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BACKGROUND: Non-AIDS defining malignancies present a growing challenge for persons with HIV (PWH), yet tailored interventions for timely cancer diagnosis are lacking. The Spanish IMPAC-Neo protocol was designed to compare two comprehensive cancer screening strategies integrated into routine HIV care. This study reports baseline data on the prevalence and types of precancerous lesions and early-stage cancer among participants at enrolment. Acceptability of the procedure was additionally assessed. METHODS: Cross-sectional analysis of a comprehensive screening protocol to detect precancer and cancer. The readiness of healthcare providers to implement the protocol was evaluated using a validated 4-item survey. RESULTS: Among the 1430 enrolled PWH, 1172 underwent 3181 screening tests, with positive findings in 29.4% of cases, leading to further investigation in 20.7%. Adherence to the protocol was 84%, with HIV providers expressing high acceptability (97.1%), appropriateness (91.4%), and feasibility (77.1%). A total of 145 lesions were identified in 109 participants, including 60 precancerous lesions in 35 patients (3.0%), 9 early-stage cancers in 9 patients (0.8%), and 76 low-risk lesions in 65 subjects (5.5%). Adverse events related to screening occurred in 0.8% of participants, all mild. The overall prevalence of cancer precursors or early-stage cancer was 3.8% (95% CI, 2.74%-5.01%), with highest rates observed in individuals screened for anal and colorectal cancers. CONCLUSIONS: The baseline comprehensive cancer screening protocol of the IMPAC-Neo study successfully identified a significant proportion of PWH with precancerous lesions and early-stage cancer. High adherence rates and positive feedback from providers suggest effective implementation potential in real-world healthcare settings.
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Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a comorbidity that generally increases in people living with HIV (PLWH). This condition is usually accompanied by persistent inflammation and premature immune system aging. In this prospective cohort study, we describe a straightforward methodology for quantifying biomarkers of aging, such as DNA methylation and telomere length, in PLWH and in the context of another relevant condition, such as MAFLD. Fifty-seven samples in total, thirty-eight from PLWH and nineteen from non-PLWH participants with or without MAFLD, were obtained and subjected to DNA extraction from peripheral blood mononuclear cells (PBMCs). Global DNA methylation and telomere length quantification were performed using an adapted enzyme-linked immunosorbent assay (ELISA) and qPCR, respectively. The quantification results were analysed and corrected by clinically relevant variables in this context, such as age, sex, and metabolic syndrome. Our results show an increased association of these biomarkers in PLWH regardless of their MAFLD status. Thus, we propose including the quantification of these age-related factors in studies of comorbidities. This will allow a better understanding of the effect of comorbidities of HIV infection and MAFLD and prevent their effects in these populations in the future.
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Envejecimiento Prematuro , Infecciones por VIH , Enfermedad del Hígado Graso no Alcohólico , Humanos , Metilación de ADN , Enfermedad del Hígado Graso no Alcohólico/genética , Infecciones por VIH/complicaciones , Infecciones por VIH/genética , Leucocitos Mononucleares , Estudios Prospectivos , Envejecimiento/genética , Telómero/genéticaRESUMEN
OBJECTIVES: To evaluate the efficacy and safety of the two-pill regimen bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) plus darunavir/cobicistat as a switching strategy in heavily treatment-experienced people living with HIV (PLWH). METHODS: Multicentre, prospective, single-arm pilot clinical trial. Participants were virologically suppressed adults receiving a stable antiretroviral regimen of at least three pills from at least three drug families due to previous virological failures and/or toxicities with no documented resistance to integrase strand transfer inhibitors or darunavir (≥15 points, Stanford). Clinical and laboratory assessments were performed at 0, 4, 12, 24, 36 and 48 weeks. HIV-1 proviral DNA was amplified and sequenced by Illumina at baseline. Plasma bictegravir concentrations were determined in 22 patients using UHPLC-MS/MS. The primary study endpoint was viral load (VL)<â50 copies/mL at Week 48 (ITT). RESULTS: We enrolled 63 participants (92% men) with median baseline CD4 count of 515 cells/mm3 (IQR: 334.5-734.5), 24 years on ART (IQR: 15.9-27.8). The median number of pills was 4 (range: 3-10). At baseline, proviral DNA was amplified in 39 participants: 33/39 had resistance mutations. Three participants discontinued owing to toxicity. At 48 weeks, 95% had VLâ<â50 copies/mL by ITT and 100% by PP analysis. A modest increase was observed in the bictegravir plasma concentration, and a significant decrease in estimated glomerular filtration rate was observed only at Week 4, probably related to interaction with renal transporters. CONCLUSIONS: Our data suggest that BIC/FTC/TAFâ+âdarunavir/cobicistat is an effective, well-tolerated regimen that may improve convenience and, potentially, long-term success in stable heavily pre-treated PLWH.
