Abstract: We compared 48 week effectiveness and safety of first-line antiretroviral regimens. Methods We analysed HIV treatment-naive adults from the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) starting the most commonly used antiretroviral regimens from 2014 to 2018. We used multivariable regression models to assess the impact of initial regimen on: (i) viral suppression (VS) (viral load & lt;50 copies/mL); (ii) change in CD4 cell count; (iii) CD4/CD8 normalization ( & gt;0.4 and & gt;1); (iv) CD4 percentage normalization ( & gt;29%); (v) multiple T-cell marker recovery (MTMR: CD4  & gt; 500 cells/mm3 plus CD4 percentage & gt;29% plus CD4/CD8  & gt; 1); (vi) lipid, creatinine and transaminase changes; and (vii) discontinuations due to adverse events (AE). Results Among 3945 individuals analysed, the most frequently prescribed regimens were ABC/3TC/DTG (34.0%), TAF/FTC/EVG/CBT (17.2%), TDF/FTC + DTG (11.9%), TDF/FTC/EVG/CBT (11.7%), TDF/FTC/RPV (11.5%), TDF/FTC + bDRV (8.3%) and TDF/FTC + RAL (5.3%). At 48 weeks, 89.7% of individuals achieved VS with no significant differences by initial regimen. CD4 mean increase was 257.8 (249.3; 266.2) cells/mm3, and it was lower with TAF/FTC/EVG/CBT and TDF/FTC/RPV compared with ABC/3TC/DTG. CD4 percentage normalization was less likely with TAF/FTC/EVG/CBT, and MTMR was less likely with TAF/FTC/EVG/CBT and TDF/FTC + RAL. The proportion of discontinuations due to AE was higher with TDF/FTC + bDRV (9.7%), followed by TDF/FTC/EVG/CBT (9.5%) and TDF/FTC + DTG (7.9%). Compared with ABC/3TC/DTG, cholesterol and LDL mean increases were higher with TAF/FTC/EVG/CBT and lower with TDF/FTC + DTG, TDF/FTC/RPV and TDF/FTC + RAL. Higher mean increases in triglycerides were significantly associated with TAF/FTC/EVG/CBT. Regimens containing DTG showed higher creatinine increases. Conclusions The significantly greater immunological response and safety of some combinations may be useful for making decisions when initiating treatment.

Abstract: The aim of this study was to investigate the effectiveness and tolerability of the combination elvitegravir/cobicistat/tenofovir/emtricitabine plus darunavir (EVG/COB/TFV/FTC + DRV) in treatment-experienced patients from the cohort of the Spanish HIV/AIDS Research Network (CoRIS). Methods Treatment-experienced patients starting treatment with EVG/COB/TFV/FTC + DRV during the years 2014–2018 and with more than 24 weeks of follow-up were included. TFV could be administered either as tenofovir disoproxil fumarate or tenofovir alafenamide. We evaluated virological response, defined as viral load (VL)  〈  50 copies/ml and  〈  200 copies/ml at 24 and 48 weeks after starting this regimen, stratified by baseline VL ( 〈  50 or ≥ 50 copies/ml at the start of the regimen). Results We included 39 patients (12.8% women). At baseline, 10 (25.6%) patients had VL  〈  50 copies/ml and 29 (74.4%) had ≥ 50 copies/ml. Among patients with baseline VL  〈  50 copies/ml, 85.7% and 80.0% had VL  〈  50 copies/ml at 24 and 48 weeks, respectively, and 100% had VL  〈  200 copies/ml at 24 and 48 weeks. Among patients with baseline VL ≥ 50 copies/ml, 42.3% and 40.9% had VL  〈  50 copies/ml and 69.2% and 68.2% had VL  〈  200 copies/ml at 24 and 48 weeks. During the first 48 weeks, no patients changed their treatment due to toxicity, and 4 patients (all with baseline VL ≥ 50 copies/ml) changed due to virological failure. Conclusions EVG/COB/TFV/FTC + DRV was well tolerated and effective in treatment-experienced patients with undetectable viral load as a simplification strategy, allowing once-daily, two-pill regimen with three antiretroviral drug classes. Effectiveness was low in patients with detectable viral loads.

