Statins and aspirin in the prevention of cardiovascular disease among HIV-positive patients between controversies and unmet needs: review of the literature and suggestions for a friendly use.

BACKGROUND: As in non-infected subjects, statins and aspirin have a pivotal preventive role in reducing the cardiovascular related morbidity and mortality in HIV infected patients. The persistence of immune activation in these subjects, could contribute to accelerate atherosclerosis, therefore, these treatments that reduce inflammation could provide additional cardiovascular protection. However the current guidelines for the use of these drugs in general population are dissimilar, with important differences between American and European ones. Aim of the present position paper is to provide recommendations aimed to overcome the actual differences and limitations among the current ones and to adapt them to the needs of HIV infected patients. RESULTS: We propose to adopt the new ACC/AHA guidelines, simple to use and cost effective, to use the ASCVD score that seems to estimate more accurately the cardiovascular risk among these patients. We suggest to start statin therapy in all patients with a calculated 10-year risk of a cardiovascular event of 10% or greater. Rosuvastatin and atorvastatin should be preferred. LDL-C target may be adopted. Aspirin should be always associated with a statin, in secondary prevention, while in primary prevention it should be reserved only to patients with ≥ 20% 10-year risk particularly adherent to treatments, and with low risk of bleeding. We suggest to start with a dose of 100 mg/day. Finally, management of antiplatelet agents or novel oral anticoagulants may include selecting antiretrovirals with a lower potential for drug interactions or choosing agents least likely to interact with antiretrovirals. CONCLUSIONS: As demonstrated in surveys, HIV physicians are generally highly committed regarding CVD and autonomous in prescribing statins and ASA. Consequently, in the light of the previously discussed discrepancies among the different guidelines and of the incomplete indications regarding HIV-positive persons, the present suggestions could overcome the actual differences and limitations among the current ones.

Insights into reasons for discontinuation according to year of starting first regimen of highly active antiretroviral therapy in a cohort of antiretroviral-naïve patients.

OBJECTIVES: The aim of the study was to determine whether the incidence of first-line treatment discontinuations and their causes changed according to the time of starting highly active antiretroviral therapy (HAART) in an Italian cohort. METHODS: We included in the study patients from the Italian COhort Naïve Antiretrovirals (ICoNA) who initiated HAART when naïve to antiretroviral therapy (ART). The endpoints were discontinuation within the first year of >or= 1 drug in the first HAART regimen for any reason, intolerance/toxicity, poor adherence, immunovirological/clinical failure and simplification. We investigated whether the time of starting HAART (stratified as 'early', 1997-1999; 'intermediate', 2000-2002; 'recent', 2003-2007) was associated with the probability of reaching the endpoints by a survival analysis. RESULTS: Overall, the 1-year probability of discontinuation of >or= 1 drug in the first regimen was 36.1%. The main causes of discontinuation were intolerance/toxicity (696 of 1189 patients; 58.5%) and poor adherence (285 of 1189 patients; 24%). The hazards for all-reason change were comparable according to calendar period [2000-2002, adjusted relative hazard (ARH) 0.82, 95% confidence interval (CI) 0.69-0.98; 2003-2007, ARH 0.94, 95% CI 0.76-1.16, vs. 1997-1999; global P-value = 0.08]. Patients who started HAART during the 'recent' period were less likely to change their initial regimen because of intolerance/toxicity (ARH 0.67, 95% CI 0.51-0.89 vs. 'early' period). Patients who started in the 'intermediate' and 'recent' periods had a higher risk of discontinuation because of simplification (ARH 15.26, 95% CI 3.21-72.45, and ARH 37.97, 95% CI 7.56-190.64, vs. 'early' period, respectively). CONCLUSIONS: It seems important to evaluate reason-specific trends in the incidence of discontinuation in order to better understand the determinants of changes over time. The incidence of discontinuation because of intolerance/toxicity has declined over time while simplification strategies have become more frequent in recent years. Intolerance/toxicity remains the major cause of drug discontinuation.

Use of efavirenz or atazanavir/ritonavir is associated with better clinical outcomes of HAART compared to other protease inhibitors: routine evidence from the Italian MASTER Cohort.

