Reversal of major genotypic tipranavir mutations under long-term treatment with tipranavir/ritonavir itself with very limited optimized background, during deep salvage antiretroviral therapy.

A reversal of key HIV protease mutations against tipranavir has been observed in a patient undergoing a late salvage antiretroviral therapy. Our patient initially introduced tipranavir/ritonavir in absence of an optimized background and novel drug classes, and nevertheless he experienced a virological-immunological benefit. Our report is a contribution to the present debate around the role of each single HIV protease mutation, and the validation of mutational "scores" (like the so-called tipranavir weighted score), to be applied to last-generation protease inhibitor compounds initially targeted on patients with limited, residual therapeutic options.

Associated actinomycosis and rhinopharyngeal adenocarcinoma during HIV infection: diagnostic and therapeutic issues.

An extremely infrequent episode of nasopharyngeal actinomycosis associated with squamous adenocarcinoma occurred in an HIV-infected male patient with a previous diagnosis of AIDS, treated with combined antiretroviral therapy taken with insufficient adherence, such that a satisfactory immune system recovery (as expressed by a CD4 lymphocyte count persistently above 400 cells/mcl), contrasted with a low-level persistence of detectable HIV viraemia, and enlarged genotypic resistance mutations. Interestingly, a number of local and specific risk factors for both infectious and neoplastic disorders were recognized by healthcare staff (tobacco smoke, long-term inhalatory substance abuse, in particular cocaine, and semi-professional mushroom-truffle hunting, including evaluation by systematic smelling). Despite appropriate and timely diagnostic assessment carried out with repeated, combined computerized tomography, magnetic resonance imaging, and fiberoptic rhinoscopy with biopsy and histopathologic studies, the final diagnosis of a combined dual infectious-neoplastic pathology occurred only after a demolishing surgical intervention and subsequent pathology studies. Despite proper antimicrobial therapy, and an associated radiotherapy and cytotoxic chemotherapy schedule, rapid dissemination of multiple secondary lesions to the brain rapidly led to our patient's death. The imaging and histopathological diagnostics of the dual illnesses of our HIV-infected patient, and its therapeutic and outcome features, are presented and discussed on the basis of the evidence from the available literature. To the best of our knowledge, this is the first described case of actinomycosis associated with a local, underlying squamous cell adenocarcinoma of the same ear, nose, and throat district in either HIV-infected or HIV-non-infected subjects.

Associated thyreoiditis, myasthenia gravis, thymectomy, Chron's disease, and erythema nodosum: pathogenetic and clinical correlations, immune system involvement, and systemic infectious complications.

The case of a young woman suffering from multiple autoimmune-dysreactive disorders (including thyreoiditis, myasthenia gravis, thymectomy, Crohn's disease, and erythema nodosum), while undergoing steroideal therapy, was complicated by a severe infectious disorder (severe upper urinary tract infection). While the pathogenetic and clinical relationship between the different autoimmune-dysreactive complications is still unclear, and the supporting role of the frequent immunosuppressive treatment may add significantly to these risk factors, clinicians who are engaged in the management of these patients should be aware that multiple, concurrent or subsequent disorders might occur in these subjects, and also that severe infections might be of relevant concern.

Emergence of amphotericin B-resistant Cryptococcus laurentii meningoencephalitis shortly after treatment for Cryptococcus neoformans meningitis in a patient with AIDS.

A unique occurrence of two subsequent episodes of HIV-associated Cryptococcus neoformans followed by C. laurentii meningoencephalitis (successfully cured with fluconazole after demonstrated amphotericin B resistance) is presented and discussed. The available literature reported only two cases of HIV-associated C. laurentii infection to date, while a concurrent infection by C. neoformans and C. laurentii has been reported only once in a patient without HIV disease. The absence of prior descriptions of documented central nervous system infection by C. laurentii in non-HIV-infected patients is emphasized as well as the unpredictable in vitro and in vivo antifungal susceptibility of this non-neoformans Cryptococcus spp., and its apparent prevalence in hospitalized patients who received prior antifungal treatments. All epidemiologic, diagnostic, clinical, and therapeutic implications are discussed on the basis of the evolving characteristics of opportunism in the era of highly active antiretroviral therapy (HAART).

