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OBJECTIVES: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. METHODS: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. RESULTS: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). CONCLUSIONS: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population.
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Coinfecção , Infecções por HIV , Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Coinfecção/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos , Cirrose Hepática/epidemiologia , RNA/uso terapêutico , Espanha/epidemiologiaRESUMO
INTRODUCTION: In people living with HIV (PLWH), bone mineral density (BMD) discordance between the lumbar spine (LS) and femoral neck (FN) could be frequent given the high frequency of secondary osteoporosis, including HIV-related factors for bone disease. MATERIALS AND METHODS: Retrospective cohort of PLWH with a dual X-ray absorptiometry scan. Hip-spine BMD discordance was defined as different T-score or Z-scores categories at LS and FN. RESULTS: Overall, 865 individuals (mean 49.5 years, female 27%) were included. Osteoporosis diagnosis was four-to-seven times lower when both skeletal sites were affected than when considering the lowest T-score at any site (overall, 21% vs 4%). Hip-spine BMD discordance was observed in 381 (44%) individuals, it increased with age (from 43 to 52%, P = 0.032), and it was mainly due to lower LS-BMD. A lower FN-BMD was associated with older age, lower BMI (P < 0.01), and HIV-related factors, such as low CD4 + T-cell counts, duration of HIV infection, and time on antiretroviral therapy (ART). In a multivariate regression analysis, sex male (Odds Ratio, OR 4.901), hyperparathyroidism (OR, 2.364), and time on ART (OR 1.005 per month) were independently associated with discordance. A higher estimated fracture risk by FRAX equation was observed in individuals with BMD discordance due to lower FN-BMD compared to those with lower LS-BMD (+ 36% for major osteoporotic fracture, P = 0.04; + 135% for hip fracture, P < 0.01). CONCLUSION: Hip-spine BMD discordance is highly prevalent in PLWH and it is associated with classical and HIV-related risk factors, modifying the rate of osteoporosis and fracture risk estimation.
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Infecções por HIV , Osteoporose , Fraturas por Osteoporose , Humanos , Masculino , Feminino , Densidade Óssea , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Estudos Retrospectivos , Absorciometria de Fóton , Osteoporose/complicações , Fraturas por Osteoporose/complicações , Vértebras Lombares/diagnóstico por imagem , Fatores de RiscoRESUMO
PURPOSE: SARS-CoV-2 infection produces lymphopenia and CD4+ T-cell decrease, which could lead to a higher risk of bacterial co-infection or impair immunological evolution in people living with HIV (PLWH). METHODS: We investigated the rate of co-infection and superinfection, and the evolution of CD4+ count and CD4+/CD8+ ratio, in hospitalized PLWH with COVID-19. RESULTS: From March to December 2020, 176 PLWH had symptomatic COVID-19 and 62 required hospitalization (median age, 56 years, 89% males). At admission, 7% and 13% of patients had leukocytosis or increased procalcitonin values and 37 (60%) received empiric antibiotic therapy, but no bacterial co-infection was diagnosed. There were seven cases of superinfection (12%), and one case of P. jiroveci pneumonia during ICU stay. No significant change in CD4+ count or CD4+/CD8+ ratio was observed after discharge. CONCLUSION: Bacterial co-infection is not frequent in PLWH with COVID-19. Immune recovery is observed in most of patients after the disease.