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Fármacos Anti-VIH , Infecciones por VIH , Adulto , Femenino , Humanos , Masculino , Adenina/uso terapéutico , Alanina/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Antirretrovirales/uso terapéutico , Cobicistat/uso terapéutico , Darunavir/uso terapéutico , ADN/uso terapéutico , Emtricitabina/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Estudios Prospectivos , Espectrometría de Masas en TándemRESUMEN
Hepatitis C virus (HCV) and HIV are major causes of worldwide disease. We aimed to evaluate the effect of a combined screening programme, which included a risk-assessment questionnaire and rapid tests for point-of-care diagnosis, on screening and new diagnosis rates. This prospective, cluster randomized study was carried out in primary care. The intervention arm included a 4-hour educational programme, the use of a risk-assessment questionnaire and rapid tests. In the control centres, only the educational intervention was provided. The main variables compared were the screening coverage and the number and rate of new HCV and HIV diagnoses. Of a total of 7991 participants, 4670 (58.5%) and 2894 (36.2%) presented a risk questionnaire for HIV or HCV, respectively. The younger participants, men and those from Latin America and Eastern Europe, showed the greatest risk of presenting with a positive questionnaire. The overall screening coverage was higher within the intervention arm (OR 17.7; 95% CI 16.2-19.5; P < .001). Only two HIV-positives were identified compared to one in control centres. The rate of HCV diagnoses was higher among intervention centres, with 37 versus seven positive tests (OR 5.2; 95% CI 2.3-11.6; P < .001). Of them, 10 were new diagnoses and 27 had been previously diagnosed, although not linked to care. In conclusion, a simple operational programme can lead to an increase in HCV and HIV screening rates, compared to an exclusively educational programme. The selection of at-risk patients with a self-questionnaire and the use of rapid tests significantly increased the diagnostic rate of HCV infection.
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Infecciones por VIH , Hepatitis C , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Hepacivirus , Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Humanos , Masculino , Tamizaje Masivo , Atención Primaria de Salud , Estudios ProspectivosRESUMEN
BACKGROUND: Ending AIDS by 2030 requires improvements across all stages of the HIV care continuum. We used a longitudinal approach to assess changes in the HIV care continuum in Spain and transition probabilities across different stages. METHODS: We used data from the prospective Cohort of the Spanish HIV/AIDS Research Network to analyse the time from diagnosis to linkage to care, linkage to care to antiretroviral therapy (ART), and ART to viral suppression in five calendar periods defined by milestones in ART, from 2005 to 2022. We used the Kaplan-Meier method and Cox proportional hazard models to estimate cumulative probabilities of stage transition within 1, 3, 6, and 12 months of stage eligibility, by period. FINDINGS: We included 18 529 participants. Comparing the initial (2005-09) and final (2020-22) periods, time to linkage to care decreased from a median of 6·0 weeks to 1·3 weeks, time to ART initiation from 15·9 weeks to 0·4 weeks, and time to viral suppression from 13·3 weeks to 7·1 weeks. Adjusted hazard ratios for the comparison between the last period and the initial period were 3·1 (95% CI 2·8-3·4) for linkage to care within 1 month, 11·4 (10·1-12·3) for ART initiation within 1 month, and 2·2 (1·2-2·4) for viral suppression within 3 months. The aggregate proportion of late diagnoses was 38·6%, increasing after 2012 to 46·4% in the 2020-22 period. Same-day ART initiation increased from 18% to 39% from 2005 to 2022. The overall incidence rate of virological failure was 1·05 failures per 1000 person-years and showed a non-significant decline throughout the study. INTERPRETATION: The great improvement in transition times through the HIV care cascade might put Spain on the verge of achieving the UNAIDS targets for HIV elimination. However, late diagnosis remains a challenge that should be addressed. FUNDING: Instituto de Salud Carlos III and Spanish AIDS Research Network.
