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Background: Efavirenz (EFV) administration is still controversial for its high rates of interruption mainly related to central nervous system side effects (CNS-SE). Aim of the study was to define if single tablet regimen (STR) as compared to bis-in-die (BID) or once-daily (OD) with ≥2 pills-a-day EFV formulations reduced the risk of interruption., Methods: Patients starting any cART regimen including EFV + 2NRTIs or switching to EFV + 2NRTIs for simplification after virological suppression were retrospectively selected. Incidence, probability and prognostic factors of interruption by different causes were assessed by survival analysis and Cox regression model., Results: Overall, 553 patients starting EFV-containing regimens were included: 38.2% started BID regimen, 44.5% OD regimens ≥2 pills and 17.4% STR. The overall proportion of EFV interruption was 37.4% at 4 years; at the same time point, interruptions for virological failure and toxicity were 8.8% and 16.5% (8% for CNS-SE), respectively. Starting EFV co-formulated in STR was associated with lower proportion of overall interruption at 4 years (17.1% vs. 40.6%, p < 0.01). Only one virological failure was observed with STR up to 4 years (1.1% vs. 10.3% in non-STR, p = 0.051). STR also accounted for lower proportion of interruption by patient decision (1.5% vs. 11.8%, p = 0.01). No differences of interruption by overall toxicity and CNS-SE were observed. In multivariable analysis, STR and male gender were associated with lower risk of EFV interruption, while higher CD4 nadir and IDU with higher risk., Conclusions: In our experience, starting EFV co-formulated in STR was associated with lower virological failure and higher adherence, despite a similar proportion of CNS toxicity, thus reducing the risk of treatment interruption.

We investigated whether polymorphisms in human candidate genes could be associated with a different risk of developing lipodystrophy and dyslipidemia in HIV-infected patients starting combination antiretroviral therapy (cART). Genomic DNA samples from white HIV-1-infected patients were analyzed for seven polymorphisms located in the MDR1, TNF-α, APM1, APOE, and LPL genes. Lipid data were retrospectively collected beginning with the initiation of cART. Lipodystrophy was assessed cross-sectionally and then prospectively. The association with lipodystrophy and National Cholesterol Evaluation Program Adult Treatment Panel III-defined lipid thresholds was analyzed using survival analysis and logistic regression. One-hundred and seventy-four patients were genotyped. In 151 patients assessed for lipodystrophy, MDR1 3435 T homozygosis was associated with a higher hazard (adjusted hazard ratio, aHR, versus CT 0.25; p=0.02) and tumor necrosis factor (TNF)-α 308 G homozygosis with a lower hazard (vs. AA aHR 2.14; p=0.04) of developing trunk fat accumulation after adjusting for gender and initial cART type. The TNF 238 GG genotype was associated with a higher risk of developing low HDL-cholesterol levels (adjusted odd ratio, aOR, 5.91; p=0.01) while patients carrying the LPL S477X mutation were at lower risk of reaching high non-HDL-cholesterol levels (aOR 0.39; p=0.05). The APOEe3/3 genotype patients were at lower risk (aOR 0.26, p=0.015), whereas the adiponectin 276 GT carriers were at higher risk of developing hypertriglyceremia (vs. GG aOR 3.10; p=0.04). Knowledge of the effect of genetic determinants on dyslipidemia and lipodystrophy may prompt the investigation of potential pathogenetic mechanisms and might eventually be used for guiding individualized treatment decisions.

