Publications by authors named "Esteban Martinez"

278 Publications

Daily tenofovir disoproxil fumarate/emtricitabine and hydroxychloroquine for pre-exposure prophylaxis of COVID-19: a double-blind placebo controlled randomized trial in healthcare workers.

Clin Microbiol Infect 2022 Aug 5. Epub 2022 Aug 5.

Ministry of Health, Madrid, Spain.

Objective: To assess the effect of hydroxychloroquine (HCQ) and Tenofovir disoproxil fumarate/Emtricitabine (TDF/FTC) as pre-exposure prophylaxis on COVID-19 risk.

Methods: EPICOS is a double-blind, placebo-controlled randomized trial conducted in Spain, Bolivia, and Venezuela. Healthcare workers with negative SARS-CoV-2 IgM/IgG test were randomly assigned to: daily TDF/FTC plus HCQ for 12 weeks, TDF/FTC plus HCQ placebo, HCQ plus TDF/FTC placebo and TDF/FTC placebo plus HCQ placebo. Randomization was performed in groups of four. Primary outcome was laboratory-confirmed, symptomatic COVID-19. We also studied any (symptomatic or asymptomatic) COVID-19. We compared group-specific 14-week risks via differences and ratios with 95% confidence intervals (CI).

Results: Of 1002 individuals screened, 926 (92.4%) were eligible and there were 14 cases of symptomatic COVID-19: 220 were assigned to the TDF/FTC plus HCQ group (3 cases), 231 to the TDF/FTC placebo plus HCQ group (3 cases), 233 to the TDF/FTC plus HCQ placebo group (3 cases), and 223 to the double placebo group (5 cases). Compared with the double placebo group, 14-week risk ratios (95% CI) of symptomatic COVID-19 were 0.39 (0.00, 1.98) for TDF+HCQ, 0.34 (0.00, 2.06) for TDF, and 0.49 (0.00, 2.29) for HCQ. Corresponding risk ratios of any COVID-19 were 0.51 (0.21, 1.00) for TDF+HCQ, 0.81 (0.44, 1.49) for TDF, and 0.73 (0.41, 1.38) for HCQ. Adverse events were generally mild.

Conclusion: The target sample size was not met. Our findings are compatible with both benefit and harm of pre-exposure prophylaxis with TDF/FTC and HCQ, alone or in combination, compared with placebo.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmi.2022.07.006DOI Listing
August 2022

Lipoprotein Profile in Immunological Non-Responders PLHIV after Antiretroviral Therapy Initiation.

Int J Mol Sci 2022 Jul 22;23(15). Epub 2022 Jul 22.

Infection and Immunity Research Group (INIM), Universitat Rovira i Virgili, 43003 Tarragona, Spain.

Nuclear magnetic resonance (NMR)-based advanced lipoprotein tests have demonstrated that LDL and HDL particle numbers (LDL-P and HDL-P) are more powerful cardiovascular (CV) risk biomarkers than conventional cholesterol markers. Of interest, in people living with HIV (PLHIV), predictors of preclinical atherosclerosis and vascular dysfunction may be associated with impaired immune function. We previously stated that immunological non-responders (INR) were at higher CV risk than immunological responders (IR) before starting antiretroviral therapy (ART). Using Liposcale tests, we characterized the lipoprotein profile from the same cohort of PLHIV at month 12 and month 36 after starting ART, intending to explore what happened with these indicators of CV risk during viral suppression. ART initiation dissipates the differences in lipoprotein-based CV risk markers between INR and IR, and only an increase in the number of HDL-P was found in INR + IR when compared to controls ( = 0.047). Interestingly, CD4 T-cell counts negatively correlated with medium HDL-P concentrations at month 12 in all individuals (ρ = -0.335, = 0.003). Longitudinal analyses showed an important increase in LDL-P and HDL-P at month 36 when compared to baseline values in both IR and INR. A proper balance between a proatherogenic and atherogenic environment may be related to the reconstitution of CD4 T-cell count in PLHIV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms23158071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330003PMC
July 2022

PrEP program experience in a hospital HIV unit. Description of baseline user profile and identification of opportunities for improvement.

Enferm Infecc Microbiol Clin (Engl Ed) 2022 Jul 6. Epub 2022 Jul 6.

Unidad de VIH, Hospital Clínic e IDIBAPS, Universidad de Barcelona, Barcelona, Spain.

Introduction: Pre-Exposure Prophylaxis (PrEP) is a biomedical intervention to prevent HIV infection in seronegative people at high risk of becoming infected. This strategy was endorsed in October 2019 by the Spanish Ministry of Health.

Objective: To present the PrEP initial experience in the HIV Unit of the Hospital Clínic of Barcelona, paying special attention to the analysis of the vulnerability factors in the cohort.

Materials And Methods: Retrospective, descriptive study. The epidemiological, sociodemographic, and clinical characteristics of the users included in the program during the first year are analyzed, paying particular attention to Infections, risky practices, and substance use.

Results: 190 individuals were included, 177 men and 12 trans women with a mean age of 35 years (8 SD). 70% had higher education, and half had Spanish nationality. An average of 10 couples per trimester and 60% reported unprotected anal sex. 31% had at least one positive PCR for STIs, with N. gonorrhoeae being the most prevalent microorganism (51%) and the rectal sample the most affected (21%). 63% reported chemsex use, 19% polydrug use, and 8% "slamming". Half expressed concern about consumption and/or sexual practices and 25% the need for help.

Conclusions: The PrEP user profile attended in our Hospital Unit justifies the creation of multidisciplinary teams that allow us to provide holistic attention to the sexual life of these people.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eimce.2022.06.009DOI Listing
July 2022

Chemsex Practices in PrEP: Beyond Addiction and Risk Toward a Healthy Sex Life-Baseline Experiences from a Hospital-Based PrEP Program in Barcelona, Spain.

AIDS Behav 2022 Jun 22. Epub 2022 Jun 22.

HIV Unit, Infectious Diseases Service, Hospital Clinic, IDIBAPS, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain.