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Fármacos Anti-VIH , Continuidad de la Atención al Paciente , Infecciones por VIH , Humanos , España/epidemiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Masculino , Femenino , Adulto , Estudios Longitudinales , Estudios Prospectivos , Persona de Mediana Edad , Fármacos Anti-VIH/uso terapéutico , Carga Viral/efectos de los fármacos , Factores de Tiempo , Modelos de Riesgos Proporcionales , Adulto JovenRESUMEN
Despite remarkable improvement in the human immunodeficiency virus (HIV) and hepatitis C virus (HCV) care continuum, the rate of late diagnosis of HIV and HCV in high-income countries remains unacceptably high. Testing relies mainly on primary care physicians' identification of risk factors. We aimed to adapt an analogic to an online questionnaire to help HIV and HCV screening and perform a pilot study to assess its accuracy and acceptability. We used the Delphi method to adapt a previously validated analogical questionnaire to a user-friendly online tool. It aimed to identify participants who should be screened for HIV or HCV and those who should be referred for pre-exposure prophylaxis (PrEP). We then designed a proof-of-concept pilot study from July to October 2022 to test its feasibility and suitability for use on a larger scale and to assess its accuracy in identifying patients at risk for HIV or HCV or with indication for PrEP. The final questionnaire consisted of 37 questions. A total of 142 participants provided informed consent, and 102 completed the questionnaire: 41 random patients recruited at the primary care level, 10 participants recently diagnosed with HIV, 20 participants with HIV on follow-up, 21 participants from the PrEP program, and 10 patients diagnosed with HCV. The tool adequately indicated the need for testing in more than 98% of participants with confirmed HIV/HCV infections or in the PrEP program. Furthermore, it adequately assessed PrEP referral in 94% of participants already on PrEP or with known HIV infection. Participants were highly satisfied with the tool, and 98% of them recommended its use. A self-administered web-based tool to identify patients who should be tested for HIV or HCV or referred to PrEP could simplify patient selection and help reduce late diagnosis.
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OBJECTIVE: Multiple strategies have been utilised to reduce the incidence of HIV, including PrEP and rapid antiretroviral therapy initiation. The study objectives were to evaluate the efficacy, safety, satisfaction, treatment adherence, and system retention obtained with rapid initiation of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in naïve patients. METHODS: This phase IV, multicenter, open-label, single-arm, 48-week clinical trial enrolled patients between January 2020 and June 2022. Adherence to treatment was evaluated with the SMAQ questionnaire and patient satisfaction with the EQ-5D. RESULTS: Two hundred eight participants were enrolled with mean age of 35.6 years; 87.6% were males; mean CD4 count was 393.5 cells/uL (<200 cells/uL in 22.1%); viral load log was 5.6 (VL>100 000 cop/mL in 43.3%); 22.6% had AIDS, and 4.3% were coinfected with HBV. BIC/FTC/TAF was initiated on the day of their first visit to the HIV specialist in 98.6% of participants, and 9.6% were lost to follow-up. The efficacy at week 48 was 84.1 % by intention-to- treat (ITT), 94.6% by modified ITT, and 98.3% by per protocol analysis. The regimen was discontinued in two subjects (0.9%) during week 1 for grade 3 adverse events. Treatment adherence (weeks 4 [90%, IQR: 80-99%] vs. 48 [90%, IQR: 80-95%; P = 0.49]) and patient satisfaction (weeks 4 [90%, IQR: 80-99%] vs. 48 [90%, IQR: 80-95 P = 0.49]) rates were very high over the 48- week study period. CONCLUSIONS: BIC/FTC/TAF is an appropriate option for rapid ART initiation in naïve HIV patients, offering high efficacy, safety, durability, treatment adherence, retention in the healthcare system, and patient satisfaction. Number Clinical Trial registration: NCT06177574.
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Alanina , Fármacos Anti-VIH , Emtricitabina , Infecciones por VIH , Compuestos Heterocíclicos de 4 o más Anillos , Piperazinas , Piridonas , Tenofovir , Humanos , Masculino , Femenino , Adulto , Infecciones por VIH/tratamiento farmacológico , Tenofovir/uso terapéutico , Tenofovir/análogos & derivados , Emtricitabina/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Piridonas/uso terapéutico , Alanina/uso terapéutico , Alanina/análogos & derivados , Piperazinas/uso terapéutico , Combinación de Medicamentos , Carga Viral/efectos de los fármacos , Persona de Mediana Edad , Adenina/análogos & derivados , Adenina/uso terapéutico , Cumplimiento de la Medicación , Amidas/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Satisfacción del Paciente , Recuento de Linfocito CD4 , Resultado del Tratamiento , Adulto JovenRESUMEN
The COVID-19 pandemic and associated lockdown measures have been associated with substantial disruptions to health care services, including screening for human immunodeficiency virus (HIV) and management of people living with HIV (PLWH). Data from 3265 patients were examined in a retrospective cohort study. We compared outpatient follow-up for PLWH, the number of new patients, treatment adherence, hospitalizations, and deaths during the "pandemic period" (March 2020 to February 2021), the "pre-pandemic period" (the equivalent time frame in 2019), and the "post-pandemic period" (March to September 2021). During the pandemic period, the number of new patients seen at the HIV clinic (116) as well as the requested viral load tests (2414) decreased significantly compared to the pre-pandemic (204 and 2831, respectively) and post-pandemic periods (146 and 2640, respectively) (p < 0.01 for all the comparisons). However, across the three study periods, the number of drug refills (1385, 1330, and 1411, respectively), the number of patients with undetectable viral loads (85%, 90%, and 93%, respectively), and the number of hospital admissions among PLWH remained constant. Despite the COVID-19 pandemic's impact, our findings show stability in the retention of clinical care, adherence to treatment, and viral suppression of PLWH, with no significant impact on hospitalization rates or all-cause mortality.
