Incidence of Diabetes Mellitus and Associated Factors in the Era of Antiretroviral Drugs With a Low Metabolic Toxicity Profile.

Objective: The incidence of type 2 diabetes mellitus (T2DM) has risen dramatically. Among people living with HIV (PLHIV), chronic disease (now >15 cases/1000 in the general population worldwide) and long-term exposure to antiretroviral therapy (ART) can alter metabolic processes early, favoring insulin resistance and T2DM. We retrospectively studied the incidence of T2DM and associated factors in the Cohort of the Spanish AIDS Research Network, a prospective cohort of PLHIV enrolled at diagnosis and before initiation of ART. Methods: PLHIV were aged >18 years and ART naive at inclusion. The incidence of new diagnoses of T2DM after initiation of ART (per 1000 person-years) was calculated. Predictors of a diagnosis of T2DM were identified by a Cox proportional hazards model adjusted for statistically significant and clinically relevant variables. Results: Cumulative incidence was 5.9 (95% CI, 5.1-6.7) per 1000 person-years, increasing significantly in persons aged >50 years to 14.4 (95% CI, 10.4-19.3). Median time to diagnosis of T2DM was 27 months. Only age and higher education were significant. Interestingly, higher education was associated with a 33% reduction in the incidence of T2DM. Having received tenofovir disoproxil fumarate + (lamivudine or emtricitabine) + rilpivirine was almost significant as a protective factor (hazard ratio, 0.49; 95% CI, .24-1.01; P = .05). Conclusions: The incidence of T2DM in PLHIV in Spain was high, especially in persons aged >50 years. Age was the factor most closely associated with onset, and educational level was the factor most associated with reduced risk. We highlight the lack of association between HIV-related factors and T2DM and show that, within nonnucleoside reverse transcriptase inhibitors, rilpivirine could prove more benign for metabolic comorbidities.

Sex differences in the effectiveness and tolerability of dolutegravir plus rilpivirine as a switch strategy in people living with HIV.

INTRODUCTION: Dolutegravir + rilpivirine (DTG + RPV) is an effective antiretroviral therapy regimen approved in clinical guidelines as a switch therapy for virologically suppressed people with HIV. Our study aimed to compare the effectiveness and tolerability of DTG + RPV in women and men in real-world clinical practice. METHODS: This was a retrospective analysis of treatment-experienced people with HIV from a large HIV unit who switched to DTG + RPV. We analysed treatment effectiveness, rates of adverse events and discontinuation, and metabolic changes after 48 weeks of treatment. HIV-RNA levels <50 copies/mL were analysed at 48 weeks using both intention-to treat analysis (where missing data were interpreted as failures) and per-protocol analysis (excluding those with missing data or changes due to reasons other than virological failure). Outcomes were compared between women and men based on sex at birth. RESULTS: A total of 307 patients were selected (71 women and 236 men). No transgender people were included. At baseline, women had lived with HIV infection and received antiretroviral therapy for longer than men (23.2 vs 17.4 years and 18.9 vs 14.2 years, respectively). In the intention-to-treat analysis, 74.6% (95% confidence interval [CI] 63.4-83.3%) of women and 83.5% (95% CI 78.2-87.7) of men had HIV-RNA <50 copies/mL. In the per-protocol analysis, 96.4% (95% CI 87.7-99) of women and 99% (95% CI 98.9-99.7) of men had HIV-RNA levels <50 copies/mL. Two women and two men had HIV-RNA >50 copies/mL at 48 weeks. Discontinuation due to adverse events was more frequent in women than in men: 12.7% vs 7.2% (p < 0.02). Neuropsychiatric and gastrointestinal events were the most frequently reported. A median (interquartile range) weight gain of 1.9 kg (0-4.2) in women and 1.2 kg (-1-3.1) in men was reported (median of differences between baseline visit and week 48); the remaining changes in metabolic parameters were neutral. CONCLUSIONS: DTG + RPV exhibited good and similar virological effectiveness in women and men in real-world settings. However, poorer tolerability and more treatment interruptions were observed in women.

Patient-Reported Outcomes (PROs) in HIV Infection: Points to Consider and Challenges.

