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We identify factors associated with the normalization of the CD4+:CD8+ T cell ratio among UK Collaborative HIV Cohort study participants, and describe the association of the CD4+ and CD8+ T cell counts and the CD4+:CD8+ T cell ratio, with the risk of new AIDS events among individuals who achieve a suppressed viral load. Participants initiating combination antiretroviral therapy (cART) after 2006 with a CD4+:CD8+ T cell ratio 500 vs. ≤200 cells/mm3, adjusted hazard ratio (95% confidence interval): 7.93 (6.97–9.01)], low CD8+ T cell count [>1,150 vs. ≤500 cells/mm3: 0.18 (0.16–0.21)], and low CD4+:CD8+ T cell ratio [>0.8 vs. 500 vs. ≤200 cells/mm3: adjusted rate ratio 0.24 (0.16–0.34)] and CD4+:CD8+ T cell ratio [>0.8 vs.

Objective to estimate the prevalence of HCV infection in the general population of a health area through an intervention in Primary Care, differentiating between new diagnoses and infections previously diagnosed but not treated. Methods participants were selected through a risk assessment questionnaire, with all those who gave at least one affirmative answer and all those over 50 years of age undergoing a rapid test. Positive tests were confirmed in the lab by determination of anti-HCV antibodies by chemiluminescent microparticle immunoassay (CMIA) and determination of viraemia. Results Of the 7991 participants, 36.2% presented a positive HCV risk questionnaire. 4717 tests were performed, finding an anti-HCV percentage of 0.65% in the screened population, with 0.46% of active infections. Among the individuals with a positive test result, 51.9% had a known prior diagnosis but had not received treatment, because they were not aware of it or were not linked to the health system, and 19.2% had a positive result for the first time. The prevalence of hidden infection was higher in men, those over 50 years of age and people from Eastern Europe. Conclusion We found a prevalence of active infections higher than recently described nationwide, and a higher percentage of newly diagnosed infections than recent similar studies in other areas. These differences justify the need to perform local assessments of the prevalence of HCV infection in each of the health areas where it is planned to implement and monitor a microelimination programme.

There is little information on the effectiveness of the pneumococcal vaccines (PVs), especially for the pneumococcal conjugate vaccines (PCVs), in HIV-infected patients in the modern antiretroviral era. This is a case–control study where cases were people living with HIV (PLWH) with confirmed pneumococcal infection (CPI) and controls were PLWH without CPI matched with cases by gender and year of HIV diagnosis. The selection process was blinded to the study factor (vaccination). Sample size estimation yielded 61 cases and 183 controls. We analyzed the effect of PV on CPI using Cox proportional-hazards regression model with time-dependent covariates. We included 256 subjects: 64 cases, and 192 controls. PVs had been administered to 115 (45%) patients. Only the modified Charlson Comorbidity Index (HR 1.16, 95%CI 1.06–1.27, P = 0.001) and the CD4 nadir (HR 0.99, 95% CI 0.98–0.99, P = 0.001) were independently associated with CPI. Receipt of PV was not associated with CPI after adjusting in the multivariate model with time protection as a dependent covariate (HR 0.65, 95% CI 0.35–1.32 P = 0.250). We also investigated the influence of different immunization schedules. In an adjusted model, we found no evidence of protection against CPI, including double immunization schedules (HR 0.42 95%CI 0.15–1.19 P = 0.102). In this case–control study, we could not show an association between pneumococcal vaccination and confirmed pneumococcal infection, although a protective effect of particular schedules of immunization cannot be ruled out.