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INTRODUCTION: We analyzed epidemiological, clinical characteristics, and the response to treatment in people living with HIV (PLHIV) who recently acquired hepatitis C (RAHC) in a multicentre study in Madrid (Spain). METHODS: Multicenter, ambispective, observational study of RAHC in men who have sex with men (MSM) infected with HIV. Clinical, epidemiological, and RAHC evolution were recorded prospectively in 2019 and 2020 and retrospectively in 2017 and 2018. In patients who received HCV treatment, sustained virological response (SVR) was provided 12 weeks after the end of treatment in an intention to treat analysis (ITT): all treated patients were included; and in analysis per-protocol (PP): missing patients were excluded. RESULTS: Overall, 133 patients were included. Median (IQR) age was 40 (34.3-46.1) years, 90.9% had at least one previous sexual transmission disease (STD), and 33.6% had previously hepatitis C. More than half of the prospective sample included patients using chemsex related drugs (57.3%), 45.7% of them intravenously. The most prevalent genotype was G1a (66.2%), followed by G4 (11.3%). Ten of 90 patients evaluated for spontaneous cure (11%) cured the infection spontaneously, and 119 had treatment after a median time of 1.8 (0.7-4.6) months: sustained virological response (SVR) was achieved in 90.7% in the ITT and 94.7% in the PP analysis, with no differences regarding the direct-acting antiviral agents (DAA) combination used. CONCLUSIONS: MSM infected by HIV with a RAHC were exposed to high-risk sexual behavior. Spontaneous cure rate was low, while SVR after treatment was achieved by more than 90%.
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Introduction: Second-generation integrase strand transfer inhibitors (INSTIs) are preferred treatment options worldwide, and dolutegravir (DTG) is the treatment of choice in resource-limited settings. Nevertheless, in some resource-limited settings, these drugs are not always available. An analysis of the experience with the use of INSTIs in unselected adults living with HIV may be of help to make therapeutic decisions when second-generation INSTIs are not available. This study aimed to evaluate the real-life effectiveness and safety of dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), and raltegravir (RAL) in a large Spanish cohort of HIV-1-infected patients. Methods: Real-world study of adults living with HIV who initiated integrase INSTIs DTG, EVG/c, and RAL-based regimens in three settings (ART-naïve patients, ART-switching, and ART-salvage patients). The primary endpoint was the median time to treatment discontinuation after INSTI-based regimen initiation. Proportion of patients experiencing virological failure (VF) (defined as two consecutive viral loads (VL) ≥200 copies/mL at 24 weeks or as a single determination of VL ≥1,000 copies/mL while receiving DTG, EVG/c or RAL, and at least 3 months after INSTI initiation) and time to VF were also evaluated. Results: Virological effectiveness of EVG/c- and RAL-based regimens was similar to that of DTG when given as first-line and salvage therapy. Treatment switching for reasons other than virological failure was more frequent in subjects receiving EVG/c and, in particular, RAL. Naïve patients with CD4+ nadir <100 cells/µL were more likely to develop VF, particularly if they initiated RAL or EVG/c. In the ART switching population, initiation of RAL and EVG/c was associated with both VF and INSTI discontinuation. There were no differences in the time to VF and INSTI discontinuation between DTG, EVG/c and RAL. Immunological parameters improved in the three groups and for the three drugs assessed. Safety and tolerability were consistent with expected safety profiles. Discussion: Whereas second-generation INSTIs are preferred treatment options worldwide, and DTG is one of the treatment of choices in resource-limited settings, first-generation INSTIs may still provide high virological and immunological effectiveness when DTG is not available.