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COVID-19 , Infecções por HIV , Infecções Bacterianas/epidemiologia , COVID-19/epidemiologia , COVID-19/imunologia , Coinfecção/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Humanos , Terapia de Imunossupressão/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/epidemiologia , Medição de RiscoAssuntos
Exantema , Mpox , Humanos , Monkeypox virus , Mpox/diagnóstico , Mpox/epidemiologia , Mpox/patologia , Exantema/epidemiologia , Surtos de DoençasRESUMO
Current guidelines recommend screening people with HIV (PWH) for bone disease using predictive tools developed for the general population, although data on PWH are scarce. In this study, we assessed the performance of FRAX and QFracture scoring systems to predict the occurrence of fragility fractures in a prospective cohort of 17,671 adults with human immunodeficiency virus (HIV) included in the HIV/AIDS research network (CoRIS) in Spain. The survival estimates of fragility fractures during follow-up were calculated and FRAX and QFracture scores were computed at cohort inclusion. For both tools, discriminatory measures and the observed-to-expected (O/E) ratios were assessed. During a follow-up time of 42,411.55 person-years, 113 fragility fractures were recorded. Areas under the curve were 0.66 [95% confidence interval (95% CI) 0.61-0.71] for FRAX and 0.67 (95% CI 0.62-0.73) for QFracture for major osteoporotic fractures, and 0.72 (95% CI 0.57-0.88) and 0.81 (95% CI 0.68-0.95) for hip fracture, respectively. The O/E was 1.67 for FRAX and 5.49 for QFracture for major osteoporotic fractures, and 11.23 for FRAX and 4.87 for QFracture for hip fractures. Moreover, O/E raised as the risk increased for both tools and in almost all age groups. When using the recommended assessment thresholds, <6% and 10% of major osteoporotic and hip fractures would have been identified, respectively. In conclusion, FRAX and QFracture displayed acceptable discrimination, although both tools significantly underestimated the risk of fragility fractures in PWH. The recommended assessment thresholds may not be appropriate for this population as they were unable to identify individuals with fragility fractures during follow-up.
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Infecções por HIV , Fraturas do Quadril , Fraturas por Osteoporose , Adulto , Humanos , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/diagnóstico , HIV , Estudos Prospectivos , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Medição de Risco , Fraturas do Quadril/epidemiologia , Fatores de Risco , Densidade ÓsseaRESUMO
People with HIV have a higher risk of fracture than the general population. Because of the low performance of the existing prediction tools, there is controversy surrounding fracture risk estimation in this population. The aim of the study was to develop a model for predicting the long-term risk of fragility fractures in people with HIV. We included 11,899 individuals aged ≥30 years from the Spanish HIV/AIDS research network cohort. We identified incident fragility fractures from medical records, defined as nontraumatic or those occurring after a casual fall, at major osteoporotic sites (hip, clinical spine, forearm, proximal humerus). Our model accounted for the competing risk of death and included 12 candidate predictors to estimate the time to first fragility fracture. We assessed the discrimination and calibration of the model and compared it with the FRAX tool. The incidence rate of fragility fractures was 4.34 (95% CI 3.61 to 5.22) per 1000 person-years. The final prediction model included age, chronic kidney disease, and chronic obstructive pulmonary disease as significant predictors. The model accurately predicted the 5- and 10-year risk of fragility fractures, with an area under the receiving operator characteristic curve of 0.768 (95% CI 0.722 to 0.814) and agreement between the observed and expected probabilities. Furthermore, it demonstrated better discrimination and calibration than the FRAX tool, improving the classification of over 35% of individuals with fragility fractures compared to FRAX. Our prediction model demonstrated accuracy in predicting the long-term risk of fragility fractures. It can assist in making personalized intervention decisions for individuals with HIV and could potentially replace the current tools recommended for fracture risk assessment in this population. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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People living with HIV-1 and HTLV-2 concomitantly show slower CD4+ T cell depletion and AIDS progression, more frequency of the natural control of HIV-1, and lower mortality rates. A similar beneficial effect of this infection has been reported on HCV coinfection reducing transaminases, increasing the spontaneous clearance of HCV infection and delaying the development of hepatic fibrosis. Given the critical role of CD8+ T cells in controlling HIV-1 infection, we analysed the role of CD8+ T cell-mediated cytotoxic activity in coinfected individuals living with HIV-1. One hundred and twenty-eight individuals living with HIV-1 in four groups were studied: two groups with HTLV-2 infection, including individuals with HCV infection (N = 41) and with a sustained virological response (SVR) after HCV treatment (N = 25); and two groups without HTLV-2 infection, including individuals with HCV infection (N = 25) and with a sustained virological response after treatment (N = 37). We found that CD8+ T cell-mediated HIV-1 inhibition in vitro was higher in individuals with HTLV-2. This inhibition activity was associated with a higher frequency of effector memory CD8+ T cells, higher levels of granzyme A and granzyme B cytolytic enzymes, and perforin. Hence, cellular and soluble cytolytic factors may contribute to the lower HIV-1 pre-ART viral load and the HIV-1 proviral load during ART therapy associated with HTLV-2 infection. Herein, we confirmed and expanded previous findings on the role of HTLV-2 in the beneficial effect on the pathogenesis of HIV-1 in coinfected individuals.
