Highly active antiretroviral therapy decreases the incidence of visceral leishmaniasis in HIV-infected individuals.
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Biomedical subjects
Publications and source records attributed to M Tumbarello.
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To evaluate the changing characteristics of HIV-associated bacteremia in the highly active antiretroviral therapy (HAART) era, we conducted a prospective case control study, comparing two periods of time, before (period A) and after (period B) the introduction of HAART. In total, 174 patients with bacteremia and 348 controls were studied. By comparing incidence in periods A and B, a statistically significant reduction of bacteremia, from 11.8 to 6.3/100 person-years (PY), was observed (p = .0001). Incidence of hospital-acquired bacteremia decreased from 5.8 episodes/100 PY in period A to 2.4/100 PY in period B (p = .0005). A similar trend was also observed for community-acquired episodes of bacteremia, with a value close to statistical significance. Logistic regression analysis indicated that intravenous drug abuse, central venous catheter (CVC) use, high value on APACHE III score, and neutropenia were independent risk factors for bacteremia in both the study periods. Interestingly, comparing the prevalence of bacteremia risk factors in the two study periods, we observed a significant reduction in the use of CVC (p = .04, period A versus period B) and in neutropenia (p = .04). The crude mortality rate was 31% in period A and 23% in period B (p = not significant [ns]). Logistic regression analysis indicated that an high value of Acute Physiology and Chronic Health Evaluation III (APACHE III) score (p < .001) predicted an increased risk of death. Analysis of prognostic factors of bacteremia did not significantly differ in both the study periods. We conclude that HAART has determined a significant reduction of the incidence and a modification of the characteristics of bacteremia. This reduced incidence may produce a substantial impact on future morbidity and health care costs of patients with HIV.
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The aim of the study was to assess the incidence of hospital and community acquired bacterial pneumonia in HIV-infected subjects prior to and after the introduction of highly active antiretroviral therapy (HAART). We studied 266 patients with bacterial pneumonia over two separate periods, 154 in the first period and 112 in the second period. A statistically significant difference in the incidence of bacterial pneumonia in the two study periods was observed ranging from 13.1 to 8.5 episodes per 100 persons. The incidence of community-acquired bacterial pneumonia decreased from 10.7 to 7.7 (P=0.01), while that of nosocomial episodes decreased from 2.4 to 0.8 episodes (P=0.003). Low levels of peripheral CD(4+) cells (<100/mm(3)) and intravenous drug abuse (IVDA) were significantly associated with the development of community-acquired bacterial pneumonia, while an increasing value of APACHE III score and prolonged hospitalisation increased the risk of nosocomial bacterial pneumonia in both study periods.
Technical complications and nosocomial bloodstream infections associated with short-term central venous catheterization remain a heavy burden in terms of morbidity, mortality and cost in HIV-positive subjects. Between 1994 and 1997, 327 central venous catheters (CVCs) inserted in 212 patients for a total of 5005 catheter days were investigated. Forty-two technical complications (13%) occurred in 40 patients. Logistic regression analysis revealed that a high APACHE III score was associated with development of CVC-related complications (P = 0.01). One hundred and eight of 327 CVCs (33%) were suspected as being infected. However only 61 episodes (61/327, 19%) were finally diagnosed as CVC-related sepsis. Three variables affecting the rate of CVC-related sepsis were identified: 1) administration of TPN (P = 0.01); 2) low number of circulating CD4+ cells (P = 0.04); 3) high APACHE III score (P = 0. 04). Doctors responsible for AIDS patients should carefully consider the relative risks and benefits of CVC insertion in an individual patient.
