Respiratory syndrome and respiratory tract infections in foreign-born and national travelers hospitalized with fever in Italy.

BACKGROUND: We measured frequency and epidemiologic, clinical, and hematochemical variables associated with respiratory tract infections (RTIs) in foreign-born and national patients hospitalized with fever with a history of international travel, and compared the final diagnosis of RTI with the presence of a respiratory syndrome (RS) at presentation. METHODS: A prospective, multicenter, observational study was conducted at tertiary care hospitals in Northern Italy from September 1998 to December 2000. RESULTS: A final diagnosis of RTI was obtained in 40 cases (7.8%), 27 (67.5%) with lower RTI and 13 (32.5%) with upper RTI. The most common RTIs were pneumonia (35%) and pulmonary tuberculosis (15%). A white blood cell count > or = 10,000 and an erythrocyte sedimentation rate > or = 20 mm/h were independently associated with a final diagnosis of RTI; onset of symptoms at > or = 16 days and > or = 75% neutrophils were independently associated with lower RTI. An RS was identified in 51 (9.9%) of 515 travelers. Sensitivity, specificity, and positive and negative predictive values of a diagnosis of RS for a final diagnosis of RTI were 67.5%, 94.9%, 52.9%, and 97.2%, respectively. CONCLUSIONS: Pneumonia and pulmonary tuberculosis were frequent among foreign-born and national travelers with fever admitted to a tertiary care hospital. Half of the pneumonia cases did not present with an RS at first clinical examination.

Similar adherence rates favor different virologic outcomes for patients treated with nonnucleoside analogues or protease inhibitors.

BACKGROUND: This prospective study verified the effect of adherence on the risk of virologic failure. METHODS: At enrollment in the study, a total of 543 patients who were following a steady (duration, >or=6 months) and effective (viral load, <50 human immunodeficiency virus [HIV] RNA copies/mL) regimen of highly active antiretroviral therapy (HAART) completed a self-reported questionnaire derived from the Adult AIDS Clinical Trials Group Adherence Follow-up Questionnaire. Patients were followed up for the subsequent 6 months to document virologic failure, which was defined as 2 consecutive viral load measurements of >500 HIV RNA copies/mL. RESULTS: Only the type of treatment and the adherence rate at baseline were significantly associated with the virologic end point. Among patients who reported an adherence rate of 95%. When analysis was adjusted according to the type of regimen received, patients who were receiving protease inhibitor (PI)-based HAART and who had an adherence rate of up to 85% had a virologic failure rate of >20%, whereas, only for patients who were receiving nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based HAART and who had an adherence rate of 10%. For the comparison of NNRTI-treated patients and PI-treated patients with an adherence rate of 75%-95%, the odds ratio was 0.157 (95% confidence interval, 0.029-0.852). The number of pills and daily doses received correlated with the reported adherence rate. CONCLUSIONS: Patients receiving NNRTIs report a higher rate of adherence than do patients receiving PIs. Adherence is significantly influenced by the number of pills and daily doses received. Low adherence is a major determinant of virologic failure; however, different therapies have different cutoff values for adherence that determine a significant increment of risk.

New times for an old disease: intracranial mass lesions caused by Mycobacterium tuberculosis in 5 HIV-negative African immigrants.

