The increasing burden and complexity of multi-morbidity and polypharmacy in geriatric HIV patients: a cross sectional study of people aged 65 - 74 years and more than 75 years.

BACKGROUND: Geriatric Patients Living with HIV/AIDS (GEPPO) is a new prospective observational multicentre cohort consisting of all the HIV-positive geriatric patients being treated at 10 clinics in Italy, and HIV-negative controls attending a single geriatric clinic. The aim of this analysis of the GEPPO cohort was to compare prevalence and risk factors of individual non-communicable diseases (NCD), multi-morbidity (MM) and polypharmacy (PP) amongst HIV positive and HIV negative controls at enrolment into the GEPPO cohort. METHODS: This cross-sectional study was conducted between June 2015 and May 2016. The duration of HIV infection was subdivided into three intervals: < 10, 10-20 and > 20 years. The NCD diagnoses were based on guidelines defined criteria, including cardiovascular disease, hypertension, type 2 diabetes, chronic kidney disease, dyslipidaemia, chronic obstructive pulmonary disease. MM was classified as the presence of two or more co-morbidities. The medications prescribed for the treatment of comorbidities were collected in both HIV positive and HIV negative group from patient files and were categorized using the Anatomical Therapeutic Chemical (ATC) classification. PP was defined as the presence of five or more drug components other than anti-retroviral agents. RESULTS: The study involved a total of 1573 patient: 1258 HIV positive and 315 HIV negative). The prevalence of individual comorbidities was similar in the two groups with the exception of dyslipidaemia, which was more frequent in the HIV-positive patients (p <  0.01). When the HIV-positive group was stratified based on the duration of HIV infection, most of the co-morbidities were significantly more frequent than in control patients, except for hypertension and cardiovascular disease, while COPD was more prevalent in the control group. MM and PP were both more prevalent in the HIV-positive group, respectively 64% and 37%. CONCLUSIONS: MM and PP burden in geriatric HIV positive patients are related to longer duration of HIV-infection rather than older age per se.

Ageing with HIV: a multidisciplinary review.

INTRODUCTION: After the introduction of highly active antiretroviral treatment, the course of HIV infection turned into a chronic disease and most of HIV-positive patients will soon be over 50 years old. MATERIAL AND METHODS: This paper reviews the multiple aspects that physicians have to face while taking care of HIV-positive ageing patients including the definitions of frailty and the prevalence and risk factors of concomitant diseases. From a therapeutic point of view pharmacokinetic changes and antiretroviral-specific toxicities associated with ageing are discussed; finally therapeutic approaches to frailty are reviewed both in HIV-positive and negative patients. CONCLUSION AND DISCUSSION: We conclude by suggesting that the combined use of drugs with the least toxicity potential and the promotion of healthy behaviours (including appropriate nutrition and exercise) might be the best practice for ageing HIV-positive subjects.

Induced first abortion rates before and after HIV diagnosis: results of an Italian self-administered questionnaire survey carried out in 585 women living with HIV.

OBJECTIVES: The aim of the study was to investigate whether HIV diagnosis affected reproductive planning over time and to assess independent predictors of abortion overall and following HIV diagnosis. METHODS: Donne con Infezione da HIV (DIDI) is an Italian multicentre study based on a questionnaire survey carried out in 585 HIV-positive women between November 2010 and February 2011. The incidence and predictors of abortion were measured by person-years analysis and Poisson regression. RESULTS: The crude incidence rate of abortion was 18.8 [95% confidence interval (CI) 16.5-21.4] per 1000 person-years of follow-up (PYFU). Compared with women who terminated their pregnancy before HIV diagnosis, women who terminated their pregnancy after HIV diagnosis but before 1990 showed a 2.56-fold (95% CI 1.41-4.65) higher risk. During 1990-1999 and 2000-2010, HIV diagnosis was not significantly associated with outcome [adjusted rate ratio (ARR) 0.93 (95% CI 0.55-1.59) and ARR 0.69 (95% CI 0.32-1.48), respectively]. Age [ARR 0.96 (95% CI 0.94-0.99) per 1 year older] and injecting drug use [ARR 1.38 (95% CI 0.98-1.94)] were found to be predictors of abortion overall. After HIV diagnosis, being on combination antiretroviral therapy [ARR 0.54 (95% CI 0.28-1.02)], monthly income < €800 [ARR 1.76 (95% CI 0.99-3.12)], younger age [ARR 0.95 (95% CI 0.91-1.00) per 1 year older] and fear of vertical transmission [ARR 1.95 (95% CI 1.04-3.67)] were found to be independently associated with abortion. CONCLUSIONS: We observed a higher incidence of abortion compared with data available for the general Italian population. Awareness of HIV diagnosis was predictive of abortion only in the 1980s. Women with HIV infection are still worried about vertical HIV transmission. Interventions promoting HIV screening among women who plan to have an abortion and informative counselling on motherhood planning in the setting of HIV care are needed.

