Short-term adverse effects from and discontinuation of antiretroviral post-exposure prophylaxis.

OBJECTIVE: To evaluate short-term toxicity from and discontinuation of antiretroviral combination prophylaxis in HIV-exposed individuals in Italy. DESIGN: Longitudinal, open study conducted by prospective collection of data in the National Registry of PEP. SETTING: All the Italian centres dedicated to HIV related care and licensed by the Ministry of Health to dispense antiretroviral drugs. STUDY POPULATION: Health care workers and other persons consenting to be treated with post exposure prophylaxis (PEP) after exposures to HIV. RESULTS: 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), p < 0.03). 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. CONCLUSION: 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.

Insights into the reasons for discontinuation of the first highly active antiretroviral therapy (HAART) regimen in a cohort of antiretroviral naïve patients. I.CO.N.A. Study Group. Italian Cohort of Antiretroviral-Naïve Patients.

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, naïve 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 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). CONCLUSIONS: 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.

Effectiveness of infection control measures in controlling a nosocomial outbreak of multidrug-resistant tuberculosis among HIV patients in Italy.

SETTING: 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. OBJECTIVE: To evaluate risk factors for transmission and the effectiveness of infection control measures. DESIGN: 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. RESULTS: 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. CONCLUSION: Simple control measures were effective in significantly reducing nosocomial transmission among patients.

Chorea in patients with AIDS.

OBJECTIVE: To describe differing etiologies and possible anatomoclinical correlates of choreic movements in a series of AIDS patients. METHODS: We analyzed the clinical records and neuroimaging data of 5 consecutive AIDS patients who developed choreic movements at our center from January, 1994 to December, 1996. RESULTS: There were 2 cases of focal choreic dyskinesias, 1 of right hemichorea, and 2 of generalized chorea. Onset was acute and febrile in 1 case, and subacute in the other 4. In 1 patient the chorea was the AIDS onset symptom; in another choreic movements were the first neurological symptom following AIDS diagnosis; in 2 patients AIDS had a neurological onset other than chorea; and in the fifth patient buccofacial dyskinesias appeared following the development of bacterial encephalitis. CONCLUSION: Chorea was associated with cerebral toxoplasmosis in 2 patients, progressive multifocal leukoencephalopathy in 1, subacute HIV encephalopathy in another, and was probably iatrogenic in the last. Chorea is not unusual in AIDS, however the causes are variable and careful neuroradiological and clinical evaluation is required to identify them. AIDS-related disease should be considered in young patients presenting with chorea without a family history of movement disorders.

Mediterranean leishmaniasis in HIV-infected patients: epidemiological, clinical, and diagnostic features of 22 cases.

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.

PIP: 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.

Anaplastic large cell (CD30/Ki-1+) lymphoma in HIV+ patients: clinical and pathological findings in a group of ten patients.

We compared the clinical and pathological features of 10 HIV+ CD30+ anaplastic large cell lymphoma (ALCL) patients with 28 HIV+ CD30- non-Hodgkin's lymphoma (NHL) patients. The incidence of ALCL among 38 HIV+ systemic NHL patients was 26%. Clinical features were similar in all the HIV-related NHL cases, but ALCL patients seemed to differ from HIV+ CD30- systemic NHL only in the greater frequency of lung tumours (40% v 21%) without concomitant mediastinal mass, bone marrow (75% v 18%) and gastroenteric involvement (40% v 25%). Among the HIV+ ALCL patients, histologic subtypes did not differ in frequency from ALCL in the general population. The B phenotype was predominant (50%) as in other HIV-related NHL. EBV genoma, studied in all HIV+ ALCL patients, was present in 3/10 by in situ hybridization (ISH) and in 5/10 cases using PCR. The clinical course of lymphomas was similar in CD30 positive and negative NHL patients. Overall survival also was short in our series, particularly in HIV+ ALCL (84 v 188 d), probably because of profound immunodepression of the ALCL patients. Our findings suggest that severe immunodepression due to HIV infection determines-more than any other factor-the clinical features of HIV+ ALCL, making them very similar to those of other high-grade systemic HIV+ NHL.

Thrombotic thrombocytopenic purpura associated with HIV infection: report of two cases.

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.

Comparison of two dose regimens of zidovudine in an open, randomized, multicentre study for severe HIV-related thrombocytopenia.

OBJECTIVE: To compare the effect of two dose regimens of zidovudine in the treatment of severe HIV-related thrombocytopenia (TP). DESIGN: Eighty-four patients with severe HIV-related TP and platelet counts < 50 x 10(9)/l were enrolled in an open study at six centres. Patients were randomized into two groups to receive zidovudine (group A, 500 mg per day; group B, 1000 mg per day) for 6 months. METHODS: Platelet counts were determined monthly and patients categorized as complete responders (CR; platelets > 100 x 10(9)/l), partial responders (PR; platelets > 50 to < 100 x 10(9)/l), or failures (F; platelets to < 50 x 10(9)/l). CD4+ and CD8+ lymphocytes, HIV antigenaemia, beta 2-microglobulin, white blood cells, mean cell volume and haemoglobin were also determined. RESULTS: Seventy-one patients (35 and 36 in groups A and B, respectively) completed the study; 11.4% of group A patients were CR and 45.7% PR; 38.9% of group B were CR and 33.3% PR. Increase in mean platelet counts was dose-related, more rapid in the higher dose group and remained significantly higher after 6 months of treatment (56.4 x 10(9)/l in group A versus 98.2 x 10(9)/l in group B; P < 0.01). CONCLUSIONS: The results confirm the efficacy of zidovudine in the treatment of severe HIV-related TP. The average for CR and PR in the two groups was 64.8%; the higher dose of zidovudine was more effective at increasing platelet counts.

HIV-related thrombocytopenia: four different clinical subsets.

BACKGROUND: Many factors have been considered in the pathogenesis of HIV-related Thrombocytopenia (HIV-rel TP): immunological destruction, retroviral infection of megakaryocytes and altered reticulo-endothelial function. Nevertheless the pathogenesis is still controversial. MATERIALS AND METHODS: We reviewed 52 patients (all intravenous drug users) with HIV-rel TP (< 100 x 10(9)/L) by evaluating bone marrow morphology, antiplatelet antibodies (28/52), kinetic studies with 111In Oxine and response to therapy. RESULTS: Seventeen percent of TP were evaluated as "acute ITP-like", and 40% as "chronic ITP-like"; 35% were evaluated as "pooling" TP and 8% as "hypoplastic" TP. Twenty-four patient with moderate TP (> 30 x 10(9)/L) were followed for a mean time of 27 months and no hemorrhages were seen during the period of observation despite the fact that no treatment was given; twenty-eight others with severe TP (< 30 x 10(9)/L) were treated in different ways: 18% responded to steroids and/or HDIg, 70% to splenectomy and 56% to zidovudine. CONCLUSIONS: The term "HIV-related thrombocytopenia" should include more than one kind of TP: "Acute ITP-like" TP, "chronic ITP-like" TP, "pooling" TP and "hypoplastic" TP have to be evaluated differently for pathogenesis, clinical manifestations and treatment.

[Neuropathology of the acquired immunodeficiency syndrome]. / Neuropatologia della sindrome da immunodeficienza acquisita.

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.