Simplification to dual antiretroviral therapy including a ritonavir-boosted protease inhibitor in treatment-experienced HIV-1-infected patients.

Objectives: To assess the effectiveness of simplification to a dual antiretroviral regimen containing a ritonavir-boosted protease inhibitor (PI/r) in treatment-experienced HIV-1-infected patients.

Methods: Retrospective analysis of 131 HIV-1-infected patients on suppressive antiretroviral treatment (HIV-RNA <50 copies/mL) who switched to a maintenance dual antiretroviral regimen, containing a PI/r, in three hospitals in Spain. Virological failure was defined as confirmed HIV-RNA >50 copies/mL.

Fat tissue measurements by dual-energy x-ray absorptiometry: cross-calibration of 3 different fan-beam instruments.

Analysis of total tissue composition and, particularly, body fat measurements has become progressively important in the diagnosis and follow-up of patients with different clinical conditions. Dual-energy X-ray absorptiometry (DXA) fan-beam scanners are widely used to measure body composition, but the development of translational equations to be able to compare data of different scanning systems is necessary. The aim of this study was to assess the extent of agreement for regional measurements of body composition among the following 3 fan-beam DXA scanners: (1) Hologic Discovery (Hologic, Inc.

Fat redistribution syndromes associated with HIV-1 infection and combination antiretroviral therapy.

More than 15 years after the introduction of highly active antiretroviral therapy, HIV/HAART-associated lipodystrophy syndrome still shadows the indisputable efficacy of antiretroviral therapy. Several issues related to this complication (prevalence, diagnosis, pathogenesis, prevention, or clinical management) have not been completely clarified. However, in the last years, substantial progress has been made in elucidating some of these basic aspects.

Response to combined antiretroviral therapy according to gender and origin in a cohort of naïve HIV-infected patients: GESIDA-5808 study.

Background: We analyzed differences in response to combined antiretroviral therapy (cART) according to sex and geographic origin in a retrospective comparative study of Spanish-born and immigrant patients initiating cART.

Methods: The primary endpoint was time to treatment failure (TTF), defined as virological failure, death, opportunistic infection, interruption of cART, or loss to follow-up. Late diagnosis was defined as a CD4+ cell count ≤ 200 cells/mm3 and/or AIDS at initiation of cART.

Adipogenic/lipid, inflammatory, and mitochondrial parameters in subcutaneous adipose tissue of untreated HIV-1-infected long-term nonprogressors: significant alterations despite low viral burden.

Background: HIV-1 can induce disturbances in adipose tissue in infected subjects through the effects of some of its proteins or inflammation. It is not known whether this also takes place in HIV-1-infected long-term nonprogressors (LTNPs). Our objectives were to determine whether adipocyte differentiation/lipid, inflammatory, and mitochondrial parameters are perturbed in abdominal wall subcutaneous adipose tissue of untreated HIV-1-infected patients LTNPs.

Ritonavir boosting dose reduction from 100 to 50 mg does not change the atazanavir steady-state exposure in healthy volunteers.

Objectives: To evaluate the pharmacokinetics, tolerability and safety of 300 mg of atazanavir boosted with 100 or 50 mg of ritonavir, both once daily, at steady state.

Methods: This was a single-blind, multiple-dose, crossover, sequence-randomized trial. Thirteen healthy HIV-1-negative men received witnessed once-daily doses of atazanavir (300 mg) and 100 or 50 mg of ritonavir for 10 days (15 day washout).

[Costs and cost-efficacy analysis of the preferred treatments by GESIDA/National Plan for AIDS for the initial antiretroviral therapy in adult human immunodeficiency virus (HIV) infected patients in 2012].

Introduction: The GESIDA and National AIDS Plan panel of experts propose «preferred regimens» of antiretroviral treatment (ART) as initial therapy in HIV infected patients for 2012. The objective of this study is to evaluate the costs and the efficiency of initiating treatment with these «preferred regimens».

Methods: Economic assessment of costs and efficiency (cost/efficacy) using decision tree analysis model.