INTRODUCTION: The aim of this study was to reach consensus on the use of PROs (patient-reported outcome measures) in people living with HIV (PLHIV). METHODS: A scientific committee of professionals with experience in PROMs methodology issued recommendations and defined the points to support by evidence. A systematic review of the literature identified the coverage, utility, and psychometric properties of PROMs used in PLHIV. A Delphi survey was launched to measure the degree of agreement with the recommendations of a group of practicing clinicians and a group of patient representatives. RESULTS: Four principles and ten recommendations were issued; however, the results of the Delphi showed significant differences in the opinion between health professionals and PLHIV, and polarization within collectives, hampering consensus. CONCLUSIONS: Despite a wealth of evidence on the benefit of PROMs, there are clear barriers to their use by healthcare professionals in HIV care. Intervention on these barriers is paramount to allow truly patient-centered care.

Eficacia en vida real del cambio a bictegravir/ emtricitabina/tenofovir alafenamida en pacientes previamente tratados con pautas triples que contienen rilpivirina / Real-world efficacy of switching to bictegravir/ emtricitabine/tenofovir alafenamide in pretreated patients with triple therapy containing rilpivirine

Objetivo. Analizar la eficacia y tolerabilidad de la estrategia de cambio desde regímenes basados en rilpivirina (RPV)a bictegravir/emtricitabina/tenofovir alafenamida (B/F/TAF) enla vida real.Métodos. Estudio unicéntrico, observacional y retrospectivo. Se seleccionaron pacientes que cambiaron de un régimencon RPV a B/F/TAF antes de febrero del 2020 analizándose losresultados después de 24 y 48 semanas. Se determinó el porcentaje que permanecía con carga viral indetectable, así comolos cambios en linfocitos CD4+, parámetros metabólicos y función renal.Resultados. Se incluyeron en el estudio 42 pacientes. 32de los 35 (91,4%) que completaron las 48 semanas de seguimiento tenían carga viral indetectable. El recuento de linfocitos CD4+ permaneció estable a las 24 y a las 48 semanas. Eltipo de análogos recibidos previamente no influyó en la respuestaConclusión. El cambio desde una triple terapia con RPV aB/F/TAF es una estrategia segura y eficaz en la vida real. (AU)

Objective. To analyze the efficacy and tolerability of thestrategy to change from rilpivirine (RPV) based regimens tobictegravir / emtricitabine / tenofovir alafenamide (B/F/TAF).Methods. Single-center, observational and retrospectivestudy. Patients who made the change to B/F/TAF before February 2020 were selected, analyzing the results after 24 and48 weeks. The percentage that remained with an undetectableviral load was determined, as well as the changes in CD4 +lymphocytes, metabolic parameters and renal function.Results. A total of 42 patients were included. Thirty-twoof the 35 patients (91.4%) who completed the 48 weeks offollow-up had an undetectable viral load. The CD4 + lymphocyte count remained stable at 24 and 48 weeks. The responseto B/F/TAF was not influenced by the two analogs previouslyreceived.Conclusion. Switching from triple therapy with RPV toB/F/TAF is a safe and effective strategy in real life. (AU)

Past and future of HIV infection. A document based on expert opinion / Pasado y futuro de la infección por VIH. Un documento basado en la opinión de expertos

HIV infection is now almost 40 years old. In this time, along with the catastrophe and tragedy that it has entailed, it has also represented the capacity of modern society to take on a challenge of this magnitude and to transform an almost uniformly lethal disease into a chronic illness, compatible with a practically normal personal and relationship life. This anniversary seemed an ideal moment to pause and reflect on the future of HIV infection, the challenges that remain to be addressed and the prospects for the immediate future. This reflection has to go beyond merely technical approaches, by specialized professionals, to also address social and ethical aspects. For this reason, the Health Sciences Foundation convened a group of experts in different aspects of this disease to discuss a series of questions that seemed pertinent to all those present. Each question was presented by one of the participants and discussed by the group. The document we offer is the result of this reflection. (AU)

La infección por VIH cumple ahora casi 40 años de existencia. En este tiempo, junto a la catástrofe y la tragedia que ha supuesto, ha representado también la capacidad de la sociedad moderna de asumir un reto de esta magnitud y de transformar, gracias al tratamiento antirretroviral, una enfermedad mayoritariamente letal en una enfermedad crónica, compatible con una vida personal y de relación prácticamente normales. Este aniversario parecía un momento idóneo para pararse a reflexionar sobre el futuro de la infección VIH, los retos que todavía quedan por abordar y las perspectivas para el inmediato futuro. Esa reflexión tiene que ir más allá de planteamientos meramente técnicos, de profesionales especializados, para abordar aspectos sociales y éticos. Por este motivo, la Fundación de Ciencias de la Salud convocó a un grupo de expertos en distintos aspectos de esta infección para discutir una serie de preguntas que parecieron pertinentes a todos los convocados. Cada pregunta era expuesta por uno de los participantes y discutida por el grupo. El documento que ofrecemos es el resultado de esa reflexión. (AU)

Massive Release of CD9+ Microvesicles in Human Immunodeficiency Virus Infection, Regardless of Virologic Control.