Objective: To design a Health-related Quality of Life (HRQoL) instrument for HIV-infected people in the era of highly active antiretroviral therapy (HAART)., Methods: The self-administered questionnaire was developed by an Italian network including researchers, physicians, people living with HIV, national institutions and community-based organizations (CBO) through several steps: (1) review of existing HRQoL literature and questionnaires for HIV-infected people; (2) selection of relevant domains measuring HRQoL in HIV-infected people, and identification of new domains related to new aspects of HRQoL concerning HAART-treated individuals; (3) conduction of two pre-test analyses in independent groups of Italian HIV-positive people (n approximately =100) distributed throughout the country. The objectives of the first pre-test were to verify the usefulness of the questionnaire, to construct a form easily understandable by everyone, to define the domains and their significance; the second pre-test aimed at evaluating and reshaping the questionnaire based on a statistical analysis of the outcomes of first pre-test; (4) validation analysis. A large cohort of people with HIV infection was recruited for the last step., Results: The internal consistence reliability (Cronbach's alpha) was >or=0.70 for all domains. Most domains had Cronbach's coefficient >0.80. All domains demonstrated convergent and discriminant validity. The final version of ISSQoL includes two sections: HRQoL Core Evaluation Form (9 domains) and Additional Important Areas for HRQoL (6 domains). The ISSQoL was administered together with two additional forms: a Daily Impact of Symptoms Form and a Demographic Information Form. The Additional Important Areas for HRQoL include social support, interaction with medical staff, treatment impact, body changes, life planning, and motherhood/fatherhood., Conclusion: The data reported in the present paper provide preliminary evidence of the reliability and validity of the ISSQoL questionnaire for the measurement of HRQoL in HIV-infected people. The direct involvement of HIV-positive people in all the phases of the project was a key aspect of our work.

Thirty-six HIV-infected patients with chronic hepatitis C treated with peginterferon alpha-2a or 2b plus ribavirin were analysed in a prospective observational study. The were 15 (42%) treatment discontinuations; bt intent-to-treat virological responders were 19 (53%) at week 24. A higher fibrosis score predicted premature discontinuation of hepatitis C virus (HCV) therapy and a lack of early virological response. Female sex and HCV genotype predicted early virological responses. Results support the early treatment of HCV in co-infected individuals.

The objective of the study was to determine the association of neurocognitive impairment with health-related quality of life (HRQoL) in patients receiving highly active antiretroviral therapy (HAART). Seventy subjects were cross-sectionally analysed with a standardized neuropsychological test battery and a questionnaire including an Italian translation of the MOS-HIV Health Survey. The presence of neurocognitive impairment was significantly associated with lower HRQoL scores: pain (P = 0.03), physical functioning (P = 0.01), role functioning (P = 0.01), social functioning (P = 0.029), mental health (P = 0.001), energy (P = 0.036), health distress (P = 0.002), cognitive functioning (P = 0.05), current health perception (P <0.001), physical health summary score (PHS) (P = 0.005), mental health summary score (MHS) (P = 0.002). Years of education (odds ratio [OR] 0.79; 95% confidence interval [CI] 0.65-0.96), PHS (OR 0.71; 95% CI 0.54-0.95) and MHS (OR 0.67; 95% CI 0.51-0.88) were also associated with cognitive impairment. Neurocognitive impairment in patients receiving HAART was associated with reduced HRQoL. Identifying cognitive impairment may provide motivation for additional treatment to help patients to compensate for deficits in functioning.

We examined the relationship of HIV-related cognitive impairment and health-related quality of life (QoL). Subjects were administered measures of cognitive function (a battery of 17 neuropsychological tests) and of QoL (the MOS-HIV questionnaire). Study measures also included comprehensive clinical and neurological evaluation, laboratory testing, and brain imaging studies in patients with impaired neuropsychological evaluation. One-hundred and eleven subjects were examined. Cognitively impaired patients (33.3%) reported poorer QoL scores in all domains (p < 0.05): physical health summary score (PHS) (44.6 vs. 49.9), mental health summary score (MHS) (37.7 vs. 44.4), pain (67.6 vs. 79.4), physical functioning (75.9 vs. 87.7), role functioning (32.4 vs. 41.5), social functioning (70.3 vs. 83.5), mental health (48.2 vs. 61.0), energy (53.1 vs. 63.0), health distress (60.8 vs. 75.5), cognitive functioning (CF) (60.5 vs. 71.8), general health perceptions (29.2 vs. 43.4), and QoL (36.5 vs. 47.0). The number of altered neuropsychological tests correlated significantly with MHS (p < 0.001), PHS (p < 0.03), CF (p < 0.02), and QoL (p < 0.02) scores. A correlation between seven of seven neuropsychological measures exploring speed of mental processing, three of four exploring mental flexibility, four of six exploring memory, and two of two exploring fine motor functioning and MHS, PHS, CF, or QoL scores was also found. Poor performance on the Digit Symbol test was most strongly associated with poor MHS (OR 1.04, 95% CI 1.01-1.08, p < 0.009) and PHS (OR 1.04, 95% CI 1.01-1.08, p < 0.01) scores, controlling for CD4 count, previous AIDS diagnosis, receiving HAART, and drug abuse. Cognitive impairment is associated with poor QoL. People with more severe cognitive impairment have the highest probability of having a poor QoL. Cognitive impairment in any cognitive domain explored in our battery is also associated with poor QoL. Poor performance on the Digit Symbol Test is the strongest predictor of poor QoL.