Longer prior exposure to zidovudine/lamivudine-containing combination antiretroviral therapy, age, and male gender are each associated with reduced subcutaneous adipose tissue.

Objectives: Whether zidovudine (AZT)-associated lipoatrophy occurrence differs by concomitant exposure to protease (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) remains unclear. Baseline body composition data from a randomized trial in subjects stable on first-line AZT-based therapy were used to explore this issue.

Methods: In this substudy of the PREPARE trial, centrally read baseline whole-body dual energy x-ray aborptiometry (DXA) and single-slice abdominal CT scans were analyzed with respect to duration and type of prior AZT/lamivudine (3TC) combination antiretroviral therapy (cART), including by multivariate linear regression adjusted for age, gender, ethnicity, body mass index (BMI), and nadir CD4.

Liver toxicity of initial antiretroviral drug regimens including two nucleoside analogs plus one non-nucleoside analog or one ritonavir-boosted protease inhibitor in HIV/HCV-coinfected patients.

Objective: To evaluate the incidence and risk factors for grade 3 or 4 ALT or AST elevations (TE) and grade 4 total bilirubin elevations (TBE) among HIV/HCV- coinfected treatment-naïve patients with an initial regimen including 2 nucleoside analogs plus efavirenz (EFV), nevirapine (NVP), or a ritonavir-boosted protease inhibitor (PI/r).

Patients And Methods: This was a retrospective multicenter observational cohort study that recruited 745 HIV-infected drug-naïve patients with detectable plasma HCV RNA who started a regimen including EFV, NVP, or PI/r.

Results: EFV was prescribed in 323 (43%), NVP in 126 (17%), and a PI/r in 296 (40%) patients.

Drug safety evaluation profile of stavudine plus lamivudine for HIV-1/AIDS infection.

Introduction: The lamivudine (3TC) + stavudine (d4T) combination is still widely used as part of first-line therapy for HIV-1-infected patients in low-resource countries. This review is intended to assess the benefits and risks in terms of safety of d4T + 3TC-based combination antiretroviral therapy (ART) for the treatment of HIV-1 infection.

Areas Covered: The most relevant papers related to the safety of d4T + 3TC-based ART were selected and summarized.

Effects of rilpivirine on human adipocyte differentiation, gene expression, and release of adipokines and cytokines.

Rilpivirine is a nonnucleoside reverse transcriptase inhibitor (NNRTI) recently developed as a drug of choice for initial antiretroviral treatment of HIV-1 infection. Disturbances in lipid metabolism and, ultimately, in adipose tissue distribution and function are common concerns as secondary effects of antiretroviral treatment. Efavirenz, the most commonly used NNRTI, causes mild dyslipidemic effects in patients and strongly impaired adipocyte differentiation in vitro.

Association of ITPA gene polymorphisms and the risk of ribavirin-induced anemia in HIV/hepatitis C virus (HCV)-coinfected patients receiving HCV combination therapy.

Polymorphisms of the ITPA gene have been associated with anemia during combination therapy in hepatitis C virus (HCV)-monoinfected patients. Our aim was to confirm this association in HIV/HCV-coinfected patients. In this prospective, observational study, 73 HIV/HCV-coinfected patients treated with pegylated interferon plus ribavirin (RBV) were enrolled.

Impact of antiretroviral therapy interruption on plasma biomarkers of cardiovascular risk and lipids: 144-week final data from the STOPAR study.

Objective: The aim of the study was to investigate changes in plasma biomarkers of cardiovascular risk and lipids in a CD4-guided antiretroviral therapy interruption study.

Methods: This was a substudy of a prospective, randomized, multicentre treatment interruption study. At months 12, 24 and 36, monocyte chemotactic protein-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-6 (IL-6), interleukin-8 (IL-8), soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin), and tissue plasminogen activator (t-PA) were measured using a multiplex cytometric bead-based assay.

Dual therapy based on a ritonavir-boosted protease inhibitor as a novel salvage strategy for HIV-1-infected patients on a failing antiretroviral regimen.

