Efficacy and Safety of Switching to Dolutegravir/Lamivudine in Virologically Suppressed People Living with HIV-1 Aged Over 65 Years.

Clinical trials of dual regimen dolutegravir/lamivudine (DOL/3TC) demonstrated potent efficacy and favorable safety in both antiretroviral therapy-naïve and -experienced patients, but data on older people are lacking. We aimed to evaluate virological efficacy and safety of DOL/3TC in suppressed older patients over a 12-month period. We performed a retrospective cohort study evaluating people living with HIV (PLWHIV) aged ≥65 years at our HIV Clinic who were switched to DOL/3TC. Eligible patients had baseline HIV-1 RNA <20 copies/mL, and no previous virological failures or known resistance mutations for lamivudine or dolutegravir. Inclusion criteria were met by 72 patients: 59 were men, median age was 69.2 years, and one or more comorbidities were present in 89% of patients. The most common reason for switch was simplification, followed by drug-drug interactions (DDIs) and toxicities. After 12 months, 64 (88.9%, by the intention-to-treat analysis) patients maintained HIV-1 RNA <20 copies/mL, and reasons for treatment failure were virological failure in three cases, adverse events in three, and missing data in two. Genotype resistance testing showed no resistance mutations for lamivudine or dolutegravir in subjects with virological failure. The number of potential DDIs decreased from 92 to 12 after switching to DOL/3TC, and a significant reduction in median total and low-density lipoprotein cholesterol was reported, while median change in body weight was not significant. In this real-life cohort, switching to DOL/3TC was associated with maintenance of virological control and good tolerability among persons aged >65 years, supporting use of this dual regimen in older PLWHIV.

Infectious Diseases Team for the Early Management of Severe Sepsis and Septic Shock in the Emergency Department.

Background: The impact on patient survival of an infectious disease (ID) team dedicated to the early management of severe sepsis/septic shock (SS/SS) in Emergency Department (ED) has yet to be assessed. Methods: A quasiexperimental pre-post study was performed at the general ED of our hospital. During the pre phase (June 2013-July 2014), all consecutive adult patients with SS/SS were managed according to the standard of care, data were prospectively collected. During the post phase (August 2014-October 2015), patients were managed in collaboration with a dedicated ID team performing a bedside patient evaluation within 1 hour of ED arrival. Results: Overall, 382 patients were included, 195 in the pre phase and 187 in the post phase. Median age was 82 years (interquartile range, 70-88). The most common infection sources were lung (43%) and urinary tract (17%); in 22% of cases, infection source remained unknown. During the post phase, overall compliance with the Surviving Sepsis Campaign (SSC) bundle and appropriateness of initial antibiotic therapy improved from 4.6% to 32% (P < .001) and from 30% to 79% (P < .001), respectively. Multivariate analysis showed that predictors of all-cause 14-day mortality were quick sepsis-related organ failure assessment ≥2 (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.15-2.45; P = .007), serum lactate ≥2 mmol/L (HR, 2.13; 95% CI, 1.39-3.25; P < .001), and unknown infection source (HR, 2.07; 95% CI, 1.42-3.02; P < .001); being attended during the post phase was a protective factor (HR, 0.64; 95% CI, 0.43-0.94; P = .026). Conclusion: Implementation of an ID team for the early management of SS/SS in the ED improved the adherence to SSC recommendations and patient survival.

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.

Rosuvastatin for the treatment of hyperlipidaemia in HIV-infected patients receiving protease inhibitors: a pilot study.

Sixteen HIV-infected patients with protease inhibitor (PI)-related, persisting hypercholesterolaemia were treated with 10 mg a day rosuvastatin for 24 weeks. At the end of the observation period, the median reductions in total cholesterol and triglyceride levels versus median baseline values were 21.7 and 30.1%, respectively (P < 0.01). In our small pilot study, rosuvastatin was found to be effective for the treatment of PI-associated hyperlipidaemia, in association with a favourable tolerability profile, without significant clinical or laboratory adverse events.

[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.

[Tuberculosis in Italian and non-EU patients. Review of case mix (1996-2001)]. / La tubercolosi in pazienti italiani ed extra-comunitari. Revisione di casistica (1996-2001).

The Authors examined the case mix of patients with tuberculosis who were hospitalised from 1996 to the first 6 months of 2001 at the Infectious Disease Department. The patient population comprises two groups with different epidemiological characteristics. The first group consists of Italians [62] and the second of Non-EU patients [28]. The Italians have an older average age and their epidemiological and clinical risks are more serious in comparison to Non-EU's. Moreover, among Italian patients the number of subjects with HIV infection is greater. The presence of tuberculosis at the lymph nodes appears to be related to patients with HIV, whereas for HIV-negative patients the most frequent sites are the lungs and pleura. Some of the patients underwent biopsy in the sites affected by the pathology and the histopathological findings are very similar to the typical data. There does not seem to be any difference between the results of the X-rays of the lung X-rays for the Italians and the Non-EU's, whereas in general there are very few patients who show the typical location of tuberculosis at the apex of the lungs.