Randomized trials and observational cohorts reported higher rates of virological suppression after highly active antiretroviral therapy (HAART) including efavirenz (EFV), compared with boosted protease inhibitors (PIs). Correlations with immunological and clinical outcomes are unclear. Patients of the Italian MASTER cohort who started HAART from 2000 to 2010 were selected. Outstanding outcome (composite outcome for success (COS)) was introduced. We evaluated predictors of COS (no AIDS plus CD4+ count >500/mm(3)plus HIV-RNA <500 copies/mL) and of eight single outcomes either at month 6 or at year 3. Multivariable logistic regression was conducted. There were 6259 patients selected. Patients on EFV (43%) were younger, had greater CD4+ count, presented with AIDS less frequently, and more were Italians. At year 3, 90% of patients had HIV RNA <500 copies/mL, but only 41.4% were prescribed EFV, vs. 34.1% prescribed boosted PIs achieved COS (p <0.0001). At multivariable analysis, patients on lopinavir/ritonavir had an odds ratio of 0.70 for COS at year 3 (p <0.0001). Foreign origin and positive hepatitis C virus-Ab were independently associated with worse outcome (OR 0.54, p <0.0001 and OR 0.70, p 0.01, respectively). Patients on boosted PIs developed AIDS more frequently either at month 6 (13.8% vs. 7.6%, p <0.0001) or at year 3 (17.1% vs. 13.8%, p <0.0001). At year 3, deaths of patients starting EFV were 3%, vs. 5% on boosted PIs (p 0.008). In this study, naïve patients on EFV performed better than those on boosted PIs after adjustment for imbalances at baseline. Even when virological control is achieved, COS is relatively rare. Hepatitis C virus-positive patients and those of foreign origin are at risk of not obtaining COS.

Benefits of a rapid HIV test for evaluation of the source patient after occupational exposure of healthcare workers.

Rapid human immunodeficiency virus (HIV) testing for the management of occupational exposure of healthcare workers significantly decreased the number of anti-retroviral post-exposure prophylaxis regimens started whilst awaiting HIV test results. The study confirmed an equivalent performance of the rapid test in comparison with HIV enzyme immunoassay, and suggests it is cost-effective. In addition, two other potential benefits emerged: reducing the number of source patients who remain untested and increasing the number of occupational exposures reported.

Suicide probability and psychological morbidity secondary to HIV infection: a control study of HIV-seropositive, hepatitis C virus (HCV)-seropositive and HIV/HCV-seronegative injecting drug users.

BACKGROUND: Suicide ideation and psychological morbidity among HIV-positive patients has been the object of intense research. No study has investigated this area among injecting drug users (IDUs) infected with HIV and those infected with the hepatitis C virus (HCV), which has the same patterns of transmission of the HIV and may favour HIV replication and, possibly, HIV disease progression. METHODS: In order to examine the prevalence and characteristics of suicide ideation and psychological morbidity associated with HIV and HCV infection in IDUs, a sample of HIV+ (n=81), HIV-/HCV+ (n=62) and HIV-/HCV- (n=152) subjects completed the Suicide Probability Scale (SPS), The Brief Symptom Inventory (BSI) and the Hospital Anxiety and Depression Scale (HADS). RESULTS: No difference was found between the groups as far as the mean scores on SPS and the risk of suicide (no-low risk category: 70.7% HIV+, 56.09% HCV+, 65.6% HIV-/HCV-). Estimated psychological morbidity (BSI) (26.9% HIV+, 27.1% HCV+, 25.4% of HIV-/HCV-) and BSI and HADS scores were comparable across the groups. CONCLUSIONS: Suicide ideation, psychological morbidity and anxiety and depression symptoms seemed not to be directly influenced by HIV-serostatus. Careful assessment of psychological symptoms and suicide ideas among IDUs, as a vulnerable segment of population at risk of HIV and HCV infections, needs to be routinely carried out in clinical settings.

Elevated serum levels of a 90,000 daltons tumor-associated antigen in cancer and in infection by human immunodeficiency virus (HIV).