This study was conducted to evaluate the efficacy of highly active anti-retroviral therapy (HAART) in preventing recurrence of oral candidosis (OC) associated with HIV. A prospective case-controlled observational study was performed in an inner-city university-hospital HIV/AIDS clinic. Ninety-three HIV-positive study subjects with a history of recurrent OC were divided into two groups: protease inhibitors (PI)-treated patients (group 1, n = 30) and non-PI-treated patients (group 2, n = 63). Study subjects were matched for sex, age, stage of HIV infection, and peripheral CD4+ T-cell counts. The non-PI-treated group was further subdivided into the following three subgroups: HIV-positive study subjects treated with reverse transcriptase inhibitors (RTI; groups 2a and 2c) and HIV-positive study subjects not treated with RTIs (group 2b). Group 2c met the same inclusion criteria as group 2a had but was matched 6 months after the beginning of the study. We also assessed in vitro peripheral blood mononuclear cells (PBMC) and their lymphoproliferative response, as well as cutaneous delayed-type hypersensitivity (DTH) response to Candida-associated antigens in a randomly selected sample of study subjects divided into those treated with PIs and those who were not. During a 1-year follow-up, OC was diagnosed in 2 (7%) PI-treated and 23 (36%) non-PI-treated patients (p<.001). In addition to comparing findings in group 1 with those in group 2c, OC was detected in 14 (50%) non-PI-treated patients compared with no HAART-treated study subjects (p<.001). Only 41% of PI-treated study subjects had positive lymphoproliferative response in PBMCs and none was positive in terms of DTH to Candida antigens (p = not significant versus non-PI-treated study subjects). While objectively demonstrating a beneficial effect of HAART in preventing recurrence of OC infections, our findings suggest this effect cannot be not fully accounted for by reconstitution of anti-Candida cell-mediated immunity, given that other mechanisms, even of a nonimmune nature, could have some effect.
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The epidemiological features of 37 episodes of candidemia in HIV-infected subjects were analysed in a retrospective matched case-control study conducted over an 8-year period (1990-1997). Univariate analysis identified eight risk factors that were significantly associated with candidemia (P<0.05): i) use of central venous catheters; ii) administration of total parenteral nutrition; iii) previous antifungal therapy; iv) previous therapy with glycopeptides; v) presence of oral/ esophageal candidiasis; vi) concomitant bacterial infections; vii) neutropenia; and viii) concomitant AIDS dementia complex. Stepwise logistic regression analysis revealed that the only independent risk factor for developing candidemia was the use of central venous catheters (P = 0.0001). Candida albicans was the most frequently isolated pathogen, accounting for 18 (48%) episodes of candidemia, followed by Candida tropicalis (19%) and Candida glabrata (11%). The crude mortality rate was 62%. On univariate analysis concomitant opportunistic infections, presence of non-Candida albicans species of Candida and neutropenia were shown to be predictive of death. Multivariate analysis revealed that the presence of non-Candida albicans strains of Candida was the only significant factor associated with a worse prognosis (P = 0.001). In conclusion, candidemia appears to be more common in patients with advanced HIV disease. Of the factors which influenced the onset of candidemia, use of central venous catheters seemed to be the most important one.
Highly active antiretroviral therapy that includes human immunodeficiency virus (HIV) aspartyl protease inhibitors (PIs) causes a decline in the incidence of some opportunistic infections in AIDS, and this decline is currently attributed to the restoration of specific immunity. The effect of two PIs (indinavir and ritonavir) on the enzymatic activity of a secretory aspartyl protease (Sap) of Candida albicans (a major agent of mucosal disease in HIV-infected subjects) and on growth and experimental pathogenicity of this fungus was evaluated. Both PIs strongly (>/=90%) and dose dependently (0.1-10 microM) inhibited Sap activity and production. They also significantly reduced Candida growth in a nitrogen-limited, Sap expression-dependent growth medium and exerted a therapeutic effect in an experimental model of vaginal candidiasis, with an efficacy comparable to that of fluconazole. Thus, besides the expected immunorestoration, patients receiving PI therapy may benefit from a direct anticandidal activity of these drugs.
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The purpose of this study was to characterise the epidemiological and the clinical features of non-AIDS-defining neoplasms (NAN) in HIV-infected subjects in the era of highly active antiretroviral therapy (HAART). A retrospective cohort of 4,041 subjects was established. Patients were recruited from January 1989 to December 1998. We observed 51 NAN over the study period. The overall incidence rate was 0.21 per 100 person-years (PY) and it remained stable, also after the introduction, in 1996 of HAART. Moreover, stratifying according to the type of neoplasms there was no statistically significant difference in the incidence of NAN over the study period. While the epidemiological features of NAN generally was not different from that observed in immunocompetent individuals, the neoplasms had a more aggressive clinical course and a poor prognosis. Survival analysis showed that the presence of NAN significantly reduced the survival of patients with AIDS (P=0.01; OR=0.62; 95% CI=0.47-0.96) compared with matched controls. The overall mortality-rate was 63% with an incidence rate of 0.13 per 100 PY. Although the incidence rate of NAN is not of great magnitude, as the number of HIV-infected individuals continues to increase and their survival improves, the number of HIV-infected subjects with NAN might consequently increase as well as the related morbidity and mortality.
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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.
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.
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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.
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.