Drug-resistant tuberculosis in HIV-infected persons: Italy 1999-2000.

BACKGROUND: Patients with HIV infection may be a valuable target for assessing the impact of drug-resistant tuberculosis (TB). PATIENTS AND METHODS: An observational, prospective study was conducted in 96 infectious disease hospital units in Italy during 1999-2000. A total of 140 HIV-infected patients with diagnosis of TB and with an isolate tested for drug susceptibility entered the analysis. Drug resistance (DR) was defined as resistance to either isoniazid (INH) or rifampin (RIF), while multidrug resistance (MDR) was defined as resistance to INH and RIF. RESULTS: A total of 117 (83.6%) episodes of TB were classified as new cases and 23 (16.4%) as previously treated cases. Prevalence of resistance to INH or RIF was 12.8% and 4.3% among new cases, and 17.4% and 26.1% among previously treated cases, respectively. Prevalence rates of DR and MDR were 14.5% and 2.6% among new cases and 30.4% and 12.5% among previously treated cases, respectively. No statistically significant risk factors associated with DR or MDR TB emerged in this analysis. CONCLUSION: High prevalence rates of DR and MDR are present among HIV-infected TB patients in Italy, in particular among previously treated cases.

Tuberculosis in HIV-infected persons in the context of wide availability of highly active antiretroviral therapy.

Highly active antiretroviral therapy (HAART) greatly reduces the risk of developing tuberculosis for HIV-infected persons. Nonetheless, HIV-associated tuberculosis continues to occur in countries where HAART is widely used. To identify the characteristics of HIV-infected persons who develop tuberculosis in the context of the availability of HAART, the current authors analysed data taken from 271 patients diagnosed, in Italy, during 1999-2000. These patients represent 0.7% of the 40,413 HIV-infected patients cared for in the clinical units participating in this current study. From the data it was observed that 20 patients (7.4%) had a previous episode of tuberculosis whose treatment was not completed. Eighty-one patients (29.9%) were diagnosed with HIV at tuberculosis diagnosis, 108 (39.8%) were aware of their HIV status but were not on antiretroviral treatment and 82 (30.3%) were on antiretroviral treatment. Patients on antiretroviral treatment were significantly less immunosuppressed than patients with HIV diagnosed concurrently with tuberculosis, or other patients not on antiretrovirals (median CD4 lymphocytes count: 220 cells x mm(-3) versus 100 cells x mm(-3), and 109 cells x mm(-3), respectively). No significant differences in clinical presentation of tuberculosis according to antiretroviral therapy status were recorded. Failure of tuberculosis control interventions (e.g. noncompletion of treatment) and of HIV care (delayed diagnosis of HIV infection and suboptimal uptake of therapy) may contribute to continuing occurrence of HIV-associated tuberculosis in a country where highly active antiretroviral therapy is largely available. However, a significant proportion of cases occur in patients who are on antiretroviral treatment.

Guidelines of tuberculosis preventive therapy for HIV-infected persons: a prospective, multicentre study. GISTA (Gruppo Italiano di Studio Tubercolosi e AIDS).

The aim of this study was to assess the degree of implementation of national guidelines for isoniazid preventive therapy (IPT) among human immunodeficiency virus (HIV)-infected individuals and factors affecting the impact of the programme. Twenty-eight infectious disease hospital units in Italy participated in this observational, multicentre, prospective cohort study. A number of HIV-infected subjects, (n=1,705) seen for the first time as outpatients, were included in this analysis. Of the subjects considered, 1,215 out of the 1,705 completed purified protein derivative (PPD) screening. Variables independently associated with offering and completion of PPD screening included having acquired immune deficiency syndrome (AIDS), higher educational levels and currently receiving therapy. Overall, 103 subjects were identified as candidates for IPT. Of these subjects, five had tuberculosis and 15 had contraindications to IPT. Forty subjects agreed to start IPT, and 29 completed a full-course regimen. The incidence of tuberculosis among IPT candidates who either did not begin or discontinued IPT was 6.1 per 100 person-yrs, while no cases of tuberculosis were observed in subjects completing IPT. Several factors may limit the implementation of an isoniazid preventive therapy programme for human immunodeficiency virus-infected persons. Physicians fail to offer purified protein derivative screening to patients with high degrees of immunodeficiency, and those with a more intense workload seem to pay less attention to this test. The high number of contraindications among patients and their low level of acceptance further affects the impact of isoniazid preventive therapy.

Role of guidelines in clinical practice for the management of HIV-related diseases.