BACKGROUND: The tuberculosis epidemic is still a global emergency, and its spread in the past 20 years has been fueled by the acquired immune deficiency syndrome pandemic and increasing drug resistance. International travel and migration may increase the incidence of tuberculosis in industrialized countries. METHODS: We reviewed the clinical charts of patients admitted to the infectious diseases unit of Ospedali Riuniti (Bergamo, Italy) to identify patients with intracranial mass lesions caused by Mycobacterium tuberculosis. RESULTS: During the past 6.5 years, 5 of 30 patients with a mass of infectious origin in the brain had tuberculous brain lesions diagnosed. All 5 were human immunodeficiency virus (HIV)-negative adults and African immigrants. No patient had concomitant meningitis, 1 had a concomitant pulmonary disease, and 3 subjects reported a past history of tuberculosis. At presentation, no patient had fever and 3 had seizures. Examination of cerebrospinal fluid revealed normal findings for 4 of 4 subjects, and neuroimaging showed multiple intracranial mass lesions in 4 of 5 patients. The diagnosis was definite for 2 subjects (based on analysis of brain specimens) and presumptive for 3 subjects (1 had concomitant pulmonary tuberculosis, and 2 had clinical response to therapy). Results of susceptibility tests for M. tuberculosis were available for 2 patients: both isolates were resistant to isoniazid, and 1 was also resistant to streptomycin. Duration of medical treatment ranged from 11 to 23 months, and 2 subjects underwent surgical procedures at the time of diagnosis. All 5 patients recovered. CONCLUSIONS: Clinicians in western countries should consider the possible role of tuberculosis in causing mass lesions in the brain, particularly in immigrants from regions where tuberculosis is endemic.

A randomized, controlled trial of triple antiviral therapy as initial treatment of chronic hepatitis C in HIV-infected patients.

BACKGROUND/AIMS: Interferon and ribavirin combination therapy for chronic hepatitis C induces a low response rate in human immunodeficiency virus (HIV) infected patients. To assess the impact of intensification of interferon administration and of the addition of amantadine on the efficacy and safety of standard anti-hepatitis C virus (HCV) treatment in HIV-infected patients. METHODS: Multicentre, prospective, open-label, randomized, phase III clinical trial. Eighty co-infected patients were randomized to receive ribavirin 800-1,000 mg/day in combination with, group A: interferon alpha 2a 3MIU thrice weekly; group B: IFN alpha 2a 3MIU daily, plus amantadine 200 mg/day; treatment duration was 24-48 weeks according to HCV genotype. RESULTS: Forty-one patients were randomized in group A and 39 in group B. Intention-to-treat analysis showed a sustained virological response, defined as HCV-RNA negativization, 6 months after stopping treatment in 22% of patients from group A and 13% from group B (P>0.05). The lack of a 2-log drop in HCV-RNA levels after 12 weeks of treatment showed a 100% predictive value of lack of sustained response. CONCLUSIONS: Amantadine addition and interferon intensification do not improve the low efficacy of combination of interferon alfa plus ribavirin in HIV/HCV co-infected patients. Patients with no early virologic response did not have any probability of sustained response.

Hepatitis C infection increases the risk of the modification of first highly active antiretroviral therapy in HIV-infected patients.

We assessed predictors of discontinuation or change of the first regimen of highly active antiretroviral therapy in 465 HIV-infected adults, in the first year. A total of 187 patients modified their regimen: 45 discontinuing and 142 changing because of clinical/virological failure, intolerance/toxicity or non-adherence. Predictors of modification of the regimen were hepatitis C seropositivity, liver cirrhosis, higher baseline viral load, sex (women had a lower risk) and calendar year (lower risk staring in 2000).

Once-a-day therapy for HIV infection: a controlled, randomized study in antiretroviral-naive HIV-1-infected patients.

BACKGROUND: Complex antiretroviral regimens require optimal adherence to maintain long-lasting effectiveness. Simpler regimens, possibly with easy schedule and low pill burden, are needed for the long-term treatment of HIV infection. OBJECTIVE: To assess the efficacy and tolerability of a once-a-day highly active antiretroviral therapy (HAART) compared with two other conventional twice-a-day regimens. METHODS: In a prospective and randomized study, antiretroviral-naive patients received either EFV+ddl+3TC (once-a-day regimen; OD), or EFV+Combivir (twice-a-day and low-pill burden regimen; BID-low) or NFV+Combivir (twice-a-day and high-pill burden regimen; BID-high). Primary outcome was the proportion of patients with viral load <50 copies/ml at week 52 of follow-up. Results were evaluated according to intention-to-treat and on-treatment analysis. RESULTS: Thirty-four patients in each arm were enrolled. Baseline characteristics were similar in the three groups. The proportion of patients with viral load <50 copies/ml at week 52 were 74.4, 74.4 and 50.0% for OD group, BID-low group and BID-high group, respectively (P=0.02, ITT analysis). According to on-treatment analysis, the same figures were 88.9, 85.7 and 60% (P<0.02). Overall, 26 (25.5%) patients discontinued treatment for different reasons and immune recovery was similar in all study arms. CONCLUSIONS: Once-a-day HAART with ddl+3TC+EFV is a safe and effective alternative to twice-a-day regimens. Once-a-day therapy, with its simple daily schedule, may be proposed as one of the first choice treatments in HIV infection.

