Mitochondrial Toxicogenomics for Antiretroviral Management: HIV Post-exposure Prophylaxis in Uninfected Patients.

Mitochondrial genome has been used across multiple fields in research, diagnosis, and toxicogenomics. Several compounds damage mitochondrial DNA (mtDNA), including biological and therapeutic agents like the human immunodeficiency virus (HIV) but also its antiretroviral treatment, leading to adverse clinical manifestations. HIV-infected and treated patients may show impaired mitochondrial and metabolic profile, but specific contribution of viral or treatment toxicity remains elusive.

Renal safety of coformulated tenofovir/emtricitabine vs other nucleoside analogues in combination therapy in antiretroviral-naive patients aged 50 years or older in Spain: The TRIP study.

Objectives: Our aim is to describe the impact of emtricitabine (FTC)/tenofovir (TDF) versus other nucleoside reverse transcriptase inhibitor (NRTIs)-based regimens on renal function of human immunodeficiency virus (HIV) naïve patients >50 years old who started combination antiretroviral therapy (cART).

Design: National, retrospective cohort analysis of patients >50 years old when they started cART (January 1, 2006-December 31, 2009).

Methods: We compared renal safety (changes in estimated glomerular filtration rate [eGFR] during the first year, and time to renal events during 4 years of follow-up) in FTC/TDF versus non-FTC/TDF users.

[Consensus statement on metabolic disorders and cardiovascular risks in patients with human immunodeficiency virus].

Objective: This consensus document is an update of metabolic disorders and cardiovascular risk (CVR) guidelines for HIV-infected patients.

Methods: This document has been approved by an expert panel of GEAM, SPNS and GESIDA after reviewing the results of efficacy and safety of clinical trials, cohort and pharmacokinetic studies published in biomedical journals (PubMed and Embase) or presented in medical scientific meetings. Recommendation strength and the evidence in which they are supported are based on the GRADE system.

Executive summary of the consensus document on metabolic disorders and cardiovascular risk in patients with HIV infection.

The importance of the metabolic disorders and their impact on patients with HIV infection requires an individualized study and continuous updating. HIV patients have the same cardiovascular risk factors as the general population. The HIV infection per se increases the cardiovascular risk, and metabolic disorders caused by some antiretroviral drugs are added risk factors.

[Reasons for antiretroviral treatment change in HIV+ patients in Spain in 2010-2011. SWITCH AUDIT Study].

Survey in 349 HIV infected subjects in 19 Spanish Hospitals in 2010-2011, to assess the reasons for antiretroviral treatment change. Simplification was the most frequent reason for change (37%), followed by toxicity (30%) and treatment failure (21%). There were statistically significant differences according to treatment line and transmission category.

Safety, efficacy, and persistence of emtricitabine/tenofovir versus other nucleoside analogues in naive subjects aged 50 years or older in Spain: the TRIP study.

Objectives: Current antiretroviral guidelines state that being older than 50 to 55 years of age is an indication to start antiretroviral therapy (ART), regardless of CD4 status. However, no references to the preferred combination ART (cART) for these patients have been described. Our study compares emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) versus other nucleoside reverse transcriptase inhibitor (NNRTI) regimens in HIV ART-naïve patients who are ≥50 years.

[Reasons for the introduction of darunavir in the antirretroviral treatment in HIV-infected patients].

Introduction: In 2009 a deep change in ARV treatment took place in Spain with the introduction of new ARV drugs. The principal objective of the study was to determine the clinical situation of the patients in which DRV/r was introduced in the ARV therapy.

Methods: Observational, cross sectional and multicentre study in which 91 reference hospitals participated.

Dyslipidaemia in HIV-infected women on antiretroviral therapy. Analysis of 922 patients from the Spanish VACH cohort.

Background: Information concerning lipid disturbances in HIV-infected women on antiretroviral therapy (ART) is scarce. The objective of the study is to describe the lipid profile in a large cohort of HIV-infected women on contemporary ART and analyse differences between regimes and patient's characteristics.

Methods: Observational, multicentre, cross-sectional study from the Spanish VACH Cohort.

Evaluation of the safety and effectiveness of nevirapine plus coformulated tenofovir/emtricitabine as first-line therapy in routine clinical practice.

Despite having demonstrated noninferior efficacy against atazanavir/ritonavir plus coformulated tenofovir/emtricitabine (cTDF/FTC), the combination of nevirapine plus cTDF/FTC is not included among preferred regimens in some international guidelines. This combination is frequently used in Spain. We analyzed its effectiveness and safety as first-line therapy in a routine clinical practice.

Effect of TNF-alpha genetic variants and CCR5 Delta 32 on the vulnerability to HIV-1 infection and disease progression in Caucasian Spaniards.

Background: Tumor necrosis factor alpha (TNF-alpha) is thought to be involved in the various immunogenetic events that influence HIV-1 infection.

Methods: We aimed to determine whether carriage of the TNF-alpha-238G>A, -308G>A and -863 C>A gene promoter single nucleotide polymorphisms (SNP) and the CCR5 Delta 32 variant allele influence the risk of HIV-1 infection and disease progression in Caucasian Spaniards. The study group consisted of 423 individuals.

[Cardiovascular risk assessment and intervention in HIV-infected patients].

Because of the increased cardiovascular risk (CVR) in HIV-positive patients, preventive measures are essential, requiring algorithms for risk estimation, such as the Framingham risk equation, the Prospective Cardiovascular Munster Study (PROCAM) algorithm and the Systematic Coronary Risk Evaluation (SCORE) chart. Classical cardiovascular risk factors (CVRF) are closely related to CVR in HIV-infected patients but whether this risk is comparable to that in the general population is unknown. Therefore, these algorithms probably underestimate the risk in these patients.