BACKGROUND: The role of extracellular vesicles (EVs) in human immunodeficiency virus (HIV) pathogenesis is unknown. We examine the cellular origin of plasma microvesicles (MVs), a type of ectocytosis-derived EV, the presence of mitochondria in MVs, and their relationship to circulating cell-free mitochondrial deoxyribonucleic acid (ccf-mtDNA) in HIV-infected patients and controls. METHODS: Five participant groups were defined: 30 antiretroviral therapy (ART)-naive; 30 ART-treated with nondetectable viremia; 30 elite controllers; 30 viremic controllers; and 30 HIV-uninfected controls. Microvesicles were quantified and characterized from plasma samples by flow cytometry. MitoTrackerDeepRed identified MVs containing mitochondria and ccf-mtDNA was quantified by real-time polymerase chain reaction. RESULTS: Microvesicle numbers were expanded at least 10-fold in all HIV-infected groups compared with controls. More than 79% were platelet-derived MVs. Proportions of MVs containing mitochondria (22.3% vs 41.6%) and MV mitochondrial density (706 vs 1346) were significantly lower among HIV-infected subjects than controls, lowest levels for those on ART. Microvesicle numbers correlated with ccf-mtDNA levels that were higher among HIV-infected patients. CONCLUSIONS: A massive release of platelet-derived MVs occurs during HIV infection. Some MVs contain mitochondria, but their proportion and mitochondrial densities were lower in HIV infection than in controls. Platelet-derived MVs may be biomarkers of platelet activation, possibly reflecting pathogenesis even in absence of HIV replication.

Innate and adaptive abnormalities in youth with vertically acquired HIV through a multicentre cohort in Spain.

INTRODUCTION: Immune abnormalities have been described among youth with vertically acquired HIV (YWVH) despite antiretroviral treatment (ART). The CD4/CD8 ratio could be a useful prognostic marker. We assess immune activation and senescence in a cohort of YWVH in comparison to youth without vertically acquired HIV. METHODS: YWVH under suppressive ART were included and compared to a group of HIV-negative donors (HD) matched by age and sex, from September 2019 to September 2020. Subset distribution and expression of activation, maturation, senescence and exhaustion markers on T and NK cells were studied on peripheral blood mononuclear cells by multiparametric flow cytometry. RESULTS: Thirty-two YWVH (median age: 24.4 years (interquartile range: 22.5 to 28.3 years)) were included. Among YWVH, CD4- and CD8-T cells showed high levels of activation (HLA-DR/CD38), IL-7 receptor expression (CD127) and exhaustion (TIM-3). Regarding NK cells, YWVH showed increased levels of activation and exhaustion markers compared to HD. Strong inverted correlations were observed between T-cell activation (HLA-DR/CD38), senescence (CD57) and exhaustion (TIGIT, PD-1) levels with the CD4/CD8 ratio among YWVH. HLA-DR, CD69, NKG2D and NKG2A expression levels on NK cells also correlated with the CD4/CD8 ratio. Age at ART initiation was directly associated with higher frequency of CD16high NK-cell subsets, exhaustion T-cell levels (CD57, TIM3) and NK cells activation levels. CONCLUSIONS: Immunological changes associated with vertically acquired HIV, characterized by increased activation and exhaustion levels in innate and adaptive immune components, are only partially restored by ART. The CD4/CD8 ratio can be a useful marker of disease progression for routine clinical practice.

Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure.

OBJECTIVES: We analysed the prevalence of M184V/I and/or K65R/E/N mutations archived in proviral DNA (pDNA) in youths with perinatal HIV, virological control and who previously carried these resistance mutations in historic plasma samples. METHODS: We included vertically HIV-infected youths/young adults aged ≥10 years in the Madrid Cohort of HIV-1 Infected Children and Adolescents, exposed to lamivudine and/or emtricitabine, with M184V/I and/or K65R/E/N in historic plasma samples, on antiretroviral therapy (ART), virologically suppressed (HIV-1 RNA <50 copies/mL), and with available PBMCs in the Spanish HIV BioBank. Genomic DNA was extracted from PBMCs and HIV-1 RT gene was amplified and sequenced for resistance testing by Stanford HIV Resistance tool. RESULTS: Among the 225 patients under follow-up in the study cohort, 13 (5.8%) met selection criteria, and RT sequences were recovered in 12 (92.3%) of them. All but one were Spaniards, carrying subtype B, with a median age at PBMCs sampling of 21.3 years (IQR: 15.6-23.1) with 4 years (IQR 2.1-6.5) of suppressed viral load (VL). Nine (75%) youths did not present M184V/I in pDNA after at least 1 year of viral suppression. In December 2019, the remaining three subjects carrying M184V/I in pDNA maintained suppressed viraemia, and two still used emtricitabine in ART. CONCLUSIONS: The prevalence of resistance mutations to lamivudine and emtricitabine in pDNA in a cohort of youths perinatally infected with HIV who remain with undetectable VL, previously lamivudine and/or emtricitabine experienced, was infrequent. Our results indicate that ART including lamivudine or emtricitabine may also be safe and successful in youths with perinatal HIV with previous experience of and resistances to these drugs detected in plasma.