Pre-exposure prophylaxis (PrEP) is a biomedical intervention that has demonstrated efficacy in HIV prevention in individuals at high-risk, among them chemsex users. Out of 190 PrEP users followed at Hospital Clinic of Barcelona until October 2020, 89% reported drug use, and 63% disclosed that they had engaged in chemsex practices, initiated in 64% of cases within the past year. Twenty-one percent used 3 or more drugs simultaneously, being GHB/GBL, nitrites, sildenafil, and methamphetamine the most prevalent combination. Eight percent reported slamming. Forty-one percent described having had negative experiences and 8% did not remember the last time they had sober sex. Methamphetamine, mephedrone, GHB/GBL, and having had open relationships, group sex, double penetration, and fisting were significantly more prevalent. Forty-nine percent admitted being worried about chemsex use, and 18% said they needed help. A comprehensive, interdisciplinary approach is mandatory to enable the attainment of a healthy approach to one's sex life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10461-022-03730-5DOI Listing
June 2022

Dolutegravir Monotherapy as Maintenance Strategy: A Meta-Analysis of Individual Participant Data From Randomized Controlled Trials.

Open Forum Infect Dis 2022 Jun 4;9(6):ofac107. Epub 2022 Mar 4.

INSERM U1311 DYNAMICURE, Université Caen Normandie, Caen, France.

Background: Dolutegravir monotherapy (DTG-m) results in virological failure (VF) in some people with human immunodeficiency virus (PWH). We sought to identify the independent factors associated with the risk of VF and to explore the effect size heterogeneity between subgroups of PWH enrolled in DTG-m trials.

Methods: We searched for randomized clinical trials (RCTs) evaluating DTG-m versus combined antiretroviral therapy (cART) among PWH virologically controlled for at least 6 months on cART. We performed an individual participant data meta-analysis of VF risk factors and quantified their explained heterogeneity in random-effect models. Definition of VF was a confirmed plasma human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) >50 copies/mL by week 48.

Results: Among 416 PWH from 4 RCTs, DTG-m significantly increased the risk of VF (16 of 227 [7%] versus 0 of 189 for cART; risk difference 7%; 95% confidence interval [CI], 1%-2%;  = .02; I = 51%). Among 272 participants exposed to DTG-m, VF were more likely in participants with the following: first cART initiated ≥90 days from HIV acute infection (adjusted hazard ratio [aHR], 5.16; 95% 95% CI, 1.60-16.65), CD4 T cells nadir <350/mm (aHR, 12.10; 95% CI, 3.92-37.40), HIV RNA signal at baseline (aHR, 4.84; 95% CI, 3.68-6.38), and HIV-deoxyribonucleic acid (DNA) copy number at baseline ≥2.7 log/10 peripheral blood mononuclear cells (aHR, 3.81; 95% CI, 1.99-7.30). Among these independent risk factors, the largest effect size heterogeneity was found between HIV DNA subgroups (I = 80.2%; for interaction = .02).

Conclusions: Our study supports the importance of a large viral reservoir size for explaining DTG-m simplification strategy failure. Further studies are needed to link size and genetic diversity of the HIV-1 reservoir.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ofid/ofac107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125303PMC
June 2022

Simplification from tenofovir disoproxil fumarate plus lamivudine or emtricitabine plus ritonavir-boosted protease inhibitor to ritonavir-boosted atazanavir plus lamivudine in virologically suppressed HIV-infected adults with osteopenia: a pilot study.

J Antimicrob Chemother 2022 06;77(7):1974-1979

Infectious Diseases Department Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.

Background: Tenofovir disoproxil fumarate, particularly when given with a ritonavir-boosted PI, reduces bone mineral density (BMD) and increases bone turnover markers (BTMs). Ritonavir-boosted atazanavir plus lamivudine is a feasible simplified option. We evaluated whether switching from a triple ritonavir-boosted PI plus tenofovir disoproxil fumarate to a two-drug regimen of lamivudine plus ritonavir-boosted atazanavir would improve BMD.

Methods: Single-arm pilot study. Virologically suppressed patients on tenofovir disoproxil fumarate plus lamivudine or emtricitabine plus ritonavir-boosted PI with low BMD, without previous resistance mutations and/or virological failure to study drugs were switched to 100/300 mg of ritonavir-boosted atazanavir plus 300 mg of lamivudine once daily. The primary endpoint was BMD change by DXA at Week 48.

Results: There were 31 patients, 4 (13%) female, and median age was 40 years. Seven participants (22.5%) had osteoporosis. At 48 weeks, mean (SD) changes in spine and hip BMD were +0.01 (0.03) (P = 0.0239) and +0.013 (0.03) g/cm2 (P = 0.0046), respectively. Mean (SD) T-score changes were +0.1 (0.23) (P = 0.0089) and +0.25 (0.76) (P = 0.0197), respectively. N-telopeptide and urine tenofovir disoproxil fumarate toxicity markers showed significant improvements. One participant withdrew from the study and two were lost to follow-up. There were no virological failures, or serious or grade 3-4 adverse events.

Conclusions: Switching from a tenofovir disoproxil fumarate plus ritonavir-boosted PI triple therapy to a lamivudine plus ritonavir-boosted atazanavir two-drug regimen in virologically suppressed HIV-infected adults with low BMD was safe, increased low BMD and reduced plasma markers of bone turnover and urine markers of tenofovir disoproxil fumarate toxicity over 48 weeks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkac137DOI Listing
June 2022

The ERK2-DBP domain opposes pathogenesis of a mouse JAK2V617F-driven myeloproliferative neoplasm.

Blood 2022 Jul;140(4):359-373

Blood Cell Development and Function Program.

Although Ras/mitogen-activated protein kinase (MAPK) signaling is activated in most human cancers, attempts to target this pathway using kinase-active site inhibitors have not typically led to durable clinical benefit. To address this shortcoming, we sought to test the feasibility of an alternative targeting strategy, focused on the ERK2 substrate binding domains, D and DEF binding pocket (DBP). Disabling the ERK2-DBP domain in mice caused baseline erythrocytosis. Consequently, we investigated the role of the ERK2-D and -DBP domains in disease, using a JAK2-dependent model of polycythemia vera (PV). Of note, inactivation of the ERK2-DBP domain promoted the progression of disease from PV to myelofibrosis, suggesting that the ERK2-DBP domain normally opposes progression. ERK2-DBP inactivation also prevented oncogenic JAK2 kinase (JAK2V617F) from promoting oncogene-induced senescence in vitro. The ERK2-DBP mutation attenuated JAK2-mediated oncogene-induced senescence by preventing the physical interaction of ERK2 with the transcription factor Egr1. Because inactivation of the ERK2-DBP created a functional ERK2 kinase limited to binding substrates through its D domain, these data suggested that the D domain substrates were responsible for promoting oncogene-induced progenitor growth and tumor progression and that pharmacologic targeting of the ERK2-D domain may attenuate cancer cell growth. Indeed, pharmacologic agents targeting the ERK2-D domain were effective in attenuating the growth of JAK2-dependent myeloproliferative neoplasm cell lines. Taken together, these data indicate that the ERK-D and -DBP domains can play distinct roles in the progression of neoplasms and that the D domain has the potential to be a potent therapeutic target in Ras/MAPK-dependent cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood.2021013068DOI Listing
July 2022

Atherogenicity of low-density lipoproteins after switching from a protease inhibitor to dolutegravir: a substudy of the NEAT022 study.

