RESUMO
INTRODUCTION: The DOLAM trial revealed that switching from triple antiretroviral therapy (three-drug regimen; 3DR) to dolutegravir plus lamivudine (two-drug regimen; 2DR) was virologically non-inferior to continuing 3DR after 48â weeks of follow-up. Weight increased with 2DR relative to 3DR but it did not impact on metabolic parameters. METHODS: Multiomics plasma profile was performed to gain further insight into whether this therapy switch might affect specific biological pathways. DOLAM (EudraCT 201500027435) is a Phase 4, randomized, open-label, non-inferiority trial in which virologically suppressed persons with HIV treated with 3DR were assigned (1:1) to switch to 2DR or to continue 3DR for 48â weeks. Untargeted proteomics, metabolomics and lipidomics analyses were performed at baseline and at 48â weeks. Univariate and multivariate analyses were performed to identify changes in key molecules between both therapy arms. RESULTS: Switching from 3DR to 2DR showed a multiomic impact on circulating plasma concentration of N-acetylmuramoyl-L-alanine amidase (Q96PD5), insulin-like growth factor-binding protein 3 (A6XND0), alanine and triglyceride (TG) (48:0). Correlation analyses identified an association among the up-regulation of these four molecules in persons treated with 2DR. CONCLUSIONS: Untargeted multiomics profiling studies identified molecular changes potentially associated with inflammation immune pathways, and with lipid and glucose metabolism. Although these changes could be associated with potential metabolic or cardiovascular consequences, their clinical significance remains uncertain. Further work is needed to confirm these findings and to assess their long-term clinical consequences.
Assuntos
Infecções por HIV , Compostos Heterocíclicos com 3 Anéis , Lamivudina , Oxazinas , Piperazinas , Piridonas , Humanos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Infecções por HIV/tratamento farmacológico , Lamivudina/uso terapêutico , Lamivudina/administração & dosagem , Masculino , Oxazinas/uso terapêutico , Feminino , Adulto , Pessoa de Meia-Idade , Metabolômica , Lipidômica , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Plasma/química , Proteômica , Terapia Antirretroviral de Alta Atividade , Substituição de Medicamentos , Triglicerídeos/sangue , Alanina/sangue , MultiômicaRESUMO
OBJECTIVES: To assess the effectiveness and tolerability of dolutegravir (DTG)/lamivudine (3TC) among treatment-naive and virologically suppressed treatment-experienced individuals in the multicentre cohort of the Spanish HIV/AIDS Research Network (CoRIS) during the years 2018-2021. METHODS: We used multivariable regression models to compare viral suppression (VS) [HIV RNA viral load (VL) <50 copies/mL] and the change in CD4 cell counts at 24 and 48 (±12) weeks after initiation with dolutegravir/lamivudine or other first-line ART regimens. RESULTS: We included 2160 treatment-naive subjects, among whom 401 (18.6%) started with dolutegravir/lamivudine. The remaining subjects started bictegravir (BIC)/emtricitabine (FTC)/tenofovir alafenamide (TAF) (nâ=â949, 43.9%), DTGâ+âFTC/tenofovir disoproxil fumarate (TDF) (nâ=â282, 13.1%), DTG/3TC/abacavir (ABC) (nâ=â255, 11.8%), darunavir (DRV)/cobicistat(COBI)/FTC/TAF (nâ=â147, 6.8%) and elvitegravir (EVG)/COBI/FTC/TAF (nâ=â126, 5.8%). At 24 and 48 weeks after starting dolutegravir/lamivudine, 91.4% and 93.8% of the subjects, respectively, achieved VS. The probability of achieving VS with dolutegravir/lamivudine was not significantly different compared with any other regimen at 24 or 48 weeks, with the exception of a lower chance of achieving VS at 24 weeks for DRV/COBI/FTC/TAF (adjusted OR: 0.47; 95% CI: 0.30-0.74) compared with dolutegravir/lamivudine.For the analysis of treatment-experienced virally suppressed subjects we included 1456 individuals who switched to dolutegravir/lamivudine, among whom 97.4% and 95.5% maintained VS at 24 and 48 weeks, respectively. During the first 48 weeks after dolutegravir/lamivudine initiation, 1.0% of treatment-naive and 1.5% of treatment-experienced subjects discontinued dolutegravir/lamivudine due to an adverse event. CONCLUSIONS: In this large multicentre cohort, effectiveness and tolerability of dolutegravir/lamivudine were high among treatment-naive and treatment-experienced subjects.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Humanos , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Lamivudina/efeitos adversos , Oxazinas/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Piridonas/uso terapêutico , Emtricitabina/uso terapêuticoRESUMO