Response to direct-acting antivirals for hepatitis C treatment in vertically HIV/HCV co-infected patients.

Direct-acting antivirals (DAAs) for HCV treatment have improved tolerance and efficacy among adults, but experience in vertical transmission is scarce. In our vertically HIV/HCV co-infected youth cohort of 58 patients, DAA achieved excellent rates of cure among naïve and pretreated individuals. Treating vertically infected seems important as 29.6% displayed advanced fibrosis at treatment initiation.

Infección por Helicobacter pylori en la población VIH+: una comorbilidad en la que pensar / Helicobacter pylori infection in the HIV + population: a comorbidity to think about

INTRODUCCIÓN: Las alteraciones gastrointestinales, son frecuentes en VIH+. Helicobacter pylori puede ser una causa infradiagnosticada. MATERIAL Y MÉTODOS: Se realizó una búsqueda retrospectiva de pacientes VIH+ con infección por H. pylori entre enero de 1998 hasta diciembre de 2017. RESULTADOS: Se incluyeron 132 pacientes. La dispepsia fue la sintomatología más frecuente. Un 88,5% tuvo gastritis crónica atrófica. Se consiguió la erradicación en 102 (77,3%). La curación fue más frecuente con pauta cuádruple (p = 0,004) y en los más jóvenes (p = 0,041). CONCLUSIÓN: La infección por H. pylori podría ser responsable de manifestaciones digestivas inespecíficas en los pacientes VIH+

INTRODUCTION: Gastrointestinal disorders are frequent in HIV+. Helicobacter pylori may be an underdiagnosed cause. MATERIAL AND METHODS: Patients with HIV and H. pylori were described since January 1998 up to December 2017. RESULTS: A total de 132 patients were included. The most frequent symptom was dyspepsia. 88.5% had chronic atrophic gastritis. Eradication was achieved in 102 (77.3%). Healing was more frequent with quadruple regimen (p = 0.004) and in the youngest (p = 0.041). CONCLUSION: H. pylori infection could be responsible for nonspecific digestive manifestations in HIV + patients

Effectiveness and safety of antiretroviral treatment in pre- and postmenopausal women living with HIV in a multicentre cohort.

BACKGROUND: To compare effectiveness and safety of initial antiretroviral therapy (ART) among premenopausal and postmenopausal women living with HIV aged 45-60 years from the cohort of the Spanish HIV/AIDS Research Network (CoRIS) who initiated ART between 2004 and 2015. METHODS: Multivariable regression models were used to compare post- versus premenopausal women regarding viral suppression (≤50 copies/ml), change in CD4+ T-cell count and time to treatment change (TC) at 48 and 96 weeks after ART initiation. RESULTS: Among 230 women, 154 (67%) were premenopausal at ART initiation. The most frequent initial regimen was tenofovir disoproxil fumarate/emtricitabine/efavirenz prescribed in 49 (32%) premenopausal and 22 (29%) postmenopausal women. The proportion of TC was 35.7% and 30.3% at 48 weeks and 51.3% and 47.4% at 96 weeks, for pre- and postmenopausal women, respectively. There were no significant differences in CD4+ T-cell count changes from ART initiation, viral load suppression, time to TC or reason for TC between both groups. The main reason for TC was occurrence of an adverse event, followed by simplification, in both groups. CONCLUSIONS: ART effectiveness and safety did not differ significantly between pre- and postmenopausal women.

Impact of HIV on the health-related quality of life in youth with perinatally acquired HIV.