In the era of new antiretroviral treatments that have dramatically reduced both morbidity and mortality, a primary goal is to maximize function and wellbeing in the everyday life of HIV-infected patients. To be able to do so, it would be important for clinicians and policy makers to identify factors that influence health-related quality of life (HRQoL). The objective of this multicentre prospective cohort study was to identify determinants of HRQoL in a cohort of Italian HIV-infected patients, the majority of whom were taking highly active antiretroviral therapy (HAART). A total of 809 patients were enrolled. The MOS-HIV Health Survey (summarized using two scores, physical health (PHS) and mental health (MHS)), and an HIV-related symptom scale were administered at enrolment and six months later. At baseline, low CD4+ cell count, hospitalization during the three months before the enrollment and symptoms were independently related to poor PHS; hospitalization during the three months before the enrollment, symptoms and poor satisfaction with information from providers were independently related to MHS. Predictors of PHS at six months included the stage of HIV infection, baseline CD4+ cells count, PHS and symptom score; while age, baseline MHS, symptom score and education predicted six-month MHS. Among these factors, symptoms, recent hospitalization and satisfaction with information are most amenable to clinical intervention.

A number of metabolic disorders, including hypercholesterolemia, hypertriglyceridemia, insulin resistance, elevated fasting glucose and diabetes mellitus, were reported in a high proportion of HIV-infected patients receiving highly active antiretroviral therapy (HAART). Less frequently, coagulative disorders were described in patients receiving HAART. Since all these metabolic disorders may predispose to coronary heart disease, an early evaluation and treatment is advisable. Existing guidelines for uninfected patients may be applied, taking into account, however, the potential for drug interactions and accumulated toxicity. It may be helpful to stratify all patients in three risk groups to plan regular diagnostic screening. Treatment of dyslipidemia and diabetes mellitus should include a first-line approach with non-pharmacological interventions. Statins and fibrates are proposed for HIV-infected patients with HAART-related hyperlipidemia, but concern has been raised on their potential for interaction with antiretrovirals and hepatic and muscle toxicity. Metformin and thiazolidenediones (or glitazones), hypoglycemic agents that increase insulin sensitivity, are presently under evaluation in diabetic and glucose-intolerant HIV-infected patients treated with HAART. Glitazones also have a potential for ameliorating the lipodystrophic syndrome. The routine evaluation of coagulative parameters is probably not advisable until a benefit of widespread screening is assessed in prospective studies. A heightened awareness of the possiblity of coagulative disorders, together with controlled trials and basic research, is needed.

The clinical management of HIV-infected individuals is based on highly active antiretroviral combination therapy, which provides significant clinical benefit in most patients, but causes in a high proportion of them a metabolic syndrome that includes body fat redistribution, hypercholesterolemia, hypertriglyceridemia, and insulin resistance. These effects are particularly evident in patients treated with protease inhibitors. It is likely that the metabolic disorders related to anti-HIV treatment will eventually translate into an increased cardiovascular risk in patients submitted to such regimens.