J Antimicrob Chemother 2022 06;77(7):1980-1988

Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute, Hospitalet de Llobregat, Spain.

Background: The aim of this study was to investigate whether switching from a ritonavir-boosted PI-based regimen to a dolutegravir-based regimen improved the atherogenic properties of LDL particles in patients with HIV.

Methods: This was a substudy of the NEAT022 study (ClinicalTrials.gov NCT02098837). Adults with HIV with a Framingham score >10% or aged >50 years and being treated with a stable boosted PI-based regimen were randomized to either switch to dolutegravir or continue with boosted PI. At baseline and Week 48, we assessed atherogenic LDL properties: LDL particle size and phenotype (A, intermediate, B), oxidized LDL (ox-LDL) and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity.

Results: Eighty-six participants (dolutegravir 44; PI 42) were included. Participants had a median (IQR) age of 54 (51-57) years and 79.1% were male. In the dolutegravir arm, after 48 weeks, we observed: (1) an increase in LDL size [median 1.65 Å (IQR -0.60 to 4.20); P = 0.007], correlated with the decrease in triglyceride concentration [Spearman correlation = -0.352 (P = 0.001)], with a corresponding decrease of subjects with atherogenic LDL phenotype B (36.4% to 20.5%; P = 0.039); (2) a decrease in Lp-PLA2 activity [median 1.39 μmol/min/mL (IQR -2.3 to 0.54); P = 0.002]; and (3) a decrease in ox-LDL [median 14 U/L (IQR -102 to 13); P = 0.006]. In the PI arm, none of these favourable lipid modifications was observed.

Conclusions: Forty-eight weeks after switching from a PI-based to a dolutegravir-based regimen, patients with Framingham score >10% or aged >50 years showed improvement of several atherogenic lipid features, including LDL particle phenotype, ox-LDL and Lp-PLA2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkac117DOI Listing
June 2022

Perception of HIV physicians in Spain towards diagnosis and management of neuropsychiatric comorbidities in people with HIV.

HIV Med 2022 Mar 16. Epub 2022 Mar 16.

Department of Infectious Diseases, Hospital Clínic de Barcelona, Barcelona, Spain.

Objectives: Despite the importance of neuropsychiatric comorbidities (NPCs) in people with HIV, the degree of physician compliance with recommendations for diagnosis and management is unknown. This study assessed the perceptions, knowledge, skills, and attitudes of physicians regarding the diagnosis and management of NPCs in people with HIV in hospital settings in Spain.

Methods: This was a cross-sectional study including non-psychiatrist HIV specialist physicians responsible for antiretroviral therapy (ART) prescription and clinical care of ≥50 people with HIV/month, who completed an online survey of 34 questions.

Results: The 115 physicians who completed the survey (totally) agreed that assessing mental health was relevant (97.4%) and that NPCs were underdiagnosed (76.6%) and were very/fairly sensitized (67.8%). However, they reported receiving little/no training on the detection of NPCs (64.3%). Physicians considered that patients underreported NPCs (53.9%) and that alcohol (94.8%), recreational substances (97.4%), and tobacco consumption (95.6%) were (very) relevant. Physicians agreed that NPCs were difficult to identify (52.2%) and that few tools were available (53.0%) and failed to use questionnaires (79.1%) and follow guidelines (77.4%) for the detection of NPCs. The main reasons precluding appropriate diagnosis and evaluation were lack of proactive attitudes and specific training and limited visit time. Upon detection of NPCs, physicians referred patients to the in-house psychiatry/psychology centre (61.7%), adjusted ART to minimize interactions (96.5%), and managed NPCs in conjunction with mental health professionals (71.3%).

Conclusions: Physicians in hospital settings in Spain were aware of the relevance of NPC diagnosis and their underdiagnosis. However, they still failed to routinely evaluate NPCs, follow guideline recommendations, and use questionnaires, highlighting opportunities for improved NPC detection and management in people with HIV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/hiv.13296DOI Listing
March 2022

Real-life experience with bictegravir/emtricitabine/tenofovir alafenamide in a large reference clinical centre.

J Antimicrob Chemother 2022 03;77(4):1133-1139

HIV Unit, Infectious Disease Service, Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.

Background: The use of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) is mainly based on robust, pivotal clinical trials.

Objectives: To provide data on clinical use of BIC/FTC/TAF in real life.

Patients And Methods: This was an observational, retrospective and single-centre study. We included all adult, treatment-naive (TN) and treatment-experienced (TE) people living with HIV (PLWH) starting BIC/FTC/TAF from 8 June 2018. We evaluated effectiveness [on treatment (OT), modified intention-to-treat (mITT) and intention-to-treat (ITT)], tolerability and safety in those patients who reached 6 months of follow-up (M6).

Results: We included 1584 PLWH [213 TN (13%) and 1371 TE (87%)]. The median (IQR) follow-up was 16 (7-21) months, with 81% and 53% of PLWH reaching M6 and M12, respectively. By OT, mITT and ITT, HIV-RNA <50 copies/mL was 77%, 70% and 62% at M6 and 92%, 77% and 63% at M12 for TN PLWH and 94%, 89% and 83% at M6 and 93%, 85% and 78% at M12 for TE PLWH, respectively. In PLWH carrying an M184V/I substitution, OT RNA <50 copies/mL was 89.5% at M6. The median CD4 cell count increased from 329 to 511/μL in TN PLWH and from 630 to 683/μL in TE PLWH at M6. Of the total, 1148 (88%) PLWH continued on BIC/FTC/TAF at M6. The most frequent known reason for discontinuation was toxicity [42 (69%) cases]; only 7 cases were considered virological failures (0.6% of the total OT cohort at M6), with no emerging resistance substitutions.

