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.

Objectives 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). Methods All newly diagnosed cryptococcosis cases identified retrospectively from among a series of AIDS patients hospitalized consecutively at a single institution in Italy in 1985-1996 (pre-HAART period, n=165) and 1997-2006 (post-HAART period, n=40) were analysed comparatively. Results The prevalence of cryptococcosis decreased from 4.7% (165/3543) to 2.2% (40/1805) between the pre- and post-HAART periods (P=0.0001). There were no differences in the clinical features or immunological status of the patients between the two cohorts. The variables associated with the occurrence of cryptococcosis in the post-HAART era were older age (P<0.001), no previous diagnosis of HIV infection (P<0.001) and infection in homosexual males (P=0.004). During the post-HAART period, immune reconstitution inflammatory syndrome associated with cryptococcosis was observed in five patients (19.3%) a median of 15 weeks after the start of HAART. Thirty-day survival (P=0.045) and overall survival (P=0.0001) were significantly better among patients diagnosed with cryptococcosis in the post-HAART compared to those diagnosed in the pre-HAART era. Conclusions The AIDS-associated cryptococcosis observed in Western countries in the HAART era has similar clinical and immunological characteristics to that observed in the pre-HAART era, but a significantly better outcome.

Long-term remission of Kaposi sarcoma-associated herpesvirus-related multicentric Castleman disease with anti-CD20 monoclonal antibody therapy.

Kaposi sarcoma-associated herpesvirus (KSHV)-related multicentric Castleman disease (MCD) is potentially lethal. Growing evidence indicates that, as in Epstein-Barr virus-driven lymphoproliferative disorders after transplantation, KSHV DNA burden in peripheral blood mononuclear cells (PBMCs) may represent the most accurate marker of disease activity. This report describes a patient with human immunodeficiency virus who was followed up clinically and by quantitative polymerase chain reaction for KSHV DNA sequences in PBMCs for more than 3 years following the diagnosis of KSHV-related MCD. Therapy with the antiherpesvirus agent cidofovir, antihuman interleukin-6 antibody BE-8, antiblastic chemotherapy, and combination antiretroviral agents did not achieve durable clinical or virologic remission of the disease. By contrast, administration of the anti-CD20 monoclonal antibody rituximab was well tolerated and allowed a 14-month remission of clinical symptoms and KSHV viremia. Rituximab should be added to the therapeutic armamentarium for KSHV-related MCD.

Human immunodeficiency virus-related non-Hodgkin lymphoma: activity of infusional cyclophosphamide, doxorubicin, and etoposide as second-line chemotherapy in 40 patients.

BACKGROUND: The prognosis of patients with human immunodeficiency virus (HIV)-related non-Hodgkin lymphoma (NHL) is poor. In fact, despite a high complete response (CR) rate, approximately 50% of these patients die from progressive lymphoma. METHODS: From November 1994 to April 2000, the authors treated 40 patients with resistant or recurrent HIV-related NHL with a 96-hour continuous intravenous infusion of cyclophosphamide (187.5 mg/m(2) per day), doxorubicin (12.5 mg/m(2) per day), and etoposide (60 mg/m(2) per day). RESULTS: The median number of cycles administered was two (range, one to six cycles). A CR was documented in 4 of 40 patients (10%), and a partial remission (PR) was documented in 7 of 40 patients (18%). The CR median duration was 6 months (range, 4--30+ months), whereas PRs lasted for 5 months (range, 2--8 months). The overall median survival was 4 months (range, < 1--33 months), and the median survival for responding patients was 10 months. CONCLUSIONS: The current data confirm that infusional cyclophosphamide, doxorubicin, and etoposide is active in patients with refractory or recurrent HIV-related NHL. However, the median survival of these patients remains poor, and the other innovative approaches should be used.

Cryptococcus neoformans infection in a cohort of Italian AIDS patients: natural history, early prognostic parameters, and autopsy findings.

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.

Vinorelbine is an effective and safe drug for AIDS-related Kaposi's sarcoma: results of a phase II study.