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Cobicistat , Infecciones por VIH , Adulto , Humanos , España , Estudios Prospectivos , Integrasas , Infecciones por VIH/tratamiento farmacológicoRESUMEN
Modern ART has now achieved the goal of maintaining HIV RNA suppression with minimum drug-related toxicities. Indeed, in high-income settings, the main health issues in adult people living with HIV (PLWH) today are diseases not directly associated with HIV. These conditions have become the central topic of discussion in HIV clinical forums. While they are common in the general population and typically associated with the aging process, their burden, diagnosis, clinical course and subsequent therapy alongside treated HIV infection exhibit specific features. Currently, we are confronted with the formidable challenge of normalizing the health of PLWH and creating a more comprehensive HIV management program. Here, we compile the opinions of a joint effort of 30 HIV specialists who reviewed the literature and debated the latest major challenges in the field of HIV-associated comorbidities and delineated future strategies to fully normalize health in HIV. Six key questions are answered and developed, such as the relevance of comorbidities in the management of HIV-infected patients, their drivers, management, prevention strategies, and possible evolution in the future.
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Envejecimiento/efectos de los fármacos , Antirretrovirales/efectos adversos , Antirretrovirales/uso terapéutico , Comorbilidad , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Changes in the microbiota have been linked to persistent inflammation during treated HIV infection. In this pilot double-blind study, we study 30 HIV-infected subjects on antiretroviral therapy (ART) with a CD4/CD8 ratio < 1 randomized to either weekly fecal microbiota capsules or placebo for 8 weeks. Stool donors were rationally selected based on their microbiota signatures. We report that fecal microbiota transplantation (FMT) is safe, not related to severe adverse events, and attenuates HIV-associated dysbiosis. FMT elicits changes in gut microbiota structure, including significant increases in alpha diversity, and a mild and transient engraftment of donor's microbiota during the treatment period. The greater engraftment seems to be achieved by recent antibiotic use before FMT. The Lachnospiraceae and Ruminococcaceae families, which are typically depleted in people with HIV, are the taxa more robustly engrafted across time-points. In exploratory analyses, we describe a significant amelioration in the FMT group in intestinal fatty acid-binding protein (IFABP), a biomarker of intestinal damage that independently predicts mortality. Gut microbiota manipulation using a non-invasive and safe strategy of FMT delivery is feasible and deserves further investigation. Trial number: NCT03008941.
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Trasplante de Microbiota Fecal , Infecciones por VIH/microbiología , Infecciones por VIH/terapia , Biodiversidad , Biomarcadores/sangre , Análisis Discriminante , Microbioma Gastrointestinal , Infecciones por VIH/sangre , Humanos , Masculino , Persona de Mediana Edad , Filogenia , Proyectos Piloto , Placebos , Donantes de TejidosRESUMEN
Human immunodeficiency virus (HIV) remains incurable due to latent reservoirs established in non-activated CD4 T cells. Current efforts to achieve a functional cure rely on immunomodulatory strategies focused on enhancing the functions of cytotoxic cells. Implementation of these actions requires a coordinated activation of the viral transcription in latently infected cells so that the reservoir became visible and accessible to cytotoxic cells. As no latency reversing agent (LRA) has been shown to be completely effective, new combinations are of increasing importance. Recent data have shown that maraviroc is a new LRA. In this work, we have explored how the combination of maraviroc with other LRAs influences on HIV reactivation using in vitro latency models as well as on the cell viability of CD8 T cells from ART-treated patients. Maraviroc reactivated HIV with a potency similar to other LRAs. Triple combinations resulted toxic and were rejected. No dual combination was synergistic. The combination with panobinostat or disulfiram maintained the effect of both drugs without inducing cell proliferation or toxicity. Maraviroc does not alter the viability of CD8 T cells isolated from patients under antiretroviral treatment. This finding enhances the properties of maraviroc as a LRA.