Cutaneous manifestations in a series of 417 patients with SARS-CoV-2 infection: epidemiological and clinical correlates of chilblain like lesions.

A variety of dermatological lesions have been described in COVID-19, although the prevalence and pathogenic relationship remain unclear particularly for chilblain-like lesions. Dermatological examination was performed in a prospective cohort of consecutive patients seen at the service for SARS-CoV-2 infection. Out of 417 patients with confirmed SARS-CoV-2 infection [median age 29.5 years (range 15-65); 62.5% males], dermatological lesions were detected in 7 (1.7%). Three patients had acral lesions; their age (range) was 15-29 years; all had a negative nasopharyngeal swab and developed IgG and/or IgM-specific antibodies; all presented none or mild symptoms. A fourth patient remained negative at repeated testing; mother, father and sister had a documented mild COVID-19. Non-acral lesions were observed in four older patients, with severe COVID-19. Chilblain-like lesions may be the sole manifestation of SARS-CoV-2 infection; their presence in asymptomatic school children and adolescents should be considered a potential signal of familial or community spread of the virus.

Where is West Nile fever? Lessons learnt from recent human cases in northern Italy.

West Nile disease in humans has been detected for the first time in Italy in two regions, Emilia-Romagna and Veneto. We conclude that also West Nile fever cases should be specifically targeted by surveillance.

The societal burden of HIV/AIDS in Northern Italy: an analysis of costs and quality of life.

This study aims to measure the direct and indirect costs of HIV/AIDS care and quality of life (QoL) of HIV-infected patients in Northern Italy. We conducted a prospective cohort study over 12 months, enrolling a sample of 121 patients with HIV infection from two cities in Northern Italy. Patients were surveyed at baseline and were followed-up at 6 and 12 months. To assess the relationship between costs and stage of disease, patients were categorized into three groups at baseline: "No HAART" (asymptomatic and never before on highly active antiretroviral therapy (HAART)), "Stable HAART" (HAART with mild HIV infection and no prior opportunistic infections) and "HAART failure" (primary HAART regimen was altered because of severe side effects or immunological failure). Direct medical costs were based on utilization of (day) hospital admissions, diagnostic procedures, laboratory tests, clinic visits, consultations and antiretroviral drug use. Indirect costs included production losses due to absence from work, reduced productivity at work and reduced unpaid labour participation. QoL was assessed by visual analogue scale. Parametric regression was used to estimate the expected value and the standard deviation of annual costs per patient. The expected value of total annual costs was 1818 euros and 9820 euros and 12,332 euros, for groups "No HAART", "Stable HAART" and "HAART failure" respectively. We estimated annual expected earnings as 14,994 euros and 10,811 euros and 9820 euros for the same respective groups. The expected value of QoL on a scale of 0-1 in these same patient groups was 0.80, 0.78 and 0.64. We conclude that indirect costs contribute substantially to total costs and are comparable in magnitude to the direct costs excluding antiretroviral drugs. The costs of inpatient care in our cohort were almost negligible compared to total costs. Despite being in treatment, many patients were still gainfully employed and generated substantial expected annual earnings.

Acquired immunodeficiency syndrome-related Kaposi's sarcoma regression after highly active antiretroviral therapy: biologic correlates of clinical outcome.