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Coinfecção , Infecções por HIV , Soropositividade para HIV , HIV-1 , Infecções por HTLV-II , Hepatite C , Humanos , Vírus Linfotrópico T Tipo 2 Humano , HIV-1/fisiologia , Provírus , Linfócitos T CD8-Positivos/patologia , Carga Viral , Hepatite C/complicaçõesRESUMO
BACKGROUND AND AIMS: There are no population data on bone mass in individuals with HIV in Spain, adjusted for age and sex. MATERIALS AND METHODS: Bone mineral density (BMD) data were obtained by dual X-ray absorptiometry in a cohort of individuals with HIV infection compared with cohort data from the general population in Spain and the United States of America. RESULTS: Of 928 individuals (mean 46 years, 25% women), the prevalence of osteoporosis in the lumbar spine/femoral neck was 18%/5% in men, and 17%/10% in women, respectively. The rate increased from the age of 40 in men and from 50 in women (osteoporosis in 20% and 27%, respectively). BMD was lower than that observed in the general population in almost all age groups (mean, -6%; between 0%-11% lower compared to the Spanish cohort, and -8%; between 0%-14% lower than the American cohort). CONCLUSIONS: Our cohort of individuals with HIV had a lower BMD in all age groups after adjustment for age and sex, compared with the general population. This fact must be considered when making recommendations.
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Infecções por HIV , Osteoporose , Absorciometria de Fóton , Densidade Óssea , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Osteoporose/epidemiologia , Osteoporose/etiologia , Prevalência , Estados UnidosRESUMO
People with HIV (PWH) might have a higher risk of adverse coronavirus disease 2019 (COVID-19) outcomes. Several scores were developed to predict COVID-19 progression to critical disease and are often used among PWH. We assessed the performance of two commonly used risk equations among PWH and COVID-19. Participants were identified from a multicenter cohort of 6,361 PWH on regular follow-up at 2 university hospitals. Of 99 HIV-infected individuals with confirmed SARS-CoV-2 infection, 63 had complete data and were included in this analysis. CALL and COVID-GRAM scores were calculated and participants were stratified into low-, intermediate-, and high-risk groups for each. Discrimination was assessed using receiver operating characteristic curves. Calibration was evaluated using observed versus expected (O:E) ratios and the Hosmer-Lemeshow χ2 goodness-of-fit statistic. Scores were adjusted by increasing one category level in individuals with nadir CD4 lymphocyte count <200/µL. Participants had a median nadir and current CD4 counts of 207 [interquartile range (IQR) 119-345] and 440 (IQR 280-719) cells/µL. Ten (15.9%) individuals progressed to critical disease and 4 (6.3%) died. Assessed scores showed acceptable discrimination (area under the curve 0.701-0.771) and were overall calibrated (O:E ratio 1.01). However, both overestimated the risk of progression among individuals in the low- and high-risk categories, whereas they underestimated the risk in the intermediate category (O:E 1.20-1.21). Thus, 50% of critically ill individuals were not identified as high risk. Assigning PWH with low nadir CD4 counts a higher risk of progression reduced the proportion of individuals not identified to 20%. COVID-19 risk scores had lower performance in PWH compared with that described in the general population and failed to adequately identify individuals who progressed to critical disease. Adjustment for nadir CD4 partially improved their accuracy. Risk equations incorporating HIV-related factors are needed.