To evaluate the prevalence of transmitted drug resistance (TDR) to nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTI, NNRTI), protease inhibitors (PI), and integrase strand transfer inhibitors (INSTI) in Spain during the period 2019-2021, as well as to evaluate transmitted clinically relevant resistance (TCRR) to antiretroviral drugs. Reverse transcriptase (RT), protease (Pro), and Integrase (IN) sequences from 1824 PLWH (people living with HIV) were studied. To evaluate TDR we investigated the prevalence of surveillance drug resistance mutations (SDRM). To evaluate TCRR (any resistance level ≥ 3), and for HIV subtyping we used the Stanford v.9.4.1 HIVDB Algorithm and an in-depth phylogenetic analysis. The prevalence of NRTI SDRMs was 3.8% (95% CI, 2.8%-4.6%), 6.1% (95% CI, 5.0%-7.3%) for NNRTI, 0.9% (95% CI, 0.5%-1.4%) for PI, and 0.2% (95% CI, 0.0%-0.9%) for INSTI. The prevalence of TCRR to NRTI was 2.1% (95% CI, 1.5%-2.9%), 11.8% for NNRTI, (95% CI, 10.3%-13.5%), 0.2% (95% CI, 0.1%-0.6%) for PI, and 2.5% (95% CI, 1.5%-4.1%) for INSTI. Most of the patients were infected by subtype B (79.8%), while the majority of non-Bs were CRF02_AG (n = 109, 6%). The prevalence of INSTI and PI resistance in Spain during the period 2019-2021 is low, while NRTI resistance is moderate, and NNRTI resistance is the highest. Our results support the use of integrase inhibitors as first-line treatment in Spain. Our findings highlight the importance of ongoing surveillance of TDR to antiretroviral drugs in PLWH particularly with regard to first-line antiretroviral therapy.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Espanha/epidemiologia , Filogenia , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/farmacologia , Antirretrovirais/uso terapêutico , Integrases/genética , Integrases/uso terapêutico , Mutação , Farmacorresistência Viral/genética , Inibidores da Transcriptase Reversa/farmacologia , Inibidores da Transcriptase Reversa/uso terapêutico , PrevalênciaRESUMO
BACKGROUND: People living with HIV (PLWH) face structural and psychosocial factors that affect health-related quality of life (HRQoL). We aimed to evaluate how syndemic conditions affected HRQoL in PLWH. METHODS: A cross-sectional survey was conducted among 861 PLWH, to determine whether syndemic conditions (monthly income; sexual satisfaction; depressive symptoms; social role satisfaction; social isolation; cognitive function; nicotine dependence; perception of stigma) have an effect on HRQoL. A linear regression model and measures of Additive Interaction (AI) were used to determine the effects of syndemic conditions on HRQoL, controlling for other risk factors. RESULTS: Overall, the most frequently observed were stigma perception (56.9%), poor cognitive function (50.6%) and the perception of social isolation (51.6%). The presence of depressive symptoms was the risk factor most associated with worse Physical Health (PH) (B 3.93, 2.71-5.15) and Mental Health (MH) (B 5.08, 3.81-6.34) in linear regression model. Specifically, an interaction was observed between poor cognitive function and poor satisfaction with social role on worse PH and MH (AI 2.08, 0.14-4.02; AI 2.69, 0.15-5.22, respectively); and low income and perception of stigma (AI 2.98, 0.26-5.71), low income and perception of social isolation (AI 2.79, 0.27-5.32), and low income and poor satisfaction with social role (AI 3.45, 0.99-5.91) on MH. CONCLUSION: These findings provide evidence that syndemic factors impact HRQoL. HIV prevention programs should screen and address co-occurring health problems to improve patient-centered health care and outcomes.
