Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: the data collection on adverse events of anti-HIV drugs (D:A:D) study.

BACKGROUND. The risk of myocardial infarction (MI) in patients with human immunodeficiency virus (HIV) infection has been assessed in 13 anti-HIV drugs in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. METHODS.

Abacavir and cardiovascular risk.

Purpose Of Review: This review focuses on current studies addressing the association of abacavir (ABC) therapy and myocardial risk in HIV-infected patients, discusses potential pathogenetic mechanisms, and suggests a preliminary algorithm for decision making regarding ABC therapy in daily clinical practise.

Recent Findings: The D:A:D study was the first to reveal an increased rate of myocardial infarction in patients recently treated with ABC. Subsequent analyses of both cohort studies as well as prospective randomized clinical trials largely confirmed this association.

Safety and efficacy of once-daily nevirapine dosing: a multicohort study.

Background: Nevirapine (NVP) is often prescribed once daily in clinical practice in combination with a once daily nucleoside backbone. We investigated the relationship of NVP dosing with safety and efficacy.

Methods: Patients from the Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort study, Canadian HAART Observational Medical Evaluation and Research (HOMER) cohort and Swiss HIV Cohort Study (SHCS) using NVP-based combination therapy either once daily or twice daily were included.

High prevalence of the metabolic syndrome in HIV-infected patients: impact of different definitions of the metabolic syndrome.

Introduction: This study describes the characteristics of the metabolic syndrome in HIV-positive patients in the Data Collection on Adverse Events of Anti-HIV Drugs study and discusses the impact of different methodological approaches on estimates of the prevalence of metabolic syndrome over time.

Methods: We described the prevalence of the metabolic syndrome in patients under follow-up at the end of six calendar periods from 2000 to 2007. The definition that was used for the metabolic syndrome was modified to take account of the use of lipid-lowering and antihypertensive medication, measurement variability and missing values, and assessed the impact of these modifications on the estimated prevalence.

Insulin sensitivity in multiple pathways is differently affected during zidovudine/lamivudine-containing compared with NRTI-sparing combination antiretroviral therapy.

Objective: The extent and manner by which HIV nucleoside reverse transcriptase inhibitors contribute to insulin resistance is unclear. We evaluated the effect of zidovudine/lamivudine (ZDV/3TC) on glucose metabolism.

Methods: combination antiretroviral therapy-naive men were randomized to lopinavir/ritonavir (LPV/r, 400/100 mg twice a day) + ZDV/3TC or LPV/r (533/133 mg twice a day) + nevirapine (NVP).

Implementing the number needed to harm in clinical practice: risk of myocardial infarction in HIV-1-infected patients treated with abacavir.

Objectives: The D:A:D study group reported a 1.9-fold increased relative risk (RR) of myocardial infarction (MI) associated with current or recent use of abacavir. The number needed to harm (NNH) incorporates information about the underlying risk of MI and the increased RR of MI in patients taking abacavir.

Assisted reproductive technologies to establish pregnancies in couples with an HIV-1-infected man.

For HIV -1-infected men and women the introduction of highly active antiretroviral therapy (HART) in 1996 led to a spectacular increase in life expectancy and quality of life. In Western society where HART is readily available, HIV -1 is now considered to be a chronic disease and as a consequence quality of life is an important aspect for men and women with HIV-1. Many of them express the desire to father or mother a child.

Effective methods to improve recruitment and retention in school-based substance use prevention studies.

Background: Poor recruitment and high attrition may invalidate results of research studies. This paper describes successful recruitment and retention strategies in a school-based substance use prevention trial and explores factors associated with intervention attendance and retention.

Methods: A total of 384 parent-child dyads from 15 schools in the New York Metropolitan area participated in a control trial, testing the efficacy of parent-training to prevent youth substance use.

A rosiglitazone-induced increase in adiponectin does not improve glucose metabolism in HIV-infected patients with overt lipoatrophy.

HIV-infected patients on antiretroviral therapy frequently develop changes in body fat distribution and disturbances in glucose metabolism, associated with reduced adiponectin levels. Because adiponectin, principally the high-molecular-weight (HMW) form, has insulin-sensitizing properties, we investigated the effects of an increase in adiponectin on glucose metabolism in HIV-lipodystrophy. In this randomized, double-blind, placebo-controlled trial, we included HIV-1-infected patients with severe lipoatrophy, with an undetectable viral load and who had received neither protease inhibitors nor stavudine for ≥6 mo.