Levels of a 90,000 daltons monoclonal antibody-defined tumor-associated antigen, termed 90K, were measured in the serum from 649 patients with various types of cancer and 1215 patients infected by the human immunodeficiency virus (HIV). Significantly increased 90K serum levels (12.1 +/- 0.5 U/ml) were found in cancer patients with respect to healthy controls (5.7 +/- 0.3 U/ml), with the highest levels in neoplasms of the breast, lung and gastrointestinal tract. In 355 patients with breast cancer, the elevation of serum 90K levels was more pronounced at advanced stages of disease. Mean levels of 90K for 1215 HIV-infected subjects (21.2 +/- 0.8 U/ml) were significantly higher than controls and cancer patients, and the levels progressively increased with disease worsening from asymptomatic infection to full blown AIDS. These data suggest that 90K is not merely a tumor-associated antigen and lead us to postulate it to be a signalling molecule whose production might be related to the immune deficit caused by pathogenetic events such as neoplastic progression and virus infection.

90K (Mac-2 BP) predicts CD4 decline in human immunodeficiency virus-infected patients with CD4 counts above 200 x 10(6) cells/L.

OBJECTIVE: To evaluate the ability of serum levels of 90K, previously reported as a progression marker of human immunodeficiency virus infection, to predict the future rate of CD4 lymphocyte decline. DESIGN: Retrospective analysis of data from outpatients enrolled in a multi-institutional study. PATIENTS: One hundred five human immunodeficiency virus-positive intravenous drug users who had at least six serial CD4 lymphocyte measurements and starting CD4 levels of 200 x 10(6) cells/L or higher. MAIN OUTCOME MEASURE: Rate of CD4 lymphocyte decline. RESULTS: During a median follow-up of 28 months (range, 20-36 months), the estimated loss of CD4 cells in the whole patient population was 3.4 x 106 cells/L per month (P = .0045). Subjects who were on zidovudine treatment at study entry showed an average loss of 3.8 x 10(6) cells/L per month, significantly higher than in untreated subjects (P = .02), but similar to the loss observed for those requiring initiation of treatment during the course of the study. At baseline, 56 subjects had 90K levels of 10 microg/mL or less, and 49 had more than 10 microg/mL. The rate of CD4 decline in the high-90K group was approximately 5 x 10(6) cells/L per month (P < .0015), whereas in the low-90K group it was not different from zero (P = ns). No difference emerged in the rate of CD4 decline when subjects were stratified according to baseline 90K levels and zidovudine treatment, beta2-microglobulin, or neopterin serum levels. CONCLUSION: 90K serum levels are predictive of CD4 decline.

[Incidence of giardiasis in adults patients with acute enteritis]. / Incidenza della giardiasi in pazienti adulti con enterite acuta.

The Authors report the findings of a perspective study carried out in 214 cases of acute diarrhoea to estimate the presence of giardia intestinalis infections. The incidence of 3.2% has been discussed on the bases of recent epidemiological advances.

[Pneumocystosis]. / Pneumocistosi.

On the basis of personal experience, the microbiological, epidemiological, clinical and therapeutic features of Pneumocystis carinii pneumonia are analysed.

[Zinc and lymphocyte subsets in patients with HIV infection]. / Zinco e assetto linfocitario in pazienti con infezione da HIV.

Serum zinc levels were assayed in patients with AIDS and related syndromes, using spectrophotometry and atomic absorption. Statistical data have shown that serum zinc levels, in addition to being significantly lower (p less than 0.001) among different groups and controls, decrease progressively with the worsening of the clinical and immunological picture from LAS to AIDS. Serum zinc levels in patients with AIDS and ARC have, moreover, been demonstrated to be related (r = 0.8240; p less than 0.001) to the lymphocyte subset CD4 helper-induced. These results suggest that serum zinc determination and possibly zinc therapy might be reasonably considered in the management of patients with symptoms of HIV infection.

[Usefulness of microbial investigations in community-acquired pneumonia]. / Utilità delle ricerche microbiologiche nel trattamento delle polmoniti comunitarie.