Assuntos
Infecções por HIV , Qualidade de Vida , Humanos , Estudos Transversais , Qualidade de Vida/psicologia , Espanha/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/complicações , Sindemia , Estigma SocialRESUMO
OBJECTIVES: To assess the clinical and immunovirological outcomes among naive patients with advanced HIV presentation starting an antiretroviral regimen in real-life settings. METHODS: This was a multicentre, prospective cohort study. We included all treatment-naive adults with advanced HIV disease (CD4+ T cell countâ<â200â cells/mm3or presence of an AIDS-defining illness) who started therapy between 2010 and 2020. The main outcomes were mortality, virological effectiveness (percentage of patients with viral load of ≤50â copies/mL) and immune restoration (percentage of patients with CD4+ T cell count above 350â cells/mm3). Competing risk analysis and Cox proportional models were performed. A propensity score-matching procedure was applied to assess the impact of the antiretroviral regimen. RESULTS: We included 1594 patients with advanced HIV disease [median CD4+T cell count of 81â cells/mm3and 371 (23.3%) with AIDS-defining illness] and with a median follow-up of 4.44â years. The most common ART used was an integrase strand transfer inhibitor (InSTI) regimen (46.9%), followed by PI (35.7%) and NNRTI (17.4%), with adjusted mortality rates at 3â years of 3.1% (95% CI 1.8%-4.3%), 4.7% (95% CI 2.2%-7.1%) and 7.6% (95% CI 5.4%-9.7%) (Pâ=â0.001), respectively. Factors associated with increased mortality included older age and history of injection drug use, whilst treatment with an InSTI regimen was a protective factor [HR 0.5 (95% CI 0.3-0.9)]. A sensitivity analysis with propensity score procedure confirms these results. Patients who started an InSTI achieved viral suppression and CD4+ T cell count above 350â cells/mm3significantly earlier. CONCLUSIONS: In this large real-life prospective cohort study, a significant lower mortality, earlier viral suppression and earlier immune reconstitution were observed among patients with advanced HIV disease treated with InSTIs.
Assuntos
Síndrome da Imunodeficiência Adquirida , Fármacos Anti-HIV , Infecções por HIV , Inibidores da Protease de HIV , Adulto , Humanos , Fármacos Anti-HIV/uso terapêutico , Estudos Prospectivos , Inibidores da Protease de HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Carga Viral , Terapia Antirretroviral de Alta AtividadeRESUMO
OBJECTIVES: To pinpoint factors associated with low-level viraemia (LLV) and virological failure (VF) in people living with HIV in the era of high-efficacy antiretroviral treatment (ART) and widespread use of integrase strand transfer inhibitor (INSTIs)-based ART. METHODS: We included adults aged > 18 years starting their first ART between 2015 and 2018 in the Spanish HIV/AIDS Research Network National Cohort (CoRIS). Low-level viraemia was defined as plasma viral load (pVL) of 50-199 copies/mL at weeks 48 and 72 and VF was defined as pVL ≥ 50 copies/mL at week 48 and pVL ≥ 200 copies/mL at week 72. Multivariable logistic regression models assessed the impact on LLV and VF of baseline CD4 T-cell count, CD4/CD8 T-cell ratio and pVL, initial ART classes, age at ART initiation, time between HIV diagnosis and ART initiation, gender and transmission route. RESULTS: Out of 4186 participants, 3120 (76.0%) started INSTIs, 455 (11.1%) started boosted protease inhibitors (bPIs) and 443 (10.8%) started nonnucleoside reverse transcriptase inhibitors (NNRTIs), either of them with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs). Low-level viraemia was met in 2.5% of participants and VF in 4.3%. There were no significant differences throughout the years for both virological outcomes. Baseline HIV-1 RNA > 5 log10 copies/mL was the only consistent predictor of higher risk of LLV [adjusted odds ratio (aOR) = 9.8, 95% confidence interval (CI): 2.0-48.3] and VF (aOR = 5.4, 95% CI: 1.9-15.1), even in participants treated with INSTIs. CONCLUSIONS: The rates of LLV and VF were low but remained steady throughout the years. Baseline HIV-1 RNA > 5 log10 copies/mL showed a persistent association with LLV and VF even in participants receiving INSTIs.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Inibidores de Integrase de HIV , HIV-1 , Adulto , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , Humanos , Inibidores de Integrase/uso terapêutico , RNA/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Carga Viral , Viremia/tratamento farmacológicoRESUMO
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 (p = 0.047). Interestingly, CD4+ T-cell counts negatively correlated with medium HDL-P concentrations at month 12 in all individuals (ρ = -0.335, p = 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.
