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To pinpoint factors associated with low-level viraemia (LLV) and virological failure (VF) in people living with HIV in the era of high-efficacy antiretroviral treatment (ART) and widespread use of integrase strand transfer inhibitor (INSTIs)-based ART.We included adults aged 18 years starting their first ART between 2015 and 2018 in the Spanish HIV/AIDS Research Network National Cohort (CoRIS). Low-level viraemia was defined as plasma viral load (pVL) of 50-199 copies/mL at weeks 48 and 72 and VF was defined as pVL ≥ 50 copies/mL at week 48 and pVL ≥ 200 copies/mL at week 72. Multivariable logistic regression models assessed the impact on LLV and VF of baseline CD4 T-cell count, CD4/CD8 T-cell ratio and pVL, initial ART classes, age at ART initiation, time between HIV diagnosis and ART initiation, gender and transmission route.Out of 4186 participants, 3120 (76.0%) started INSTIs, 455 (11.1%) started boosted protease inhibitors (bPIs) and 443 (10.8%) started nonnucleoside reverse transcriptase inhibitors (NNRTIs), either of them with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs). Low-level viraemia was met in 2.5% of participants and VF in 4.3%. There were no significant differences throughout the years for both virological outcomes. Baseline HIV-1 RNA 5 logThe rates of LLV and VF were low but remained steady throughout the years. Baseline HIV-1 RNA 5 log

Plasma extracellular vesicle (EV)-associated cytokines were quantified in people with HIV (PWH) with different virological control status, including elite controllers (EC) who maintain persistent control (PC) or not (TC). Cytokine signatures and pathways were determined for each group. Median EV-associated cytokine levels were higher among PWH than HIV-uninfected. EC showed the highest levels of EV-associated cytokines among PWH with PC levels higher than TC levels. IL-18 levels best distinguished PWH from uninfected controls, and EC from ART-treated, and IL-3 distinguished PC from TC. The role of EV-cytokines in intercellular communication and endogenous control of HIV expression should be investigated further.

Objectives: We compared the characteristics and clinical outcomes of hospitalized individuals with COVID-19 with [people with HIV (PWH)] and without (non-PWH) HIV co-infection in Spain during the first wave of the pandemic. Methods: This was a retrospective matched cohort study. People with HIV were identified by reviewing clinical records and laboratory registries of 10 922 patients in active-follow-up within the Spanish HIV Research Network (CoRIS) up to 30 June 2020. Each hospitalized PWH was matched with five non-PWH of the same age and sex randomly selected from COVID-19@Spain, a multicentre cohort of 4035 patients hospitalized with confirmed COVID-19. The main outcome was all-cause in-hospital mortality. Results: Forty-five PWH with PCR-confirmed COVID-19 were identified in CoRIS, 21 of whom were hospitalized. A total of 105 age/sex-matched controls were selected from the COVID-19@Spain cohort. The median age in both groups was 53 (Q1-Q3, 46-56) years, and 90.5% were men. In PWH, 19.1% were injecting drug users, 95.2% were on antiretroviral therapy, 94.4% had HIV-RNA

Objective: To assess the prevalence of serological markers of HBV and endemic acute and chronic infections (HAV, HCV, CMV, HTLV-1/2 and syphilis) in HIV-infected children, adolescents and pregnant women in Sierra Leone. Method: We conducted a cross-sectional study at the national children’s and women’s hospitals in Freetown. Logistic regression was used to assess predictors of HBsAg positivity. Results: 183 HIV-infected participants were enrolled, comprising children (n = 88), adolescents (n = 47) and pregnant women (n = 48). All participants (100%) were CMV IgG-positive, while 56.8%, 93.6% and 100% of children, adolescents and pregnant women, respectively, were HAV IgG-positive. The prevalence of HCV, HTLV-1/2 and syphilis were 10 years, i.e., being born pre-2009 before implementation of routine hepatitis B immunization (aOR 5.05 [1.18−21.28]; p = 0.029) and CD4 count

