Lack of Response to HBHA in HIV-Infected Patients with Latent Tuberculosis Infection.

Heparin-binding haemagglutinin (HBHA) has been proposed as an immunological biomarker for discriminating active tuberculosis (TB) from latent TB infection (LTBI) and to identify those at higher risk of progressing to active disease. Few data are available in immune-compromised patients, which are those with increased risk of TB reactivation. The aim of this stusy was to evaluate the immune response to HBHA in HIV-infected subjects with LTBI (HIV-LTBI) or active TB (HIV-TB) in comparison with the immune response to additional Mycobacterium tuberculosis (Mtb) or HIV and CMV antigens. The responses are evaluated in relation to TB status and in the LTBI subjects with the progression to active TB within 2 years. Forty-one HIV-infected antiretroviral-naïve subjects were prospectively enrolled: 18 were HIV-TB and 23 HIV-LTBI. Whole blood was in vitro stimulated overnight with several antigens and mitogen. Interferon-γ response in the harvested plasma was evaluated by ELISA. Despite that CD4 cell count was significantly different between HIV-LTBI and HIV-TB, no differences were observed in response to Mtb- or HIV-specific antigens. Differently, low responses to HBHA were observed in both HIV-LTBI and HIV-TB subjects. Importantly, none of the six HIV-LTBI responding to HBHA developed TB, while two of 17 non-HBHA responders developed active disease. HIV-TB-coinfected subjects, regardless of their TB status, showed low responses to HBHA despite maintaining detectable responses to other antigens; moreover, among the HIV-LTBI, the lack of HBHA responses indicated an increased risk to develop active TB. These results, although preliminary, suggest that a positive response to HBHA in HIV-LTBI correlates with Mtb containment.

Ageing with HIV: newly diagnosed older adults in Italy.

The prevalence of HIV/AIDS among people in midlife and late adulthood has been increasing in Western countries over the last decade. We analyzed data from a prospective, observational multi-centre study on individuals newly diagnosed with HIV between January 2004 and March 2007 in 10 public counselling and testing sites in Latium, Italy. At diagnosis, routine demographic, epidemiological, clinical and laboratory data are recorded, and patients are asked to complete a questionnaire investigating socio-demographic and psycho-behavioural aspects. To analyze the association of individual characteristics with age, we compared older adults (> or = 50 years) with their younger counterpart (18-49 years). To adjust for potential confounding effect of the epidemiological, clinical and behavioural characteristics, to identify factors associated with older age at HIV diagnosis, multivariate logistic regression analysis was performed. Overall, 1073 individuals were identified, 125 of whom (11.6%) were aged 50 years or above. The questionnaire was completed by 41% (440/1073). Compared with their younger counterparts, a higher proportion of older patients were males, born in Italy, reported heterosexual or unknown HIV risk exposure, were never tested for HIV before and were in a more advanced stage of HIV infection at diagnosis. In addition, older adults had a lower educational level and were more frequently living with their partners or children. With respect to psycho-behavioural characteristics, older patients were more likely to have paid money for sex and have never used recreational drugs. Interestingly, no differences were found regarding condom use, which was poor in both age groups. These findings may have important implications for the management of older adults with HIV, who should be targeted by appropriate public health actions, such as opportunistic screening and easier access to healthcare. Moreover, strategies including information on HIV and prevention of risk behaviours are needed.

Neurocognitive impairment influences quality of life in HIV-infected patients receiving HAART.

The objective of the study was to determine the association of neurocognitive impairment with health-related quality of life (HRQoL) in patients receiving highly active antiretroviral therapy (HAART). Seventy subjects were cross-sectionally analysed with a standardized neuropsychological test battery and a questionnaire including an Italian translation of the MOS-HIV Health Survey. The presence of neurocognitive impairment was significantly associated with lower HRQoL scores: pain (P = 0.03), physical functioning (P = 0.01), role functioning (P = 0.01), social functioning (P = 0.029), mental health (P = 0.001), energy (P = 0.036), health distress (P = 0.002), cognitive functioning (P = 0.05), current health perception (P <0.001), physical health summary score (PHS) (P = 0.005), mental health summary score (MHS) (P = 0.002). Years of education (odds ratio [OR] 0.79; 95% confidence interval [CI] 0.65-0.96), PHS (OR 0.71; 95% CI 0.54-0.95) and MHS (OR 0.67; 95% CI 0.51-0.88) were also associated with cognitive impairment. Neurocognitive impairment in patients receiving HAART was associated with reduced HRQoL. Identifying cognitive impairment may provide motivation for additional treatment to help patients to compensate for deficits in functioning.

Changes in neurocognitive performance in a cohort of patients treated with HAART for 3 years.

