A prospective evaluation of maraviroc administration in patients with advanced HIV disease and multiple comorbidities: focus on efficacy and tolerability issues.

In our HIV outpatient centre where over 1,200 patients are followed, maraviroc as an entry inhibitor was introduced in 2010. We aimed to assess the background, the therapeutic challenges and the prospective monitoring of all patients treated with a combination antiretroviral therapy (cART) including maraviroc. Sixty-six patients started a maraviroc-containing cART with a history of HIV infection lasting 13.9±10.7 years. This interim analysis presents patients who had at least 12 (mean 16.9±12.8) months of follow-up. One to 17 previous cART changes prompted the introduction of maraviroc in rescue regimens in the great majority of patients considered (53 of 66); in 13 cases, maraviroc was given to patients with advanced HIV disease and no immune recovery after 2-3 years of a virologically-effective cART. The most frequent companion antiretroviral agents were: darunavir/ritonavir (51 cases), raltegravir (49 subjects), and etravirine (36 cases). The most common underlying conditions were: AIDS (41 cases), liver cirrhosis (21), AIDS-related or other malignancies (20 cases), major cardiovascular events (18 cases), osteonecrosis and haemodialysis-treated kidney failure (3 cases each). A chronic HCV and HBV hepatitis were of concern in 25 and 13 patients. The addition of maraviroc added favourably to clinical-laboratory markers of HIV disease progression, and those of comorbid conditions. HIV viraemia became (or remained) undetectable in 55 patients of 66 (83.3%). An improvement in CD4+ count was observed in all 66 patients, based on a mean 24.9±19.2% increase versus baseline, paralleled by an improvement in mean absolute CD4+ count of 134.7±121.1 cells/µL. A tendency towards an increased mean and peak CD4+ count was observed in the subgroup receiving a maraviroc-raltegravir-based cART. As no clinical-laboratory adverse events attributable to maraviroc occurred, nobody discontinued the study drug. Only mild-transient gastrointestinal disturbances, fatigue and anorexia, were reported during maraviroc administration, but their relationship with the study drug was difficult to assess because of the multiple comorbidities and polypharmacy. Our preliminary experience with maraviroc, even considering the limits of the proportionally reduced sample, the patients' salvage stage of advanced disease and the related-unrelated morbidities, underlines its excellent efficacy and safety profile.

Raltegravir use prospectively assessed in a major HIV outpatient clinic in Italy: sample population, virological-immunological activity, and tolerability profile.

Raltegravir, as the first HIV integrase inhibitor, has been used and prospectively monitored since 2010 in our HIV outpatient centre, where over 1,200 patients are monitored. The aim of our report is to perform an interim assessment of the background, the safety profile and the clinical-laboratory monitoring of all patients treated with a combination antiretroviral therapy (cART) including raltegravir, for at least 12 months. In all, 109 pretreated patients started a raltegravir-containing cART when aged 44.8 plus or minus 19.2 years, with a history of HIV infection lasting 13.4 plus or minus 9.7 years. All subjects were monitored for at least 12 months (mean 17.2 plus or minus 10.3 months). In the vast majority of cases (93 of 109: 85.3%), multiple (3-16) prior cART changes prompted raltegravir introduction in advanced-salvage lines: 72 of 109 (66.1%) patients had even developed a concurrent triple-class resistance to anti-HIV compounds. The most frequent companion antiretroviral agents were: darunavir/ritonavir (75 cases), maraviroc (47 subjects), and etravirine (38 cases). The most common underlying conditions were: AIDS (46 patients), liver cirrhosis (31 cases), AIDS-related or other malignancies (23 cases), and major cardio-cerebro-vascular events (18 cases). A chronic HCV and HBV hepatitis were of concern in 48 and 23 patients, respectively. The adjunct of raltegravir favourably affected all clinical-laboratory markers of HIV disease progression, and those of the broad spectrum of comorbidities, except for two patients who failed the raltegravir-containing cART due to insufficient adherence. Despite the already compromised clinical situation, a minority of subjects experienced mild-transient clinical-laboratory untoward events possibly attributable to raltegravir, such that no patients discontinued raltegravir during the observation period. Only three AIDS-defining conditions became apparent during raltegravir-based cART; chemotherapy and/or radiotherapy cycles were performed as scheduled in patients suffering from cancer; chronic hepatitis B and C progressed to liver cirrhosis and/or hepatocarcinoma in only 2 and 6 patients. Otherwise, treatment with pegylated interferon-ribavirin became feasible in 25 patients of 48 with chronic HCV. During raltegravir-containing cART, neither autoimmune disorders nor novel malignancies were diagnosed. Only mild-transient gastrointestinal disorders, fatigue, dizziness, insomnia and cutaneous rash were reported, although their relationship with the study drug was difficult to assess due to multiple comorbidities and polypharmacy. Abnormal liver function testings were observed in 57 patients (52.3%), all suffering from concurrent hepato-biliary disorders. Significant increases in serum lipids and/or lipase levels versus baseline values were never registered: serum lipid levels significantly improved after raltegravir introduction. Our experience with raltegravir underlines its excellent efficacy and safety profile, which exploits a novel mechanism of action, and displays no cross-resistance with any other antiretroviral. A progressively extended prescription in naive patients and early cART lines will allow the therapeutic potential of raltegravir to be exploited.