BACKGROUND: Kaposi's sarcoma (KS) is the most common cancer seen in subjects with acquired immunodeficiency syndrome (AIDS). KS etiology and pathogenesis are still ill defined, and no definite improvement in survival has been obtained with current chemotherapeutic regimens. This open prospective study was aimed at evaluating the clinical response of AIDS-related KS to highly active antiretroviral therapy (HAART), a combination of protease and reverse transcriptase inhibitors, as well as the relationship between clinical response, human immunodeficiency virus type 1 (HIV-1) burden, and antibody titer against human herpesvirus 8 (HHV8) proteins. PATIENTS AND METHODS: Fourteen KS patients were studied; 12 were in the poor-risk group. At given intervals, the patients underwent clinical examination, and their CD4(+) cell counts, plasma HIV-1 RNA levels, and antibody titers to lytic-phase ORF65 and latent-phase HHV8 proteins were determined. RESULTS: When last seen, the overall clinical response rate was 86% (median follow-up, 22 months); 10 complete and two partial responses were achieved, and two patients showed disease progression. All patients with complete or partial response showed a consistent decrease in HIV-1 RNA levels, with a corresponding increase in CD4(+) cell counts; HIV-1 RNA levels in the two progressors remained persistently high, despite a change in HAART. HHV8 ORF65 antibody titers were generally higher in patients with extensive skin or mucosal/visceral involvement versus patients with limited disease; no differences in latent-phase HHV8 antibody titers were observed in relation to tumor burden. CONCLUSION: The findings indicate that antiretroviral therapy with protease inhibitors is effective for AIDS-related KS; the clinical response was correlated with a decrease in plasma HIV-1 RNA levels and an increase in CD4(+) lymphocytes, whereas antibody levels to the lytic-phase HHV8 protein were influenced by the extent of tumor involvement.

Regression of AIDS-related Kaposi's sarcoma following antiretroviral therapy with protease inhibitors: biological correlates of clinical outcome.

The clinical response of AIDS-related Kaposi's sarcoma (KS) to highly active antiretroviral therapy (HAART), a combination of human immunodeficiency virus type 1 (HIV-1) protease and reverse transcriptase inhibitors, was studied in 11 patients, all but one with progressive KS. CD4+ cell counts, plasma HIV-1 RNA levels, and antibody titres to lytic ORF65 and latency-associated human herpes virus type 8 (HHV-8) proteins were determined in sequential samples. Six complete and three partial clinical responses were achieved in a median time of 6 and 3 months, respectively, and confirmed after a median time of 16 months on HAART. 2 patients showed disease progression. A consistent decrease in HIV-1 RNA levels, paralleled by an increase in CD4+ cell counts, was observed in all patients who showed complete or partial clinical response; HIV-1 RNA levels remained persistently high in the two patients who progressed, despite a change in HAART. HHV-8 antibody titres were generally higher in patients with mucosal/visceral involvement compared with patients with limited disease; a decrease in ORF65 antibody titre was significantly associated with a clinical response. These results indicate that HAART is effective for AIDS-related KS; the clinical response correlates with a decrease in plasma HIV-1 RNA levels, an increase in CD4+ lymphocytes, and a decrease in antibodies to ORF65 HHV-8 protein.

Different distribution of HIV type 1 genetic variants in European patients with distinct risk practices.

The use of two genetic markers has permitted the analysis of the distribution of two different human immunodeficiency virus type 1 (HIV-1) variants in patients of the homosexual (HO) and intravenous drug user (IDU) groups in distinct European countries. In Germany, Holland, and Italy the variants circulating in each risk group of HO and IDU patients were genetically distinguishable according to the genetic markers used. In contrast, in France and Spain, the same variant has been recovered from patients with different risk practices. These data highlight the diversity of the HIV-1 epidemic in Europe and the different patterns of HIV-1 variant distribution in European countries.

Toxic epidermal necrolysis induced by nevirapine therapy: description of two cases and review of the literature.

We describe two cases of toxic epidermal necrolysis developed during an antiretroviral therapy regimen containing nevirapine. It seems likely that the poor adherence to the dose escalation regimen of nevirapine has caused this life-threatening disease. A complete and written information on the scheduled antiretroviral therapy is mandatory, above all for individuals coming from developing countries where language barriers have not yet been successfully overcome.