OBJECTIVES: To describe changes in HIV-associated neurocognitive impairment in patients treated with highly active antiretroviral therapy (HAART) for at least 3 years. METHODS: Prospective, observational study of comprehensive neuropsychologic (NP) testing, neurologic examination, and laboratory measures before HAART and after 6, 15 and 45 months of HAART, on 28 consecutive patients seen in our department since April 1996. RESULTS: At baseline, 16 patients were neurocognitively impaired and 12 were not. Among the 16 impaired patients, 5 patients failed to meet the criteria for impairment after 6 months and 9 patients after both 15 and 45 months of HAART, respectively. Statistically significant improvements ( p < or =.01) were seen in two of six measures exploring the concentration and speed of mental processing, two of three measures exploring mental flexibility, in one of five measures exploring memory, and in two of two measures exploring fine motor functions. Unimpaired study subjects performed better than impaired ones in 10 of 17 measures at baseline, in eight of 17 after 6 months, in six of 17 after 15 months, and in seven of 17 after 45 months of HAART. CONCLUSIONS: During the course of HAART, patients experienced a positive and sustained improvement in their neurocognitive performance. However, the presence of 7 of 16 (43.7%) patients with neurocognitive impairment, and the persistence of statistically significant differences in the neurocognitive performance between impaired and unimpaired patients after more than 3 years of HAART, suggests that ongoing HIV-related neurologic damage can occur even during potent antiretroviral treatment.

Increasing proportion of late diagnosis of HIV infection among patients with AIDS in Italy following introduction of combination antiretroviral therapy.

We analyzed trends over time and determinants of late diagnosis of HIV infection among people diagnosed with AIDS in 1986 to 1998 in a tertiary care center in Rome, Italy. Information on the date of a first HIV test was collected prospectively, in addition to data routinely collected for AIDS reporting. Patients with AIDS were defined as "late testers" if the time interval between first positive HIV test result and AIDS diagnosis was < or = 3 months. Overall, 503 people with AIDS of 1977 included in the analysis (25.4%) were late testers. the proportion of late testers decreased from 62.5% in 1986 to 16% in 1995. Thereafter, this proportion increased to 20.5% in 1996, 33.7% in 1997, and 36.6% in 1998. In multivariate analysis, the following variables were significantly associated with late testing: AIDS diagnosis in years 1986 to 1993 or 1997 to 1998 compared with 1995, male gender, age > or = 45 years, men who have sex with men, heterosexual contacts, or having unknown transmission mode compared with intravenous drug users, and being born outside Italy. Since 1996, the overall number of AIDS cases diagnosed at our center began to decrease whereas the number of late-testing AIDS patients did not decrease, resulting in an increasing proportion of late testers during the last 3 years of the study. This findings may reflect the effect of combination antiretroviral therapy in slowing progression to AIDS of HIV-infected persons aware of their status. A relevant number of people still discover their HIV infection late and may therefore miss treatment opportunities. New testing strategies are needed to reach more people who engage in high-risk behaviors, especially those at risk for sexual transmission, and those born outside Italy.

Coronary venous retroperfusion support during high risk angioplasty in patients with unstable angina: preliminary experience.

Synchronized coronary venous retroperfusion was used during coronary balloon angioplasty to support the ischemic myocardium of 20 patients with unstable angina and anatomy at high risk of a coronary event. Hemodynamics and left ventricular function were the major end points of the study. Coronary venous catheterization and retroperfusion were successfully performed in 15 patients. The target vessel was an unprotected left main artery in 2, left anterior descending artery in 10, left circumflex coronary artery in 1 and right coronary artery in 2 patients. A nonsupported balloon inflation (mean 44 +/- 13 s) was compared with a later retroperfusion-supported inflation (mean 145 +/- 21 s). Right anterior oblique left ventriculograms, aortic blood pressure, pulmonary artery pressure and thermodilution cardiac output were obtained before and during peak untreated and treated balloon inflations and on completion of angioplasty. All patients had either a baseline left ventricular ejection fraction less than 0.40 or greater than 40% of contracting myocardium estimated to be at risk for severe ischemia during angioplasty. The cardiac (liters/min per m2) and stroke work (g.m/m2) indexes decreased from mean baseline values of 2.5 +/- 0.52 and 52 +/- 15 to 1.7 +/- 0.47 and 27 +/- 12 (mean +/- SD), respectively, during nonsupported balloon inflations but decreased only to 2.1 +/- 0.52 (p less than 0.01 vs. nonsupported) and to 36 +/- 14 (p = 0.01 vs. nonsupported), respectively, during retroperfusion-supported inflations. Ejection fraction (n = 8) decreased from a baseline value of 55 +/- 13% to 27 +/- 7.3% during nonsupported inflations but only to 39 +/- 10% during retroperfusion-supported inflations (p = 0.01 vs. nonsupported). Regional wall motion (area change) in the ischemic (target) region was reduced from a baseline value of 49 +/- 17% to 11 +/- 16% during nonsupported inflations but only to 27 +/- 15% during retroperfusion-supported inflations (p less than 0.01 vs. nonsupported). All but two patients had a favorable hemodynamic response to retroperfusion. There were no serious adverse effects related to the procedures and no hospital deaths. It is concluded from this preliminary study that coronary venous retroperfusion appears to be safe, to provide hemodynamic support and to improve left ventricular function during angioplasty in patients with unstable angina and anatomy at high risk of a coronary event.