Characteristics and outcome of HIV infection in gypsies in the Spanish VACH Cohort.

Objective: To study the characteristics of HIV infection in the gypsy (Roma) population in Spain, as compared with those of the Caucasian, non-gypsy majority.

Design: Cross-sectional, historical cohort study from the Spanish VACH Cohort.

Methods: Patients attending VACH clinics between 1 June 2004 and 30 November 2004 were classified according to their racial and ethnic origin as "gypsies", Caucasian non-gypsy Spanish natives (CNGN), and "other" (the last being excluded from this study).

Genetic and functional mitochondrial assessment of HIV-infected patients developing HAART-related hyperlactatemia.

Background: Mitochondrial damage of HIV and antiretrovirals, especially nucleoside-analogue interference on mitochondrial DNA (mtDNA) replication, is reported to underlay highly active antiretroviral therapy (HAART)-related hyperlactatemia, but scarce approaches have been performed to correlate clinical manifestations and mitochondrial abnormalities.

Methods: We obtained lymphocytes and monocytes of 26 HIV-infected and treated patients who developed hyperlactatemia and after recovery, 28 nonhyperlactatemic HIV subjects on HAART, 31 naive individuals, and 20 uninfected controls. Mitochondrial replication and transcription analysis were performed by quantitative real-time PCR, mitochondrial translation quantification by western blot and mitochondrial enzymatic activities by spectrophotometry.

Efficacy and safety of switching from boosted lopinavir to boosted atazanavir in patients with virological suppression receiving a LPV/r-containing HAART: the ATAZIP study.

Objectives: To evaluate the efficacy and safety of switching from boosted lopinavir (LPV/r) to boosted atazanavir (ATV/r) in virologically suppressed HIV-1-infected patients versus continuing LPV/r.

Methods: Forty-eight weeks analysis of a randomized, open-label, noninferiority trial including patients with virological suppression (< or = 200 copies/mL for > or = 6 months) on LPV/r-containing triple highly active antiretroviral therapy. Patients (n = 248) were randomized 1:1 either to continue LPV/r twice a day (n = 127) or to switch to ATV/r every day (ATV/r; n = 121), with no change in nucleoside reverse transcriptase inhibitor backbone.

Saquinavir exposure in HIV-infected patients with chronic viral hepatitis.

Objectives: The aim of this study was to assess the influence of hepatitis B virus or hepatitis C virus co-infection and the extent of liver fibrosis on saquinavir and ritonavir pharmacokinetics in HIV-infected subjects without liver function impairment.

Methods: A cross-sectional, comparative study enrolling HIV-infected adults receiving saquinavir/ritonavir 1000/100 mg twice daily or 1500/100 mg once daily was conducted. Patients with chronic viral hepatitis (HEP+) were grouped as having advanced liver fibrosis (HEP+/FIB+) or not (HEP+/FIB-) based on the FIB-4 index.

Safety of Switching Nevirapine Twice Daily to Nevirapine Once Daily in Virologically Suppressed Patients.

Background: The strategy of switching nevirapine (NVP) twice daily to once daily was evaluated.

Methods: Forty-eight-week randomized, open, multicenter trial. Stable HIV-infected patients on NVP twice daily for >12-18 weeks with alanine aminotransferase (ALT) <2.

Effectiveness and safety of didanosine, lamivudine and efavirenz versus zidovudine, lamivudine and efavirenz for the initial treatment of HIV-infected patients from the Spanish VACH cohort.

Background: Preliminary data suggest that a once-daily combination of lamivudine, didanosine and efavirenz is an effective alternative regimen for antiretroviral-naive HIV-1-infected patients. However, data from randomized trials comparing this combination versus standard first-line regimens are not available yet. In an observational study, we analyse the efficacy and tolerability of didanosine plus lamivudine and efavirenz versus zidovudine plus lamivudine and efavirenz in a cohort of therapy naive patients.

Didanosine, lamivudine, and efavirenz versus zidovudine, lamivudine, and efavirenz for the initial treatment of HIV type 1 infection: final analysis (48 weeks) of a prospective, randomized, noninferiority clinical trial, GESIDA 3903.

Background: The combination of didanosine, lamivudine, and efavirenz (ddI/3TC/EFV) for the initial treatment of human immunodeficiency virus type 1 (HIV-1) infection has been insufficiently analyzed in clinical trials.

Methods: We conducted an open-label, randomized study to compare the noninferiority of ddI/3TC/EFV with the lamivudine-zidovudine tablet and EFV (COM/EFV), both administered with food to improve tolerability and convenience. Patients were stratified by HIV-1 RNA level of <5.

Zidovudine/lamivudine/abacavir plus tenofovir in HIV-infected naive patients: a 96-week prospective one-arm pilot study.

We evaluated a single-class quadruple nucleoside/nucleotide regimen in a 96-week prospective one-arm pilot study in adult HIV-infected naive patients with CD4 >100 cells/microl. Standard zidovudine/lamivudine/abacavir and tenofovir doses were given. Virologic efficacy was evaluated by intent-to-treat (ITT), switch = failure and on-treatment (OT) analyses.

Induction therapy with trizivir plus efavirenz or lopinavir/ritonavir followed by trizivir alone in naive HIV-1-infected adults.

Background: Induction-maintenance strategies were associated with a low response rate. We compared the virological response with two different induction regimens with trizivir plus efavirenz or lopinavir/ritonavir.

Methods: A randomized, multicentre, open-label clinical trial with 209 antiretroviral-naive HIV-infected patients assigned to trizivir plus either efavirenz or lopinavir/ritonavir during 24-36 weeks.