On distance-based permutation tests for between-group comparisons.

Permutation tests based on distances among multivariate observations have found many applications in the biological sciences. Two major testing frameworks of this kind are multiresponse permutation procedures and pseudo-F tests arising from a distance-based extension of multivariate analysis of variance. In this article, we derive conditions under which these two frameworks are equivalent.

Effect of baseline CD4 cell counts on the clinical significance of short-term immunologic response to antiretroviral therapy in individuals with virologic suppression.

Background: Achieving virologic suppression is a clear therapeutic goal for patients receiving combination antiretroviral therapy (cART). However, the effects of immunologic responses, whether measured as CD4 count changes from baseline or CD4 counts at follow-up, in patients with virologic suppression, have not been clearly established.

Methods: Treatment-naive individuals aged > or =16 years, who initiated cART between 1998 and 2005 in participating cohorts of the ART Cohort Collaboration and achieved viral load < or =400 copies per milliliter 6 months after cART initiation, were included.

Nevirapine increases high-density lipoprotein cholesterol concentration by stimulation of apolipoprotein A-I production.

Objective: The purpose of this study was to investigate the mechanism by which the nonnucleoside reverse transcriptase inhibitor (NNRTI) nevirapine (NVP) increases high-density lipoprotein cholesterol (HDLc) in treatment-experienced human immunodeficiency virus-1 (HIV-1)-infected patients.

Methods And Results: Twelve HIV-1 infected patients, with stably suppressed HIV-1 viral load using AZT/3TC/abacavir for > or =6 months, added NVP to their current antiretroviral regimen. Patients received a primed bolus infusion of the stable isotope L-[1-(13)C]-valine for 12 hours before, as well as 6 and 24 weeks after, the addition of NVP to study apolipoprotein A-I (apoA-I) kinetics.

Baseline lipid levels rather than the presence of reported body shape changes determine the degree of improvement in lipid levels after switching to atazanavir.

Purpose: To study factors influencing lipid changes after switching to atazanavir (ATV) and the effectiveness of ATV in maintaining virus suppression.

Methods: Retrospective cohort study in patients with viral suppression, comparing patients switching to ATV with those continuing combination antiretroviral therapy (cART). Outcome measures were 48-week total (TC), high-density (HDL) and low-density lipoprotein (LDL) cholesterol, and triglycerides (TG) changes, stratified for dyslipidemia and lipodystrophy and virological failure (time to first of two consecutive detectable HIV RNA).

Continuous antiretroviral therapy decreases bone mineral density.

Objectives: To assess the effects of antiretroviral therapy (ART) on bone mineral density (BMD) DESIGN: Randomized comparison of continuous ART (viral suppression group; VS) with intermittent ART (drug conservation group; DC) SETTING: Outpatient clinics in the United States, Australia, and Spain.

Participants: Participants in the Strategies for Management of Antiretroviral Therapy (SMART) Body Composition substudy.

Main Outcome Measures: Annual hip and spine BMD by dual-energy radiographic absorptiometry (DXA) and spine BMD by quantitative computed tomography (qCT).

L-dopa modulates functional connectivity in striatal cognitive and motor networks: a double-blind placebo-controlled study.

Functional connectivity (FC) analyses of resting-state fMRI data allow for the mapping of large-scale functional networks, and provide a novel means of examining the impact of dopaminergic challenge. Here, using a double-blind, placebo-controlled design, we examined the effect of L-dopa, a dopamine precursor, on striatal resting-state FC in 19 healthy young adults. We examined the FC of 6 striatal regions of interest (ROIs) previously shown to elicit networks known to be associated with motivational, cognitive and motor subdivisions of the caudate and putamen (Di Martino et al.

Risk factors for treatment-limiting toxicities in patients starting nevirapine-containing antiretroviral therapy.

Background: This collaboration of seven observational clinical cohorts investigated risk factors for treatment-limiting toxicities in both antiretroviral-naive and experienced patients starting nevirapine-based combination antiretroviral therapy (NVPc).

Methods: Patients starting NVPc after 1 January 1998 were included. CD4 cell count at starting NVPc was classified as high (>400/microl/>250/microl for men/women, respectively) or low.