Conclusions: In real life, BIC/FTC/TAF showed high rates of virological suppression and also in PLWH carrying lamivudine/emtricitabine resistance substitutions. The tolerability and safety of BIC/FTC/TAF were good, with high persistence observed for patients on this regimen at M6.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkab481DOI Listing
March 2022

Impact of coronavirus disease 2019 epidemics on prevention and care for HIV and other sexually transmitted infections.

AIDS 2022 May 16;36(6):829-838. Epub 2022 Feb 16.

Department of Infectious Diseases, HIV Unit, Hospital Clinic.

Objective: To assess the impact of coronavirus disease 2019 (COVID-19) epidemics on the prevention and care for HIV and other sexually transmitted infections at a major reference centre providing preventive and clinical services in Catalonia, Spain.

Design: We retrospectively compared anonymized clinical and laboratory data from March to December 2020 vs. 2019.

Methods: Monthly clinical data on HIV preexposure and postexposure prophylaxis users and on adults with HIV infection were retrieved from the administrative hospital database. Monthly tests for HIV, hepatitis B and C, Treponema pallidum, Neisseria gonorrhoeae,and Chlamydia trachomatis, and plasma lipids and glucose were recovered from the laboratory database.

Results: There were less (↓28%, P  = 0.003) but more advanced (mean CD4+ cells/μl 305 vs. 370, P  < 0.001) HIV infections and more gonorrhoea (↑39%, P  < 0.001) and chlamydia (↑37%, P  < 0.001) infections in 2020 vs. 2019. In people with HIV, rates of HIV RNA less than 50 copies/ml remained stable (11 vs. 11%, P  = 0.147) despite less scheduled visits (↓25%, P  < 0.001). However, they had less antiretroviral prescription changes (↓10%, P  = 0.018), worse plasma lipids [mean total cholesterol 190 vs. 185 mg/dl, P  < 0.001;mean low-density lipoprotein (LDL) cholesterol 114 vs. 110 mg/dl, P  < 0.001; mean triglycerides 136 vs. 125 mg/dl, P  < 0.001; mean high-density lipoprotein (HDL) cholesterol 47 vs. 48 mg/dl, P  = 006], and an excess of mortality (↑264%, P  = 0.006) due in great part not only to COVID-19 but also to other causes.

Conclusion: In our setting, COVID-19 epidemics was associated with an increase in some prevalent sexually transmitted infections, with less but more advanced HIV infections, and with worse nonvirologic healthcare outcomes and higher mortality in people living with HIV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAD.0000000000003164DOI Listing
May 2022

Development of the HIV360 international core set of outcome measures for adults living with HIV: A consensus process.

HIV Med 2022 07 28;23(6):639-649. Epub 2021 Dec 28.

Division of Intervention in Addictive Behaviours and Dependencies (DICAD), Regional Health Administration of Lisbon and Tagus Valley, Lisbon, Portugal.

Objectives: HIV outcomes centre primarily around clinical markers with limited focus on patient-reported outcomes. With a global trend towards capturing the outcomes that matter most to patients, there is agreement that standardizing the definition of value in HIV care is key to their incorporation. This study aims to address the lack of routine, standardized data in HIV care.

Methods: An international working group (WG) of 37 experts and patients, and a steering group (SG) of 18 experts were convened from 14 countries. The project team (PT) identified outcomes by conducting a literature review, screening 1979 articles and reviewing the full texts of 547 of these articles. Semi-structured interviews and advisory groups were performed with the WG, SG and people living with HIV to add to the list of potentially relevant outcomes. The WG voted via a modified Delphi process - informed by six Zoom calls - to establish a core set of outcomes for use in clinical practice.

Results: From 156 identified outcomes, consensus was reached to include three patient-reported outcomes, four clinician-reported measures and one administratively reported outcome; standardized measures were included. The WG also reached agreement to measure 22 risk-adjustment variables. This outcome set can be applied to any person living with HIV aged > 18 years.

Conclusions: Adoption of the HIV360 outcome set will enable healthcare providers to record, compare and integrate standardized metrics across treatment sites to drive quality improvement in HIV care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/hiv.13221DOI Listing
July 2022

Assessment of Obesity and Cardiometabolic Status by Integrase Inhibitor Use in REPRIEVE: A Propensity-Weighted Analysis of a Multinational Primary Cardiovascular Prevention Cohort of People With Human Immunodeficiency Virus.

Open Forum Infect Dis 2021 Dec 20;8(12):ofab537. Epub 2021 Nov 20.

Massachusetts General Hospital, Boston, Massachusetts, USA.

Background: Emerging data demonstrate that the use of integrase inhibitor (INSTI)-based antiretroviral treatment (ART) is associated with increased weight, but the cardiometabolic health consequences of increased weight remains poorly understood.

Methods: This analysis examined INSTI use (>6 months) at entry among REPRIEVE participants enrolled in High Income and Latin America/Caribbean Global Burden of Disease regions. Primary analyses used linear and logistic regression; secondary analyses used quantile regression to examine differences across the full data distribution. Characteristics of those with and without INSTI use were balanced using inverse probability of treatment weighting.

Results: Among 4500 REPRIEVE participants, 1848 were on an INSTI-based regimen at entry for an average of 2.1 ± 1.8 years. Integrase inhibitor use (vs no INSTI use) was associated with higher odds of obesity (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.4-1.9) and higher mean body mass index ([BMI] +1.5kg/m2; 95% CI, 1.0-1.9) and waist circumference (+3.6cm; 95% CI, 2.6-4.6). Differences in weight related to INSTI use were greater in the upper tails of the distribution (+3.1kg/m2 [95% CI, 1.9-4.4] at the 90th centile vs +0.7kg/m2 [95% CI, 0.2-1.2] at the 50th centile) and among women and nonwhite participants, with sex and race having an additive effect on BMI. Conversely, INSTI use was not associated with differences in glucose, low-density lipoprotein cholesterol, or higher odds of metabolic syndrome or hypertension.