Mediastinitis due to cryptococcal infection: a new clinical entity in the HAART era.

OBJECTIVES: Highly active antiretroviral therapy (HAART) produces a rapid decline in plasma HIV-1 RNA levels with concomitant immune reconstitution. Probably due to the enhanced immune function, shortly after starting HAART, some latent opportunistic infections precipitated. The aim of this study was to illustrate the results of a survey on Cryptococcus associated mediastinitis occurring after HAART introduction, carried out at a referral centre of Infectious Diseases in the north-east of Italy, between October 1999 and October 2000. METHODS: All consecutive HIV-positive patients, naive to HIV-protease inhibitor therapy, and diagnosed with culture-proven cryptococcal infection were included in the study. Clinical and immuno-virological parameters before HAART and subsequently for 12 months were evaluated. RESULTS: Three of five patients were diagnosed with cryptococcal mediastinitis within a median time of 90 days (range, 60-150) after commencing HAART and fluconazole prophylaxis. Diagnosis was established by lymph node biopsy alone. Clinical improvement was documented when systemic anti-fungal therapy was combined with surgical drainage of the suppurative lesions. The role of immune restoration was confirmed by the significant increase in CD4 cell count, the reduction of HIV-RNA to undetectable levels and the prominent inflammatory reactions of lymph nodes. CONCLUSIONS: Our report suggests that HIV-positive patients with prior cryptococcal systemic infection may present a re-exacerbation of atypical cryptococcosis as a manifestation of immune restoration, even when fluconazole prophylaxis is ongoing.

Chemo-immunotherapy of advanced AIDS-related Kaposi's sarcoma.

AIMS AND BACKGROUND: Kaposi's sarcoma (KS) is the most common neoplastic complication of HIV infection and AIDS. Multiple cytotoxic chemotherapy regimens have been used with various response rates. We have evaluated the efficacy and toxicity of low-dose chemotherapy in patients with poor-prognosis AIDS-related KS and the role of interferon alpha (IFN-alpha) in complete responders. METHODS: Twenty-five previously untreated patients with advanced KS received bleomycin (BL) 10 mg/m2 and vinblastine (VB) 6 mg/m2 on days 1 and 15 every two weeks. After six cycles, patients in complete remission received IFN-alpha (3 million U s.c. 3 times/week) combined with antiretroviral therapy. All patients were evaluated for toxicity using the World Health Organization (WHO) toxicity schedule. Both Eastern Cooperative Oncology Group (ECOG) and AIDS Clinical Trials Group (ACTG) response criteria were used to evaluate response and survival. RESULTS: The overall response rate was 84% (95% confidence interval, 51-117%) with six complete remissions (24%) and 15 partial remissions (60%) by ECOG criteria, and 92% (95% confidence interval: 58-128%) with 17 partial remissions (68%) by ACTG criteria. The median duration of response on IFN-alpha treatment was 4.5 months (range, 2-10). The overall median survival duration for all 25 patients was 9 months (range 2-39). Grade 3-4 anemia was observed in five patients and grade 3-4 neutropenia in two patients. No other clinically significant (> or = grade 3) toxicities were observed. CONCLUSIONS: Combination of BL and VB is effective and well tolerated, even if new therapeutic options are developing. This disease remains a challenging problem, so larger studies using the combination of chemotherapy and/or IFN-alpha with antiretroviral treatment are warranted.

[Long-term sequelae of deep venous thrombosis of the legs. Experience with mesoglycan]. / Sequele a lungo termine della trombosi venosa profonda degli arti inferiori. Esperienza con il mesoglicano.