The mycoarray as an aid for the diagnosis of an imported case of histoplasmosis in an Italian traveler returning from Brazil.

We describe an imported case of histoplasmosis, whose serological profile was established by means of a protein-based microarray platform, the recently described mycoarray. Because of its peculiarities, such a novel tool greatly facilitates the rapid and multiparametric assessment of patients' serological status and lends itself to be employed as an aid in the diagnosis of primary mycoses, especially in nonendemic countries.

Amiodarone-related pneumonitis and peripheral neuropathy in an elderly patient.

Amiodarone, which has been used since 1967 as an antiarrhythmic drug, gives rise to a variety of cardiac and extracardiac adverse side-effects. Among these, pulmonary toxicity is considered the most frequent and serious extracardiac side-effect, since it may occur in various atypical forms and often limits the drug's clinical use. We encountered a 67-year-old white male patient with suspected amiodarone pneumonitis characterized by multiple lung nodules associated with pleural and pericardial effusion and peripheral neuropathy. Because differential diagnosis with pulmonary infectious diseases may be extremely difficult, the attending physician should therefore bear in mind the possibility of amiodarone pneumonitis whenever the drug is given.

Meningoencephalitis with persistent parvovirus B19 infection in an apparently healthy woman.

A case of meningoencephalitis, associated with persistent parvovirus B19 infection, is described in a 36-year-old immunocompetent woman. Parvovirus B19 DNA was detected in samples of cerebrospinal fluid and serum; no parvovirus B19-specific clinical symptoms were seen, but neurological episodes were observed in the presence of parvovirus B19 infection and despite the onset of a specific immune response.

Epstein-Barr Virus Associated Nasopharyngeal Carcinoma and Local Polymorphic B-Cell Lymphoproliferative Disorder in a Patient With HIV Disease.

A rare case report of HIV-associated nasopharyngeal carcinoma concurrent with local polymorphic B-cell lymphoproliferative disorder is reported and discussed on the ground of the most recent literature evidences. Only very few reports of nasopharyngeal carcinoma have been described until now in patients infected with HIV (one case in adults), and a coexisting lymphoid cell proliferation with a concurrent role of Epstein-Barr virus in prompting both disorders was never reported to date. The relevant pathogenetic, diagnostic, and therapeutic questions raised by this infrequent intriguing association retrieved in a patient with prominent HIV-related immunodeficiency are focused on.

[Nocardiosis as the first opportunistic disease in a patient with missed HIV infection. Pathomorphism of presentation, clinical course, and evolution]. / Nocardiosi come prima patologia opportunistica in un paziente con infezione da HIV rimasta indiagnosticata.

It is reported on the ground of the most updated literature evidences an infrequent case of multiple cavitating pulmonary infiltrates and a probable liver abscess caused by a Nocardia asteroides disseminated infection heralding a HIV-related profound immunodeficiency who remained missed and undiagnosed until the emerging of this severe opportunistic infection.

Reactivation of severe, acute pulmonary tuberculosis during treatment with pegylated interferon-alpha and ribavirin for chronic HCV hepatitis.