PURPOSE: To assess the safety and efficacy of vinorelbine in patients with AIDS-related Kaposi's sarcoma (KS). PATIENTS AND METHODS: From December 1994 to May 1997, within the Italian Cooperative Group on AIDS and Tumors, we enrolled 36 patients with AIDS-related KS who experienced disease progression after one or more regimens of systemic chemotherapy. Patients were treated with vinorelbine 30 mg/m(2) every 2 weeks by intravenous bolus. RESULTS: Of 35 assessable patients, three (9%) had a clinical complete response and 12 (34%) had a partial remission, for an overall objective response rate of 43% (95% confidence interval, 26% to 61%). For the 15 patients with objective responses, the median duration of response from the beginning of therapy until the development of progression was 176 days, whereas the median progression-free survival and the median survival durations for 35 assessable patients were 151 days and 216 days, respectively. Vinorelbine also induced responses in patients who had become resistant to regimens that included other vinca alkaloids. Overall, vinorelbine was well tolerated. Toxicity, including neurologic toxicity, was mild and reversible. Neutropenia was the most frequent dose-limiting toxicity. CONCLUSION: Vinorelbine is safe and effective in the treatment of patients with advanced KS who have been previously treated with one or more chemotherapy regimens.

Role of brain biopsy in the management of focal brain lesions in HIV-infected patients. Gruppo Italiano Cooperativo AIDS & Tumori.

In this multicenter, retrospective study of 160 brain biopsies in the assessment of HIV-related focal brain lesions, diagnostic sensitivity was acceptable (87%), but the procedure carried considerable morbidity (7.5%) and mortality (3.1%). Moreover, it is not always possible to initiate the changes in therapy indicated by the results, and overall survival remains poor, with a median of 2 months. Criteria for brain biopsy for the diagnosis of focal brain lesions should be redefined to include selected patients for whom a less invasive approach does not yield a definitive diagnosis.

Lung carcinoma in 36 patients with human immunodeficiency virus infection. The Italian Cooperative Group on AIDS and Tumors.

BACKGROUND: The current study describes the clinicopathologic characteristics of 36 patients with lung carcinoma and human immunodeficiency virus (HIV) infection observed within the Italian Cooperative Group on AIDS and Tumors (GICAT). METHODS: Patients with lung carcinoma and HIV infection collected by the GICAT between 1986-1998 were evaluated retrospectively. As a control group, the authors analyzed 102 patients age < 60 years with lung carcinoma but without HIV infection who were seen at the CRO, National Cancer Institute, Aviano, Italy between 1995-1996. RESULTS: Patients with lung carcinoma and HIV infection were younger (38 years vs. 53 years) and previously smoked more cigarettes per day (40 vs. 20) than the control group. The main histologic subtype was adenocarcinoma. TNM Stage III-IV disease was observed in 53% of the patients. The median CD4 cell count was 150/mm(3). The median overall survival was significantly shorter in the patients with HIV compared with the control group (5 months vs. 10 months; P = 0.0001). CONCLUSIONS: The results of the current study demonstrate that lung carcinoma in the HIV setting affects mainly young individuals with a history of heavy tobacco smoking and a moderately advanced immunodeficiency status. Lung carcinoma is associated with a more adverse outcome in HIV patients and represents the cause of death in the majority of these patients.

Therapy of non-small-cell lung cancer (NSCLC) in patients with HIV infection. GICAT. Cooperative Group on AIDS and Tumors.