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Fármacos Anti-VIH/farmacología , Linfocitos T CD8-positivos/efectos de los fármacos , Inhibidores de Fusión de VIH/farmacología , VIH-1/efectos de los fármacos , Maraviroc/farmacología , Activación Viral/efectos de los fármacos , Latencia del Virus/efectos de los fármacos , Adulto , Fármacos Anti-VIH/uso terapéutico , Linfocitos T CD8-positivos/fisiología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Inhibidores de Fusión de VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/fisiopatología , VIH-1/fisiología , Humanos , Masculino , Maraviroc/uso terapéutico , Persona de Mediana Edad , Activación Viral/fisiología , Latencia del Virus/fisiología , Replicación Viral/efectos de los fármacos , Replicación Viral/fisiologíaRESUMEN
BACKGROUND: Despite evidence shown of dolutegravir (DTG)-related neurotoxicity, which may be more common when combined with abacavir (ABC), its reversibility has not been explored in a clinical trial. METHODS: We conducted a randomized, multicenter, open-label, pilot trial to evaluate the reversibility of patient-reported neuropsychiatric symptoms, developed or worsened on DTG/ABC/lamivudine (DTG/ABC/3TC), in virologically suppressed patients switched to cobicistat-boosted-elvitegravir/emtricitabine/tenofovir-alafenamide (EVG/COBI/FTC/TAF). Participants were randomized to immediate switch (baseline) or to defer switch (week 4), and then all completed 24 weeks of follow up on EVG/COBI/FTC/TAF. At each visit, participants completed Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression (HAD) scales and were interviewed about 11 neuropsychiatric symptoms potentially related with DTG through a questionnaire. At baseline and at the end of follow up, they also performed neurocognitive testing. Our primary objective was to compare changes in neuropsychiatric symptoms and PSQI and HAD scales between arms at week 4. Secondary objectives were to evaluate changes in neuropsychiatric symptoms and PSQI and HAD scales at weeks 4, 12, and 24 after switching to EVG/COBI/FTC/TAF and in neurocognitive performance and magnetic resonance imaging biomarkers at end of follow up. RESULTS: Thirty-eight participants were included. Study arms were similar at baseline. At week 4, neuropsychiatric symptoms and PSQI and HAD scores remained unchanged in participants receiving DTG/ABC/3TC and improved significantly in participants receiving EVG/COBI/FTC/TAF. These significant improvements were also observed at weeks 4, 12, and 24 after all participants switched to EVG/COBI/FTC/TAF. In addition, global neurocognitive performance improved (NPZ-7) after switching to EVG/COBI/FTC/TAF. CONCLUSIONS: Neuropsychiatric symptoms in patients on DTG/ABC/3TC could resolve or improve after switching to EVG/COBI/FTC/TAF.
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Objectives: There are scarce data on the combination of dolutegravir (DTG) plus rilpivirine (RPV) in the real world, including patients with hepatitis C virus (HCV) coinfection, toxicity or previous failure, or at risk for severe drug-drug interactions (DDIs). Methods: Prospective cohort study of virologically suppressed HIV-1 infected patients, without resistance to DTG or RPV, switched to this dual regimen because of toxicity or risk of DDIs (NCT02491242). Results: Overall, 102 patients (mean age 54 years, 28% women) were included. Fifty-seven were coinfected with HCV (fibrosis grade 4 in 27 cases, 1 liver transplantation). Seven patients had chronic kidney disease (1 renal transplantation). At week 48, only 1 virologic failure occurred (<1%), and 6 patients (6%) left the regimen (3 with central nervous system adverse events, 1 each due to pregnancy, metformin interaction, and lost to follow up). Thus, the overall treatment success rates were 93% (95% CI, 88%-98%; ITT-e, snapshot analysis) and 96% (95% CI, 92%-99%; per protocol analysis). The CD4/CD8 ratio increased slightly (median, +0.03). Triglycerides levels improved significantly (-18.8%, p < 0.01). The creatinine-based estimated glomerular filtration rate decreased by a mean of -8.4 ml/min/1.73 m2, but tubular renal parameters improved. A paired dual X-ray absorptiometry scan showed a mild improvement in spine (mean, +1.15%; -0.57 to +3.3%) and in femoral neck bone mineral density (mean, +0.4%; -3.3% to +2.57%). Conclusions: In the clinical setting, switching to the combination of DTG plus rilpivirine in virologically suppressed HIV-1 patients is effective and safe, and improves lipid, renal and bone evolution.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Rilpivirina/uso terapéutico , Respuesta Virológica Sostenida , Adulto , Anciano , Anciano de 80 o más Años , Coinfección/tratamiento farmacológico , Coinfección/virología , Sustitución de Medicamentos/métodos , Sustitución de Medicamentos/estadística & datos numéricos , Quimioterapia Combinada , Femenino , VIH-1/efectos de los fármacos , Humanos , Persona de Mediana Edad , Oxazinas , Piperazinas , Estudios Prospectivos , Piridonas , Resultado del Tratamiento , Carga Viral/efectos de los fármacosRESUMEN
INTRODUCTION: Cancer is a leading cause of death in individuals with HIV. METHODS: The incidence of cancer in HIV patients of the CoRIS cohort in the 2004-2009 and 2010-2015 periods has been analysed and compared to the incidence in the Spanish general population, estimated from data of the Spanish Cancer Registry Network. RESULTS: Between January 2004 and November 2015, 12,239 patients were included in CoRIS and 338 incident cancer cases were diagnosed. The overall incidence of cancer per 100,000 persons-year (95% CI) was 702.39 (629.51-781.42) with no significant differences between the 2periods. A 38% of the incident cancer cases were AIDS defining cancers (ADC) and 62% non-AIDS defining cancers (NADC). In the period 2010-2015, there was a significant decrease in the incidence of ADC (standardised incidence ratio [SIR]); 95% CI: 0.38; 0.21-0.66) and NADC predominated. Compared to the general population, the incidence of cancer was double in men with HIV. Higher relative risks were documented (SIR; 95% CI) for Hodgkin's lymphoma in both sexes (males: 8.37, 5.13-14.17; females: 21.83, 2.66-47.79), non-Hodgkin's lymphoma in males (5.30, 2.86-8.45) and cervical cancer (7.43, 3.15-13.87) and head and neck cancer (3.28, 1.21-5.82) in women. CONCLUSIONS: The overall incidence of cancer in individuals with HIV is higher than in the Spanish general population, and it has remained stable since 2004 with a current predominance of NADC. These data suggest that additional efforts should be made in the prevention and the early detection of cancer in these patients.
