APRI and FIB-4 scores are not associated with neurocognitive impairment in HIV-infected persons.

Introduction: Chronic liver disease leads to neurocognitive impairment (NCI) and more advanced liver fibrosis is associated with greater deficits. Further, cognitive performances do not differ significantly among patients affected by diverse types of chronic liver diseases. Thus, it would be useful to have a clinical tool associated with early cognitive change applicable to the HIV-infected population with high HCV prevalence.

Impact of pre-therapy viral load on virological response to modern first-line HAART.

Background: We tested whether pre-HAART viraemia affects the achievement and maintenance of virological success in HIV-1-infected patients starting modern first-line therapies.

Methods: A total of 1,430 patients starting their first HAART (genotype-tailored) in 2008 (median; IQR: 2006-2009) were grouped according to levels of pre-HAART viraemia (≤ 30,000, 30,001-100,000, 100,001-300,000, 300,001-500,000 and > 500,000 copies/ml). The impact of pre-therapy viraemia on the time to virological success (viraemia ≤ 50 copies/ml) and on the time to virological rebound (first of two consecutive viraemia values > 50 copies/ml after virological success) were evaluated by Kaplan-Meier curves and Cox regression analyses.

Virological Response in Cerebrospinal Fluid to Antiretroviral Therapy in a Large Italian Cohort of HIV-Infected Patients with Neurological Disorders.

The aim of the present study was to analyse the effect of antiretroviral (ARV) therapy and single antiretroviral drugs on cerebrospinal fluid (CSF) HIV-RNA burden in HIV-infected patients affected by neurological disorders enrolled in a multicentric Italian cohort. ARVs were considered "neuroactive" from literature reports. Three hundred sixty-three HIV-positive patients with available data from paired plasma and CSF samples, were selected.

Comparative analysis of drug resistance among B and the most prevalent non-B HIV type 1 subtypes (C, F, and CRF02_AG) in Italy.

In recent years, increasing numbers of patients infected with HIV-1 non-B subtypes have been treated with modern antiretroviral regimens. Therefore, a better knowledge of HIV drug resistance in non-B strains is crucial. Thus, we compared the mutational pathways involved in drug resistance among the most common non-B subtypes in Italy (F, C, and CRF02_AG) and the B subtype.

Study of genotypic and phenotypic HIV-1 dynamics of integrase mutations during raltegravir treatment: a refined analysis by ultra-deep 454 pyrosequencing.

Background: The dynamics of raltegravir-resistant variants and their impact on virologic response in 23 HIV-1-infected patients, who started a salvage raltegravir-containing regimen, were investigated.

Methods: Integrase population sequencing and Ultra-Deep-454 Pyrosequencing (UDPS) were performed on plasma samples at baseline and at raltegravir failure. All integrase mutations detected at a frequency ≥1% were considered to be reliable for the UDPS analyses.

'Sentinel' mutations in standard population sequencing can predict the presence of HIV-1 reverse transcriptase major mutations detectable only by ultra-deep pyrosequencing.

Objectives: This proof-of-concept study aimed to identify whether mutations considered not yet relevant for drug resistance (but located at key drug-resistance positions) can act as 'sentinels' of minority resistant variants in HIV-1 drug-naive patients.

Methods: We focused our attention on three reverse transcriptase (RT) mutations (T69S, L210M and K103R) easily detected by standard population sequencing [i.e.

Prevalence of hypovitaminosis D and factors associated with vitamin D deficiency and morbidity among HIV-infected patients enrolled in a large Italian cohort.

Background: A high prevalence of hypovitaminosis D (hypD) in HIV-infected patients has been reported, but reasons are unclear.

Methods: The 25 hydroxy vitamin D (vitD) concentration was measured in a sample of HIV-positive patients from Italy enrolled in the Icona Foundation Study. The change in absolute levels of vitD pre/post combination antiretroviral treatment was modelled by linear regression controlling for confounders and seasonality.

Immediate versus delayed surgical intervention for reconstructive therapy of HIV-associated facial lipoatrophy: a randomized open-label study.

We assessed the safety and efficacy of reconstructive therapy with facial fillers for the treatment of HIV-associated facial lipoatrophy (FLA) through a randomized, controlled, open-label single-center study. A total of 134 HIV-infected patients with severe FLA were randomly assigned to receive immediate (67 patients) or delayed (67 patients) facial injections of poly-l-lactic acid (PLA) or polyacrylamide gel (PAIG). Outcome measures included changes in physician and patient FLA severity scale, adverse events, and changes in health-related quality of life (HRQoL) and anxiety using validated measures.