Several guidelines have been developed for the diagnosis, treatment and prevention of infectious diseases. Actually, evidence-based clinical practice guidelines provide physicians and other health care professionals with scientific information about the most appropriate strategy for the management of these patients, in order to avoid unnecessary or inappropriate interventions. As medical technology rapidly increases and becomes more complex, clinical guidelines can help health care providers to assess current practices and integrate new technological advances. Since AIDS was first recognized nearly 20 years ago, remarkable progress has been made in improving the quality and duration of life for HIV+ patients. In this area, clinical guidelines have been developed to manage patient care, focusing on: antiretroviral therapy, prevention of opportunistic infections, and treatment of tuberculosis. The quality of the guideline is notable when appropriate methodologies are applied. Different methods for developing guidelines are evaluated here: Agency for Health Care Policy and Research (AHPCR) methodology is designed to produce evidence-based guidelines that are valid, clinically applicable, and flexible. Finally, the problems associated with the implementation of guidelines for HIV-related diseases and other infectious diseases are examined.

Impact of combination antiretroviral therapy on the risk of tuberculosis among persons with HIV infection.

OBJECTIVE: To assess the association between use of different antiretroviral regimens and incidence of tuberculosis among HIV-infected individuals. DESIGN: Observational, multicenter, prospective cohort study. SETTING AND PATIENTS: Twenty-eight infectious diseases hospital units in Italy. A total of 2160 HIV-infected persons were considered for enrolment in a study on the implementation of tuberculosis preventive therapy between 1 May 1995 and 30 April 1996. The 1360 subjects who completed tuberculin screening at base-line were included in this analysis. Information on the use of antiretroviral therapies over time was collected. The median duration of follow-up was 104 weeks and 997 subjects (73.3%) completed the study. MAIN OUTCOME MEASURE: Incidence of active tuberculosis according to different types of antiretroviral therapy. RESULTS: Eighteen cases of tuberculosis were observed with an overall incidence rate of 0.79 per 100 person-years of observation [95% confidence interval (CI), 0.51-1.31]. Tuberculin positivity and low CD4+ lymphocyte count were the only base-line variables independently associated with the risk of tuberculosis. During follow-up, 637 patients took double combination antiretroviral therapy and 387 took triple combination therapy. After adjusting for base-line characteristics of enrolled individuals, the relative hazard of tuberculosis was 0.16 (95% CI, 0.03-0.74) for double combination therapy and 0.08 (95% CI, 0.01-0.88) for triple combination therapy compared with no therapy or monotherapy. CONCLUSIONS: Combination antiretroviral therapy significantly reduced the risk of tuberculosis in HIV-infected persons. In industrialized countries, the widespread use of this treatment may determine a decrease in the incidence of HIV-associated tuberculosis, possibly contributing to a reduction in the overall incidence of tuberculosis.

CD4 Lymphocyte enumeration: comparison between flow cytometry and enzyme immunoassay.

Assessment of the CD4 lymphocyte number, currently performed by flow cytometry, is one of the main laboratory tests for establishing progression to acquired immunodeficiency syndrome (AIDS). An enzyme immunoassay has recently been commercialized which can be very useful for counting CD4 cells in laboratories where flow cytometers are not available. In the present study, a comparative evaluation of CD4 positive lymphocytes with flow cytometry and the enzyme assay was made in healthy subjects (N = 30, R = 0.88, P < 0.0001), human immunodeficiency virus (HIV)-infected individuals (N = 80, R = 0.91, P < 0.0001), and patients with autoimmune diseases (N = 28, R = 0.82, P < 0.001) or psoriasis (N = 18, R = 0.76, P = 0.01). A correlation between the two methodologies was not found in psoriatic patients under treatment with cyclosporin A (N = 7, R = 0.05, not significant). Some differences could be found at low CD4 lymphocyte levels since the influence of CD4 antigen eluted from monocytes or soluble CD4 in the whole blood sample could cause overestimation of CD4 cell numbers by the enzyme assay.

Apoptosis in HIV infection: protective role of IL-2.

Peripheral blood mononuclear cells from HIV-infected subjects have been demonstrated by different methods to die by apoptosis after short time in culture. In the present study the percentages of apoptotic cells have been measured by propidium iodide staining and flow cytometry in PBMC from healthy controls (15) and HIV-infected subjects with asymptomatic (10) or advanced (15) disease, with or without anti-viral treatment. The percentage of apoptosis significantly correlated with clinical stage (CDCII: 15.85% +/- 9.17, CDCIV: 22.6% +/- 5.97, P < 0.001) and the CD4/CD8 CD3 cell ratio. R = -0.57, P = 0.012), while no differences were found in relation to AZT therapy. By adding IL-2 to the cultures the percentages of apoptosis of PBMC from HIV-infected patients were significantly reduced in all experiments.