The advent of potent antiretroviral drugs in recent years has had an impressive impact on mortality and disease progression in HIV-infected patients, so that issues related to long-term effects of drugs are of growing importance. Hyperlipidemia, hyperglycemia, and lipodystrophy are increasingly described adverse effects of highly active antiretroviral therapy (HAART), in particular when protease inhibitors are used. Hyperlipidemia is strikingly associated with the use of most available protease inhibitors, with an estimated prevalence of up to 50%. Because of the short observation period and the small number of cardiovascular events, epidemiological evidence for an increased risk of coronary heart disease in HIV-infected patients treated with HAART is not adequate at present; however, it is likely that shortly more data will accumulate to quantify this risk. Before starting HAART and during treatment it is reasonable to evaluate all patients for traditional coronary risk factors, including lipid profile. Among the drugs that are currently used in HIV+ patients, antibacterials, antifungals, psychotropic drugs and anti-histamines have been associated with QT prolongation or torsade de pointe, a life-threatening ventricular arrhythmia. Among the risk factors that may precipitate an asymptomatic electrocardiographic abnormality into a dangerous arrhythmia is the concomitant use of drugs that share the CYP3A metabolic pathway. Since most protease inhibitors are potent inhibitors of CYP3A, clinicians should be aware of this potentially dangerous effect of HAART. Anthracyclines are potent cytotoxic antibiotics that have been widely used for the treatment of HIV-related neoplasms. Their cardiotoxicity is well known, ranging from benign and reversible arrhythmias to progressive severe cardiomyopathy. The increased survival and quality of life of HIV+ patients emphasize the importance of a high awareness of adverse drug-related cardiac effects.

Objective: To evaluate short-term toxicity from and discontinuation of antiretroviral combination prophylaxis in HIV-exposed individuals in Italy., Design: Longitudinal, open study conducted by prospective collection of data in the National Registry of PEP., Setting: All the Italian centres dedicated to HIV related care and licensed by the Ministry of Health to dispense antiretroviral drugs., Study Population: Health care workers and other persons consenting to be treated with post exposure prophylaxis (PEP) after exposures to HIV., Results: Until October, 2000, 207 individuals receiving two nucleoside reverse transcriptase inhibitors (NRTIs), and 354 receiving two NRTIs plus a protease inhibitor (PI) were enrolled. More individuals experienced side-effects in the 3-drug group (53% and 62%, respectively; OR 0.68, (95% CI 0.48-0.98), p < 0.03). However, the proportion of individuals discontinuing prophylaxis because of side-effects did not differ significantly between the 2 groups (21% and 25% respectively; OR 0.82 (95% CI 0.53-1.26); p=0.4). The 43 individuals in the 2 NRTI group discontinued PEP after a mean of 10.4 days of treatment (median 8, range 1-27), similarly to the 88 discontinuations observed in the 3-drug group (mean duration 10.5 days, median 7.5, range 1-26). Type and incidence of specific adverse effects were similar to those reported in the literature., Conclusion: Our study indicates that the difference in the proportion of individuals developing side effects and discontinuing PEP is not significant. The rate of discontinuation because of protease inhibitor side-effects does not justify per se the initial use of a less potent PEP regimen. We suggest initiating PEP with a three-drug regimen and discontinuing the protease inhibitor in the case of adverse effects.

To study the prevalence, intensity, and quality of pain in patients with human immunodeficiency virus (HIV) infection and to evaluate factors influencing the different components of pain, a self-administered multidimensional pain questionnaire (Italian Pain Questionnaire [IPQ]) was administered to 153 HIV patients admitted to the Department of Infectious Diseases of a teaching hospital over a 7-month period. Ninety-three (60.8%) patients experienced pain for a total of 131 pain sites. The intensity and the nonsensorial components of pain were greater in ward patients compared to outpatients. In 70% of pain syndromes it was not possible to define the etiology at the time of the visit. Pain was observed more frequently in intravenous drug users (IDUs) (72.9%) compared to patients with other HIV modalities of transmission (50.6%) (p = 0.008). The mean value of sensory class was greater in patients who were not IDUs. Within IDUs group there was a predominance of descriptors of the affective class over the sensory class. The prevalence of pain is high in HIV-infected individuals. The different components of pain are influenced by the modality of transmission and the setting of care. The assessment of scores of different components of pain could help to select and monitor appropriate interventions in pain control.