GEHEP-004 Study Group: María Dolores Ocete, Miguel Ángel Simón, Pilar Rincón, Sergi Reus, Alberto De la Iglesia, Isabel García-Arata, Miguel Jiménez, Fernando Jiménez, José Hernández-Quero, Carlos Galera, Mohamed Omar Balghata, Joaquín Primo, Mar Masiá, Nuria Espinosa, Marcial Delgado, Miguel Ángel von-Wichmann, Antonio Collado, Jesús Santos, Carlos Mínguez, Felícitas Díaz-Flores, Elisa Fernández, Enrique Bernal, José De Juan, José Joaquín Antón, Mónica Vélez, Antonio Aguilera, Daniel Navarro, Juan Ignacio Arenas, Clotilde Fernández, María Dolores Espinosa, María José Ríos, Roberto Alonso, Carmen Hidalgo, Rosario Hernández, María Jesús Téllez, Francisco Javier Rodríguez, Pedro Antequera, Cristina Delgado, Patricia Martín, Javier Crespo, Berta Becerril, Óscar Pérez, Antonio García-Herola, José Montero, Carolina Freyre, Concepción Grau., [Background & Aims] Most hepatitis C virus (HCV)-infected patients failing NS5A inhibitors develop resistance-associated substitutions (RASs). Here we report the use of resistance-guided retreatment of patients who failed prior NS5A inhibitor-containing regimens in the GEHEP-004 cohort. This is the largest direct-acting antiviral (DAA)-resistance cohort study conducted in Spain. We aim to provide indications on how to use resistance information in settings where sofosbuvir/velpatasvir/voxilaprevir may not be available., [Methods] GEHEP-004 is a prospective multicenter cohort enrolling HCV-infected patients treated with interferon (IFN)-free DAA regimens. Prior to retreatment, population-based sequencing of HCV NS3, NS5A and NS5B genes was performed. After receiving a comprehensive resistance interpretation report, the retreatment regimen was chosen and the sustained virological response (SVR) at 12 weeks after treatment completion (SVR12) was recorded., [Results] A total of 342 patients experiencing virological failure after treatment with sofosbuvir/ledipasvir±ribavirin (54%), sofosbuvir/daclatasvir±ribavirin (23%), or paritaprevir-ritonavir/ombitasvir±dasabuvir±ribavirin (20%) were studied. After a resistance report, 186 patients were retreated. An SVR12 was achieved for 88.1% of the patients who failed after sofosbuvir/ledipasvir±ribavirin, 83.3% of the patients who failed after sofosbuvir/daclatasvir±ribavirin, 93.7% of the patients who failed after paritaprevir-ritonavir+ombitasvir±dasabuvir±ribavirin., [Conclusions] In our study, we show how resistance-guided retreatment in conjunction with an interpreted report allows patients to achieve SVR rates close to 90%. We hypothesize that SVR rates may even be improved if resistance data are discussed between experienced virologists and treating clinicians. We believe that our data may be relevant for countries where the access to new DAA combination regimens is limited., [Lay summary] Hepatitis C infection can be cured with currently available antiviral agents. Only a small proportion of patients experience treatment failure, however, in absolute numbers, a high number of patients may require retreatment. Highly effective combinations of antivirals are also available for retreatment. However, these antivirals might not be available in resource-limited settings. Herein, we show how, by analyzing the cause of resistance, retreatment efficacy with old drugs can get very close to the efficacy of new drug combinations., This work was supported in part by grants from Fondo de Investigación Sanitaria (www.isciii.es) (PI15/00713), Plan Nacional de I+D+I and Fondo Europeo de Desarrollo Regional-FEDER (www.redes/redes/inicio) (RD16/0025/0040), Fundación Progreso y Salud, Junta de Andalucia (http://www.juntadeandalucia.es/fundacionprogresoysalud/es) (PI-0411-2014), and GEHEP-SEIMC (GEHEP-004).