Incidence and mortality of AIDS patients have significantly declined in the developed countries due to the very active anti-HIV combination therapy available today. Because of the prolongation of the survival expectancy of these patients, other non-AIDS defining tumours have been recently reported in several cohort studies with increased frequency. We want to report the clinico-pathological features and the outcome of 39 patients with lung cancer and HIV infection, collected by the Italian Cooperative Group on AIDS and Tumors (GICAT) between 1986 and December 1997. As a control group, we decided to evaluate patients, less than 60 years of age, with lung cancer but without HIV infection seen at the CRO, Aviano, during 1995 and 1996. The median age of the study group patients was 38 years (range 28-58) and 90% of them were males. Sixty-nine percent of patients were intravenous drug users and HIV infection was asymtomatic in 41% of patients. NSCLC was observed in 78% of patients, SCLC in 13% and mesothelioma in 8%. Among NSCLC, adenocarcinoma was the most frequently observed histological subtype (48%). No differences were found as regards the stage of disease at diagnosis and the histologic subtype in comparison with the control group. The median overall survival was significantly shorter for patients with HIV infection when compared to that of the control group (5 months vs. 10 months, P < 0.0001). In conclusion, the outcome of patients with SNCLC and HIV infection seems worse than that of the general population, suggesting a synergistic and/or addictive adverse effect of HIV on the outcome of lung cancer.

Combination chemotherapy with doxorubicin, bleomycin, and vindesine for AIDS-related Kaposi's sarcoma.

BACKGROUND: Kaposi's sarcoma is the most common neoplasm in patients with human immunodeficiency virus (HIV) infection. Although the best therapeutic approach is still unclear, patients with advanced KS are usually treated with systemic chemotherapy. METHODS: A prospective multiinstitutional Italian study evaluated the efficacy and toxicity of combination chemotherapy with doxorubicin, bleomycin, and vindesine (ABVi) in patients with progressive and extensive HIV-related KS. Patients were given doxorubicin, 20 mg/m2 on Day 1; bleomycin, 15 mg on Day 1, and vindesine, 4 mg on Day 1 biweekly +/- granulocyte-colony stimulating factor. RESULTS: Overall, 21 of 38 evaluable patients (55%) achieved an objective response (OR): there was 1 complete response and 20 partial responses. The most important bone marrow toxicity was granulocytopenia in 61% of the evaluable patients; 34% had Grades 3-4 toxicity, according to the World Health Organization Classification. The majority of patients (64%) developed some type of opportunistic infection (OI) during chemotherapy or the follow-up, with cytomegalovirus infection being the most frequent OI observed. The median duration of survival from KS diagnosis and from the start of ABVi therapy was 19 months (range, 3.4-88.5 months) and 9.9 months (range, 0.1-42.4 months), respectively. CONCLUSIONS: The high rate of OI during ABVi chemotherapy and the follow-up is of concern, although these infections possibly could be due to our patients' low CD4+ lymphocyte counts. However, no toxic death was observed in our patients, suggesting that ABVi could be used in patients with aggressive disease, especially those who were previously untreated.

Severe abdominal pain in patients with AIDS: frequency, clinical aspects, causes, and outcome.

BACKGROUND: The exact prevalence of abdominal pain in AIDS patients, as well as the entire spectrum of causative disorders, has not yet been well defined. In addition, the existing data derive almost exclusively from surgical series describing only those patients who have undergone emergency surgical procedures. METHODS: We reviewed our experience with patients presenting with severe abdominal pain from a large series of non-selected consecutive AIDS patients seen at our institution over a period of 4 years. RESULTS: Of 458 patients, 71 (15%) had severe abdominal pain, and its occurrence was associated with a reduced patient survival. Specific diagnoses were made premortem in 42 patients (59%), potential causes of pain were identified at postmortem examination in 23 patients (33%), whereas no specific causes were found in 6 patients (8%). Most of the causative disorders (65%) were AIDS-related, whereas HIV-independent pathologic conditions were found in only 18% of the patients. The predominant site of pain, combined with a few key symptoms, had a high predictive diagnostic value in nearly half of the patients. The indications for emergency laparotomy were limited and substantially similar to those of the non-HIV population. CONCLUSIONS: Severe abdominal pain frequently complicates the course of AIDS, and its occurrence is associated with reduced survival. In most patients it is due to disorders closely associated with the HIV infection. Specific causes of pain may be identified in most of the cases by an appropriate diagnostic evaluation.

Lipid-based amphotericin B in the treatment of cryptococcosis.