BACKGROUND: Studies investigating health-related quality of life (HRQoL) in youth with perinatally acquired HIV (PHIV+) are scarce. This study aimed to compare HRQoL of PHIV+ to sociodemographic-matched youth not living with HIV (HIV-), Spanish general youth population, and to explore associations between sociodemographic variables, drug consumption, and HRQoL. METHODS: PHIV+ youth were randomly selected from CoRISpe database (Cohort of the Spanish Pediatric HIV Network). HRQoL was evaluated by SF-12v2. RESULTS: Thirty-nine PHIV+ youth (mean age: 23.36 years, SD = 3.83) and thirty-nine HIV- youth (mean age: 22.97 years, SD = 3.80) participated in this study. PHIV+ obtained lower scores in SF-12 physical health subscale (PCS) than HIV- (P = 0.001) and Spanish general youth population (P = 0.006). PHIV+ had lower scores on the mental health subscale (MCS) than the Spanish general youth population (P < 0.001). PHIV+ who were at school obtained better scores than those were not at school. PHIV+ youth who had used cocaine and cannabis had lower scores in MCS (P = 0.002). CONCLUSIONS: There is a need for HRQoL management in the associated medical follow-up.

Immediate Versus Deferred Switching From a Boosted Protease Inhibitor-based Regimen to a Dolutegravir-based Regimen in Virologically Suppressed Patients With High Cardiovascular Risk or Age ≥50 Years: Final 96-Week Results of the NEAT022 Study.

Background: Both immediate and deferred switching from a ritonavir-boosted protease inhibitor (PI/r)-based regimen to a dolutegravir (DTG)-based regimen may improve lipid profile. Methods: European Network for AIDS Treatment 022 Study (NEAT022) is a European, open-label, randomized trial. Human immunodeficiency virus (HIV)-infected adults aged ≥50 years or with a Framingham score ≥10% were eligible if HIV RNA was <50 copies/mL. Patients were randomized to switch from PI/r to DTG immediately (DTG-I) or to deferred switch at week 48 (DTG-D). Week 96 endpoints were proportion of patients with HIV RNA <50 copies/mL, percentage change of lipid fractions, and adverse events (AEs). Results: Four hundred fifteen patients were randomized: 205 to DTG-I and 210 DTG-D. The primary objective of noninferiority at week 48 was met. At week 96, treatment success rate was 92.2% in the DTG-I arm and 87% in the DTG-D arm (difference, 5.2% [95% confidence interval, -.6% to 11%]). There were 5 virological failures in the DTG-I arm and 5 (1 while on PI/r and 4 after switching to DTG) in the DTG-D arm without selection of resistance mutations. There was no significant difference in terms of grade 3 or 4 AEs or treatment-modifying AEs. Total cholesterol and other lipid fractions (except high-density lipoprotein) significantly (P < .001) improved both after immediate and deferred switching to DTG overall and regardless of baseline PI/r strata. Conclusions: Both immediate and deferred switching from a PI/r to a DTG regimen in virologically suppressed HIV-infected patients ≥50 years old or with a Framingham score ≥10% was highly efficacious and well tolerated, and improved the lipid profile. Clinical Trials Registration: NCT02098837 and EudraCT: 2013-003704-39.

Sexualized Drug Use (Chemsex) Is Associated with High-Risk Sexual Behaviors and Sexually Transmitted Infections in HIV-Positive Men Who Have Sex with Men: Data from the U-SEX GESIDA 9416 Study.

The magnitude of sexualized drug use (SDU), also known as chemsex, and its association with sexually transmitted infections (STI) has not been systematically explored in HIV-positive patients. This study aimed to calculate the prevalence of SDU and associated factors in a sample of HIV-positive men who have sex with men (MSM) in Spain. We calculated the frequency of SDU in a sample of HIV-positive MSM who responded to an anonymous online survey on sexual behavior and recreational drug use. We also analyzed differences between those who responded and those who did not (data taken from the physician's registry). The association between SDU, sexual risk behaviors, and STI was evaluated using a univariate and a multivariate analysis. Data were collected and managed using Research Electronic Data Capture (REDCap). The survey was completed by 742 HIV-positive MSM, of whom 60% had had unprotected anal intercourse (UAI), 62% had been diagnosed with a STI, and 216 (29.1%) reported recent SDU (slamsex in 16% of cases). In the multivariate analysis, patients who engaged in SDU were more likely to have had high-risk sexual behaviors and a diagnosis of STI than participants who did not engage in SDU. A diagnosis of hepatitis C was independently associated with slamsex (5.2 [95% confidence interval (CI), 2.06-13.13]; p < 0.001), chemsex (2.51 [95% CI, 1.28-4.91]; p = 0.007), and UAI (1.82 [95% CI, 0.90-3.70]; p = 0.094). The magnitude of SDU or chemsex in our sample is relatively high. We found a clear association between SDU, high-risk sexual behaviors, and STI including hepatitis C.