Zidovudine/lamivudine for HIV-1 infection contributes to limb fat loss.

Background: Lipoatrophy is known to be associated with stavudine as part of the treatment for HIV infection, but it is less clear if this serious side effect is also related to other nucleoside reverse transcriptase inhibitors like zidovudine. We aimed to determine whether zidovudine-sparing first-line antiretroviral therapy would lead to less lipoatrophy and other metabolic changes than zidovudine-containing therapy.

Methodology/principal Findings: Fifty antiretroviral therapy-naïve HIV-1 infected men with an indication to start antiretroviral therapy were included in a randomized single blinded clinical trial.

Effect of poly(ethylene glycol) length on the in vivo behavior of coated quantum dots.

The use of nanoparticles, either for the delivery of drugs or for imaging contrast agents, or a combination of both (theranostics), is very appealing in biological and biomedical research. The design of high-quality NIR-emitting quantum dots (QDs), with outstanding optical properties in comparison to that of organic dyes, should lead to novel contrast agents with improved performance for optical and multimodal imaging. Moreover, these nanocrystals could also be used for exploring therapeutic applications, such as drug delivery or phototherapy.

Functional generalized linear models with images as predictors.

Functional principal component regression (FPCR) is a promising new method for regressing scalar outcomes on functional predictors. In this article, we present a theoretical justification for the use of principal components in functional regression. FPCR is then extended in two directions: from linear to the generalized linear modeling, and from univariate signal predictors to high-resolution image predictors.

First line zidovudine/lamivudine/lopinavir/ritonavir leads to greater bone loss compared to nevirapine/lopinavir/ritonavir.

Objective: We studied changes in bone mineral density (BMD) and bone turnover after initiation of combination antiretroviral therapy (cART) and the contribution of zidovudine/lamivudine (ZDV/3TC) in particular.

Design: Randomized clinical trial comparing lopinavir/ritonavir(LPV/r) + ZDV/3TC with LPV/r + nevirapine (NVP) in 50 cART-naive men.

Methods: Dual energy X-ray absorptiometry (DXA) and quantitative computed tomography scans (QCT) were performed at baseline and 3, 12, and 24 months after cART initiation.

Drug interactions between statins and antiretroviral agents.

Purpose Of Review: Both antiretroviral agents and statins are well known for their independent roles in causing drug-drug interactions.

Recent Findings: Not surprisingly, combined use of statins and antiretroviral agents may lead to a variety of clinically relevant drug-drug interactions, including reduced lipid-lowering effects (as a result from increased metabolism of statins) as well as an increased risk of potentially fatal rhabdomyolysis (as a result of reduced metabolism of the statin or impaired hepatic uptake). Initially, attention has focused on the cytochrome P450 system as being the source of the observed drug-drug interactions, but nowadays it is clear that other pathways, such as UDP-glucuronosyltransferase and the organic anion polypeptide B transporter, may also be involved.

Hepatitis C virus coinfection does not influence the CD4 cell recovery in HIV-1-infected patients with maximum virologic suppression.

Background: Conflicting data exist whether hepatitis C virus (HCV) affects the CD4 cell recovery in patients with HIV starting antiretroviral treatment.

Objective: To investigate the influence of HCV coinfection on the CD4 recovery in patients with maximum virologic suppression within the EuroSIDA cohort.

Methods: Patients tested for anti-HCV antibodies and with at least 2 consecutive HIV viral loads (VLs) <50 copies per milliliter after starting combination antiretroviral therapy were eligible for inclusion.

On the function and structure of synthetically modified porins.

The attachment of modulators to a trimeric porin ion channel was investigated (see picture of the trimer with a crown ether modulator (orange)). The interplay of modulator and protein is essential for the conformational heterogeneity of the hybrid channel. Single-site attachment in large pores is not sufficient to change the electrophysiological characteristics of the pores-such change requires additional noncovalent interactions or second-site attachments.

Expanding the scope of protein trans-splicing to fragment ligation of an integral membrane protein: towards modulation of porin-based ion channels by chemical modification.

It's raining, it's porin: Fragment ligation of OmpF ion channels was achieved by using the split Psp-GBD Pol intein; this allowed reconstitution of active trimeric porin. In combination with cysteine modification at an internal position, the porin's conductance properties were altered.