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COVID-19/complicações , COVID-19/diagnóstico , Progressão da Doença , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Adulto , Idoso , Contagem de Linfócito CD4 , Estudos de Coortes , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , SARS-CoV-2 , Adulto JovemRESUMO
In this pilot program of low-dose computed tomography (LDCT) for the screening of lung cancer (LC) in a targeted population of people with HIV (PWH), its prevalence was 3.6%; the number needed to screen in order to detect one case of lung cancer was 28, clearly outweighing the risks associated with lung cancer screening. While data from additional cohorts with longitudinal measurements are needed, PWH are a target population for lung cancer screening with LDCT.
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Infecções por HIV/metabolismo , Neoplasias Pulmonares/diagnóstico , Detecção Precoce de Câncer/métodos , Humanos , Neoplasias Pulmonares/metabolismo , Mortalidade , Estudos Prospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
: Changes in weight and body composition were assessed in long-term suppressed HIV-infected patients switching to dolutegravir/rilpivirine (nâ=â37), and compared with similar patients switching to darunavir/lamivudine (nâ=â17). At month 12, weight significantly increased with dolutegravir/rilpivirine (1.8âkg, IQR -1.2 to 4.1; 2.5%; Pâ=â0.03). A follow-up DXA (median, 16 months) showed similar increases in trunk (7.8%), arms (5.6%), and legs (6.2%) fat mass, without changes in lean mass. Despite lower weight gain (0.70âkg, IQR -0.8 to 4.0, Pâ=â0.28), fat mass increase was similar in the darunavir/lamivudine group. Baseline fat mass and CD4 counts were the only factors explaining fat mass gain.
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Adiposidade , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Substituição de Medicamentos , Infecções por HIV/tratamento farmacológico , Aumento de Peso/efeitos dos fármacos , Adulto , Idoso , Contagem de Linfócito CD4 , Feminino , Compostos Heterocíclicos com 3 Anéis , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Oxazinas , Piperazinas , Estudos Prospectivos , Piridonas , RilpivirinaRESUMO
BACKGROUND: Information about incidence, clinical characteristics, and outcomes of HIV-infected individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is scarce. We characterised individuals with COVID-19 among a cohort of HIV-infected adults in Madrid. METHODS: In this observational prospective study, we included all consecutive HIV-infected individuals (aged ≥18 years) who had suspected or confirmed COVID-19 as of April 30, 2020, at the Hospital Universitario Ramón y Cajal (Madrid, Spain). We compared the characteristics of HIV-infected individuals with COVID-19 with a sample of HIV-infected individuals assessed before the COVID-19 pandemic, and described the outcomes of individuals with COVID-19. FINDINGS: 51 HIV-infected individuals were diagnosed with COVID-19 (incidence 1·8%, 95% CI 1·3-2·3). Mean age of patients was 53·3 years (SD 9·5); eight (16%) were women, and 43 (84%) men. 35 (69%) cases of co-infection had laboratory confirmed COVID-19, and 28 (55%) required hospital admission. Age and CD4 cell counts in 51 patients diagnosed with COVID-19 were similar to those in 1288 HIV-infected individuals without; however, 32 (63%) with COVID-19 had at least one comorbidity (mostly hypertension and diabetes) compared with 495 (38%) without COVID-19 (p=0·00059). 37 (73%) patients had received tenofovir before COVID-19 diagnosis compared with 487 (38%) of those without COVID-19 (p=0·0036); 11 (22%) in the COVID-19 group had previous protease inhibitor use (mostly darunavir) compared with 175 (14%; p=0·578). Clinical, analytical, and radiological presentation of COVID-19 in HIV-infected individuals was similar to that described in the general population. Six (12%) individuals were critically ill, two of whom had CD4 counts of less than 200 cells per µL, and two (4%) died. SARS-CoV-2 RT-PCR remained positive after a median of 40 days from symptoms onset in six (32%) individuals, four of whom had severe disease or low nadir CD4 cell counts. INTERPRETATION: HIV-infected individuals should not be considered to be protected from SARS-CoV-2 infection or to have lower risk of severe disease. Generally, they should receive the same treatment approach applied to the general population. FUNDING: None.