Objective: To assess rates of prescriptions of protease inhibitors (PI) and determinants of not being prescribed PIs in a cohort of HIV-infected people eligible (according to published guidelines) for highly active antiretroviral therapy (HAART)., Design: Cross-sectional survey., Methods: A total of 684 patients with CD4+ counts <500 cells/microl were enrolled from seven Italian HIV treatment centers from October 1997 to April 1998. A questionnaire on health-related quality of life (MOS-HIV) and patient ratings of the quality of care was administered. Sociodemographic variables, HIV disease-related factors, and prescribed antiretroviral therapy were also recorded., Results: 61% of those enrolled were prescribed PI (median, 7.5 months). In addition, 75% of patients had previously received antiretroviral therapy. Fewer than 1% were prescribed nonnucleoside reverse transcriptase inhibitors (NNRTIs). Using multivariable logistic regression considering those with CD4+ counts <500 cells/microl, patients reporting the least information received (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.23-2.58), injecting drug users (IDUs; OR, 1.73; 95% CI, 1.18-2.54), people with CD4+ counts >200 cells/microl (OR, 1.76; 95% CI, 1.19-2.61), and patients with early stage disease (OR, 2.24; 95% CI, 1.73-2.90) were less likely to have be prescribed PIs., Conclusions: Of patients eligible for HAART, only 61% were prescribed PIs. People who wanted more information, IDUs, and patients in earlier disease stages are significantly less likely to be prescribed PIs. Access to HAART remains a critical issue in the management of HIV disease.

The Karnofsky Scale of Performance Status (KPS) is a measure of health status that is widely used for HIV-infected persons, although few studies have documented its reliability and validity for HIV. We developed a modified KPS in an attempt to make it more appropriate for use in HIV-infected persons and evaluated its inter-rater reliability in a multicenter study. Patients (N = 657) were recruited from five hospitals in three Italian cities; responses were scored using the modified scale by three different raters in each hospital: one experienced physician, one young physician, and one nurse. Kendall's correlation test showed a strong inter-rater agreement for the total of observations: 0.82 between the two physicians, 0.77 between the experienced physician and the nurse, and 0.76 between the young physician and the nurse. The analysis of variance showed a strong effect of the stage of the disease on the KPS score. The specific hospital had little effect, whereas the effect of the type of rater disappeared when the nurse was excluded from the analysis. This modified scale demonstrated a good reliability, although training of raters could help to eliminate differences among raters and among hospitals.

Objective: This study was intended to present evidence for the reliability and validity of an Italian version of the MOS-HIV Health Survey and to identify important disease-related factors associated with health-related quality of life (HRQoL) in people with nonadvanced HIV., Design: In this cross-sectional study, HRQoL was measured using an Italian version of the MOS-HIV Health Survey questionnaire in 213 HIV-infected people without previous opportunistic infections or neoplasms attending an outpatient clinic in a university hospital. Distribution of scores, reliability, and validity were calculated, and presence and frequency of HIV-related symptoms were recorded and transformed into a score. The relation of HRQoL values to sociodemographic, epidemiologic, and clinical data was assessed., Results: The level of internal consistency of the Italian version of the MOS-HIV Health Survey was high (Cronbach's alpha, 0.80-0.93), and items demonstrated acceptable discrimination across scales. At linear regression analysis, all domains of HRQoL correlated with symptom score (r2 range, 0.07-0.41), but only the pain and physical-functioning scores showed a significant correlation with CD4 cell count. A weighted sum of single domains of HRQoL, TOTQoL, is also strongly correlated with symptom score (r2 = 0.57; p < .0001) but not with CD4 cell count (r2 = 0.01; p = .1). Using multivariate analysis, only symptom score (p < .0001) and total number of daily pills (p = .03) showed significant association with HRQoL. The same results were observed when analysis was performed only on people with CD4 levels <200/microl., Conclusions: This study presents the first evidence for the reliability and validity of a HRQoL instrument in Italian for people with HIV. Results also suggest a strong impact of symptoms on all measured dimensions of health status. The number of pills required to be taken daily is the only other significant factor associated with a lower HRQoL, whereas no relations were found with CD4 cell count or Karnofsky performance status values. To improve HRQoL in persons with nonadvanced HIV disease, symptom control could be a crucial element of medical treatment.