Ninety consecutive patients, affected by venographically proven deep-vein thrombosis (DVT) of the lower limbs, were given full-dose heparin followed by oral anticoagulants for 12 weeks, and then selected randomly to receive, for one year, either mesoglycan (72 mg/day orally) or placebo with a double-blind protocol. All patients wore elastic graduated compression stockings, and were prospectively followed for a period ranging from 5 to 48 months. In each scheduled examination programmed every three months for one year and then twice per year, an accurate clinical evaluation was performed and a predetermined objective score was applied. Furthermore, impedance plethysmography and Doppler ultrasound tests were executed serially to assess the persistence of venous obstruction and/or the development of valve incompetence. After a mean follow-up of 3 years, 80% of the patients were totally asymptomatic, and severe post-thrombotic sequelae (ulcer and/or edema associated with skin induration) were recorded in only 6 patients (6.6%). We failed to identify any correlation between post-thrombotic sequelae and persistence of venous obstruction (as shown by impedance plethysmography) or development of valve incompetence (as shown by Doppler ultrasound test). The behaviour of patients treated with mesoglycan did not differ from that of patients treated with placebo. However, objectively documented recurrences of DVT and/or pulmonary embolism were less frequent in patients treated with mesoglycan (6.6 vs 11.1%, non-significant difference), and the only two deaths attributable to pulmonary embolism occurred among the patients treated with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

[Occult pulmonary embolism in patients with proximal deep venous thrombosis]. / Embolia polmonare occulta in pazienti con trombosi venosa profonda prossimale.

It is known that proximal deep-vein thrombosis (DVT) of the lower limbs is associated with a high risk of pulmonary embolism (PE). However, only a few patients presenting with clinically symptomatic DVT exhibit symptoms or signs suggestive of this complication. The prevalence of silent PE in these patients is unknown. In order to assess the true prevalence of PE in a patient population presenting with venographically proven proximal DVT but without symptoms of PE, a perfusion lung scan was performed in 100 consecutive patients at presentation. Fifty-nine patients (59%) had a high probability lung scan (segmental or larger perfusion defects in lung areas free from abnormalities as shown by conventional chest x-ray) at the initiation of heparin treatment. At repeated lung scanning, performed after 10 days of anticoagulant treatment, complete to partial improvement was observed in 41 of these patients (71%), whereas in 13 (23%) the picture was unchanged and in 3 (5.2%) it worsened. In 6 patients who developed symptoms suggestive of PE during the study period, a lung scan was immediately repeated and correct interpretation of the clinical manifestation was permitted by comparison with the initial scan. It is concluded that lung-scan--detected asymptomatic PE occurs frequently in patients with proximal DVT, and that the majority of these emboli resolve within 10 days of anticoagulant treatment. In order to manage correctly patients who develop clinical manifestations suggestive of PE while undergoing therapy for venous thrombosis, a baseline lung scan is strongly recommended in all patients with proven proximal DVT.

Treatment of deep venous thrombosis by fixed doses of a low-molecular-weight heparin (CY216).

Ninety consecutive outpatients with acute proximal and/or distal deep-vein thrombosis (DVT), as shown by phlebography, were entered into a prospective randomized trial comparing intravenous adjusted unfractionated heparin (UFH) with subcutaneous fixed doses of a low-molecular-weight heparin (CY216; 225 IC anti-Xa U/kg 12 hourly) for 10 days. The incidence of pulmonary embolism did not differ in the two groups (one episode per group). The comparison between pre- and posttreatment venograms and perfusion lung scans showed a statistically significant improvement (p less than 0.01 and p less than 0.05, respectively) only in the CY216-treated group. The incidence of major adverse reactions (major hemorrhages, relevant hemoglobin fall, and serious thrombocytopenia) was significantly higher (22 vs. 4.5%; p = 0.01) in the UFH-treated group. After a mean follow-up period of 2 years, the incidence of thromboembolic recurrences and that of post-thrombotic manifestations did not differ in the two groups. It is concluded that subcutaneous fixed doses of CY216 are more effective and safer than intravenous adjusted UFH in the treatment of acute DVT.

Sarcoidosis and HIV infection: a case report and a review of the literature.

Sarcoidosis occurring in patients with AIDS is rare. This infrequent association has been attributed to the impairment of the immune system that may interfere with the granuloma formation in HIV infected patients. However, the introduction of highly active antiretroviral therapy (HAART) has brought about a substantial and sustained increase in CD4+ T lymphocyte cells, and has consequently led to the development of the so called "immune restoration disease". The case of an HIV infected man who developed sarcoidosis after the initiation of HAART is described. Skin nodule images and histological specimens are reported. The association between sarcoidosis and HIV infection is also reviewed.