Disseminated, lethal prostate cancer during human immunodeficiency virus infection presenting with non-specific features. Open questions for urologists, oncologists, and infectious disease specialists.

INTRODUCTION: Prostate cancer is a very infrequent occurrence in persons aged 55 years or less, and it has been rarely reported in HIV-infected patients (10 overall cases so far); therefore, an increased incidence compared with the general population has not been established, although a younger age seems more frequent among population with HIV disease. CASE REPORT: We report a case of metastatic prostate cancer occurred in a 53-year-old HIV-infected man, admitted due to non-specific signs, and symptoms: impaired general conditions, fever, weight loss, fatigue, and exertional dyspnea. A remarkable anemia and an aortic systolic murmur were the prominent initial findings, while AIDS-related conditions were not suspected due to a sustained CD4+ count and a contained viremia, which never required antiretroviral therapy. Repeated red blood cell transfusions and an empiric, combined antimicrobial therapy were promptly carried out, under the suspicion of infectious endocarditis, but no appreciable improvement of clinical conditions was achieved. Subsequently, our patient complained not only of an increasingly severe pain at the root of his left thigh, together with overcoming dysuria and urgency, but also urinary tract infection that was rapidly ruled out. During the diagnostic workup for an HIV-associated fever of undetermined origin, a bone marrow biopsy disclosed a metastatic prostatic cancer, with elevated prostate specific antigen (PSA) and acid phosphate levels. An abdominal-pelvic ultrasonography and computerized tomographic scan allowed to detect a dyshomogeneous endopelvic expansive mass with extrinsic compression of the urinary bladder, and involvement of the last lumbar vertebra, large portions of pelvis, and the proximal epiphysis of the right femur. A skeleton scintigraphy pointed out multiple hypercaptation (areas of concentrated traces of radioactivity) areas with involvement of cranial, cervical, dorsal, lumbar, and sacral vertebrae, as well as the pelvis and upper portions of both femurs. Despite therapeutic attempts, our patient deceased after seven weeks due to an overwhelming disseminated intravascular coagulation (DIC). CONCLUSIONS: The non-specific clinical presentation of our case (mimicking other generalized or focal illnesses), and the final, lethal complication (DIC) pose striking problems related to the differential diagnosis during HIV disease, while the rapid evolution into an advanced, complicated, and widely metastatic disease with extensive bone marrow invasion which preceded the appearance of local signs-symptoms, and the lethal overwhelming DIC, deserves attention by specialists who care for HIV-infected subjects.

[HIVAb, HCVAb and HBsAg seroprevalence among inmates of the prison of Bologna and the effect of counselling on the compliance of proposed tests]. / Prevalenza per HIV, HBV e HCV nei detenuti del carcere di Bologna ed effetti del counselling sul livello di adesione alla proposta dei test.