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Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por HIV/complicações , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Fármacos Anti-HIV/uso terapêutico , Índice de Massa Corporal , Contagem de Linfócito CD4 , COVID-19 , Comorbidade , Infecções por Coronavirus/tratamento farmacológico , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pandemias , Pneumonia Viral/tratamento farmacológico , Estudos Prospectivos , Espanha/epidemiologia , Tenofovir/uso terapêutico , Adulto JovemRESUMO
BACKGROUND: Among HIV-infected individuals, screening for bone disease is encouraged to assess reversible risk factors and plan therapeutic interventions. OBJECTIVE: We assessed the usefulness of Fracture Risk Assessment (FRAX) tool to identify candidates for dual X-ray absorptiometry (DXA) scan, or individuals with bone loss progression. We further explored how secondary causes of osteoporosis are reflected on FRAX. METHODS: Longitudinal study of 217 consecutive individuals (mean, 45.8 years, 24% females) included after DXA scan. FRAX was calculated without/with femoral neck bone mineral density (BMD), checking the box of "secondary osteoporosis" for all the individuals. RESULTS: Low BMD was observed in 133/217 (61%) individuals, of whom 98.5% had not been selected as candidates for DXA by current FRAX thresholds. Specifically, 23% of individuals aged <50 had low BMD but none was candidate for DXA. Adding BMD data, FRAX results increased by 50-100%, with 2/217 individuals (1%) above the thresholds. Classical and HIV-related secondary causes of osteoporosis (observed in 98% overall) correlated with low BMD, modifying significantly FRAX results (HCV coinfection, +124%; longer time of HIV infection, +93%; longer time on antiretroviral therapy, +147%; tenofovir exposure +36%). Individuals with lower BMD and higher FRAX results at inclusion had less bone decline in a follow-up DXA after a median of 3.5 years. CONCLUSIONS: Currently recommended FRAX thresholds are not useful to select candidates for DXA scan, which could delay its performance in a population with a high prevalence of secondary factors for low BMD. Classical and HIV-related factors alter BMD and fracture risk estimation.
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Infecções por HIV/complicações , Osteoporose/diagnóstico por imagem , Osteoporose/etiologia , Fraturas por Osteoporose/etiologia , Medição de Risco/normas , Absorciometria de Fóton , Adulto , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , Doenças Ósseas Metabólicas/complicações , Doenças Ósseas Metabólicas/diagnóstico , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/virologia , Estudos Prospectivos , Medição de Risco/métodos , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: A low CD4/CD8 ratio during antiretroviral therapy (ART) identifies people with heightened immunosenescence and increased risk of mortality. We aimed to assess the effects of integrase strand transfer inhibitor (INSTI)-based, protease inhibitor-based, or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART on long-term CD4/CD8 ratio recovery. METHODS: This prospective cohort study included 13â026 individuals with HIV registered in the Spanish HIV Research Network (CoRIS) cohort recruited from 45 Spanish hospitals. We included HIV-positive people who started triple ART (two nucleoside reverse transcriptase inhibitors [NRTI] with a NNRTI, protease inhibitor, or INSTI) and had HIV RNA suppression within 48 weeks. We used piecewise linear mixed models adjusted for potential confounders to compare longitudinal changes in the CD4/CD8 ratio between people receiving three different types of ART. We used Cox proportional-hazard models to compare the times to CD4/CD8 normalisation between the treatment groups, using cutoff ratios of 0·4, 1·0, and 1·5. FINDINGS: 6804 individuals contributing 37â149 persons-years and 37â680 observations were analysed; median follow-up was 49 months (IQR 22-89). INSTI-based ART was associated with greater CD4/CD8 gain (change per year compared with INSTI was coefficient -0·07 [95% CI -0·08 to -0·06] for NNRTI and was -0·08 [-0·09 to -0·08] for protease inhibitors). Differences were observed from the first year of therapy and were driven by changes in both CD4 and CD8 cell counts. Subanalyses at different time periods suggested that these differences were driven by changes during the first year of