Assuntos
Fármacos Anti-HIV , Aterosclerose , Infecções por HIV , Fármacos Anti-HIV/uso terapêutico , Aterosclerose/etiologia , Biomarcadores , Colesterol/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Humanos , Lipoproteínas/sangueRESUMO
A significant proportion of people living with HIV (PLHIV) who successfully achieve virological suppression fail to recover CD4+ T-cell counts. Since adipose tissue has been discovered as a key immune organ, this study aimed to assess the role of adipokines in the HIV immunodiscordant response. This is a multicenter prospective study including 221 PLHIV starting the first antiretroviral therapy (ART) and classified according to baseline CD4+ T-cell counts/µL (controls > 200 cells/µL and cases ≤ 200 cells/µL). Immune failure recovery was considered when cases did not reach more than 250 CD4+ T cells/µL at 144 weeks (immunological nonresponders, INR). Circulating adipokine concentrations were longitudinally measured using enzyme-linked immunosorbent assays. At baseline, apelin receptor (APLNR) and zinc-alpha-2-glycoprotein (ZAG) concentrations were significantly lower in INRs than in immunological responders (p = 0.043 and p = 0.034), and they remained lower during all ART follow-up visits (p = 0.044 and p = 0.028 for APLNR, p = 0.038 and p = 0.010 for ZAG, at 48 and 144 weeks, respectively). ZAG levels positively correlated with retinol-binding protein 4 (RBP4) levels (p < 0.01), and low circulating RBP4 concentrations were related to a low CD4+ T-cell gain (p = 0.018 and p = 0.039 at 48 and 144 weeks, respectively). Multiple regression adjusted for clinical variables and adipokine concentrations confirmed both low APLNR and RBP4 as independent predictors for CD4+ T cells at 144 weeks (p < 0.001). In conclusion, low APLNR and RBP4 concentrations were associated with poor immune recovery in treated PLHIV and could be considered predictive biomarkers of a discordant immunological response.
Assuntos
Adipocinas/metabolismo , Receptores de Apelina/metabolismo , Biomarcadores/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Infecções por HIV/metabolismo , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Adipocinas/imunologia , Adulto , Terapia Antirretroviral de Alta Atividade/métodos , Receptores de Apelina/imunologia , Contagem de Linfócito CD4/métodos , Linfócitos T CD4-Positivos/imunologia , Feminino , Infecções por HIV/imunologia , HIV-1/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Plasmáticas de Ligação ao Retinol/imunologia , Carga Viral/fisiologiaRESUMO
BACKGROUND: Early combined antiretroviral treatment (cART) in perinatally acquired HIV-1 children has been associated with a rapid viral suppression, small HIV-1 reservoir size and reduced mortality and morbidity. Immunometabolism has emerged as an important field in HIV-1 infection offering both relevant knowledge regarding immunopathogenesis and potential targets for therapies against HIV-1. OBJECTIVES: To characterize the proteomic, lipidomic and metabolomic profile of HIV-1-infected children depending on their age at cART initiation. PATIENTS AND METHODS: Plasma samples from perinatally HIV-1-infected children under suppressive cART who initiated an early cART (first 12 weeks after birth, EARLY, n = 10) and late cART (12-50 weeks after birth, LATE, n = 10) were analysed. Comparative plasma proteomics, lipidomics and metabolomics analyses were performed by nanoLC-Orbitrap, UHPLC-qTOF and GC-qTOF, respectively. RESULTS: Seven of the 188 proteins identified exhibited differences comparing EARLY and LATE groups of HIV-1-infected children. Despite no differences in the lipidomic (n = 115) and metabolomic (n = 81) profiles, strong correlations were found between proteins and lipid levels as well as metabolites, including glucidic components and amino acids, with clinical parameters. The ratio among different proteins showed high discriminatory power of EARLY and LATE groups. CONCLUSIONS: Protein signature show a different proinflammatory state associated with a late cART introduction. Its associations with lipid levels and the relationships found between metabolites and clinical parameters may potentially trigger premature non-AIDS events in this HIV-1 population, including atherosclerotic diseases and metabolic disorders. Antiretroviral treatment should be started as soon as possible in perinatally acquired HIV-1-infected children to prevent them from future long-life complications.