OBJECTIVES: The aims of the study were to evaluate the HIVAb, HCVAb and HBsAg seroprevalence among Italian and foreign inmates of the prison of Bologna, to evaluate if the extensive counselling of "new" inmates has significantly enhanced adherence to laboratory tests. DESIGN: The serological status was determined by a blood withdraw following the informed consent. Before asking their consent, patients were informed by cultural mediators who had been instructed about the aims of the study/exam during introductory meetings. The initial step managed by mediators was followed by further individual counselling interventions, carried out by hospital infective disease unit, prison and prison drug abuse service physicians. The laboratory tests were performed in an external structure. SETTING: Prison of Bologna. PARTICIPANTS: The study was conducted on 433 subjects among a whole population of 900 inmates in the local prison: 390 subjects were males (90.1%) and 43 were females (9.9%). The median age of the whole population was 34.86 years (+/- 9.9). The studied population counted 147 (33.9%) intravenous drug users (IDU) and 286 not addicts (66.1%). As regards nationality, 212 subjects were Italian (48.9%) and 221 (51.1%) foreigners. Among the total 433 inmates considered, 78 (18%) were known as previous IDU with conviction history or condemned to long term sentences, while 59 (13.6%) were inmates recently convicted active IDU assisted by the internal drug abusers service. The third group was composed by 296 inmates imprisoned during the summer (103 Italians and 193 foreigners) self declared not IDU. RESULTS: A. 12.5% of inmates were HIV positive, 8.1% HBV positive and 31.1% HCV positive. 25 subjects were found positive both to HIV and HCV; 1 both to HIV and HBV and 5 to HIV, HBV and HCV. HIV positivity is more common among Italian vs. foreigners inmates, among IDU vs. not IDU. HCV positivity is more common among Italian vs. foreigners inmates, and among IDU vs. not IDU. The distribution of HBV seropositivity among the different groups shows no statistically significant differences. All subjects receiving multi-focal counselling reached better compliance levels: 10% vs. 1% for HIV, 16% vs. 1% for HBV and 35% vs. 0.3% for HCV, with statistically significant coefficients of contingency. CONCLUSIONS: In the prison of Bologna drug addiction is prevalent in italian seropositive personers and it is often associated with HIV and HCV positivity. Foreign inmates, mostly in the not-IDU group, show a lower prevalence of these two infections. Multi-focal counselling before test increased significantly the adherence of inmates to the study.

[First evaluations of LPV/RTV (Kaletra) efficacy on HIV-positive patients treated with multiple drugs]. / Prime valutazioni sull'efficacia di LPV/RTV (Kaletra) in una casistica di pazienti HIV+ pluritrattati.

At the current epidemic stage, characterized by the rise of antiretroviral drug resistance, it is necessary to administer to HIV-positive patients increasingly effective treatments. This is possible only by means of powerful drugs. In a retrospective study, the authors evaluate 78 patients: 76 pre-treated with multiple drugs and 2 na ves. The 78 patients received LPV/RTV, starting from the fourth 3-month period of 2000 until the first 3-month period of 2002. The average treatment duration was 6.5 ( 5.5) months; the median value 6 months. The efficacy of the LPV/RTV therapeutic regimen was evaluated by a cytofluorimetric count of CD4+ and determination of the HIV viral load. There were 14 drop-out patients (17.9%): 5 because of auto-suspension, 1 due to absence of clinical and virological efficacy, 5 due to side effects (3 hepatopathy, 1 allergy and 1 nausea); three patients were lost on follow-up. There were 64 (82.1%) patients on treatment. Forty patients responded (51.3%) and 13 (16.7%) had uncontrolled viraemia (over than 200 copies/ml). However, the treatment with LPV/RTV was not interrupted for these patients, because in the follow-up they showed an increase in CD4+ values. The authors conclude that the LPV/RTV combination confirms previous findings: it is a drug with a relatively low incidence of side effects, capable of powerful results even in the treatment of patients receiving multiple drugs and thus subjected to the risk of developing antiretroviral drug resistance.

[Efficacy of efavirenz in a mixed population of patients. Identification of drop-out causes]. / Valutazione dell'efficacia di efavirenz in una casistica mista. Rilievo delle cause di drop-out.

AIM: To determine drop-out causes and EFV efficacy in ARVT. MATERIALS: We examined a case-study of 106 patients (74% males, 26% females) followed for up to 23 months. 14% of the patients were naive for ARVT, 21% had already been treated with other drugs (non effective therapy), 28% were administered EFV as a supporting drug, 37% were administered EFV as a replacement drug (side-effects). The parameters used to assess efficacy are: CD4+ lymphocyte count and HIV viral load. The statistical tests used are: Student t, Fischer F, Kruskal Wallis H. RESULTS: 33 (31.1%) patients are D.O. because of: non efficacy (11%), rash (5%), psychological disorders (8%), impotence (1%), psychosis (2%), acute hepatitis (1%), abdominal pain (2%), self-suspended ARVT (2%). After the EFV introduction, in few months it has been observed a sudden fall of the viral load while the CD4+ course increases up to the 18 month of follow up, and later on it has been observed a small decrease. CONCLUSION: This study proves the efficacy of EFV in ARVT. The D.O. patients because of side-effects are only a small number.