Abacavir/lamivudina + atazanavir no potenciado en la práctica clínica diaria: doce años de experiencia / Abacavir/lamivudine + unboosted atazanavir in routine clinical practice: Twelve years experience

Objetivo: Describir la eficacia en práctica clínica de abacavir, lamivudina y atazanavir sin potenciar (ABC/3TC+ATV) en pacientes pretratados. Pacientes y métodos: Se realizó un estudio observacional retrospectivo para describir las características clínicas y la evolución de los pacientes que, por prescripción facultativa, habían recibido tratamiento con ABC/3TC+ATV desde noviembre de 2004 hasta el 15 de junio de 2015. Resultados: Se incluyeron 236 pacientes. La mediana de edad (IQR) fue de 45años (42-50) y el 69% eran varones. Los principales motivos para su indicación fueron toxicidad en 130 pacientes (56%), simplificación en 60 (20%) y fracaso virológico (FV) en 29 (14%). El tratamiento previo contenía un inhibidor de la proteasa (IP) en 115 pacientes (48,7%), 3 inhibidores de la transcriptasa inversa análogos de nucleósido (ITIAN) en 56 (28%) y 2ITIAN y un inhibidor de la transcriptasa inversa no análogo de nucleósido (ITINAN) en 19 (8,1%). Tras una mediana de 2,2años (IQR0,8-5,3), 66 (28%) pacientes continuaban con la misma pauta, se retiró en 170 (72%), en 30 de ellos por FV (12,7%) y en 22 (9,3%) por pérdidas de seguimiento. Conclusión: En pacientes seleccionados, ABC/3TC+ATV es una alternativa de simplificación eficaz y bien tolerada, usada principalmente para minimizar la toxicidad (AU)

Objective: To describe the experience using the combination abacavir, lamivudine plus non-boosted atazanavir (ABC/3TC+ATV) in a group of pretreated patients. Patients and methods: We performed a retrospective observational study to describe baseline characteristics and the evolution of patients who had received or were treating with ABC/3TC+ATV, from November 2004 and June 15th 2015, in the clinical setting. Results: Overall, 236 patients were included in the study. Median age (IQR) was 45 (42-50) years and 69% were male. The main reasons for using this combination were previous toxicity in 130 patients (56%), simplification in 60 (20%) and virologic failure in 29 (14%). Previous treatment was based in boosted protease inhibitor in 115 patients (48.7%), 3 analogs in 56 (28%) and non-analogous based in 19 (8.1%). Median treatment length was 2.2 years (IQR0.8-5.3). A total of 66 (28%) patients continue receiving ABC/3TC+ATV (median time 5.7, IQR2.2-8.3), treatment was changed in 170 patients (72%) (median time 1.6 years, IQR0.7-3.6), and 22 (9.3%) patients were lost. Virological failure was assessed in 30 patients. Conclusion: In selected patients, ABC/3TC+ATV is a durable and attractive therapeutic alternative (AU)

Abacavir/lamivudine + unboosted atazanavir in routine clinical practice: Twelve years experience. / Abacavir/lamivudina + atazanavir no potenciado en la práctica clínica diaria: doce años de experiencia.

OBJECTIVE: To describe the experience using the combination abacavir, lamivudine plus non-boosted atazanavir (ABC/3TC+ATV) in a group of pretreated patients. PATIENTS AND METHODS: We performed a retrospective observational study to describe baseline characteristics and the evolution of patients who had received or were treating with ABC/3TC+ATV, from November 2004 and June 15th 2015, in the clinical setting. RESULTS: Overall, 236 patients were included in the study. Median age (IQR) was 45 (42-50) years and 69% were male. The main reasons for using this combination were previous toxicity in 130 patients (56%), simplification in 60 (20%) and virologic failure in 29 (14%). Previous treatment was based in boosted protease inhibitor in 115 patients (48.7%), 3 analogs in 56 (28%) and non-analogous based in 19 (8.1%). Median treatment length was 2.2 years (IQR0.8-5.3). A total of 66 (28%) patients continue receiving ABC/3TC+ATV (median time 5.7, IQR2.2-8.3), treatment was changed in 170 patients (72%) (median time 1.6 years, IQR0.7-3.6), and 22 (9.3%) patients were lost. Virological failure was assessed in 30 patients. CONCLUSION: In selected patients, ABC/3TC+ATV is a durable and attractive therapeutic alternative.