Outcome of 2 simplification strategies for the treatment of human immunodeficiency virus type 1 infection.

In a prospective, open-label, 104-week study, patients who were infected with human immunodeficiency virus type 1 (virus load, <50 copies/mL) and who were receiving protease inhibitor-based therapy were randomly assigned to continue treatment with a protease inhibitor or to replace it with abacavir or efavirenz. Treatment failure, defined as virological failure (virus load, >500 copies/microL) or any clinical or biochemical adverse event with a grade of >or=3 (on the basis of the World Health Organization [WHO] or American Heart Association [AHA] scales), was the primary outcome measurement. Failure rates were more frequent in the group treated with protease inhibitors (P<.01), and there were no significant differences in the rate of treatment failure between the group treated with efavirenz and the group treated with abacavir. Tolerability was better in the groups treated with abacavir or with efavirenz versus those treated with protease inhibitors. Fewer patients who received efavirenz experienced viral rebound. Among all groups, the mean increase in the CD4 cell count was 131 cells/microL (P<.001), with no significant difference between groups. This switching strategy maintains optimal levels of virological suppression and may improve lipid profiles in most patients.

Incidence of adipose tissue alterations in first-line antiretroviral therapy: the LipoICoNa Study.

BACKGROUND: Adipose tissue alterations (ATAs) are a frequent untoward effect of antiretroviral therapy, the causes of which remain incompletely explained. OBJECTIVES: To assess the incidence of ATAs and to identify the associated risk factors in patients infected with human immunodeficiency virus type 1 starting their first-line antiretroviral treatment. METHODS: In a multicenter investigation designed to study issues related to the treatment of patients starting antiretroviral therapy, physicians were requested to assess the presence of ATAs at enrollment and every 6 months thereafter. The ATAs were considered altogether and grouped as fat loss (lipoatrophy), adipose tissue accumulation (lipohypertrophy), and combined forms. RESULTS: A total of 655 patients were followed up for a median of 86 weeks; 128 patients (19.6%) were diagnosed as having at least 1 morphologic alteration during the study. Female gender and positivity for hepatitis C virus were independently linked to an increased risk of developing morphologic alterations. Age was another independent correlate of risk of developing ATAs. To have been infected through drug injection was a correlate of reduced risk of ATAs. Stavudine exposure was predictive at borderline statistical significance of lipoatrophy (but not of the other forms), and indinavir exposure was associated with a significantly higher risk of developing combined forms. Patients who started therapy with 2 nucleoside reverse transcriptase inhibitors and subsequently added a protease inhibitor during the follow-up had a significantly higher risk of having ATAs compared with patients who continued taking 2 nucleoside reverse transcriptase inhibitors up to the end of follow-up. CONCLUSIONS: Different types of ATAs might derive from distinct pathways and multifactorial causes. Adipose tissue alterations are a frequent and relatively early finding during first-line antiretroviral therapy.

Simpler regimens may enhance adherence to antiretrovirals in HIV-infected patients.