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Infecciones por VIH/complicaciones , Neoplasias/epidemiología , Neoplasias/etiología , Adulto , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Medición de Riesgo , España/epidemiología , Factores de TiempoRESUMEN
INTRODUCTION: HIV testing guidelines are poorly implemented in most clinical settings. The best screening strategy and healthcare scenario are still unknown. The aim of our study is to evaluate the impact of a structured HIV testing intervention (DRIVE), compared to HIV testing as routinely performed in clinical practice, in two different clinical settings: a primary care center and an emergency department. METHODS: Prospective evaluation of an HIV testing strategy in two clinical settings from the same healthcare area. The DRIVE program included trained nurse practitioners to perform the screening, a questionnaire to assess the risk of exposure and HIV indicator conditions (RE&IC), and rapid HIV tests. The main variables between the DRIVE program and clinical practice were the absolute number of newly diagnosed HIV infections and testing coverage. RESULTS: The DRIVE program included 5,329 participants, of which 51.2% reported at least one positive answer in the questionnaire. The estimated HIV testing coverage was significantly higher in the DRIVE program than in the routine clinical practice (7.17% vs. 0.96%, p < 0.001), and was better in the primary care center than in the emergency department with the two strategies. Twenty-two HIV-positive people were identified, with a rate of 8.6 in the emergency department vs. 2.2 in the primary care center (p = 0.001). A higher rate of new HIV diagnoses was found in the DRIVE program compared to routine clinical practice (29.6 vs. 3.1 per 100,000 patients attended; p < 0.001). CONCLUSIONS: An easy-to-implement, structured intervention increased the absolute number of new HIV diagnoses and HIV tests, compared to routine clinical practice.
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Serodiagnóstico del SIDA/métodos , Servicio de Urgencia en Hospital , Atención Primaria de Salud , Adulto , Femenino , Infecciones por VIH/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Programas y Proyectos de Salud , Estudios Prospectivos , Medición de Riesgo , Encuestas y CuestionariosRESUMEN
Despite high response rates associated to hepatitis C virus (HCV) treatment, no protective immunity is acquired, allowing for reinfection and continued infectiousness. Distinguishing between relapse and reinfection is crucial for patient counselling and to choose the most appropriate retreatment. Here, refined phylogenetic analysis using multiple genes served to assess genotype and reinfection for 53 patients for whom the virus was sampled before start of therapy and at time of sustained virological response evaluation at week 12. At baseline, genotypes were determined as HCV1a (41.5%), HCV1b (24.5%), HCV4 (18.9%) and HCV3a (15.1%), while six cases revealed to be discordantly assigned by phylogeny and commercial assays. Overall, 60.4% was co-infected with HIV. The large majority was classified as people who inject drugs (78.6%), often co-infected with HIV. Transmission was sexual in seven cases, of which five in HIV-positive men-who-have-sex-with-men. Overall, relapse was defined for 44 patients, while no conclusion was drawn for four patients. Five patients were reinfected with a different HCV strain, of which three with a different genotype, showing that phylogeny is needed not only to determine the genotype, but also to distinguish between relapse and intra-subtype reinfection. Of note, phylogenies are more reliable when longer fragments of the viral genome are being sequenced.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Hepatitis C/genética , Filogenia , Coinfección/tratamiento farmacológico , Coinfección/transmisión , Coinfección/virología , Genoma Viral , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/transmisión , Infecciones por VIH/virología , Hepatitis C Crónica/transmisión , Homosexualidad Masculina , Humanos , Masculino , RecurrenciaRESUMEN
Zika virus (ZIKV) and chikungunya virus (CHIKV) are currently circulating in overlapping areas in the American continents and may both be transmitted by Aedes spp. mosquitoes. The first documented case, to the authors' knowledge, of sequential CHIKV and ZIKV infections diagnosed in a nonendemic area in a returning traveler is reported. The implications for heightened clinical surveillance for these infections and specific patient recommendations are emphasized.
