Annalisa Ridolfo

AIDS‐associated cryptococcosis: a comparison of epidemiology, clinical features and outcome in the pre‐ and post‐HAART eras. Experience of a single centre in Italy

To assess the prevalence, clinical and immunological characteristics, risk factors and survival of patients with AIDS‐related cryptococcosis in the era of highly active antiretroviral therapy (HAART).

Pancreatic cancer in HIV-positive patients: a clinical case-control study.

Objectives Pancreatic cancer (PC) is the fourth and fifth most common cause of cancer-related death among men in United States and in Europe, respectively. No data are available for HIV-positive patients. The aim of this study was to investigate and to compare clinical presentation and outcome between HIV-positive and HIV-negative PC patients. Methods From April 1988 to June 2010, the Italian Cooperative Group on AIDS and Tumors identified 16 cases of HIV-positive PC patients. Each HIV-positive patient from our institution was randomly matched (ratio 1:2) with HIV-negative patients (32 controls) based on sex and year of PC diagnosis. Differences in clinical presentation, treatment, and overall survival were assessed. Results At multivariate analysis, HIV-positive patients compared with HIV-negative patients had a higher risk of an unfavorable performance status (PS ≥2) and a younger age (<50 years) at cancer diagnosis. At multivariate analysis, HIV-positive status and PS of 2 or greater were the only 2 features that significantly reduced PC patients’ survival. Conclusions Our data show, for the first time, that HIV-positive PC patients, compared with HIV-negative patients, are younger at cancer diagnosis. Furthermore, they share a more unfavorable PS and a shorter survival.

Cryptococcus neoformans Infection in a Cohort of Italian AIDS Patients: Natural History, Early Prognostic Parameters, and Autopsy Findings

Abstract. This observational cohort study of 4,160 AIDS patients hospitalised in a single institution in northern Italy between January 1985 and December 1999 was carried out in order to assess the natural history of cryptococcosis, the epidemiological trend of this opportunistic infection, the risk factors predictive of death at 10 weeks, the response to therapy, and autopsy findings. Cryptococcosis was diagnosed in 177 (4.2%) patients and was the AIDS-defining disease in 2.8% of cases. Its prevalence decreased significantly over time (from 6.4% in the period 1985–1989 to 5.7% in 1990–1993, 3.1% in 1994–1996, and 1.9% in 1997–1999, P<0.0001). Although neurologic disease was the most frequent clinical picture, a significant proportion of the patients (24.2%) presented with extraneural cryptococcosis. In a Cox multivariate analysis, high titres of cerebrospinal fluid antigen (>5000) and drug addiction were predictive of death at 10 weeks. A complete clinical and mycological response was achieved in 60.8% of the treated patients, with the highest response rate being observed in those treated with amphotericin plus flucytosine (66.6%). Cryptococcosis relapsed in 12.8% of patients on secondary prophylaxis. Autopsy findings demonstrated that cryptococcosis is a disseminated disease, but long-term antifungal treatment may be able to eradicate it in a subgroup of patients.

Direct‐acting antivirals in hepatitis C virus (HCV)‐infected and HCV/HIV‐coinfected patients: real‐life safety and efficacy

Clinical trials of all‐oral direct‐acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection reported high response rates in HCV/HIV coinfection, similar to those obtained in HCV monoinfection. We evaluated the safety and efficacy of these regimens in a clinical practice setting.

AIDS-associated Kaposi's sarcoma is more aggressive in women: A study of 54 patients

OBJECTIVE To describe the epidemiologic and clinical features of AIDS-associated Kaposis sarcoma (KS) in women compared with men. METHODS In a retrospective study, within the Italian Cooperative Group on AIDS and Tumors (GICAT), we compared selected characteristics of 54 women and 108 men with AIDS-associated KS, matched by date of KS diagnosis and referral hospital. The chi2 test was used to test differences among proportions; the Kaplan-Meier method to estimate the survival time, and the Cox proportional hazard model was used to assess the role of gender, age, and CD4 cell count on deaths risk. RESULTS KS occurred at an earlier age (p = .001), was associated with a more severe immunodeficiency (p = .03), more advanced stages of HIV disease (p = .05), and had more aggressive presentation and course in women than in men. At KS diagnosis, women had a significantly increased proportion of visceral disease (p = .009), in particular pulmonary involvement (p = .002) and atypical sites of involvement (p = .008). The number of deaths due to KS was significantly higher (p = .01) in female patients. Both the higher proportion of visceral disease and of KS-related deaths observed in women did not change after adjusting for CD4 cell count and age. Women showed a decreased overall survival compared with men (8.9 and 14.4 months, respectively; p = .07), and the CD4 cell count at diagnosis significantly influenced survival. CONCLUSIONS This study suggests that KS is more aggressive and life threatening in female than in male patients. This peculiar clinical behavior may reflect an inherently more aggressive biology of KS in women, possibly mediated by the level of immunodeficiency.