Community acquired pneumonia (CAP) is a common and well known disease, however there is no definite agreement on a common diagnostic-therapeutic strategy. To evaluate the usefulness of microbial investigations in the clinical practice we performed a prospective study on 93 consecutive patients with a diagnosis of CAP. Group I consisted of 46 patients that underwent a diagnostic protocol including sputum, blood cultures and detection of specific antibodies against M. pneumoniae, adenovirus, respiratory syncytial virus, and L. pneumophila. Group II consisted of 47 patients, in which only sputum samples were collected and cultured. No significant differences concerning the aetiologic diagnosis, the outcome and the length of hospitalization were observed in the two groups. The aetiological diagnosis was obtained in 17 patients (18.3%). As result of information obtained from microbiol tests, antibiotic therapy was changed only in 6 patients. Among the prognostic factors only a low albumin level was correlated with the length of hospitalization (p less than 0.01). From our data, the detection of microbial aetiology should not be routinely performed in patients with CAP, but should be reserved only to the severe forms.

Treatment of cerebral malaria by erythrocyte exchange.

A 33-years-old male presented with a severe malaria, caused by a chloroquine resistant strain of Plasmodium falciparum. The number of parasitized erythrocytes reached 20% and the patient had cerebral complication. During the second hospital day, an erythrocyte exchange was performed as an in addition to chemotherapy. The patient's clinical condition improved and the parasitemia disappeared. The erythrocyte exchange is recommended in severe malaria, when parasitemia greater than 10%, with or without cerebral, renal or blood coagulation complications.

Factors influencing the normalization of CD4+ T-cell count, percentage and CD4+/CD8+ T-cell ratio in HIV-infected patients on long-term suppressive antiretroviral therapy.

We evaluated factors associated with normalization of the absolute CD4+ T-cell counts, per cent CD4+ T cells and CD4+/CD8+ T-cell ratio. A multicentre observational study was carried out in patients with sustained HIV-RNA <50 copies/mL. Outcomes were: CD4-count >500/mm(3) and multiple T-cell marker recovery (MTMR), defined as CD4+ T cells >500/mm(3) plus%CD4 T cells >29%plus CD4+/CD8+ T-cell ratio >1. Kaplan-Meier survival analysis and Cox regression analyses to predict odds for achieving outcomes were performed. Three hundred and fifty-two patients were included and followed-up for a median of 4.1 (IQR 2.1-5.9) years, 270 (76.7%) achieving a CD4+ T-cell count >500 cells/mm(3) and 197 (56%) achieving MTMR. Using three separate Cox models for both outcomes we demonstrated that independent predictors were: both absolute CD4+ and CD8+ T-cell counts, %CD4+ T cells, a higher CD4+/CD8+ T-cell ratio, and age. A likelihood-ratio test showed significant improvements in fitness for the prediction of either CD4+ >500/mm(3) or MTMR by multivariable analysis when the other immune markers at baseline, besides the absolute CD4+ count alone, were considered. In addition to baseline absolute CD4+ T-cell counts, pretreatment %CD4+ T cells and the CD4+/CD8+ T-cell ratio influence recovery of T-cell markers, and their consideration should influence the decision to start antiretroviral therapy. However, owing to the small sample size, further studies are needed to confirm these results in relation to clinical endpoints.

Evolution of antiretroviral prescription and response over a period of 8 years: an Italian multicentre observational prospective cohort study.

BACKGROUND: There is very less information on the use of antiretroviral (ARV) drugs and viro-immunological outcome over calendar years in Italy. PATIENTS AND METHODS: We performed an analysis of a prospective observational cohort (MASTER) to assess antiretroviral drug use in first line HAART and explore whether initial treatment response changed over the years. RESULTS: 3,648 ARV-naive patients with available HIV-RNA and CD4+ T cell count at baseline who started their first HAART between 1997 and 2004 were studied. Mean age was 37.7 years; they were mostly males (72.3%) and Italians (81.4%). Prescription of non-nucleoside reverse transcriptase inhibitors and protease inhibitors boosted with ritonavir rose from 0.3% in 1997 to 58% in 2004 and from 0.3%in 1997 to 33.4% in 2004, respectively. Virological failures decreased over calendar years: from 42.9% in 1997 to 8.1%in 2004 after 6 months of HAART (p<0.001); from 42.1%(1997) to 10.7% (2004) after 12 months (p<0.001) and; from 39.5% (1997) to 8.2% (2004) after 18 months (p<0.001). The same trend, but less striking, was found for immunological failure rates. CONCLUSIONS: In the general Italian population of HIV-positive patients, evolution of treatment prescription correlated with improved viro-immunological outcome.