ART without significant differences in the adjusted CD4/CD8 ratio trajectories after the second year of ART (change per year compared with INSTI was coefficient -0·03 [95% CI -0·05 to -0·13] for NNRTI and was -0·06 [95% CI -0·08 to -0·04] for protease inhibitors). Although no differences in the time until CD4/CD8 normalisation at a cutoff ratio of no less than 0·4 were reported between any of the groups, compared with the INSTI group, both the NNRTI and protease inhibitor groups showed lower rates of normalisation at cutoff ratios of 1·0 or more (adjusted hazard ratio 0·80 [95% CI 0·72-0·89] for the NNRTI group and 0·79 [0·69-0·89] for the protease inhibitor group), and 1·5 or more (0·79 [0·65-0·95] for the NNRTI group and 0·78 [0·64-0·97] for the protease inhibitor group). No differences were found between the different integrases in the time until CD4/CD8 normalisation. Subanalyses adjusted for the backbone NRTIs and allowing observations after virological failure yielded similar results. INTERPRETATION: This study provides new evidence that reinforces the positioning of INSTI-based therapies as a first choice and underlines the importance of analysing the effects of therapeutic interventions on biomarkers linked with morbidity and mortality beyond the plasma HIV RNA and the CD4 cell counts. FUNDING: Spanish AIDS Research Network (Instituto de Salud Carlos III), European Development Regional Fund "A way to achieve Europe".
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Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Relação CD4-CD8 , Linfócitos T CD8-Positivos , Infecções por HIV/tratamento farmacológico , Adulto , Fármacos Anti-HIV/administração & dosagem , Biomarcadores Farmacológicos/análise , Estudos de Coortes , Feminino , Infecções por HIV/imunologia , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , EspanhaRESUMO
Combination antiretroviral therapy has completely changed the landscape of HIV infection through the control of viral replication of the virus, the restoration of the immune system damage, and the reduction of the complications associated with immunodeficiency. As a consequence, the average age of people living with HIV has been increasing progressively, with a high proportion of diagnosed, as well as newly diagnosed, HIV-infected patients being older than 50 years throughout the world. With the longer life expectancy, characteristics commonly observed in aging are occurring in people with long-term HIV infection, including multiple chronic diseases, changes in cognitive and physical abilities, and the use of multiple medications. HIV-related specific factors, as well as a higher prevalence of environmental, classical factors, increase the risk of comorbidities in the aging HIV-infected population. A close collaboration between different specialists (HIV specialists, geriatricians, primary care physicians, and other specialists) is required to manage the clinical problems that older HIV-infected patients may present.
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The CD4/CD8 ratio is an indirect marker of immune activation, immune senescence, and inflammation in HIV infection. We performed a prospective study of the CD4/CD8 ratio evolution in 245 virally-suppressed (median, 55 months) HIV-infected patients (29% females) who had switched to four dual antiretroviral regimens. At baseline, the median CD4/CD8 ratio was 0.71 (interquartile range, IQR, 0.46-0.97), associated with duration of HIV infection, nadir CD4+ cell count, and AIDS diagnosis. It was lower in the case of hepatitis C virus coinfection and cardiovascular disease (p = 0.09), but the ratio was higher in patients with chronic kidney disease, proteinuria, or osteoporosis. At 48 weeks, the median CD4/CD8 ratio increased by 3% (+0.02; IQR, -0.07, +0.09; p = 0.07); greater improvement was observed in patients with lower baseline ratios and previous AIDS diagnosis. The slope of increase was slower in patients with the highest baseline values. Also, there were no differences in the CD4/CD8 ratio increase according to type of dual regimen, after adjusting for baseline and HIV-related values. In conclusion, CD4/CD8 ratio increase is observed during suppressive dual regimens, and its extent is related to baseline values and previous HIV-related factors. Longer duration on antiretroviral therapy and drug toxicity could affect the evolution of this marker in the presence of comorbidities.