Oxaliplatin Based Chemotherapy and Concomitant Highly Active Antiretroviral Therapy in the Treatment of 24 Patients with Colorectal Cancer and HIV Infection

BACKGROUND Although FOLFOX4 is considered the standard chemotherapy regimen for colorectal cancer (CRC), few data are available on its results in human immunodeficiency (HIV)-related CRC. The results were analyzed to evaluate feasibility and activity of FOLFOX4 plus highly active antiretroviral therapy (HAART) in metastatic CRC (mCRC) HIV-seropositive patients. PATIENTS AND METHODS From January 2002 to March 2007, 24 patients were selected among the CRC HIV-seropositive patients treated with FOLFOX4 and concomitant HAART within the Italian Cooperative Group on AIDS and Tumors (GICAT). RESULTS Four median cycles of chemotherapy were administered; the most common severe toxicity was neutropenia (37.5%). An overall response rate of 50% was observed; 4.2% of patients achieved complete response and 45.8% partial response. No opportunistic infections occurred during or immediately after chemotherapy. The median CD4+ count was 380 (range 220-570) at diagnosis. CONCLUSIONS To our knowledge, this is the largest study describing activity and tolerability of FOLFOX4 and HAART, in this setting. FOLFOX4 plus concomitant HAART resulted feasible and active also in HIV-seropositive patients. Moreover, the concomitant use of HAART did not to seem to increase the FOLFOX4 toxicity. This study suggests the good tolerability of the FOLFOX4, making it a reasonable option for combination with HAART.

Cardiovascular Disease Risk Factors in HIV-Infected Patients in the HAART Era

Abstract: HIV infection is accompanied by disturbances in lipid and glucose metabolism, which are further compounded by changes induced by antiretroviral drugs. There is increasing concern that these changes will lead to an epidemic of cardiovascular disease. Cardiovascular disease will no doubt increase, but current data indicate that the average absolute levels are likely to remain low, although patients with additional risks (smoking, hypertension, diabetes, age, family history, etc.) are certainly more susceptible. The complications of therapy need to be taken into account when deciding on the time of treatment, and reducing risk factors should become a routine aspect of the care of an HIV population that now lives longer as a result of highly active antiretroviral therapy.

Tuberculosis cutis miliaris disseminata due to multidrug-resistant Mycobacterium tuberculosis in AIDS patients.

Two patients with AIDS and disseminated tuberculosis characterized by cutaneous involvement are reported. They developed a maculopapular skin eruption, from which a multidrug-resistantMycobacterium tuberculosis strain was isolated. In both cases the clinical course was rapidly fatal. Tuberculosis cutis miliaris disseminata should be differentiated from the skin lesions frequently seen in HIV-infected patients, especially from folliculitis. In patients with tuberculosis, the appearance of cutaneous lesions may be due to the haematogenous dissemination of mycobacteria. Therefore, early identification of the causative organism by use of optimal microbiological methods is fundamental.

Diagnosis and Therapy for Hospitalized Imported Malaria in Adults in Italy

BACKGROUND The diagnosis and treatment of malaria in non-endemic countries presents a continuing challenge. METHODS Medical records were reviewed for 291 patients hospitalized with microscopically confirmed malaria diagnosed consecutively in two infectious diseases wards in Milano, Italy, between 1998 and 2007. RESULTS One hundred eighty-six (64%) were male; median age was 35 y (range 16-72 y). Of the 291 patients, 204 (70.1%) were non-immune travelers and 87 (29.9%) were considered semi-immune. In 228 patients (78.3%), Plasmodium falciparum was identified as the only causative malarial parasite. In 48 (16.5%), 9 (3.1%), and 1 (0.3%) cases, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae were diagnosed, respectively. Five mixed infections were observed (1.7%). Of the 233 falciparum cases (including mixed infections), 222 (95.3%) were acquired in sub-Saharan Africa. Fifty-four percent of P vivax infection were acquired in the Indian subcontinent and Southeast Asia. Chemoprophylaxis was used by 23.6% (61/258) subjects with only 32 fully compliant with the recommended regimen. At admission, fever, chills, and headache were present in 95.5, 59.5, and 55.3% of cases, respectively. Elevated serum lactate dehydrogenase levels (95%) and thrombocytopenia (82%) were the most frequently detected laboratory abnormalities. Thirty-five patients (15%) with P falciparum malaria presented with severe malaria according to the WHO criteria; in 19 patients (54.3%) more than one criteria was present. All patients recovered uneventfully. Inappropriate anti-malarial treatment occurred in 25 patients (8.6%) and were recorded more frequently among patients with a diagnosis of P vivax malaria (29.1%) as opposed to those affected by P falciparum (3.9%). CONCLUSIONS In our study more than two thirds of imported malaria cases were due to P falciparum with an excess of cases diagnosed in immigrants starting from the year 2000. Despite many available guidelines inappropriate initial malaria treatment is relatively frequent even when patients are managed in an infectious diseases ward.

How relevant are the drug–drug interactions between antiretroviral boosted-based regimens and calcium channel blockers in real life?

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