Assuntos
Infecções por HIV , Soropositividade para HIV , HIV-1 , Terapia Antirretroviral de Alta Atividade , Criança , Infecções por HIV/tratamento farmacológico , Humanos , Metaboloma , ProteômicaRESUMO
OBJECTIVES: We report the results of the reverse transcriptase (RT)/protease (PR) transmitted drug resistance (TDR) prevalence study in 2018, focusing on doravirine resistance-associated mutations and the differences observed when Stanford or French National Agency for AIDS Research (ANRS)/Spanish Network of AIDS Research (RIS)/IAS-USA resistance interpretation algorithms are used to describe clinically relevant resistance. METHODS: We used the WHO 2009 list to investigate the prevalence of NNRTI, NRTI and PI TDR, in treatment-naive HIV-1-infected patients, adding mutations E138A/G/K/Q/R, V106I, V108I, V179L, G190Q, H221Y, F227C/L/V, M230IDR, L234I, P236L and Y318F in RT. The prevalence of doravirine resistance-associated mutations, as described by Soulie et al. in 2019, was evaluated. Clinically relevant TDR was investigated using the latest versions of ANRS, RIS, IAS-USA and Stanford algorithms. RESULTS: NNRTI mutations were detected in 82 of 606 (13.5%) patients. We found 18 patients (3.0%) with NRTI mutations and 5 patients (0.8%) with PI mutations. We detected 11 patients harbouring doravirine resistance-associated mutations (prevalence of 1.8%). Furthermore, we observed important differences in clinically relevant resistance to doravirine when ANRS/RIS (0.7%), IAS-USA (0.5%) or Stanford algorithms (5.0%) were used. V106I, which was detected in 3.8% of the patients, was the main mutation driving these differences. V106I detection was not associated with any of the clinical, demographic or virological characteristics of the patients. CONCLUSIONS: The prevalence of NRTI and PI TDR remains constant in Spain. Doravirine TDR is very infrequent by RIS/ANRS/IAS-USA algorithms, in contrast with results using the Stanford algorithm. Further genotype-phenotype studies are necessary to elucidate the role of V106I in doravirine resistance.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Algoritmos , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Mutação , Prevalência , Piridonas , Espanha , TriazóisRESUMO
BACKGROUND: Elite controllers (ECs) spontaneously control plasma human immunodeficiency virus type 1 (HIV-1) RNA without antiretroviral therapy. However, 25% lose virological control over time. The aim of this work was to study the proteomic profile that preceded this loss of virological control to identify potential biomarkers. METHODS: Plasma samples from ECs who spontaneously lost virological control (transient controllers [TCs]), at 2 years and 1 year before the loss of control, were compared with a control group of ECs who persistently maintained virological control during the same follow-up period (persistent controllers [PCs]). Comparative plasma shotgun proteomics was performed with tandem mass tag (TMT) isobaric tag labeling and nanoflow liquid chromatography coupled to Orbitrap mass spectrometry. RESULTS: Eighteen proteins exhibited differences comparing PC and preloss TC timepoints. These proteins were involved in proinflammatory mechanisms, and some of them play a role in HIV-1 replication and pathogenesis and interact with structural viral proteins. Coagulation factor XI, α-1-antichymotrypsin, ficolin-2, 14-3-3 protein, and galectin-3-binding protein were considered potential biomarkers. CONCLUSIONS: The proteomic signature associated with the spontaneous loss of virological control was characterized by higher levels of inflammation, transendothelial migration, and coagulation. Galectin-3 binding protein could be considered as potential biomarker for the prediction of virological progression and as therapeutic target in ECs.
Assuntos
Infecções por HIV/imunologia , Proteoma/análise , Adulto , Biomarcadores/sangue , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Feminino , Infecções por HIV/sangue , Infecções por HIV/virologia , HIV-1/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga Viral , Replicação ViralRESUMO
BACKGROUND: Integrase strand-transfer inhibitors (INSTIs) constitute at present one of the pillars of first-line ART. OBJECTIVES: To study the prevalence of and the trend in transmitted drug resistance (TDR) to INSTIs in ART-naive patients in Spain. METHODS: During the period 2012-17, 1109 patients from CoRIS were analysed. The Stanford algorithm v8.7 was used to evaluate TDR and transmission of clinically relevant resistance. To describe individual mutations/polymorphisms, the most recent IAS list (for INSTIs) and the 2009 WHO list update (for the backbone NRTIs used in combination with INSTIs in first-line treatment) were used. RESULTS: Clinically relevant resistance to the INSTI class was 0.2%: T66I, 0.1%, resistance to elvitegravir and intermediate resistance to raltegravir; and G163K, 0.1%, intermediate resistance to raltegravir and elvitegravir. No clinical resistance to dolutegravir or bictegravir was observed. The prevalence of INSTI TDR following the IAS-USA INSTI mutation list was 2.6%, with no trend towards changes in the prevalence throughout the study period. The overall prevalence of NRTI WHO mutations was 4.3%, whereas clinically relevant resistance to tenofovir, abacavir and emtricitabine/lamivudine was 1.7%, 1.9% and 0.7%, respectively. CONCLUSIONS: Given the low prevalence of clinically relevant resistance to INSTIs and first-line NRTIs in Spain, it is very unlikely that a newly diagnosed patient will present with clinical resistance to a first-line INSTI-based regimen. These patients may not benefit from INSTI and NRTI baseline resistance testing.
