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Objective: To evaluate the frequency of discontinuation of the first highly active antiretroviral regimen (HAART) and the factors predictive of discontinuing for toxicity and failure in a population-based cohort of HIV-positive individuals in Italy, naive from antiretrovirals at enrolment.Methods: The study population consisted of individuals who initiated HAART and had at least one follow-up visit. The primary end-points were discontinuation of any component of HAART for drug toxicity and discontinuation for failure. Survival analyses were performed to identify predictive factors for reaching the two end points.Results: Eight hundred and sixty-two individuals initialed HAART; in 727 of them (84.3%) this consisted of two nucleoside reverse transcriptase inhibitors (NRTI) and one protease inhibitor (PI). Over a median follow-up of 45 weeks, 312 patients (36.2%) discontinued therapy: 182 (21.1%) discontinued due to toxicity, 44 (5.1%) due to failure. The probability of discontinuing HAART at 1 year was 25.5% [95% confidence interval (Cl), 21.9-28.9] due to toxicity and 7.6% (95% Cl, 4.9-10.3) due to failure. Independent factors associated with discontinuation for toxicity were: gender [relative hazard (RH) = 0.51; 95% Cl, 0.32-0.80 for men versus women], type of treatment (indinavir-containing regimens, RH = 1.94; 95% Cl, 1.10-3.41 and ritonavir-containing regimens, RH = 3.83; 95% Cl, 2.09-7.03 versus hard-gell saquinavir) and time spent on treatment (RH = 0.89; 95% Cl, 0.80-0.98 for each additional month). Discontinuation due to failure was independently associated with the most recent HIV-RNA (RH = 3.20; 959/0 Cl, 1.74-5.88 for log(10) copies/ml higher), and with type of treatment (indinavir-containing regimens, RH = 0.21; 95% Cl, 0.06-0.78 and ritonavir-containing regimens, RH = 0.23; 95% Cl, 0.04-1.26 Versus hard-gell saquinavir).Conclusions: If the current HAART regimen caused no toxicity, less than 10% of naive patients discontinue their first HAART regimen because of failure after 1 year from starting therapy. (C) 2000 Lippincatt Williams & Wilkins.

Twenty-two Italian HIV-infected patients developed leishmaniasis, clinically manifested as visceral (13 cases), cutaneous (2 cases) and disseminated disease (7 cases). Twenty were males and two females (mean age: 32.8 years) with a mean CD4+ cell count of 46.8/microliter at diagnosis; risk factors were intravenous drug use (17 patients) and sexual behaviour (two bisexual, two homosexual, one heterosexual). All but one patient lived or travelled in hypoendemic Italian regions and other Mediterranean countries. Apart from the two patients with cutaneous leishmaniasis, the clinico-pathological and biological spectrum of the infection was often atypical, especially in patients with disseminated disease. The diagnosis was routinely made by direct recovery of parasites in biological specimens, mainly in bone marrow aspirate, whereas serology was negative or borderline in most of the patients. Among 17 in vitro isolates, Leishmania infantum was the only species involved with previously undescribed isoenzyme patterns in two cases. Treatment with antimonials and other drugs showed only temporary clinical improvement in some patients. Relapses were the rule. Leishmaniasis confirms itself as an opportunistic infection in HIV-positive persons. Secondary chemoprophylaxis should be considered in cases of relapsing disease.The majority of the 850 HIV-associated Leishmania infections reported worldwide involve men and women from Mediterranean countries, particularly Spain, Italy, and France. This article describes a retrospectively identified series of 22 patients (20 men and 2 women) from northern Italy's Lombardy region with HIV/Leishmania coinfection in the period 1989-97. At leishmania diagnosis, the mean CD4+ lymphocyte count was 46.8/mcl and 21 patients had been previously diagnosed with an AIDS-defining illness. Intravenous drug use was the HIV risk factor in 17 patients; an additional 4 were bisexual or homosexual. The diagnosis of leishmaniasis was made by direct recovery of parasites in biologic specimens, mainly in bone marrow aspirate. Serology was generally negative or borderline due to the frequent occurrence of humoral immunity imbalances. Anemia, leukopenia, thrombocytopenia, and hypergammaglobulinemia were present in all but 1 patient. Leishmaniasis was clinically manifested as visceral in 13 cases, cutaneous in 2 cases, and disseminated disease in 7 cases. The clinicopathologic and biologic spectrum of infection tended to be atypical, especially in patients with disseminated disease. Leishmania infantum was the only species involved in 17 in vitro isolates; 2 cases exhibited previously undescribed isoenzyme patterns. Treatment with antimonials and other drugs produced, at best, only temporary clinical improvement. Relapses were the rule during follow-up in all but the 2 patients with cutaneous leishmaniasis. Inclusion of Leishmania spp. among the infectious agents of AIDS-defining diseases is recommended.

To evaluate short-term toxicity from and discontinuation of antiretroviral combination prophylaxis in HIV-exposed individuals in Italy.Longitudinal, open study conducted by prospective collection of data in the National Registry of PEP.All the Italian centres dedicated to HIV related care and licensed by the Ministry of Health to dispense antiretroviral drugs.Health care workers and other persons consenting to be treated with post exposure prophylaxis (PEP) after exposures to HIV.Until October, 2000, 207 individuals receiving two nucleoside reverse transcriptase inhibitors (NRTIs), and 354 receiving two NRTIs plus a protease inhibitor (PI) were enrolled. More individuals experienced side-effects in the 3-drug group (53% and 62%, respectively; OR 0.68, (95% CI 0.48-0.98), p0.03). However, the proportion of individuals discontinuing prophylaxis because of side-effects did not differ significantly between the 2 groups (21% and 25% respectively; OR 0.82 (95% CI 0.53-1.26); p=0.4). The 43 individuals in the 2 NRTI group discontinued PEP after a mean of 10.4 days of treatment (median 8, range 1-27), similarly to the 88 discontinuations observed in the 3-drug group (mean duration 10.5 days, median 7.5, range 1-26). Type and incidence of specific adverse effects were similar to those reported in the literature.Our study indicates that the difference in the proportion of individuals developing side effects and discontinuing PEP is not significant. The rate of discontinuation because of protease inhibitor side-effects does not justify per se the initial use of a less potent PEP regimen. We suggest initiating PEP with a three-drug regimen and discontinuing the protease inhibitor in the case of adverse effects.