We investigated the prevalence and intensity of symptoms and the use of drugs for symptom control among all HIV-infected patients reporting to the outpatient clinics or wards of 15 clinical centres in central Italy, recording clinical and epidemiological data on three consecutive days. A total of 1128 patients were observed and tabulated. Their most frequent symptoms were asthenia (65%), anorexia (34%), cough (32%), pain (29%), and fever (29%). Opioid analgesics were used in 3% of these patients and non-opioid analgesics in 13%. A large majority of HIV-infected patients presented with symptoms regardless of the stage of their disease. Pain was present in fewer than one third of patients but nonetheless seemed to be undertreated. Pain was more frequent and more intense among intravenous drug users. Based on our study, a greater effort to control symptoms in HIV patients seems to be warranted.

The purpose of this study is to retrospectively review the clinical, radiographic and laboratory characteristics, the therapy and evolution of sinusitis in HIV-infected patients hospitalized between January 1, 1985 and July 31, 1994. We have observed 65 cases of sinusitis in 58 HIV-infected patients (77.6% classified as group C). Forty-five of 65 cases (69.2%) showed radiographic evidence of acute sinusitis; the remaining 20 cases (30.8%) showed chronic sinusitis. In 61 cases (93.8%) there were symptoms related to sinusitis. In 61 sinusitis cases antibiotics were administered. Although the majority of patients responded at least partially to antibiotic therapy, a complete resolution of clinical and radiographic signs was observed in only 47.4% of acute sinusitis cases. No resolution was observed in chronic sinusitis after treatment stop. Sinusitis appears to occur quite frequently in HIV-infected patients, is often related to non-specific symptoms, may be recurrent and is commonly refractory to treatment.

Purpose of the study Efavirenz (EFV) is still discussed for its high rate of interruption due to adverse event, in particular central nervous system side effects (CNS-SE). Aim of the study was to define if better drug formulations up to single tablet regimen (STR), including (EFV) plus NRTI backbone (tenofovir-emtricitabine), reduced the risk of interruption. Methods From the database of two reference centers, patients starting any cART regimen including EFV+2 NRTI or switching to EFV+2 NRTI for simplification after virological suppression were selected. Probability of interruption by virological failure, side effects, CNS-SE and any cause were assessed with survival analysis and Cox proportional hazard model. Summary of results Overall, 533 patients, starting EFV-containing regimen from May 1998 to March 2012, were included (51.2% naïve, 48.8% switched). Patients characteristics: males 70.7%, median age 39 years, injecting drug use (IDU) 11.2%, median nadir CD4 194/mmc, median CD4 at EFV start 305/mmc: 38.7% started BID regimen, 43.9% OD regimen and 17.4% STR. At survival analysis, the overall proportion of EFV interruption was 19.1% at 1 year and 33.0% at 3 years; interruption for virological failure were 2.8% and 7.4% and for toxicity 10.2% and 15.9%, respectively. CNS-SE accounted for about half of interruptions for toxicity (5.7% and 8.0% at 1 and 3 years, respectively). Naïve patients had a higher risk of interruption as compared to switched patients: 37.7% vs. 28.0% at 3 years (p=0.06). While no significant difference was observed comparing OD vs. B ID regimens, starting with STR was associated with significant lower proportion of overall interruption at 3 years (17.1% vs. 36.6%, p<0.01). No virological failure was observed with STR up to 3 years (0.0% vs. 8.9%, p=0.05); no difference of interruption by overall toxicity and higher, though non-significant, frequency of interruption by CNS-SE (12.8% vs. 6.8%) were also observed. STR also accounted for lower proportion of interruption by patient wish, including low adherence (1.5% vs. 12.3%, p=0.01). At adjusted Cox model, STR (HR: 0.44; 95% CI: 0.26-0.77) and male gender (HR: 0.71; 95% CI: 0.53-0.97) were associated with lower risk of EFV interruption and IDU with higher risk (HR: 1.64; 95% CI: 1.11-2.42). Conclusions In our experience, EFV co-formulated in STR was associated with lower virological failure and higher adherence, despite keeping CNS toxicity, thus reducing the risk of treatment interruption. [ABSTRACT FROM AUTHOR]