Objectives: To assess the efficacy and safety of dual-antiretroviral therapy containing a ritonavir-boosted protease inhibitor (PI/r) in treatment-experienced patients failing a current antiretroviral regimen.

Methods: Retrospective analysis of 60 consecutive HIV-1-infected patients who started a dual-antiretroviral rescue regimen containing a PI/r, in three hospitals in Spain. Virological failure was defined as confirmed HIV RNA >50 copies/mL at treatment week 24 or later.

Leptin and adiponectin, but not IL18, are related with insulin resistance in treated HIV-1-infected patients with lipodystrophy.

Leptin, adiponectin and IL18 are adipokines related with obesity, insulin resistance and dyslipidemia in the general population. Treated HIV-1-infected patients with lipodystrophy may develop insulin resistance and proatherogenic dyslipidemia. We assessed the relationship between plasma adipokine levels, adipokine genetics, lipodystrophy and metabolic disturbances.

HIV-1 Tat protein impairs adipogenesis and induces the expression and secretion of proinflammatory cytokines in human SGBS adipocytes.

Background: HIV-1 Tat protein has been shown to play multiple roles in the pathogenesis of AIDS; however, there is no information currently available on its effects on adipose tissue alterations. We have studied the effects of Tat on SGBS adipocytes to gain insight on its role on the development of lipodystrophy.

Methods: SGBS preadipocytes were exposed to Tat during and after differentiation.

Post-exposure prophylaxis for HIV infection: a clinical trial comparing lopinavir/ritonavir versus atazanavir each with zidovudine/lamivudine.

Background: A clinical trial comparing the rate of discontinuation and tolerability of two post-exposure prophylaxis (PEP) regimens was performed.

Methods: A total of 255 individuals attending the emergency rooms of six hospitals for exposure to HIV and criteria to receive PEP were randomized to receive zidovudine/lamivudine plus either lopinavir/ritonavir (n=131) or atazanavir (n=124; day 0). The primary end point was the rate of PEP discontinuation before day 28 of follow-up.

Treatment intensification with raltegravir in subjects with sustained HIV-1 viraemia suppression: a randomized 48-week study.

Background: Residual viraemia is a major obstacle to HIV-1 eradication in subjects receiving HAART. The intensification with raltegravir could impact latent reservoirs and might lead to a reduction of plasma HIV-1 viraemia (viral load [VL]), complementary DNA intermediates and immune activation.

Methods: This was a prospective, open-label, randomized study comprising 69 individuals on suppressive HAART randomly assigned 2:1 to add raltegravir during 48 weeks.

Zinc alpha-2 glycoprotein is implicated in dyslipidaemia in HIV-1-infected patients treated with antiretroviral drugs.

Objectives: Treated HIV-1-infected patients with lipodystrophy often develop insulin resistance and proatherogenic dyslipidaemia. Zinc alpha-2 glycoprotein (ZAG) is a recently characterized adipokine which has been shown to be involved in the development of obesity and metabolic syndrome in uninfected subjects. We assessed the relationship between circulating ZAG levels and metabolic derangements in HIV-1-infected patients receiving antiretroviral drugs.

Thymidine kinase 2 deficiency-induced mitochondrial DNA depletion causes abnormal development of adipose tissues and adipokine levels in mice.

Mammal adipose tissues require mitochondrial activity for proper development and differentiation. The components of the mitochondrial respiratory chain/oxidative phosphorylation system (OXPHOS) are encoded by both mitochondrial and nuclear genomes. The maintenance of mitochondrial DNA (mtDNA) is a key element for a functional mitochondrial oxidative activity in mammalian cells.

Methicillin-resistant Staphylococcus aureus meningitis in adults: a multicenter study of 86 cases.

Methicillin-resistant Staphylococcus aureus (MRSA) meningitis is an uncommon disease, and little is known about its epidemiology, clinical features, therapy, and outcome. We performed a multicenter retrospective study of MRSA meningitis in adults. Eighty-six adult patients were included and the following data were obtained: underlying diseases, clinical presentation, analytical and microbiologic data, response to therapy, and outcome.