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Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Relação CD4-CD8 , Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/tratamento farmacológico , HIV-1/imunologia , Inflamação/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD8-Positivos/patologia , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Carga ViralRESUMO
BACKGROUND: Dual therapies decrease toxicity, pill-burden and treatment-associated cost. The combination of high genetic barrier drugs such as dolutegravir plus boosted-darunavir may be suitable as simplification regimen for patients harbouring multidrug-resistant virus. METHODS: Patients switched to a once-daily regimen consisting of dolutegravir plus darunavir, boosted with cobicistat or ritonavir, were included in this cohort study. The primary end point was the proportion of patients with HIV RNA viral load <37 copies/ml at week 48 (NCT02491242). RESULTS: Overall, 51 patients were enrolled. At baseline, all patients had failed to ≥2 antiretroviral classes. Genotypic resistance profiles showed a mean of primary mutations of 1.2 for non-nucleoside reverse transcriptase inhibitors, 2.4 for nucleoside/nucleotide reverse transcriptase inhibitors and 3.5 for protease inhibitors (PIs), but they were virologically suppressed for a median of 33 months (IQR 12-60). Only five patients had reduced sensitivity to darunavir and mean genotypic susceptibility score of dual therapy was 1.95 over 2. At week 48, there were no virological failures, three patients discontinued the regimen due to neuropsychiatric adverse events, two were lost to follow-up, and therefore the efficacy was 90% (95% CI, 82, 99%, intention-to-treat analysis). Mean estimated glomerular filtration rate decreased by 8.8 ml/min/1.73 m2, though kidney tubular parameters, high density lipoprotein-cholesterol and triglycerides levels improved after switching to dual therapy. CONCLUSIONS: In highly treatment-experienced patients who were virologically suppressed, switching to the combination of dolutegravir plus boosted-darunavir dual therapy was effective and well tolerated, improving lipid and renal parameters.
Assuntos
Darunavir/administração & dosagem , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade , Darunavir/efeitos adversos , Farmacorresistência Viral , Feminino , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Oxazinas , Piperazinas , Piridonas , Resultado do Tratamento , Carga ViralRESUMO
BACKGROUND: Dual therapies have been tested in selected patients, but there is no evidence for its advantages in clinical practice. The aim of this study was to evaluate in the clinical setting the long-term outcomes and the impacts on comorbidities of a dual therapy based on lamivudine plus darunavir boosted with ritonavir (DRV/r). METHODS: A prospective cohort study of 106 patients who were switched to this dual regimen from April 2014 to December 2017 because of renal and bone toxicity, intolerance, or physician's decision was conducted. The primary study endpoint was the proportion of patients who were free of treatment failure at 48 and 96 weeks. RESULTS: The mean age was 50 years, and 64% were hepatitis C virus-coinfected. At 48 weeks, the efficacy was 95% (95% confidence interval, 91-99%; ITT-e analysis; two changes due to toxicity, three because of drug-drug interactions -DDIs-). At week 96, 26 patients (25%) had discontinued this therapy (two virologic failures, one additional adverse event, 18 therapy changes to avoid DDIs). An increase in lipid parameters was observed during the first 6-12 months in the group discontinuing tenofovir disoproxil fumarate (p < .01), which was partly corrected at 96 weeks. Improvements in CD4/CD8 ratio (p = .04), bone mineral density (+1.17%; p = .07), estimated glomerular filtration rate (+7.7 mL/min in CKD patients; p = .02), urinary parameters (proteinuria, -23%), and overall cost (-43%) were observed. CONCLUSIONS: Our results demonstrated the long-term efficacy and safety of an antiretroviral regimen based on dual therapy with lamivudine plus boosted darunavir in the clinical setting.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Darunavir/uso terapêutico , Infecções por HIV/tratamento farmacológico , Lamivudina/uso terapêutico , Lipídeos/sangue , Adulto , Idoso , Relação CD4-CD8 , Substituição de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ritonavir/uso terapêutico , Resultado do Tratamento , Carga Viral/efeitos dos fármacosRESUMO