BACKGROUND: Optimal adherence to highly active antiretroviral therapy (HAART) is necessary to achieve the best and the most durable benefit. Many factors may influence compliance to such demanding regimens, and their identification may help in the design of strategies to enhance adherence. PURPOSE: To assess the factors associated with lower compliance to therapy, the causes of nonadherence, and the relation of nonadherence with virologic response. METHOD: We performed an observational, cross-sectional study on HIV-infected patients (pts) receiving unrestricted HAART and attending our clinic from January to May 2001. Pts completed a self-administered (ACTG modified) questionnaire on adherence to their therapy. Virologic response was defined as undetectable viral load at the time of interview. A regression model was used to determine predictors of adherence. RESULTS: 597 out of 623 pts (95.8%) completed the survey. Mean age was 38.2 years (range, 18-79). A total of 448 pts (75.0%) were men, 323 (54.1%) were intravenous drug users, 196 (32.8%) were heterosexuals, 76 (12.7%) were men who have sex with men. Mean time on therapy was 49.3 months (range, 4-145). All pts were on stable therapy (> 4 months), 173 pts (29%) were on their first HAART regimen, 309 pts (51.7%) were on NNRTI-based regimen, and 288 pts (48.2%) were on a PI-containing treatment. A total of 304 pts (50.9%) were categorized as adherent (p = .024). Multiple logistic regression showed that older age (p = .002), lower number of pills (p = .024), fewer daily doses (p = .002), and shorter time on therapy (p < .001) were factors associated with adherent behavior. Forgetfulness (59.3%), being away from home (50.2%), and problems with schedule (37.6%) were the most frequent causes of nonadherence. Adherent pts were more likely to have undetectable viral load than nonadherent pts (76.5% vs. 55.3%; p <.0001). CONCLUSION: Younger age, higher number of pills, higher frequency of doses, and longer time on therapy were predictors of nonadherent behavior. Optimal adherence correlated with the best virologic response. Simpler regimens with a lower number of pills and doses may help patients' compliance to therapy.

Body habitus changes and metabolic alterations in protease inhibitor-naive HIV-1-infected patients treated with two nucleoside reverse transcriptase inhibitors.

BACKGROUND: Cross-sectional and retrospective surveys suggest that nucleoside reverse transcriptase inhibitors (NRTIs) contribute to the metabolic and morphologic alterations observed in patients on antiretroviral therapy (ART). OBJECTIVES: To assess the risk of developing body habitus changes (BHCs) and metabolic abnormalities in protease inhibitor (PI)-naive HIV-1-infected patients treated with two NRTIs, and the risk associated with each of these drugs. DESIGN: Prospective cohort study. PATIENTS AND METHODS: The BHCs occurring in 335 patients treated with two NRTIs were evaluated every 3 months. The laboratory tests included determination of CD4 cell counts and the measurement of HIV RNA, serum glucose, cholesterol, and triglyceride levels. Cox proportional hazard models were used to describe the factors associated with the development of BHCs. RESULTS: During a median exposure of 747.5 days, 46 patients (13.7%) developed BHCs: nine fat accumulation alone, 12 fat loss alone, and 25 combined fat loss and accumulation in different body regions. Fat loss alone occurred after a significantly longer median duration of treatment than the other two forms (p =.004). The risk of developing any BHC was significantly higher in female patients (p <.0001). Fat loss was the prevalent alteration in males. Hypertriglyceridemia was observed in 76 patients (22.7%), hypercholesterolemia in 35 (10.5%), and hyperglycemia in 48 (14.3%). The adjusted risk of developing hypertriglyceridemia was higher in the stavudine-treated patients (p =.04) and in those who had previously received ART (p =.02). The only independent factor associated with the development of hypercholesterolemia was to be ART experienced at baseline (p =.02), whereas age was associated with the development of hyperglycemia (p =.0096). CONCLUSIONS: Treatment with NRTIs may be responsible for the same morphologic alterations as those observed in patients treated with PIs. Moreover, altered triglyceride levels are also frequently observed. The different timing of presentation and gender distribution of BHCs suggest that multiple pathogenetic mechanisms are involved.