified four risk factors for pneumothorax: 1) previous P. carinii pneumonia (p=0.01); 2) current P. carinii pneumonia (p=0.02); 3) pulmonary tuberculosis (p=0.01); and 4) cysts, pneumatoceles or bullae on chest radiographs (p<0.001). Multivariate analysis indicated that current P. carinii pneumonia (p=0.01) and pulmonary tuberculosis (p=0.04) were both independent risk factors for pneumothorax. In conclusion, our findings demonstrate that, in addition to Pneumocystis carinii pneumonia, pulmonary tuberculosis enhances the risk of pneumothorax in patients with acquired immune deficiency syndrome.
AIDS-Related Opportunistic Infections↗