Background Cofactors associated with persistently abnormal CD4+:CD8+ T-cell ratio in people with HIV (PWH) on antiretroviral treatment (ART) might change over time as the population of people with HIV ages or as new ART drugs become available. The main objective of our study was to determine the long-term associations of baseline factors, including the CD4+ T-cell count and ratio, with ratio normalization (≥1). In addition to this, we explored whether the ratio remained associated with the risk of both AIDS and non-AIDS events among individuals on suppressive ART. Methods Clinic-based study in a tertiary, university hospital in Madrid. People with HIV starting a first-line ART regimen (January 2006–June 2017) were included in a prospective national multicentre cohort (CoRIS). People with controlled HIV-infection within the first year of ART initiation and complete CD4+ and CD8+ T-cell records were selected. Cox proportional hazard (PH) regression models were used to estimate the cumulative incidence of ratio normalization and to examine associations with socio-demographic and clinical variables. To investigate factors independently associated with the development of AIDS and non-AIDS events we used a time updated Poisson regression model. Results The study included 557 subjects. During follow-up (median 5.24 years), 44% of participants achieved a ratio of 1 within a median of 1.49 years. In a multivariate PH model, pre-ART factors negatively associated with ratio normalization were the pre-ART CD4+:CD8+ T-cell ratio and mode of HIV acquisition. For the secondary analysis, 1.3 events/100 person years of follow-up were observed. After adjustment, older age, HIV RNA >200 copies/ml and CD4+:CD8+ T-cell ratios over follow-up, remained significantly associated with the development of AIDS and non-AIDS events. In contrast, pre-ART ratio was not associated with the risk of AIDS and non-AIDS events. Conclusions In summary, our study showed that higher pre-ART CD4+:CD8+ T-cell ratio is associated with rates of ratio normalization ≥1. In addition, the risk of AIDS and non-AIDS events seems to be predicted by the time updated CD4+:CD8+ T-cell ratio not by the pre-ART CD4+:CD8+ T-cell ratio. Therefore, CD4+:CD8+ T-cell ratio should be considered as a dynamic marker for translation into clinical practice.

Recurrences of Clostridium difficile infections lead to hospital readmissions and high costs, in addition to the suffering and frustration for the patients. Fidaxomicin has recently been introduced as a new antibiotic that has been shown to significantly reduce the recurrence of this infection. Despite this superiority, its high cost has led to very restrictive policies in its use, as such that many institutions only use it in patients with multiple recurrences. While waiting for new predictive clinical tools, we propose the development of scoring systems that allow the more high-risk patients to be treated earlier.

DRIVE 03, OPTtest WP5 and FOCO Study Groups., [Background] Late HIV diagnosis remains one of the challenges in combating the epidemic. Primary care providers play an important role in screening for HIV infection. Our study aims to evaluate the relationship between knowledge and barriers to HIV testing and screening outcomes. The impact of an education program for primary care providers, towards improving HIV testing and late diagnosis rates, is also assessed., [Methods] A self-administered questionnaire that was developed within the framework of the European project OptTEST was used to examine HIV knowledge and barriers to HIV testing scores before and after being involved in an HIV education program. A quasi-experimental design with pre- and post-intervention measures was performed to investigate its impact. We performed multivariable logistic regression analysis to assess the relationship between variables for the HIV testing offer., [Results] A total of 20 primary care centers and 454 primary care staff were included. Baseline OptTEST results showed that more knowledgeable staff offered an HIV test more frequently (OR 1.07; CI 95% 1.01–1.13; p = 0.027) and had lower barrier scores (OR 0.89; CI 95% 0.77–0.95; p = 0.005). Nurses had lower scores in knowledge-related items (OR 0.28; CI 95% 0.17–0.46; p, [Conclusions] This study highlights the association between knowledge and barriers to HIV testing, including HIV testing rates. It shows that it is possible to modify knowledge and reduce perceived barriers through educational programs, subsequently improving HIV screening outcomes., This study was supported by two competitive Grants: GILEAD FELLOWSHIP 2015, 2016/0056 and the Ministerio de Sanidad, Seguridad Social e Igualdad Projects codes: PI16/00551; EC11-144, co-financed by the European Development Regional Fund ‘‘A way to achieve Europe’’ (ERDF) and partially funded by the RD12/0017/0017 project as part of the Plan Nacional R + D + I and cofinanced by ISCIII- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER), and also partially supported by unrestrictional grants from Janssen Cilag supporting FOCO project developed by the Spanish AIDS Interdisciplinary Society (SEISIDA), VIIF and Gilead supporting DRIVE 01, 02 and DRIVE 03 through IRYCIS.