Assuntos
Farmacorresistência Viral , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Inibidores de Integrase de HIV/farmacologia , Adulto , Idoso , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Vigilância em Saúde Pública , Espanha/epidemiologiaRESUMO
The immunological, biochemical and molecular mechanisms associated with poor immune recovery are far from known, and metabolomic profiling offers additional value to traditional soluble markers. Here, we present novel and relevant data that could contribute to better understanding of the molecular mechanisms preceding a discordant response and HIV progression under suppressive combined antiretroviral therapy (cART). Integrated data from nuclear magnetic resonance (NMR)-based lipoprotein profiles, mass spectrometry (MS)-based metabolomics and soluble plasma biomarkers help to build prognostic and immunological progression tools that enable the differentiation of HIV-infected subjects based on their immune recovery status after 96 weeks of suppressive cART. The metabolomic signature of ART-naïve HIV subjects with a subsequent late immune recovery is the expression of pro-inflammatory molecules and glutaminolysis, which is likely related to elevate T-cell turnover in these patients. The knowledge about how these metabolic pathways are interconnected and regulated provides new targets for future therapeutic interventions not only in HIV infection but also in other metabolic disorders such as human cancers where glutaminolysis is the alternative pathway for energy production in tumor cells to meet their requirement of rapid proliferation.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Glutamina/metabolismo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Lipoproteínas/sangue , Adulto , Biomarcadores/sangue , Estudos de Coortes , Seguimentos , Infecções por HIV/metabolismo , HIV-1 , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Espectrometria de Massas , Metabolômica , Pessoa de Meia-IdadeRESUMO
BACKGROUND: It is unclear whether metabolic or body composition effects differ between protease inhibitor-based regimens recommended for initial treatment of human immunodeficiency virus (HIV) infection. METHODS: ATADAR is a phase 4, open-label, multicenter, randomized clinical trial. Stable antiretroviral-naive HIV-infected adults were randomly assigned to atazanavir/ritonavir 300/100 mg or darunavir/ritonavir 800/100 mg in combination with tenofovir/emtricitabine daily. Predefined endpoints were treatment or virological failure, drug discontinuation due to adverse effects, and laboratory and body composition changes at 96 weeks. RESULTS: At 96 weeks, 56 (62%) atazanavir/ritonavir and 62 (71%) darunavir/ritonavir patients remained free of treatment failure (estimated difference 8.2%; 95% confidence interval [CI], -.6 to 21.6) and 71 (79%) atazanavir/ritonavir and 75 (85%) darunavir/ritonavir patients remained free of virological failure (estimated difference 6.3%; 95% CI, -.5 to 17.6). Seven patients discontinued atazanavir/ritonavir and 5 discontinued darunavir/ritonavir due to adverse effects. Total and high-density lipoprotein cholesterol similarly increased in both arms, but there was a greater increase in triglycerides in the atazanavir/ritonavir arm. At 96 weeks, body fat (estimated difference 2862.2 gr; 95% CI, 726.7 to 4997.7; P = .0090), limb fat (estimated difference 1403.3 gr; 95% CI, 388.4 to 2418.2; P = .0071), and subcutaneous abdominal adipose tissue (estimated difference 28.4 cm(2); 95% CI, 1.9 to 55.0; P = .0362) increased more in the atazanavir/ritonavir arm than in darunavir/ritonavir arm. Body fat changes in the atazanavir/ritonavir arm were associated with higher insulin resistance. CONCLUSIONS: We found no major differences between atazanavir/ritonavir and darunavir/ritonavir in efficacy, clinically relevant side effects, or plasma cholesterol fractions. However, atazanavir/ritonavir led to higher triglycerides and more total and subcutaneous fat than darunavir/ritonavir. Also, fat gains with atazanavir/ritonavir were associated with insulin resistance. Clinical Trials Registration. NCT01274780.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Composição Corporal/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/uso terapêutico , Adulto , Feminino , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Carga ViralRESUMO
OBJECTIVES: A relationship between obesity and intestinal bacterial translocation has been reported. Very little information is available with respect to the involvement of the bacterial translocation mechanistic pathway in HIV-1/highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (HALS). We determined whether lipopolysaccharide (LPS)-binding protein (LBP), cluster of differentiation 14 (CD14), myeloid differentiation protein 2 (MD2) and toll-like receptor 4 (TLR4) single-nucleotide polymorphisms and LPS, LBP and soluble CD14 (sCD14) plasma levels are involved in HALS. PATIENTS AND METHODS: This cross-sectional multicentre study involved 558 treated HIV-1-infected patients, 240 with overt HALS and 318 without HALS. Anthropometric, clinical, immunovirological and metabolic variables were determined. Polymorphisms were assessed by genotyping. Plasma levels were determined by ELISA in 163 patients (81 with HALS and 82 without HALS) whose stored plasma samples were available. Student's t-test, one-way ANOVA, two-way repeated measures ANOVA, the χ(2) test and Pearson and Spearman correlation analyses were carried out for statistical analysis. RESULTS: LBP rs2232582 TâC polymorphism was significantly associated with HALS (Pâ=â0.01 and Pâ=â0.048 for genotype and allele analyses, respectively). Plasma levels of LPS (Pâ=â0.009) and LBP (Pâ<â0.001) were significantly higher and sCD14 significantly lower (Pâ<â0.001) in patients with HALS compared with subjects without HALS. LPS levels were independently predicted by triglycerides (Pâ<â0.001) and hepatitis C virus (Pâ=â0.038), LBP levels by HALS (Pâ<â0.001) and sCD14 levels by age (Pâ=â0.008), current HIV-1 viral load (Pâ=â0.001) and protease inhibitor use (Pâ=â0.018). CONCLUSIONS: HALS is associated with LBP polymorphism and with higher bacterial translocation.