To evaluate the frequency of discontinuation of the first highly active antiretroviral regimen (HAART) and the factors predictive of discontinuing for toxicity and failure in a population-based cohort of HIV-positive individuals in Italy, naïve from antiretrovirals at enrolment.The study population consisted of individuals who initiated HAART and had at least one follow-up visit. The primary end-points were discontinuation of any component of HAART for drug toxicity and discontinuation for failure. Survival analyses were performed to identify predictive factors for reaching the two end-points.Eight hundred and sixty-two individuals initiated HAART; in 727 of them (84.3%) this consisted of two nucleoside reverse transcriptase inhibitors (NRTI) and one protease inhibitor (PI). Over a median follow-up of 45 weeks, 312 patients (36.2%) discontinued therapy: 182 (21.1%) discontinued due to toxicity, 44 (5.1%) due to failure. The probability of discontinuing HAART at 1 year was 25.5% [95% confidence interval (CI), 21.9-28.9] due to toxicity and 7.6% (95% CI, 4.9-1 0.3) due to failure. Independent factors associated with discontinuation for toxicity were: gender [relative hazard (RH) = 0.51; 95% CI, 0.32-0.80 for men versus women], type of treatment (indinavir-containing regimens, RH = 1.94; 95% CI, 1.10-3.41 and ritonavir-containing regimens, RH = 3.83; 95% CI, 2.09-7.03 versus hard-gell saquinavir) and time spent on treatment (RH = 0.89; 95% CI, 0.80-0.98 for each additional month). Discontinuation due to failure was independently associated with the most recent HIV-RNA (RH = 3.20; 95% CI, 1.74-5.88 for log10 copies/ml higher), and with type of treatment (indinavir-containing regimens, RH = 0.21; 95% CI, 0.06-0.78 and ritonavir-containing regimens, RH = 0.23; 95% CI, 0.04-1.26 versus hard-gell saquinavir).If the current HAART regimen caused no toxicity, less than 10% of naïve patients discontinue their first HAART regimen because of failure after 1 year from starting therapy.

Between October 1992 and February 1994, 33 cases of multidrug-resistant tuberculosis (MDR-TB) were diagnosed among patients infected by the human immunodeficiency virus (HIV) and hospitalised in an HIV ward in Milan, Italy. This outbreak was part of a much larger outbreak, begun in another hospital and probably transferred through a patient.To evaluate risk factors for transmission and the effectiveness of infection control measures.1) Active follow-up of exposed patients, 2) cohort study among HIV-infected patients exposed to MDR-TB cases before and after the implementation of control measures, 3) screening of close contacts of MDR-TB cases, and 4) molecular typing by restriction fragment length polymorphism (RFLP) analysis.The risk of MDR-TB was higher in patients with lower CD4+ lymphocyte percentages and longer duration of exposure. No difference in the daily risk was observed for in-patients vs day-hospital patients or by room distance from an infectious case. Of the 90 patients exposed before the implementation of infection control measures (i.e., October 1992-June 1993) 26 (28.9%) developed MDR-TB, whereas none of the 44 patients exclusively exposed after implementation developed MDR-TB, despite the continuing presence of infectious MDR-TB cases in the ward.Simple control measures were effective in significantly reducing nosocomial transmission among patients.

We report two cases of thrombotic thrombocytopenic purpura (TTP) in advanced stage HIV-positive patients (CD4+0.05 x 10(9)/L). Clinical symptoms were relevant, but their course was not fulminant; the two patients responded to different therapies (plasma or plasma plus plasmapheresis, and steroids), showing rapid improvement in symptoms. One patient remained asymptomatic with zidovudine only, while the other relapsed (probably due to an intercurrent infection). This second person is now asymptomatic on zidovudine plus low doses of steroids.

Neuropathology of acquired immunodeficiency syndrome. The Central Nervous System (CNS) has been examined at autopsy in 60 patients who died of AIDS in a 6-year period in our hospital. Most of the patients were intravenous drug abusers, the mean age was of 34 years, with a high prevalence of males. Neurologic symptoms were present in 62% of patients, while histologic lesions have been observed in 51 cases (85%). Opportunistic infections were found in 27 patients, the commonest being T. gondii (12) and Cytomegalovirus (7); Progressive Multifocal Leukoencephalopathy was observed in 2 cases. HIV-associated lesions included 21 cases of Multifocal Giant Cell Encephalitis (MGCE), 15 of Progressive Diffuse Leukoencephalopathy (PDL) and 7 cases of Vacuolar Myelopathy. Primary CNS lymphoma was noted in 8 patients and secondary deposits were observed in 3 cases. Simultaneous CNS lesions by more than one pathogen were frequently encountered. The main pathogenetic mechanisms for characterization of all the lesions and their relationship with clinical features of the disease are discussed. It is supposed that MGCE and PDL represent two different patterns of HIV-encephalopathy.