Conclusions: Differences in weight and waist circumference associated with INSTI use are (1) not uniform across people with human immunodeficiency virus, (2) greatest among women and nonwhites, and (3) concentrated at the upper tails of weight distribution. These data identify at-risk subgroups for whom long-term cardiovascular disease outcomes should be carefully assessed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ofid/ofab537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651160PMC
December 2021

COVID-19 Vaccination Rates in a Global HIV Cohort.

J Infect Dis 2022 02;225(4):603-607

Metabolism Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

Little is known regarding coronavirus disease 2019 (COVID-19) vaccination rates in people with HIV (PWH), a vulnerable population with significant morbidity from COVID-19. We assessed COVID-19 vaccination rates among 6952 PWH in the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) compared to region- and country-specific vaccination data. The global probability of COVID-19 vaccination through end of July 2021 was 55% among REPRIEVE participants with rates varying substantially by Global Burden of Disease (GBD) superregion. Among PWH, factors associated with COVID-19 vaccination included residence in high-income regions, age, white race, male sex, body mass index, and higher cardiovascular risk. Clinical Trials Registration. NCT02344290.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jiab575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8844595PMC
February 2022

CNS Considerations in ART Simplification Strategies.

Curr HIV/AIDS Rep 2021 12 5;18(6):549-557. Epub 2021 Nov 5.

Infectious Diseases Unit, Hospital Clínic-IDIBAPS & University of Barcelona, 08036, Barcelona, Spain.

Purpose Of The Review: This review summarizes current knowledge on central nervous system (CNS) considerations in ART simplification strategies.

Recent Findings: Antiretroviral therapies (ART) showing efficacy in plasma will usually show efficacy in the cerebrospinal fluid (CSF). ART simplification may virologically fail if the new regimen has less than two active drugs, the genetic barrier of drugs is not high, and the patient may harbour archived resistance. Dual therapies including a boosted protease inhibitor (PI) or dolutegravir (DTG) are generally effective from the CNS perspective. In cases of related neurotoxicity, switching from either efavirenz (EFV) or DTG to another equally effective drug with better CNS tolerability usually leads to complete resolution of CNS symptoms. However, improvement may be incomplete when factors other than ART that cannot be easily modified are involved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11904-021-00580-zDOI Listing
December 2021

3β-Palmitoyloxy-olean-12-ene analogs from Sapium lateriflorum (Euphorbiaceae): Their cytotoxic and anti-inflammatory properties and docking studies.

Fitoterapia 2021 Nov 22;155:105067. Epub 2021 Oct 22.

Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Coyoacán 04510, Ciudad de México, México. Electronic address:

Ten compounds, including a new anti-inflammatory acyl triterpene, 3β-palmitoyloxy-1β,11α-dihydroxy-olean-12-ene, were isolated from the bioactive organic extract prepared from the leaves of Sapium lateriflorum (syn: S. nitidum). The isolated compounds were screened for their cytotoxic activity against selected human cancer cell lines and did not display significant activity. They were also evaluated as anti-inflammatory agents in mouse models (TPA-induced edema in the ear and in a carrageenan-induced paw edema model). The results indicated that the new compound, 3β-palmitoyloxy-1β,11α-dihydroxy-olean-12-ene, was the compound with major anti-inflammatory activity similar to that of indomethacin, being the hydroxyl at C-11 important for the observed activity. The results of docking studies of the 3β-palmitoyloxy esters of olean-12-ene with NF-κB and with COX-2 receptors were consistent with possible molecular mechanisms of the anti-inflammatory activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fitote.2021.105067DOI Listing
November 2021

Human Immunodeficiency Virus (HIV) Care Models During the Coronavirus Disease 2019 (COVID-19) Era.

Clin Infect Dis 2021 09;73(5):e1222-e1227

Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain.

The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented global challenge that substantially risks reversing the progress in ending human immunodeficiency virus (HIV). At the same time, it may offer the opportunity for a new era of HIV management. This viewpoint presents the impact of COVID-19 on HIV care, including the Joint United Nations Programme on HIV/AIDS (UNAIDS) "three 90s" targets. It outlines how to enhance a patient-centered care approach, now known as the "fourth 90," by integrating face-to-face patient-physician and telemedicine encounters. It suggests a framework for prevention and treatment of multimorbidity and frailty, to achieve a good health-related quality of life, and to preserve intrinsic capacity in all people living with HIV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciaa1864DOI Listing
September 2021

Long-term evolution in liver fibrosis and immune profile after direct-acting antivirals therapy in hepatitis C virus-human immunodeficiency virus co-infected patients.

Clin Microbiol Infect 2022 Apr 28;28(4):610.e1-610.e7. Epub 2021 Aug 28.

HIV Unit, Hospital Clínic de Barcelona, Barcelona, Spain.

Objective: Hepatitis C virus (HCV) therapy with direct-acting antivirals (DAA) achieves high rates of sustained virological response in people living with human immunodeficiency virus (HIV) (PLWH). Information on its long-term clinical impact is scarce. The aim of this study was to analyse liver fibrosis and immune response evolution after DAA treatment.

Methods: Retrospective, single centre cohort study of HIV-HCV co-infected patients treated with DAA between June 2013 and June 2018. We analysed the changes during follow up in liver fibrosis (assessed by transient elastography (TE), aspartate aminotransferase to platelet ratio index (APRI) and FIB-4 scores) and immunity (CD4 and CD8 cells counts and CD4/CD8 ratio).

Results: We included 410 patients; 75% (308/407) men with a mean age of 50 years (SD 8); 78% (318/410) had long chronic HCV infection (median 21 years, interquartile range (IQR) 6-27 years) and 27% (107/393) had liver cirrhosis. Liver fibrosis improvement based on the decrease in TE value compared with the baseline occurred in 43% (131/302) of patients and 31% of patients based on biological scores (APRI: 124/398; FIB-4: 104/398) (p < 0.0001), being more frequent in those with advanced baseline fibrosis (83/144). The higher decrease was observed at 6 months after DAA therapy (-0.23; 95% CI -0.29 to -0.18), but a continuum in fibrosis regression of at least 30% from baseline value of TE was observed along the follow up (32% of patients at month 6, 51% at month 24 and 55% at month 48). Regarding the immunological profile, there was a significant decrease in CD8 counts at month 48 (-62.38; 95% CI -106.77 to -17.99; p 0.0001) and a progressive rise in the CD4/CD8 ratio after 24 months of follow up reaching an increment of +0.07 (95% CI 0.03-0.10, p 0.0001) at month 48.