Amphotericin B is the only antifungal drug which, despite its dose-limiting toxicity, can be given intravenously when an aggressive treatment is required. In an attempt to reduce the drug toxicity while retaining its therapeutic efficacy, new formulations of amphotericin B have been developed. The most promising have employed lipid vehicles such as liposomes. Three lipid-based amphotericin B formulations have been developed by pharmaceutical companies and are under active clinical investigation. Efficacy and safety data of these derivatives in animals and humans are reviewed, with particular concern to cryptococcal infection. The authors' experience with a small unilamellar liposomal amphotericin B formulation, AmBisome, in the primary therapy of cryptococcosis is reported. Nine AIDS patients affected with cryptococcosis, seven of whom had meningitis, were given AmBisome (3 mg/kg/day) for 3-6 weeks. Complete response was obtained in six patients, marked improvement in two, and failure in one. AmBisome was well tolerated and shortened the time to clinical and mycological response suggesting a further improvement in the management of cryptococcosis in AIDS patients.

Non-Hodgkin's lymphoma and AIDS: frequency of gastrointestinal involvement in a large Italian series.

Even though the close association between AIDS and non-Hodgkin's lymphoma (NHL) is widely known, few studies have evaluated the frequency of gastrointestinal involvement in a large series of AIDS patients with heterogeneous risk factors. We therefore reviewed the demographic and clinical features of patients with AIDS and NHL seen at our institution over a period of 5 years. NHLs complicated AIDS in 70 of 786 (9%) cases in our study. All but one of the tumours were of high- or intermediate-grade histologic subtype, and 80% of 56 patients with diagnosis made during lifetime had disease stages III or IV, most with extranodal localization. The gastrointestinal tract was involved in 23 cases (33%), 13 of whom had an antemortem diagnosis. All these patients complained of significant symptoms, the most frequent being GI bleeding followed by recurrent abdominal pain with or without masses. Three patients had evidence of lymphomatous disease along both the upper and lower GI tract, but more often a single localization was present. Prognosis of patients with NHLs was very poor, and there was no significant difference in survival between patients with and without GI localization at the time of initial diagnosis.

Contraceptive choice in an urban clinic in Nigeria.

PIP: Contraceptive choice in the 1st 1075 acceptors at an urban clinic in Lagos, Nigeria is studied using clinical notes of all patients who attended the clinic between September 1, 1980 and August 31, 1983. Details of previous and current contraception, age, parity and level of education are analyzed. The IUD was the most popular choice followed by the injectable contraceptive and the pill. Interval tubal ligation was chosen by some patients. Acceptors of injectables were older women of high parity and lower educational standard while pill acceptors were of lower parity and higher educational level. The IUD was acceptable to all ages and parities except those with only 1 child or none. Loss to follow-up and the wish to plan another pregnancy were the commonest reasons for discontinuing contraception. Medical reasons for discontinuing the IUD were pain, menstrual disorder, accidental pregnancy and expulsion/perforation; for discontinuing injectables the reasons were menstrual disorder, accidental pregnancy and raised blood pressure. Of acceptors of the 3 main methods, former pill and IUD users were more likely to choose the same method again. A strategy should be devised to encourage patients of lower parities and age to use contraceptives, while sterilization in patients of parity 3 and above should be even more actively advocated. Greater effort should be made to support patients through the 1st 6 months after starting any method as this is the time when a large number of discontinuations occur.^ieng

[Serum and cerebrospinal fluid antibodies against measles virus in patients with multiple sclerosis]. / Anticorpi sierici e liquorali verso il virus del morbillo in pazienti affetti da sclerosi multipla.

Measles c.f.a. and h.i.e. were titrated in sera and, when possible, in the cerebrospinal fluids of 183 SM patients and in sera from a control group of subjects. No significative difference was found by the h.i. test, whereas significantly higher was the frequence of positives by the c.f. test in the SM group, with no correlation with the therapy to which the patients were subjected. The presence of c.f.a. in 13 of 48 cerebrospinal fluids tested, together with a low value of the serum/CSF antibodies ratio and with the lack of CSF antibodies against other viral antigens tested (HSV, rubeola), could indicate an intra CNS production of measles antibodies. To sum up, our results suggest an involvement of measles virus at least in some of the MS patients considered.