Changes in Cardiovascular Disease Risk Factors With Immediate Versus Deferred Antiretroviral Therapy Initiation Among HIV-Positive Participants in the START (Strategic Timing of Antiretroviral Treatment) Trial.

INTRODUCTION: HIV infection and certain antiretroviral therapy (ART) medications increase atherosclerotic cardiovascular disease risk, mediated, in part, through traditional cardiovascular disease risk factors. METHODS AND RESULTS: We studied cardiovascular disease risk factor changes in the START (Strategic Timing of Antiretroviral Treatment) trial, a randomized study of immediate versus deferred ART initiation among HIV-positive persons with CD4+ cell counts >500 cells/mm3. Mean change from baseline in risk factors and the incidence of comorbid conditions were compared between groups. The characteristics among 4685 HIV-positive START trial participants include a median age of 36 years, a CD4 cell count of 651 cells/mm3, an HIV viral load of 12 759 copies/mL, a current smoking status of 32%, a median systolic/diastolic blood pressure of 120/76 mm Hg, and median levels of total cholesterol of 168 mg/dL, low-density lipoprotein cholesterol of 102 mg/dL, and high-density lipoprotein cholesterol of 41 mg/dL. Mean follow-up was 3.0 years. The immediate and deferred ART groups spent 94% and 28% of follow-up time taking ART, respectively. Compared with patients in the deferral group, patients in the immediate ART group had increased total cholesterol and low-density lipoprotein cholesterol and higher use of lipid-lowering therapy (1.2%; 95% CI, 0.1-2.2). Concurrent increases in high-density lipoprotein cholesterol with immediate ART resulted in a 0.1 lower total cholesterol to high-density lipoprotein cholesterol ratio (95% CI, 0.1-0.2). Immediate ART resulted in 2.3% less BP-lowering therapy use (95% CI, 0.9-3.6), but there were no differences in new-onset hypertension or diabetes mellitus. CONCLUSIONS: Among HIV-positive persons with preserved immunity, immediate ART led to increases in total cholesterol and low-density lipoprotein cholesterol but also concurrent increases in high-density lipoprotein cholesterol and decreased use of blood pressure medications. These opposing effects suggest that, in the short term, the net effect of early ART on traditional cardiovascular disease risk factors may be clinically insignificant." CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00867048.

Impact of late presentation of HIV infection on short-, mid- and long-term mortality and causes of death in a multicenter national cohort: 2004-2013.

OBJECTIVES: To analyze the impact of late presentation (LP) on overall mortality and causes of death and describe LP trends and risk factors (2004-2013). METHODS: Cox models and logistic regression were used to analyze data from a nation-wide cohort in Spain. LP is defined as being diagnosed when CD4 < 350 cells/ml or AIDS. RESULTS: Of 7165 new HIV diagnoses, 46.9% (CI95%:45.7-48.0) were LP, 240 patients died. First-year mortality was the highest (aHRLP.vs.nLP = 10.3[CI95%:5.5-19.3]); between 1 and 4 years post-diagnosis, aHRLP.vs.nLP = 1.9(1.2-3.0); and >4 years, aHRLP.vs.nLP = 1.5(0.7-3.1). First-year's main cause of death was HIV/AIDS (73%); and malignancies among those surviving >4 years (32%). HIV/AIDS-related deaths were more likely in LP (59.2% vs. 25.0%; p < 0.001). LP declined from 55.9% (2004-05) to 39.4% (2012-13), and reduced in 46.1% in men who have sex with men (MSM) and 37.6% in heterosexual men, but increased in 22.6% in heterosexual women. Factors associated with LP: sex (ORMEN.vs.WOMEN = 1.4[1.2-1.7]); age (OR31-40.vs.<30 = 1.6[1.4-1.8], OR41-50.vs.<30 = 2.2[1.8-2.6], OR>50.vs.<30 = 3.6[2.9-4.4]); behavior (ORInjectedDrugUse.vs.MSM = 2.8[2.0-3.8]; ORHeterosexual.vs.MSM = 2.2[1.7-3.0]); education (ORPrimaryEducation.vs.University = 1.5[1.1-2.0], ORLowerSecondary.vs.University = 1.3[1.1-1.5]); and geographical origin (ORSub-Saharan.vs.Spain = 1.6[1.3-2.0], ORLatin-American.vs.Spain = 1.4[1.2-1.8]). CONCLUSIONS: LP is associated with higher mortality, especially short-term- and HIV/AIDS-related mortality. Mid-term-, but not long-term mortality, remained also higher in LP than nLP. LP decreased in MSM and heterosexual men, not in heterosexual women. The groups most affected by LP are low educated, non-Spanish and heterosexual women.