Pharmacogenetics of antiretrovirals.

The introduction of highly active antiretroviral therapy (HAART) as standard of care has changed the natural history of HIV infection into a manageable chronic disease requiring long-term antiretroviral (ARV) treatment. However, response to HAART is often limited by the occurrence of toxicity or by the emergence of drug resistance. Antiretroviral treatment is characterized by differing rates of adverse events and responses.

Changes in cognition during antiretroviral therapy: comparison of 2 different ranking systems to measure antiretroviral drug efficacy on HIV-associated neurocognitive disorders.

Objective: Although HIV-associated neurocognitive disorders should be treated with highly active antiretroviral treatment (HAART) regimens with good central nervous system (CNS) penetration, the definition of neuroactive HAART remains controversial. We compared 2 ranking systems to measure HAART neuroeffectiveness.

Methods: Patients with (n = 93) or at risk for (n = 92) HIV-associated neurocognitive disorders underwent neuropsychological (NP) test batteries before HAART initiation and at follow-up.

Historical resistance profile helps to predict salvage failure.

Background: This study compared the predictive value for treatment failure of extended resistance detected in the current genotype resistance test (GRT) versus those from GRT history in patients with multiple combination antiretroviral therapy (cART) failures.

Methods: Patients who underwent three GRT between 1999 and 2007 were included. Extended resistance at genotypic sensitivity score (GSS) using the Rega 7.

HIV pharmacogenetics in clinical practice: recent achievements and future challenges.

It has long been recognized that drug metabolism and drug toxicity may vary greatly between individuals, affecting both efficacy and toxicity. Pharmacogenetics could benefit HIV therapeutics because of the high prevalence of drug-related adverse events and the long term nature and complexity of combination therapy. In recent years a number of associations between human genetic variants and predisposition to drug toxicity and risk of virologic failure have been described.

Therapeutic drug monitoring in the management of HIV-infected patients.

The rate of HIV-positive patients that fails to reach or to maintain a durable virological suppression under anti-retroviral (ARV) therapy might be as high as 50%, therefore new tools to improve ARV drug efficacy are urgently needed. Among others, therapeutic drug monitoring (TDM) is a strategy by which the dosing regimen for a patient is guided by measurement of plasma drug levels, enabling physicians to optimize ARV drug efficacy and to avoid drug-related toxicity. The most used analytical methods to determine plasma levels of ARV drugs are HPLC-UV and HPLC-MS(/MS), recently MALDI-based methods and enzyme immunoassay (EIA) technologies have been also employed.

Evaluation of HIV-1 and CD4+ T cell dynamic parameters in patients treated with genotypic resistance testing-guided HAART.

The extent of immune restoration in HIV-1 patients on antiretroviral therapy is an important marker of disease progression. In this work, we investigate the dynamics of immune reconstitution and address the question of whether the early response to antiretroviral treatments allows to predict the late immune restoration. We select a cohort of twelve patients on GRT-HAART who achieve virological suppression, but show variable recovery of immune competence.

Plasma HIV RNA decline and emergence of drug resistance mutations among patients with multiple virologic failures receiving resistance testing-guided HAART.

Early recognition of virologic failure in patients with extensive drug resistance receiving salvage-HAART is essential to avoid exposure to subinhibitory regimens. We studied plasma viral load (PVL) decline and rates of drug-resistance mutation (DRM) accumulation in such patients. A prospective, 48 week study of 38 heavily pretreated patients receiving genotypic resistance testing (GRT)-guided HAART was conducted.

Self-reported sexual dysfunction is frequent among HIV-infected persons and is associated with suboptimal adherence to antiretrovirals.

Increased occurrence of sexual dysfunction (SD) among patients treated with highly active antiretroviral therapy (HAART) has been reported. To assess prevalence of self-reported SD and to identify factors related to this alteration with special focus to its relationship with adherence behavior, we conducted an intercohort analysis among HIV-infected persons treated with HAART. In an anonymous questionnaire investigating HAART nonadherence, patients were asked to report the occurrence of dysfunction in sexual activity over the previous 4 weeks.