Background The role of extracellular vesicles (EVs) in human immunodeficiency virus (HIV) pathogenesis is unknown. We examine the cellular origin of plasma microvesicles (MVs), a type of ectocytosis-derived EV, the presence of mitochondria in MVs, and their relationship to circulating cell-free mitochondrial deoxyribonucleic acid (ccf-mtDNA) in HIV-infected patients and controls. Methods Five participant groups were defined: 30 antiretroviral therapy (ART)-naive; 30 ART-treated with nondetectable viremia; 30 elite controllers; 30 viremic controllers; and 30 HIV-uninfected controls. Microvesicles were quantified and characterized from plasma samples by flow cytometry. MitoTrackerDeepRed identified MVs containing mitochondria and ccf-mtDNA was quantified by real-time polymerase chain reaction. Results Microvesicle numbers were expanded at least 10-fold in all HIV-infected groups compared with controls. More than 79% were platelet-derived MVs. Proportions of MVs containing mitochondria (22.3% vs 41.6%) and MV mitochondrial density (706 vs 1346) were significantly lower among HIV-infected subjects than controls, lowest levels for those on ART. Microvesicle numbers correlated with ccf-mtDNA levels that were higher among HIV-infected patients. Conclusions A massive release of platelet-derived MVs occurs during HIV infection. Some MVs contain mitochondria, but their proportion and mitochondrial densities were lower in HIV infection than in controls. Platelet-derived MVs may be biomarkers of platelet activation, possibly reflecting pathogenesis even in absence of HIV replication.

Objective To assess the diagnosis, treatment outcomes, and predictors of mortality in adult tuberculosis (TB) patients in an urban setting with a high HIV prevalence. Methods A retrospective study was conducted of adult TB patients aged ≥15 years who were treated at Connaught Hospital in Freetown, Sierra Leone from January through December 2017. Multivariate logistic regression was used to identify predictors of mortality. Results Of 1127 TB cases notified in 2017, 1105 (98%) were tested for HIV, yielding a TB/HIV co-infection rate of 32.0%. Only HIV-tested cases (n = 1105) were included in the final analysis. The majority were male (69.3%), aged 25–34 years (29.2%), and had pulmonary TB (96.3%). Treatment outcomes were as follows: 29.0% cured, 29.0% completed, 0.5% treatment failure, 24.2% lost to follow-up, 12.8% transferred/not evaluated, and 4.5% died. The majority of deaths (80.0%, 40/50) occurred within 2 months of TB treatment initiation. Age 65 years or older (adjusted odds ratio 3.48, 95% confidence interval 1.15–10.56; p = 0.027) and HIV-positive status (adjusted odds ratio 3.50, 95% confidence interval 1.72–7.12; p = 0.001) were independent predictors of mortality. Conclusions Suboptimal TB treatment outcomes were observed in Sierra Leone in 2017. More local and international action is warranted to help achieve the 2035 global TB elimination targets.

SARS-CoV-2 specific T-cell response has been associated with disease severity, immune memory and heterologous response to endemic coronaviruses. However, an integrative approach combining a comprehensive analysis of the quality of SARS-CoV-2 specific T-cell response with antibody levels in these three scenarios is needed. In the present study we found that, in acute infection, while mild disease was associated with high T-cell polyfunctionality biased to IL-2 production and inversely correlated with anti-S IgG levels, combinations only including IFN-γ with absence of perforin production predominated in severe disease. Seven months after infection, both non-hospitalized and previously hospitalized patients presented robust anti-S IgG levels and SARS-CoV-2 specific T-cell response. In addition, only previously hospitalized patients showed a T-cell exhaustion profile. Finally, combinations including IL-2 in response to S protein of endemic coronaviruses, were the ones associated with SARS-CoV-2 S-specific T-cell response in pre-COVID-19 healthy donors’ samples. These results have implications for protective immunity against SARS-CoV-2 and recurrent COVID-19 and may help for the design of new prototypes and boosting vaccine strategies.