Asunto(s)
Fiebre Chikungunya/diagnóstico , Infección por el Virus Zika/diagnóstico , Adulto , Aspartato Aminotransferasas/sangre , Proteína C-Reactiva/metabolismo , Fiebre Chikungunya/complicaciones , Fiebre Chikungunya/virología , Virus Chikungunya , Femenino , Honduras , Humanos , Virus Zika , Infección por el Virus Zika/complicacionesRESUMEN
INTRODUCCIÓN: El cáncer constituye una causa importante de mortalidad en personas con VIH. MÉTODOS: Se ha analizado la incidencia de cáncer en pacientes con VIH de CoRIS en los períodos 2004-2009 y 2010-2015 y se ha comparado con la de la población general española estimada a partir de los datos de la Red Española de Registros de Cáncer. RESULTADOS: Entre enero de 2004 y noviembre de 2015 se incluyeron en CoRIS 12.239 pacientes y se diagnosticaron 338 casos incidentes de cáncer. La incidencia global por cada 100.000 personas/año (IC 95%) fue de 702,39 (629,51-781,42) sin diferencias significativas entre los 2 períodos. El 38% de las neoplasias fueron tumores definitorios de sida (TDS) y el 62% no definitorios de sida (TNDS). En el período 2010-2015 se observó un descenso significativo en la incidencia de TDS (cociente de tasas de incidencia estandarizadas [SIR]; IC 95%: 0,38; 0,21-0,66) y predominaron los TNDS. En comparación con la población general, la incidencia de cáncer fue el doble en varones con VIH. Se documentaron riesgos relativos (SIR; IC 95%) más altos de linfoma Hodgkin en ambos sexos (varones: 8,37; 5,13-14,17; mujeres: 21,83; 2,66-47,79), linfoma no Hodgkin en varones (5,30; 2,86-8,45) y cáncer de cérvix (7,43; 3,15-13,87) y cabeza y cuello (3,28; 1,21-5,82) en mujeres. CONCLUSIONES: La incidencia global de cáncer en personas con VIH es mayor que en la población general española y se mantiene estable desde 2004, con un predominio actual de los TNDS. Estos datos indican que deben realizarse esfuerzos adicionales en la prevención y detección precoz de cáncer en estos pacientes
INTRODUCTION: Cancer is a leading cause of death in individuals with HIV. METHODS: The incidence of cancer in HIV patients of the CoRIS cohort in the 2004-2009 and 2010-2015 periods has been analysed and compared to the incidence in the Spanish general population, estimated from data of the Spanish Cancer Registry Network. RESULTS: Between January 2004 and November 2015, 12,239 patients were included in CoRIS and 338 incident cancer cases were diagnosed. The overall incidence of cancer per 100,000 persons-year (95% CI) was 702.39 (629.51-781.42) with no significant differences between the 2periods. A 38% of the incident cancer cases were AIDS defining cancers (ADC) and 62% non-AIDS defining cancers (NADC). In the period 2010-2015, there was a significant decrease in the incidence of ADC (standardised incidence ratio [SIR]); 95% CI: 0.38; 0.21-0.66) and NADC predominated. Compared to the general population, the incidence of cancer was double in men with HIV. Higher relative risks were documented (SIR; 95% CI) for Hodgkin's lymphoma in both sexes (males: 8.37, 5.13-14.17; females: 21.83, 2.66-47.79), non-Hodgkin's lymphoma in males (5.30, 2.86-8.45) and cervical cancer (7.43, 3.15-13.87) and head and neck cancer (3.28, 1.21-5.82) in women. CONCLUSIONS: The overall incidence of cancer in individuals with HIV is higher than in the Spanish general population, and it has remained stable since 2004 with a current predominance of NADC. These data suggest that additional efforts should be made in the prevention and the early detection of cancer in these patients