BACKGROUND: We assessed the prevalence of antibodies against hepatitis C virus (HCV-Abs) and active HCV infection in patients infected with human immunodeficiency virus (HIV) in Spain in 2016 and compared the results with those of similar studies performed in 2002, 2009, and 2015. METHODS: The study was performed in 43 centers during October-November 2016. The sample was estimated for an accuracy of 2% and selected by proportional allocation and simple random sampling. During 2016, criteria for therapy based on direct-acting antiviral agents (DAA) were at least significant liver fibrosis, severe extrahepatic manifestations of HCV, and high risk of HCV transmissibility. RESULTS: The reference population and the sample size were 38904 and 1588 patients, respectively. The prevalence of HCV-Abs in 2002, 2009, 2015, and 2016 was 60.8%, 50.2%, 37.7%, and 34.6%, respectively (P trend <.001, from 2002 to 2015). The prevalence of active HCV in 2002, 2009, 2015, and 2016 was 54.0%, 34.0%, 22.1%, and 11.7%, respectively (P trend <.001). The anti-HCV treatment uptake in 2002, 2009, 2015, and 2016 was 23.0%, 48.0%, 59.3%, and 74.7%, respectively (P trend <.001). In 2016, HCV-related cirrhosis was present in 7.6% of all HIV-infected individuals, 15.0% of patients with active HCV, and 31.5% of patients who cleared HCV after anti-HCV therapy. CONCLUSIONS: Our findings suggest that with universal access to DAA-based therapy and continued efforts in prevention and screening, it will be possible to eliminate active HCV among HIV-infected individuals in Spain in the short term. However, the burden of HCV-related cirrhosis will continue to be significant among HIV-infected individuals.
RESUMO
Background. The purpose of this study was to assess the prevalence of anti-hepatitis C virus (HCV) antibodies (Abs) and active HCV infection in human immunodeficiency virus (HIV)-infected (HIV+) patients in Spain in 2015. This was a cross-sectional study. Methods. The study was performed in 41 centers in 2015. Sample size was estimated for an accuracy of 2%, the number of patients from each hospital was determined by proportional allocation, and patients were selected using simple random sampling. Results. The reference population was 35 791 patients, and the sample size was 1867 patients. Hepatitis C virus serostatus was known in 1843 patients (98.7%). Hepatitis C virus-Abs were detected in 695 patients (37.7%), in whom the main route of HIV acquisition was injection drug use (75.4%). Of these 695 patients, 402 had HCV RNA, 170 had had a sustained viral response (SVR) after anti-HCV therapy, and 102 cleared HCV spontaneously. Hepatitis C virus-ribonucleic acid results were unknown in 21 cases. Genotype distribution (known in 367 patients) was 1a in 143 patients (39.0%), 4 in 90 (24.5%) patients, 1b in 69 (18.8%) patients, 3 in 57 (15.5%) patients, 2 in 5 (1.4%) patients, and mixed in 3 (0.8%) patients. Liver cirrhosis was present in 93 patients (23.1%) with active HCV infection and in 39 (22.9%) patients with SVR after anti-HCV therapy. Conclusions. The prevalence of HCV-Abs and active HCV infection in HIV+ patients in Spain is 37.7% and 22.1%, respectively; these figures are significantly lower than those recorded in 2002 and 2009. The predominant genotypes in patients with active HCV infection were 1a and 4. A high percentage of patients had cirrhosis. Cirrhosis is also common in patients with SVR after anti-HCV therapy.