Abstract: Anal squamous cell carcinoma is rare, in general, but considerably higher in HIV-infected men who have sex with men. There is no consensus on the screening of at-risk populations. OBJECTIVE: This study aimed to determine the incidence rates of anal squamous cell carcinoma and the efficacy of a screening program. DESIGN: This is a cohort study (SeVIHanal/NCT03713229). SETTING: This study was conducted at an HIV outpatient clinic in Seville, Spain. PATIENTS: From 2004 to 2017, all patients with at least 1 follow-up visit were analyzed (follow-up group), including a subgroup of men who have sex with men who participated in a specialized program for screening and treating anal neoplasia (SCAN group) from 2011 onward. MAIN OUTCOME MEASURES: The primary outcome measure was the incidence rate of anal squamous cell carcinoma. RESULTS: Of the 3878 people living with HIV included in the follow-up group, 897 were transferred to the SCAN group; 1584 (41%) were men who have sex with men. Total follow-up was 29,228 person-years with an overall incidence rate for anal squamous cell carcinoma of 68.4/100,000 person-years (95% CI, 46.7–97.4). The changes in the incidence rate/100,000 person-years (95% CI) over time was 20.7 (3.40–80.5) for 2004 to 2006, 37.3 (13.4–87.3) for 2007 to 2010, and 97.8 (63.8–144.9) for 2011 to 2017 ( p 〈 0.001). The strongest impact on the incidence of anal squamous cell carcinoma was made by the lack of immune restoration (adjusted incidence rate ratio (95% CI): 6.59 (4.24–10); p 〈 0.001), the Centers for Disease Control and Prevention category C (adjusted incidence rate ratio (95% CI): 7.49 (5.69–9.85); p 〈 0.001), and non-men who have sex with men (adjusted incidence rate ratio (95% CI): 0.07 (0.05–0.10); p 〈 0.001) in a Poisson analysis. From 2010 to 2017, incidence rates (95% CI) of anal squamous cell carcinoma within the SCAN group and the men who have sex with men of the follow-up group were 95.7 (39.6–202) and 201 (101–386)/100,000 person-years (adjusted incidence rate ratio (95% CI): 0.30 (0.23–0.39); p 〈 0.001). The incidence rate ratio (95% CI) including non-men who have sex with men in the follow-up group was 0.87 (0.69–1.11); p = 0.269. LIMITATIONS: Adherence to the visits could not be quantified. CONCLUSION: Incidence rates of anal squamous cell carcinoma in people living with HIV increased significantly from 2004 to 2017, especially in men who have sex with men who were not being screened. Participation in the SCAN program significantly reduced the incidence of anal squamous cell carcinoma in men who have sex with men, in whom focus should be placed, especially on those presenting with Centers for Disease Control and Prevention category C and advanced immune suppression. See Video Abstract at http://links.lww.com/DCR/B734. TASA DE INCIDENCIA Y FACTORES DE RIESGO DEL CARCINOMA ANAL A CÉLULAS ESCAMOSAS EN UNA COHORTE DE PERSONAS QUE VIVEN CON EL VIH DE 2004 A 2017: IMPLEMENTACIÓN DE UN PROGRAMA DE DETECCIÓN ANTECEDENTES: El carcinoma anal a células escamosas es generalmente raro, pero considerablemente más alto en hombres infectados por el VIH que tienen relaciones sexuales con hombres. No hay consenso sobre el cribado de poblaciones en riesgo. OBJETIVO: Este estudio tuvo como objetivo determinar las tasas de incidencia del carcinoma anal a células escamosas y la eficacia de un programa de detección. DISEÑO: Estudio de cohorte (SeVIHanal / NCT03713229). AJUSTE: Clínica ambulatoria de VIH en Sevilla, España. PACIENTES: De 2004 a 2017, se analizaron todos los pacientes con al menos una visita de seguimiento (grupo F / U), incluido un subgrupo de hombres que tenían relaciones sexuales con hombres que participaron en un programa especializado de cribado y tratamiento de neoplasias anales (SCAN-group) a partir de 2011. PRINCIPALES MEDIDAS DE RESULTADO: Tasas de incidencia del carcinoma anal a células escamosas. RESULTADOS: De las 3878 personas que viven con el VIH incluidas en el grupo F / U, 897 fueron transferidas al grupo SCAN, 1584 (41%) eran hombres que tenían relaciones sexuales con hombres. El seguimiento total fue de 29228 personas-año con una tasa de incidencia general de carcinoma anal a células escamosas de 68,4 / 100000 personas-año [intervalo de confianza del 95%: 46,7-97,4]. El cambio en las tasas de incidencia / 100000 personas-año (intervalo de confianza del 95%) a lo largo del tiempo fue 20,7 (3,40-80,5) para 2004-2006, 37,3 (13,4-87,3) para 2007-2010 y 97,8 (63,8-144,9) para 2011-2017, p 〈 0,001. El impacto más fuerte en la incidencia del carcinoma a células escamosas anal fue la falta de restauración inmunológica [índice de tasa de incidencia ajustado (intervalo de confianza del 95%): 6,59 (4,24-10); p 〈 0,001], categoría C de los Centros de Control de Enfermedades [índice de tasa de incidencia ajustado (intervalo de confianza del 95%): 7,49 (5,69-9,85); p 〈 0,001] y no hombres que tenían relaciones sexuales con hombres [razón de tasa de incidencia ajustada (intervalo de confianza del 95%): 0,07 (0,05-0,10); p 〈 0,001] en el análisis de Poisson. Desde 2010-2017, las tasas de incidencia (intervalo de confianza del 95%) de carcinoma anal a células escamosas dentro del grupo SCAN y los hombres que tienen relaciones sexuales con hombres del grupo F / U fueron 95,7 (39,6-202) y 201 (101- 386) / 100000 personas-año [razón de tasa de incidencia ajustada (intervalo de confianza del 95%): 0,30 (0,23-0,39); p 〈 0,001]. La razón de la tasa de incidencia (intervalo de confianza del 95%), incluidos los no hombres que tenían relaciones sexuales con hombres en F / U, fue de 0,87 [0,69-1,11); p = 0,269] . LIMITACIONES: No se pudo cuantificar la adherencia a las visitas. CONCLUSIÓNES: La tasa de incidencia del carcinoma anal a células escamosas en personas que viven con el VIH aumentó significativamente de 2004 a 2017, especialmente en hombres que tenían relaciones sexuales con hombres que no se someten a pruebas de detección. La participación en el programa SCAN redujo significativamente la incidencia de carcinoma anal a células escamosas en hombres que tenían relaciones sexuales con hombres, en quienes se debe prestar una especial atención, sobre todo en aquellos que se presentan en la categoría C de los Centros de Control de Enfermedades con inmunodeficiencia avanzada. Consulte Video Resumen en http://links.lww.com/DCR/B734.

Abstract: HIV‐controllers have the ability to spontaneously maintain viraemia at low or undetectable levels in the absence of antiretroviral treatment. Furthermore, HIV‐controllers seem to have a superior capacity to spontaneously clear hepatitis C virus (HCV) compared to non HIV‐controllers. Some of these subjects eventually lose HIV‐controller status (transient controllers), whereas some HIV‐controllers show a persistent natural HIV control (persistent controllers). We aimed to analyse whether persistent controllers have superior capacity to spontaneously clear HCV compared to transient controllers. Methods We recruited HIV‐controllers from January 1981 up to October 2016 with available antibodies to HCV (anti‐HCV) data (n = 744). Factors associated with HIV spontaneous control in relation to HCV status were analysed in persistent and transient HIV‐controllers with anti‐HCV positive (n = 202 and n = 138 respectively) in comparison with 1700 HCV positive non HIV‐controllers recruited from January 1981 up to March 2018, bivariate and multivariate analyses, following a logistic regression model, were applied. In addition, the factors related to the loss and time to lose HIV‐controller status were explored (n = 744) using Log rank test and Kaplan–Meier curves, in this case the multivariate analysis consisted in a Cox regression model. Results A higher frequency of HCV spontaneous clearance was found in persistent HIV‐controllers (25.5%) compared to non‐controllers (10.2%). After adjusting for potential confounders, as sex, age, HIV transmission risk, CD4 + T‐cell nadir and time of follow‐up, HCV clearance was independently associated with persistent HIV spontaneous control ( p  = 0.002; OR (95% CI) = 2.573 (1.428 to 4.633)), but not with transient spontaneous control ( p  = 0.119; 1.589 (0.888 to 2.845)). Furthermore, persistent HIV‐controllers were more likely to spontaneously clear the HCV in comparison with transient controllers ( p  = 0.027; 0.377 (0.159 to 0.893). Finally, not to lose or lengthen the time of losing this control was independently associated with HCV spontaneous clearance ( p  = 0.010; 0.503 (0.297 to 0.850). Conclusions This study shows an association between spontaneous persistent HIV‐control and HCV spontaneous clearance. The study findings support the idea of preserved immune mechanisms in persistent HIV control implicated in HCV spontaneous clearance. These results highlight persistent HIV‐controllers but not transient controllers as a good model of functional HIV cure.