Viral and host immune kinetics during acute COVID-19 and after remission of acute symptoms need better characterization. SARS-CoV-2 RNA, anti-SARS-CoV-2 IgA, IgM, and IgG antibodies, and proinflammatory cytokines were measured in sequential samples from hospitalized COVID-19 patients during acute infection and six months following diagnosis. Twenty four laboratory confirmed COVID-19 patients with mild/moderate and severe COVID-19 were included. Most were males (83%) with a median age of 61 years. Twenty one percent were admitted to the intensive care unit (ICU) and eight of them (33.3%) met the criteria for severe COVID-19 disease. A delay in SARS-CoV-2 levels’ decline during the first six days of follow up, and viral load persistence until month 3 were related to severe COVID-19, but not viral load levels at the diagnosis. Higher levels of anti-SARS-CoV-2 IgA, IgM, IgG and the cytokines IL-6, IL-8 and MIP-1β at the diagnosis time were related to the severe COVID-19 outcome. Higher levels of MIP-1β, IL-1β, MIP-1α and IFN-γ were observed at month 1 and 3 during mild/moderate disease, compared to severe COVID-19. IgG persisted at low levels after six months of diagnosis. In conclusion, higher concentrations of IgA, IgM, and IgG, and IL-6, IL-8 and MIP-1β are identified as early predictors of COVID-19 severity, whereas no significant association is found between baseline SARS-COV-2 viral load and COVID-19 severity., This work was supported by the Plan Estatal de I+D+I 2013-2016 and 2017–2020 and cofinanced by the Instituto de Salud Carlos III (ISCIII)—Subdirección General de Evaluación y Fomento de la investigación del Fondo Europeo de Desarrollo Regional (FEDER), Fondo COVID19 of Instituto de Salud Carlos III (COV20/00698), RETICS, Red de Investigación en SIDA [RD16/0025/0026]; and Fundación Biomédica Galicia Sur. E.R-M. was supported by the Spanish Research Council (CSIC) and by the research grant CV20-85418 from the Consejería de Transformación Económica, Industria, Conocimiento y Universidades (Junta de Andalucía). A.P. was supported by the Instituto de Salud Carlos III, Subprograma Rio Hortega (CM20/00243). A.G.-V. was supported by the Instituto de Salud Carlos III, cofinanced by the European Development Regional Fund (“A way to achieve Europe”), Subprograma Miguel Servet (CP19/00159). E.M.M. was supported by the Instituto de Salud Carlos III, cofinanced by the European Development Regional Fund (“A way to achieve Europe”), Subprogram PFIS (FI19/00304). C.K. was supported by Fondo COVID19 of Instituto de Salud Carlos III (COV20/00823).

Survivors to COVID-19 have described long-term symptoms after acute disease. These signs constitute a heterogeneous group named long COVID or persistent COVID. The aim of this study is to describe persisting symptoms 6 months after COVID-19 diagnosis in a prospective cohort in the Northwest Spain. This is a prospective cohort study performed in the COHVID-GS. This cohort includes patients in clinical follow-up in a health area of 569,534 inhabitants after SARS-CoV-2/COVID-19 diagnosis. Clinical and epidemiological characteristics were collected during the follow up. A total of 248 patients completed 6 months follow-up, 176 (69.4%) required hospitalization and 29 (10.2%) of them needed critical care. At 6 months, 119 (48.0%) patients described one or more persisting symptoms. The most prevalent were: extra-thoracic symptoms (39.1%), chest symptoms (27%), dyspnoea (20.6%), and fatigue (16.1%). These symptoms were more common in hospitalized patients (52.3% vs. 38.2%) and in women (59.0% vs. 40.5%). The multivariate analysis identified COPD, women gender and tobacco consumption as risk factors for long COVID. Persisting symptoms are common after COVID-19 especially in hospitalized patients compared to outpatients (52.3% vs. 38.2%). Based on these findings, special attention and clinical follow-up after acute SARS-CoV-2 infection should be provided for hospitalized patients with previous lung diseases, tobacco consumption, and women.

Human immunodeficiency virus (HIV) drug resistance (HIVDR) is widespread in sub-Saharan Africa. Children and pregnant women are particularly vulnerable, and laboratory testing capacity remains limited. We, therefore, used a cross-sectional design and convenience sampling to characterize HIV subtypes and resistance-associated mutations (RAMs) in these groups in Sierra Leone. In total, 96 children (age 2–9 years, 100% ART-experienced), 47 adolescents (age 10–18 years, 100% ART-experienced), and 54 pregnant women (>18 years, 72% ART-experienced) were enrolled. Median treatment durations were 36, 84, and 3 months, respectively, while the sequencing success rates were 45%, 70%, and 59%, respectively, among children, adolescents, and pregnant women. Overall, the predominant HIV-1 subtype was CRF02_AG (87.9%, 95/108), with minority variants constituting 12%. Among children and adolescents, the most common RAMs were M184V (76.6%, n = 49/64), K103N (45.3%, n = 29/64), Y181C/V/I (28.1%, n = 18/64), T215F/Y (25.0%, n = 16/64), and V108I (18.8%, n = 12/64). Among pregnant women, the most frequent RAMs were K103N (20.6%, n = 7/34), M184V (11.8%, n = 4/34), Y181C/V/I (5.9%, n = 2/34), P225H (8.8%, n = 3/34), and K219N/E/Q/R (5.9%, n = 2/34). Protease and integrase inhibitor-RAMs were relatively few or absent. Based on the genotype susceptibility score distributions, 73%, 88%, and 14% of children, adolescents, and pregnant women, respectively, were not susceptible to all three drug components of the WHO preferred first-line regimens per 2018 guidelines. These findings suggest that routine HIVDR surveillance and access to better ART choices may improve treatment outcomes in Sierra Leone., This research was funded by the Roe Green Travel Medicine and Global Health Award 2019 (Award Number J0628), University Hospitals Cleveland Medical Center (G.A.Y.), Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional-FEDER, Red Española de Investigación en SIDA (RD16/0025/0026) (E.P.), Xunta Galicia-Fondo Social Europeo (IN606A-2016/023) (E.P.) and Fundación Biomédica Galicia Sur (E.P.).