Conclusions: HCV treatment with DAA in PLWH is associated with significant progressive improvement in liver fibrosis and recovery of the immune system with an increase in the CD4/CD8 ratio in long-term follow up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmi.2021.08.019DOI Listing
April 2022

Efficacy and safety of switching to dolutegravir plus lamivudine versus continuing triple antiretroviral therapy in virologically suppressed adults with HIV at 48 weeks (DOLAM): a randomised non-inferiority trial.

Lancet HIV 2021 08;8(8):e463-e473

Hospital Clínic-IDIBAPS, Barcelona, Spain; University of Barcelona, Barcelona, Spain. Electronic address:

Background: Simplified antiretroviral therapy (ART) regimens are desirable for people with HIV. We investigated the efficacy and safety of switching from triple ART to dual dolutegravir plus lamivudine therapy.

Methods: DOLAM is a phase 4, randomised, open-label, non-inferiority trial, done at six HIV clinics in Catalonia, Spain. Adults with HIV-1 receiving a triple ART regimen, aged 18 years or older, with virological suppression, a CD4 nadir of at least 200 cells per μL, who were HBsAg-negative, and without previous viral failure or resistance mutations to study drugs were eligible. Participants underwent computer-generated randomisation, stratified by the class of the third drug, and were assigned (1:1) to switch to oral dolutegravir 50 mg and lamivudine 300 mg once daily or to continue triple ART for 48 weeks. The primary endpoint was the proportion of people with an HIV RNA value of at least 50 copies per mL at week 48 (US Food and Drug Administration snapshot algorithm, 8% non-inferiority margin). Both the primary and safety outcomes were evaluated in the intention-to-treat exposed population. The study is completed and was registered with EudraCT 201500027435.

Findings: Between July 7, 2015, and Oct 31, 2018, 265 participants were randomly assigned to switch to dolutegravir plus lamivudine (n=131) or to maintain triple ART (n=134) and all received at least one dose. Nine (7%) participants in the dual therapy group and ten (7%) in the triple therapy group were excluded before 48 weeks, mostly due to treatment discontinuations or virological failure. Participants were predominantly male (116 [87%] of 134 in the triple ART group and 111 [85%] of 131 in the dolutegravir plus lamivudine group). The difference in the proportion of participants with HIV RNA values of at least 50 copies per mL at 48 weeks between the dual therapy group (three [2%] of 131) and triple therapy group (two [1%] of 134) was 0·8 percentage points (95% CI -3·3 to 5·2), showing non-inferiority of dolutegravir plus lamivudine dual therapy compared with triple ART. 73 (56%) of 131 participants allocated to dual therapy had 150 adverse effects, compared with 78 (58%) of 134 participants allocated to triple therapy who also had 150 adverse events (p=0·68). Drug discontinuation due to adverse effects occurred in four people in the triple therapy group and three people in the dual therapy group.

Interpretation: Our findings show the efficacy and safety of dolutegravir plus lamivudine as a simplified therapy switch option for selected people with HIV with virological suppression on triple ART.

Funding: Instituto de Salud Carlos III, Red de Investigación en Sida, and ViiV Healthcare.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2352-3018(21)00100-4DOI Listing
August 2021

Factors associated with the use and composition of two-drug regimens in a large single-centre HIV cohort.

J Antimicrob Chemother 2021 10;76(11):2988-2992

Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.

Objectives: We aimed to assess the clinical characteristics associated with the use of two-drug regimens (2DRs) and the factors associated with specific antiretrovirals in 2DRs in a large single-centre HIV cohort.

Methods: Retrospective analysis of demographics, HIV characteristics and AIDS events, antiretroviral prescription, virological failure and genotypic resistance testing, and laboratory results from all adult people with HIV (PWH) prospectively followed at the Hospital Clinic of Barcelona who were receiving a 3DR or a 2DR in January 2020. We assessed factors associated with the probability of receiving 2DRs relative to three-drug regimens (3DRs) using a logistic regression model, controlling for age, sex and year of HIV diagnosis. The same methodology was applied to identify factors associated with the prescription of integrase inhibitor-based regimens or PI-based regimens among PWH receiving 2DRs.

Results: There were 3432 (88%) PWH receiving 3DRs and 463 (12%) receiving 2DRs. In the final adjusted model, ≥2 previous virological failures, previous resistance mutations, previous AIDS diagnosis, longer time on current regimen, higher total cholesterol or triglycerides and lower baseline haemoglobin were independent factors associated with 2DRs. The majority of 2DRs included an integrase inhibitor or/and a PI. We identified independent factors associated with the inclusion of integrase inhibitors (lower HDL cholesterol) or PIs (prior AIDS, prior genotypic resistance mutations and lower CD4/CD8 ratio) in the 2DR.

Conclusions: In this large single-centre HIV cohort, a worse cardiometabolic status or more archived resistance were key factors associated with inclusion of integrase inhibitors or PIs, respectively, in 2DRs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkab261DOI Listing
October 2021

Remdesivir Versus Standard-of-Care for Severe Coronavirus Disease 2019 Infection: An Analysis of 28-Day Mortality.

Open Forum Infect Dis 2021 Jul 26;8(7):ofab278. Epub 2021 May 26.

Chelsea and Westminster Hospital NHS Foundation Trust, London, United Kingdom.

Background: Remdesivir is approved by the US Food and Drug Administration for the treatment of patients hospitalized with coronavirus disease 2019 (COVID-19) and has been shown to shorten time to recovery and improve clinical outcomes in randomized trials.

Methods: This was the final day 28 comparative analysis of data from a phase 3, randomized, open-label study comparing 2 remdesivir regimens (5 vs 10 days, combined for this analysis [remdesivir cohort]) and a real-world retrospective longitudinal cohort study of patients receiving standard-of-care treatment (nonremdesivir cohort). Eligible patients, aged ≥18 years, had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), oxygen saturation ≤94% on room air or required supplemental oxygen, with pulmonary infiltrates. Propensity score matching (up to 1:10 ratio) was used to ensure comparable populations. We assessed day 14 clinical recovery (determined using a 7-point ordinal scale) and day 28 all-cause mortality (coprimary endpoints).