Assuntos
Proteínas de Fase Aguda/metabolismo , Proteínas de Transporte/metabolismo , Síndrome de Lipodistrofia Associada ao HIV/etiologia , Síndrome de Lipodistrofia Associada ao HIV/metabolismo , Receptores de Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/imunologia , Antígeno 96 de Linfócito/metabolismo , Glicoproteínas de Membrana/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Proteínas de Fase Aguda/genética , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Contagem de Linfócito CD4 , Proteínas de Transporte/sangue , Proteínas de Transporte/genética , Estudos de Casos e Controles , Estudos Transversais , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1 , Síndrome de Lipodistrofia Associada ao HIV/diagnóstico , Humanos , Inflamação , Receptores de Lipopolissacarídeos/sangue , Receptores de Lipopolissacarídeos/genética , Lipopolissacarídeos/sangue , Antígeno 96 de Linfócito/genética , Masculino , Glicoproteínas de Membrana/sangue , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Fatores de Risco , Receptor 4 Toll-Like/genética , Carga ViralRESUMO
Introduction: The prognostic ability of myocardial injury across different waves of the COVID-19 pandemic is not well established. The purpose of this study was to evaluate the prevalence and prognostic implications of myocardial injury in the first and sixth wave of COVID-19. Methods: We conducted a retrospective observational study that included patients admitted to the emergency department with COVID-19 with data on concentrations of cardiac troponin during the first and sixth wave. We compared the prevalence of myocardial injury and its predictive capacity for 30-day all-cause death in both waves. Results and discussion: A total of 346 patients were included (1st wave 199 and 6th wave 147 patients). The prevalence of myocardial injury was 21% with non-significant differences between waves. Myocardial injury was associated, in both waves, with a higher prevalence of comorbidities and with an increased risk of 30-day all-cause death [1st wave HR: 3.73 (1.84-7.55); p < 0.001 and 6th wave HR: 3.13 (1.23-7.92); p = 0.016], with non-significant differences in predictive capacity between groups after ROC curve analysis [AUC: 1st wave 0.829 (95% CI: 0.764-0.895) and 6th wave 0.794 (95% CI: 0.711-0.876)]. As limitations, this is a retrospective study with a relatively small simple size and troponin assay was performed at the discretion of the emergency physician so selection bias could be present. In conclusion, the prevalence of myocardial injury and its prognostic capacity was similar in both waves despite vaccination programs. Myocardial injury predicts short-term mortality in all COVID-19 patients, so they should be treated intensively.
RESUMO
BACKGROUND: COVID-19 pneumonia causes hyperinflammatory response that culminates in acute respiratory syndrome (ARDS) related to increased multiorgan dysfunction and mortality risk. Antiviral-neutralizing immunoglobulins production reflect the host humoral status and illness severity, and thus, immunoglobulin (Ig) circulating levels could be evidence of COVID-19 prognosis. METHODS: The relationship among circulating immunoglobulins (IgA, IgG, IgM) and COVID-19 pneumonia was evaluated using clinical information and blood samples in a COVID-19 cohort composed by 320 individuals recruited during the acute phase and followed up to 4 to 8 weeks (n = 252) from the Spanish first to fourth waves. RESULTS: COVID-19 pneumonia development depended on baseline Ig concentrations. Circulating IgA levels together with clinical features at acute phase was highly associated with COVID-19 pneumonia development. IgM was positively correlated with obesity (ρb = 0.156, P = 0.020), dyslipemia (ρb = 0.140, P = 0.029), COPD (ρb = 0.133, P = 0.037), cancer (ρb = 0.173, P = 0.007) and hypertension (ρb = 0.148, P = 0.020). Ig concentrations at recovery phase were related to COVID-19 treatments. CONCLUSIONS: Our results provide valuable information on the dynamics of immunoglobulins upon SARS-CoV-2 infection or other similar viruses.
Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Imunoglobulina G , Imunoglobulina M , Anticorpos Antivirais , Imunoglobulina ARESUMO
We assessed the prevalence and factors associated with HIV-infected patients' interest in trying long-acting injectable antiretroviral treatment (LAI-ART) along with its expected benefits and concerns, and evaluated physicians' opinions about LAI-ART. This study was set within the multi-center prospective CoRIS cohort, comprising HIV-positive adults, naïve to antiretroviral treatment (ART) at study entry, recruited from 2004 onward in 48 centers in Spain. In June 2022, we conducted a 2-day cross-sectional survey among patients across 34 CoRIS centers and sent an online questionnaire to all physicians prescribing ART in 39 CoRIS centers. Of the 271 patients included, 83.3% [95% confidence interval (CI)]: 78.0 - 87.0%) expressed interest in receiving LAI-ART. This interest was higher among men (adjusted odds ratio: 2.96; 95% CI: 1.4-6.12), those aged <50 years (2.41; 1.23 - 4.73), and individuals inconvenienced by oral ART (5.03; 1.47 - 17.15), daily intake (14.65; 3.44-62.46), carrying HIV pills constantly (7.19; 2.88 - 17.96), and taking multiple medications (3.94; 1.58 - 9.85). Among the 154 physicians surveyed, 45.5% believed LAI-ART would be the preferred option for patients. Although most physicians (92.9%) thought LAI-ART could improve patients' quality of life (QoL), concerns were raised by 37.7% and 44.2% of them regarding injection site pain and visit rescheduling, respectively. Interest in LAI-ART was higher among men, those aged <50 years, and individuals finding their oral ART inconvenient. Physicians believed LAI-ART could improve QoL and overcome treatment challenges, yet concerns were raised about its potential usage difficulties. Although most patients were interested in receiving LAI-ART, only less than half of the physicians considered it their preferred option, likely owing to concerns about missed visits and injection site pain.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Injeções , Médicos , Humanos , Masculino , Infecções por HIV/tratamento farmacológico , Espanha , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Transversais , Médicos/psicologia , Inquéritos e Questionários , Estudos Prospectivos , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Preparações de Ação Retardada , Atitude do Pessoal de SaúdeRESUMO
Background: Coronavirus disease 2019 (COVID-19) disproportionately affects migrants and ethnic minorities, including those with human immunodeficiency virus (HIV). Comprehensive studies are needed to understand the impact and risk factors. Methods: Using data from the PISCIS cohort of people with HIV (PWH) in Catalonia, Spain, we investigated COVID-19 outcomes and vaccination coverage. Among 10 640 PWH we compared migrants and non-migrants assessing rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, diagnosis, and associated clinical outcomes through propensity score matching and multivariable Cox regression. Results: The cohort (mean age, 43 years; 83.5% male) included 57.4% (3053) Latin American migrants. Migrants with HIV (MWH) had fewer SARS-CoV-2 tests (67.8% vs 72.1%, P < .0001) but similar COVID-19 diagnoses (29.2% vs 29.4%, P = .847) compared to Spanish natives. Migrants had lower complete vaccination (78.9% vs 85.1%, P < .0001) and booster doses (63.0% vs 65.5%, P = .027). COVID-19 hospitalizations (8.1% vs 5.1%, P < .0001) and intensive care unit (ICU) admissions (2.9% vs 1.2%, P < .0001) were higher among migrants, with similar hospitalization duration (5.5 vs 4.0 days, P = .098) and mortality (3 [0.2%] vs 6 [0.4%], P = .510). Age ≥40 years, CD4 counts <200â cells/µL, ≥2 comorbidities, and incomplete/nonreception of the SARS-CoV-2 vaccine increased the risk of severe COVID-19 among migrants. Conclusions: MWH had lower rates of SARS-CoV-2 testing and vaccination coverage, although the rates of COVID-19 diagnosis were similar between migrants and non-migrants. Rates of COVID-19-associated hospitalizations and ICU admissions were higher among migrants in comparison with non-migrants, with similar hospitalization duration and mortality. These findings can inform policies to address disparities in future pandemic responses for MWH.