The unexpected observation of severe pulmonary tuberculosis after a 7-month combined pegylated interferon-ribavirin for chronic hepatitis C, prompted us to search an eventual immunodeficiency (lymphopenia and/or depletion of CD4+ T-lymphocytes. The retrieval of a chest radiograph incidentally performed 11 y before and showing a probable primary tuberculosis, paralleled a negligible clinical history. The enlargement of interferon indications needs careful evaluation for prior (usually missed) tuberculosis, to prevent or avoid its possible reactivation. Latent tuberculosis is increasingly reported because of extended life expectancy, immigration, and recent availability of cure for multiple chronic disorders, which are often borne by primary-secondary immunodeficiency.

Chron's disease, rare association with selective IgA immunodeficiency, and development of life-threatening bacterial infections.

Life-threatening necrotizing fasciitis and relapsing Lemierre syndrome associated with Fusobacterium necrophorum septicaemia occurred in young adults with a moderate Chron's disease and a missed profound IgA deficiency. This unexpected association of a chronic bowel inflammatory syndrome with prominent IgA abnormalities and severe bacterial infection deserves careful attention by physicians faced with young patients with Chron's disease.

Disseminated cutaneous leishmaniasis after visceral disease in a patient with AIDS.

Leishmaniasis is emerging as a common and serious opportunistic disease for patients with HIV infection. Almost all cases of HIV-Leishmania coinfection have been described in Mediterranean countries and they occur with various clinical presentations, ranging from typical visceral forms to asymptomatic or atypical cases, including cutaneous and mucocutaneous leishmaniasis. Pentavalent antimony compounds have been the mainstays of antileishmanial therapy for half a century and new lipid formulations of amphotericin B seem reliable, but the most effective treatment remains unknown. We describe a patient who was HIV infected and an intravenous drug user, with an unusual disseminated cutaneous leishmaniasis, after an initial visceral disease and after a 13-month maintenance treatment with liposomal amphotericin. The severe concurrent immunosuppression probably played an essential role in leading to this atypical cutaneous form, characterized by diffuse, nonulcerated, nonscabby maculopapular lesions.

Role of Mycobacterium xenopi disease in patients with HIV infection at the time of highly active antiretroviral therapy (HAART). Comparison with the pre-Haart period.

BACKGROUND AND SETTING: A reliable and timely clinical, radiological, and bacteriological diagnosis, and an optimal treatment of non-tubercular mycobacteriosis (including Mycobacterium xenopi disease), remain an unanswered challenge for clinicians facing immunocompromised patients, including those with HIV infection. OBJECTIVE: The aim of our survey is to report the frequency, and the epidemiological, immunological, microbiological, clinical, and therapeutic features of all confirmed HIV-associated M. xenopi disease observed from 1993-2002, with special attention paid to eventual differences that emerged after the introduction of potent antiretroviral therapy (highly active antiretroviral therapy, HAART), on the basis of an international literature update. DESIGN AND RESULTS: Our series of 17 consecutive confirmed M. xenopi infections retrieved in 14 out of 3000 patients followed for HIV disease complications raises a broad series of clinical, diagnostic, therapeutic, and prophylactic concerns. The great majority of M. xenopi disease involved the lower respiratory tract, but atypical features including cavitation and prominent exudative features became apparent in patients successfully treated with HAART, pointing out the possible role of the so-called immune reconstitution syndrome in these episodes. CONCLUSIONS: Diagnostic problems represented by late or missed identification due to slow culture and frequently concomitant opportunistic disorders, join therapeutic difficulties due to the unpredictable in vitro antimicrobial susceptibility profile of these organisms, selection of treatment and chemoprophylaxis according with clinical-radiological and microbiological suspicion, and concomitantly administered medications.

Ampicillin, gentamicin and teicoplanin as antimicrobial therapy for recurrent Streptococcus agalactiae and Enterococcus faecalis endocarditis in an intravenous drug abuser with HIV infection.

Infective endocarditis associated with human immunodeficiency virus (HIV) infection occurs almost exclusively in intravenous (i.v.) drug users and usually involves the tricuspid valve, with an increased mortality rate among patients with a severe degree of immunosuppression. The first reported case of recurrent tricuspid endocarditis sustained by Streptococcus agalactiae and Enterococcus faecalis in an i.v. drug addict during HIV infection is presented. Antimicrobial therapy with i.v. ampicillin, gentamicin and teicoplanin led to complete clinical and echocardiographical recovery.