Results: A total of 368 (remdesivir) and 1399 (nonremdesivir) patients were included in the matched analysis. The day 14 clinical recovery rate was significantly higher among the remdesivir versus the nonremdesivir cohort (65.2% vs 57.1%; odds ratio [OR], 1.49; 95% confidence interval [CI], 1.16-1.90; = 0.002). The day 28 mortality rate was significantly lower in the remdesivir cohort versus the nonremdesivir cohort (12.0% vs 16.2%; OR, 0.67; 95% CI, 0.47-.95;  = .03).

Conclusions: Remdesivir was associated with significantly higher rates of day 14 clinical recovery, and lower day 28 mortality, compared with standard-of-care treatment in hospitalized patients with COVID-19. These data, taken together, support the use of remdesivir to improve clinical recovery and decrease mortality from SARS-CoV-2 infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ofid/ofab278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244650PMC
July 2021

Cholesterol and CDON Regulate Sonic Hedgehog Release from Pancreatic Cancer Cells.

J Pancreat Cancer 2021 1;7(1):39-47. Epub 2021 Jun 1.

Molecular Therapeutics, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.

Sonic Hedgehog (Shh) is a tightly regulated membrane-associated morphogen and a known driver of tumorigenesis in pancreatic ductal adenocarcinoma (PDAC). After processing, Shh remains at the plasma membrane of Shh producing cells, thereby limiting its distribution and signal strength. In PDAC, the release of Shh from tumor cells is necessary to promote a tumor-permissive microenvironment. Mechanisms regulating Shh sequestration and/or release from tumor cells to signal distant stromal cells are not well known. Previously, our laboratory demonstrated that the Drosophila transmembrane protein Boi, sequesters Hh at the membrane of Hh-producing cells. In response to dietary cholesterol or in the absence of boi, Hh is constitutively released to promote proliferation in distant cells. In this study, we investigated the conservation of this mechanism in mammals by exploring the role of the human boi homolog, CDON, in PDAC. Using PDAC cell-lines BxPC-3, Capan-2, and MIA PaCa-2, along with normal pancreatic epithelial cells (PDEC), we investigated Shh expression via Immunoblot and real-time, quantitative polymerase chain reaction in addition to Shh release via enzyme-linked immunoassay following cholesterol treatment and/or transfection with either RNA interference to reduce CDON expression or with human to increase expression. Consistent with our Boi model, CDON suppresses Shh release, which is alleviated in response to dietary cholesterol. However, over-expressing CDON suppresses cholesterol-mediated Shh release in some PDAC contexts, which may be relative to the mutational burden of the cells. Identifying mechanisms that either sequester or stimulate Shh release from the tumor cell membrane may provide new avenues to reduce signaling between the tumor and its surrounding environment, which may restrain tumor development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/pancan.2021.0002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252898PMC
June 2021

Switching from boosted PIs to dolutegravir decreases soluble CD14 and adiponectin in high cardiovascular risk people living with HIV.

J Antimicrob Chemother 2021 08;76(9):2380-2393

Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.

Background: Switching from boosted PIs to dolutegravir in people living with HIV (PLWH) with high cardiovascular risk improved plasma lipids at 48 weeks in the NEAT022 trial. Whether this strategy may have an impact on cardiovascular biomarkers is unknown.

Methods: We assessed 48 week changes in biomarkers associated with inflammation, endothelial dysfunction, monocyte immune activation, oxidation, insulin resistance, hypercoagulability, heart failure, myocardial injury, and glomerular and tubular kidney injury.

Results: Of 415 PLWH randomized in the NEAT022 study, 313 (75.4%) remained on allocated therapy and had paired samples available. Soluble CD14 (-11%, P < 0.001) and adiponectin (-11%, P < 0.001) significantly declined and high-sensitive C-reactive protein (-13%, P = 0.069) and oxidized LDL (-13%, P = 0.084) tended to decrease with dolutegravir. Switching to dolutegravir remained significantly associated with soluble CD14 and adiponectin reductions after adjustment for baseline variables. There were inverse correlations between soluble CD14 and CD4 count changes (P = 0.05), and between adiponectin and BMI changes (P < 0.001).

Conclusions: Switching from boosted PIs to dolutegravir in PLWH with high cardiovascular risk led to soluble CD14 and adiponectin reductions at 48 weeks. While decreasing soluble CD14 may entail favourable health effects in PLWH, adiponectin reduction may reflect less insulin sensitivity associated with weight gain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkab158DOI Listing
August 2021

Factors influencing the effectiveness of the Gudair vaccine for controlling Johne's disease in sheep flocks in Australia.

Prev Vet Med 2021 Aug 31;193:105394. Epub 2021 May 31.

Sydney School of Veterinary Science, The University of Sydney, Australia.

Ovine Johne's disease is a chronic debilitating disease of sheep caused by Mycobacterium avium subsp. paratuberculosis (Mptb) which results in diarrhoea, emaciation and mortalities in infected animals. Vaccination with Gudair® has been a key strategy for controlling the disease in Australia since its approval in 2002. Previous research conducted in Australia has demonstrated that the vaccine is quite effective in reducing sheep mortalities. While some farms have also been successful in reducing the prevalence of the disease in their flocks to undetectable levels, sheep in other flocks continue to shed Mptb in faeces even after an ongoing vaccination program . This study was conducted to investigate management, husbandry and biosecurity factors associated with paratuberculosis infection in Gudair® vaccinated sheep flocks in Australia. We enrolled 64 sheep farmers and interviewed them to obtain information about their management and biosecurity practices. Pooled faecal samples were collected from sheep at each farm and cultured to create two outcome variables: Mptb positive (yes/no) and disease prevalence level (nil, < 1 %, ≥ 1 %). Binary and ordinal logistic regression analyses were conducted to evaluate the association of management, husbandry and biosecurity factors with these outcome variables. Farms were more likely to have Mptb positive sheep and a higher disease prevalence in their flocks if they: (a) provided supplementary feed on the ground (instead of in a trough); (b) had a greater number of neighbours with sheep; and (c) had introduced rams from a greater number of sources. The results suggest the effectiveness of Gudair® vaccination to control OJD can be improved if sheep producers maintain other risk management strategies and biosecurity practices. Extension agencies should advise farmers not to relax their biosecurity practices and to purchase rams from only low-risk sources, even if they are continuing to vaccinate their flocks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prevetmed.2021.105394DOI Listing
August 2021

ATF3 coordinates serine and nucleotide metabolism to drive cell cycle progression in acute myeloid leukemia.