Cardiovascular risk factors and lifetime risk estimation in HIV-infected patients under antiretroviral treatment in Spain.

BACKGROUND AND OBJECTIVES: Cardiovascular disease is a major concern in HIV-infected patients. Lifetime risk estimations use the risk of developing it over the course of remaining lifetime, and are useful in communicating this risk to young patients. We aim to describe the prevalence of cardiovascular risk factors among a representative sample of HIV-infected subjects under antiretroviral therapy in Spain, and to estimate their lifetime risk of cardiovascular disease. METHODS: Cross-sectional survey about cardiovascular risk factors in 10 HIV units across Spain. Lifetime risk assessed according to Barry was classified in two major categories: low and high lifetime risk. RESULTS: We included 895 subjects, 72% men, median age 45.7 years; median CD4 lymphocyte count 598 cells/µl, median time since HIV diagnosis 11 years, median time on antiretroviral treatment 6.3 years, 87% had undetectable HIV viral load. Tobacco smoking was the most frequent risk factor (54%), followed by dyslipidemia (48.6%) and hypertension (38.6%). Estimated 10-year coronary risk (Framingham/Regicor Risk Score) risk was low ( < 5%) in 78% of the patients, and intermediate (5-10%) in 20%. Lifetime risk estimation showed a high risk profile for 71.4% of the population studied, which was associated with increasing age, prolonged antiretroviral therapy and patient's place of origin. CONCLUSIONS: Modifiable cardiovascular risk factors in this population are very common. There are significant disparities between the low 10-year risk estimated with the Framingham/Regicor score and the higher lifetime risk in HIV patients on antiretroviral therapy. A more aggressive management of modifiable cardiovascular risk factors in these patients seems advisable.

Comparison of oxidative stress markers in HIV-infected patients on efavirenz or atazanavir/ritonavir-based therapy.

INTRODUCTION: Chronic low-grade inflammation and immune activation may persist in HIV patients despite effective antiretroviral therapy (ART). These abnormalities are associated with increased oxidative stress (OS). Bilirubin (BR) may have a beneficial role in counteracting OS. Atazanavir (ATV) inhibits UGT1A1, thus increasing unconjugated BR levels, a distinctive feature of this drug. We compared changes in OS markers in HIV patients on ATV/r versus efavirenz (EFV)-based first-line therapies. MATERIALS AND METHODS: Cohort of the Spanish Research Network (CoRIS) is a multicentre, open, prospective cohort of HIV-infected patients naïve to ART at entry and linked to a biobank. We identified hepatitis C virus/hepatitis B virus (HCV/HBV) negative patients who started first-line ART with either ATV/r or EFV, had a baseline biobank sample and a follow-up sample after at least nine months of ART while maintaining initial regimen and being virologically suppressed. Lipoprotein-associated Phospholipase A2 (Lp-PLA2), Myeloperoxidase (MPO) and Oxidized LDL (OxLDL) were measured in paired samples. Marker values at one year were interpolated from available data. Multiple imputations using chained equations were used to deal with missing values. Change in the OS markers was modelled using multiple linear regressions adjusting for baseline marker values and baseline confounders. Correlations between continuous variables were explored using Pearson's correlation tests. RESULTS: 145 patients (97 EFV; 48 ATV/r) were studied. Mean (SD) baseline values for OS markers in EFV and ATV/r groups were: Lp-PLA2 [142.2 (72.8) and 150.1 (92.8) ng/mL], MPO [74.3 (48.2) and 93.9 (64.3) µg/L] and OxLDL [76.3 (52.3) and 82.2 (54.4) µg/L]. After adjustment for baseline variables patients on ATV/r had a significant decrease in Lp-PLA2 (estimated difference -16.3 [CI 95%: -31.4, -1.25; p=0.03]) and a significantly lower increase in OxLDL (estimated difference -21.8 [-38.0, -5.6; p<0.01] relative to those on EFV, whereas no differences in MPO were found. Adjusted changes in BR were significantly higher for the ATV/r group (estimated difference 1.33 [1.03, 1.52; p<0.01]). Changes in BR and changes in OS markers were significantly correlated. CONCLUSIONS: In virologically suppressed patients on stable ART, OS was lower in ATV/r-based regimens compared to EFV. We hypothesize these changes could be in part attributable to increased BR plasma levels.