Continuous evidence of fast HIV disease progression related to class-wide resistance to antiretroviral drugs: a 6 year follow-up analysis of a large observational database.

Class-wide resistance (CWR) was increasingly associated with a higher risk of HIV progression after 72 months of follow-up among 1392 patients genotypic-tested after failure (AIDS risk 13% for no CWR to 34% for three CWR; AIDS/death risk 21-54%). At multivariate analysis, the detection of two and three CWR was significantly associated with a two and threefold increased risk, respectively, of death and AIDS/death, suggesting that extended resistance is a marker of disease progression in long-term observation.

The V118I mutation as a marker of advanced HIV infection and disease progression.

Background: The V118I mutation is included in the nucleoside analogue mutations (NAMs) set. It contributes to thymidine-analogue resistance and, consequently, to resistance to the whole nucleoside reverse transcriptase inhibitor (NRTI) class. We focused on the V1181 mutation in order to evaluate factors associated with its detection and its relationship with HIV progression.

Persistence of neuropsychologic deficits despite long-term highly active antiretroviral therapy in patients with HIV-related neurocognitive impairment: prevalence and risk factors.

Objective: Although highly active antiretroviral therapy (HAART) can reverse HIV-related neurocognitive impairment (NCI), neuropsychologic (NP) deficits may persist in a substantial proportion of patients despite antiretroviral treatment. We assessed the prevalence and predictors of persistent NP deficits despite long-term HAART in patients with HIV-related NCI.

Methods: A group of 94 patients with HIV-related NCI underwent 2 to 7 serial NP batteries, neurologic examination, and brain imaging studies.

Drug-class-wide resistance to antiretrovirals in HIV-infected patients failing therapy: prevalence, risk factors and virological outcome.

Background: Drug-class-wide resistance (DCWR) to antiretrovirals substantially reduces treatment options.

Methods: A database of 602 patients failing highly active antiretroviral therapy (HAART) undergoing genotypic resistance test (GRT) was analysed. DCWR was defined according to the International AIDS Society consensus.

Specific mutations in HIV-1 gp41 are associated with immunological success in HIV-1-infected patients receiving enfuvirtide treatment.

Objectives: To investigate gp41 variability and correlation with viro-immunological parameters in 54 HIV-1-infected patients receiving enfuvirtide added as single active drug to a failing regimen.

Methods: One hundred and two HIV-1 gp41 sequences and clinical follow-up from 54 enfuvirtide-treated patients were analysed from baseline to week 36 of treatment. The association of mutations with viraemia/CD4 count was assessed by Mann-Whitney test.

Temporal characterization of drug resistance associated mutations in HIV-1 protease and reverse transcriptase in patients failing antiretroviral therapy.

The aim of this study was to evaluate the prevalence of genotypic resistance for each drug-class, and of single resistance-mutations in 1075 HIV-1 infected multi-treated patients undergoing their first genotypic resistance-test (GRT) after virological failure, over the years 1999-2003. First GRT was requested in 2003 for patients at earlier stages of failure, with less advanced disease, higher CD4-cell-count, lower HIV-RNA, and lower drug-experience with respect to 1999. Prevalence of resistance to all three drug-classes decreased from 33.

Highly active antiretroviral therapy reduces the age-associated risk of dementia in a cohort of older HIV-1-infected patients.

Historically, older patients have shown a higher risk of HIV-1-associated dementia (HIVD). The objective of this study was to evaluate the association of aging with HIVD and minor cognitive motor disorders (MCMDs) during the late-highly active antiretroviral therapy (HAART) era and to analyze characteristics, predictive factors, and survival of older HIV-1-infected individuals affected by these disorders. A nested longitudinal study was designed for a cohort of HIV-1-infected individuals with neurological diseases.

Antiviral efficacy and genotypic resistance patterns of combination therapy with stavudine/tenofovir in highly active antiretroviral therapy experienced patients.

Objectives: To evaluate antiviral efficacy of stavudine/tenofovir (d4T/TDF) backbone combination in late-line antiretroviral therapy, and to assess clinical and virological determinants of treatment success.

Design: Multicentric retrospective analysis on patients starting d4T/TDF after highly active antiretroviral therapy (HAART) failure.

Methods: The primary endpoint was the change in plasma HIV-1 RNA from the baseline (time of d4T/TDF initiation) to 6 months of therapy; secondary endpoint was the risk of virological failure.