Mol Cell 2021 07 2;81(13):2752-2764.e6. Epub 2021 Jun 2.

Blood Cell and Development Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA; Division of Hematology/Oncology, Department of Pediatrics, Washington University of Saint Louis, Saint Louis, MO 63110, USA. Electronic address:

Metabolic reprogramming is a common feature of many human cancers, including acute myeloid leukemia (AML). However, the upstream regulators that promote AML metabolic reprogramming and the benefits conferred to leukemia cells by these metabolic changes remain largely unknown. We report that the transcription factor ATF3 coordinates serine and nucleotide metabolism to maintain cell cycling, survival, and the differentiation blockade in AML. Analysis of mouse and human AML models demonstrate that ATF3 directly activates the transcription of genes encoding key enzymatic regulators of serine synthesis, one-carbon metabolism, and de novo purine and pyrimidine synthesis. Total steady-state polar metabolite and heavy isotope tracing analyses show that ATF3 inhibition reduces de novo serine synthesis, impedes the incorporation of serine-derived carbons into newly synthesized purines, and disrupts pyrimidine metabolism. Importantly, exogenous nucleotide supplementation mitigates the anti-leukemia effects of ATF3 inhibition. Together, these findings reveal the dependence of AML on ATF3-regulated serine and nucleotide metabolism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molcel.2021.05.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452149PMC
July 2021

PrEP program experience in a hospital HIV unit. Description of baseline user profile and identification of opportunities for improvement.

Enferm Infecc Microbiol Clin (Engl Ed) 2021 May 24. Epub 2021 May 24.

Unidad de VIH, Hospital Clínic e IDIBAPS, Universidad de Barcelona, Barcelona, España.

Introduction: Pre-Exposure Prophylaxis (PrEP) is a biomedical intervention to prevent HIV infection in seronegative people at high risk of becoming infected. This strategy was endorsed in October 2019 by the Spanish Ministry of Health.

Objective: To present the PrEP initial experience in the HIV Unit of the Hospital Clínic of Barcelona, paying special attention to the analysis of the vulnerability factors in the cohort.

Materials And Methods: Retrospective, descriptive study. The epidemiological, sociodemographic, and clinical characteristics of the users included in the program during the first year are analyzed, paying particular attention to Infections, risky practices, and substance use.

Results: 190 individuals were included, 177 men and 12 trans women with a mean age of 35 years (8 SD). 70% had higher education, and half had Spanish nationality. An average of 10 couples per trimester and 60% reported unprotected anal sex. 31% had at least one positive PCR for STIs, with N. gonorrhoeae being the most prevalent microorganism (51%) and the rectal sample the most affected (21%). 63% reported chemsex use, 19% polydrug use, and 8% "slamming". Half expressed concern about consumption and/or sexual practices and 25% the need for help.

Conclusions: The PrEP user profile attended in our Hospital Unit justifies the creation of multidisciplinary teams that allow us to provide holistic attention to the sexual life of these people.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eimc.2021.04.005DOI Listing
May 2021

Overview of SARS-CoV-2 infection in adults living with HIV.

Lancet HIV 2021 05;8(5):e294-e305

Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain. Electronic address:

Around 2·5 million deaths and more than 110 million COVID-19 cases have been reported globally. Although it initially appeared that HIV infection was not a risk factor for COVID-19 or more severe disease, more recent large studies suggest that people living with HIV (particularly with low CD4 cell counts or untreated HIV infection) might have a more severe clinical course than those who are HIV-negative. Moreover, the COVID-19 pandemic has disrupted HIV prevention and treatment services worldwide, creating huge challenges to the continuity of essential activities. We have reviewed the most relevant features of COVID-19 in people living with HIV and highlighted topics where further research is required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2352-3018(21)00070-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075775PMC
May 2021

Impact of Sexualized Substance Use and Other Risk Practices on HCV Microelimination in gbMSM Living with HIV: Urgent Need for Targeted Strategies. Results of a Retrospective Cohort Study.

Infect Dis Ther 2021 Sep 29;10(3):1253-1266. Epub 2021 Apr 29.

Department of Infectious Diseases, HIV Unit, Hospital Clinic and IDIBAPS, Barcelona University, Barcelona, Spain.

Introduction: The objective of the present study is to describe the incidence of recently acquired hepatitis C (RAHCV) in a large cohort of people living with HIV (PLWHIV) and sexualized drug use and other related risk behaviours.

Methods: Observational study including all PLWHIV with a RAHCV episode between June 2005 and December 2019 at the Hospital Clinic of Barcelona, Spain. Incidence of RAHCV was determined per person calendar year (py) in those patients who were HCV RNA negative. Data were collected on high-risk sexual practices for HCV transmission focused on gay, bisexual and other men having sex with men (gbMSM).

Results: A total of 340 RAHCV were diagnosed in 290 PLWHIV; 274 (94%) of them were gbMSM and developed 324 RAHCV, mainly since 2010 (90%). Overall incidence rate (IR) of RAHCV in gbMSM was 0.10 py (95% CI 0.09-0.11), with a 40% decreased observed since 2017 (IR 0.06, 95% CI 0.03-0.09 in 2019). Sixty reinfections were detected in 50 gbMSM (n = 244, 20%). The overall reinfection IR was 0.17 per py (95% CI 0.12-0.23) and the proportion of reinfection among total RAHCV increased to 47% cases in 2019, mainly in patients engaged in sexualized substance use (76%), unprotected anal intercourse (94%), sex partying (80%), fisting (43%), slamming (14%) and 60% of concomitant sexually transmitted infections (STIs).

Conclusions: Despite RAHCV incidence decline in our cohort since 2017, HCV reinfection increased. High sexualized substance use and other risk behaviours are described in this context, indicating the need for public health tailored strategies to reduce this transmission and achieve HCV microelimination in gbMSM living with HIV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40121-021-00448-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322221PMC
September 2021

Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving Antiretroviral Therapy.

Ann Intern Med 2021 04;174(4):581-582

Harvard T.H. Chan School of Public Health and Harvard-MIT Division of Health Sciences and Technology, Boston, Massachusetts.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7326/L20-1399DOI Listing
April 2021
-->