Abstract: The activation phenotypes and functional changes in monocyte subsets during hepatitis C virus (HCV) elimination in HIV/HCV-coinfected patients were evaluated. Twenty-two HIV/HCV-coinfected patients on suppressive combination antiretroviral treatment (cART) achieving HCV elimination after direct-acting antiviral (DAA) therapy and 10 HIV-monoinfected patients were included. The activation phenotype (10 markers) and polyfunctionality (intracellular interleukin-1α [IL-1α] , IL-1β, IL-6, IL-8, tumor necrosis factor alpha [TNF-α], and IL-10 production) in three monocyte subsets (classical, intermediate, and nonclassical) were evaluated by flow cytometry before and at the end of treatment. Cell-associated HIV DNA levels were assayed by droplet digital PCR. After HCV clearance, there was a significant increase in classical monocyte and decreases in intermediate and nonclassical monocyte levels. The levels of the activation markers CD49d, CD40, and CX3CR1 were decreased after treatment in the monocyte subsets, reaching the levels in HIV-monoinfected patients. After lipopolysaccharide (LPS) stimulation, although polyfunctionality significantly decreased in intermediate and nonclassical monocytes, some combinations, such as the IL-1α − (IL-1α-negative) IL-1β − IL-6 + (IL-6-producing) IL-8 − TNF-α − IL-10 − combination, were remarkably increased at the end of treatment compared to the control group. Cell-associated HIV DNA levels correlated with activation markers before but not after treatment. HCV clearance after DAA treatment in patients on cART exerts an anti-inflammatory profile on monocyte subsets, activation phenotypes, and polyfunctionality. However, there is not a complete normalization compared with HIV-monoinfected patients.

Abstract: Between 15% and 30% of HIV-infected subjects fail to increase their CD4+ T-cell counts despite continuous viral suppression (immunological nonresponders [INRs]). These subjects have a higher morbidity and mortality rate, but there are no effective treatments to reverse this situation so far. This study used data from an interrupted phase I/II clinical trial to evaluate safety and immune recovery after INRs were given four infusions, at baseline and at weeks 4, 8, and 20, with human allogeneic mesenchymal stromal cells from adipose tissue (Ad-MSCs). Based on the study design, the first 5 out of 15 INRs recruited received unblinded Ad-MSC infusions. They had a median CD4+ nadir count of 16/μL (range, 2-180) and CD4+ count of 253 cells per microliter (171-412) at baseline after 109 (54-237) months on antiretroviral treatment and 69 (52-91) months of continuous undetectable plasma HIV-RNA. After a year of follow-up, an independent committee recommended the suspension of the study because no increase of CD4+ T-cell counts or CD4+/CD8+ ratios was observed. There were also no significant changes in the phenotype of different immunological lymphocyte subsets, percentages of natural killer cells, regulatory T cells, and dendritic cells, the inflammatory parameters analyzed, and cellular associated HIV-DNA in peripheral blood mononuclear cells. Furthermore, three subjects suffered venous thrombosis events directly related to the Ad-MSC infusions in the arms where the infusions were performed. Although the current study is based on a small sample of participants, the findings suggest that allogeneic Ad-MSC infusions are not effective to improve immune recovery in INR patients or to reduce immune activation or inflammation. ClinicalTrials.gov identifier: NCT0229004. EudraCT number: 2014-000307-26.