HIV coinfection with hepatitis B virus (HBV), hepatitis C virus (HCV), and human T-cell lymphotropic viruses 1 and 2 (HTLV-1 and HTLV-2) is common because of shared transmission routes. There is no published data on the prevalence of these infections in people living with HIV in Sierra Leone. We conducted a cross-sectional study of 211 HIV-positive patients aged ≥ 18 years in Freetown, Sierra Leone, in November 2017. Plasma samples were analyzed using the chemiluminescent microparticle immunoassay (Architect System, Abbott ARCHITECT Analyzer, Abbott Park, IL. The majority were female (63.5%), with median age 36 years (interquartile range [IQR]: 32–44) and median CD4 count of 396 cells/µL (IQR: 214–534). Sixty patients (28.4%) were newly diagnosed and antiretroviral therapy (ART) naive; 151 patients (71.6%) were ART experienced. The prevalence of the hepatitis B surface antigen (HBsAg), total anti-hepatitis B core antibody, and anti-HCV was 21.7%, 82.9%, and 4.3%, respectively. No cases of HTLV-1 or HTLV-2 were detected. Male gender (P = 0.004) and CD4 < 350 cells/µL (P = 0.017) were associated with the HBsAg positive status.

Objectives: The aim of this study was to assess the prevalence of HIV drug resistance (HIVDR) in HIV-infected ART-naive and -experienced patients in Sierra Leone. Patients and methods: We conducted a cross-sectional study of HIV-positive adults aged 18 years at Connaught Hospital in Freetown, Sierra Leone in November 2017. Sequencing was performed in the reverse transcriptase, protease and integrase regions, and interpreted using the Stanford HIVDR database andWHO 2009mutation list. Results: Two hundred and fifteen HIV-infected patients were included (64 ART naive and 151 ART experienced). The majority (66%) were female, the median age was 36 years and the median ART exposure was 48months. The majority (83%) were infected with HIV-1 subtype CRF02_AG. In the ART-naive group, the pretreatment drug resistance (PDR) prevalence was 36.7% (14.2% to NRTIs and 22.4% to NNRTIs). The most prevalent PDR mutations were K103N (14.3%), M184V (8.2%) and Y181C (4.1%). In the ART-experienced group, 64.4% harboured resistance-associated mutations (RAMs) and the overall prevalence of RAMs to NRTIs and NNRTIs was 85.2% (52/61) and 96.7% (59/61), respectively. The most prevalent RAMs were K103N (40.7%), M184V (28.8%), D67N (15.3%) and T215I/F/Y (15.3%). Based on the genotypic susceptibility score estimates, 22.4% of ART-naive patients and 56% of ART-experienced patients were not susceptible to first-line ART used in Sierra Leone. Conclusions: A high prevalence of circulating NRTI- and NNRTI-resistant variants was observed in ART-naive and -experienced HIV-1-infected patients in Sierra Leone. This necessitates the implementation of HIVDR surveillance programmes to inform national ART guidelines for the treatment and monitoring of HIV-infected patients in Sierra Leone. Xunta Galicia-Fondo Social Europeo | Ref. IN606A-2016/023 Case Western Reserve University | Ref. NIH NIAID T32 AI07024 Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional-FEDER | Ref. RD16/0025/0026

[Abstract] Two elvitegravir/cobicistat‐based therapies combined with emtricitabine/tenofovir disoproxil fumarate (EVG/c/FTC/TDF) or emtricitabine/tenofovir alafenamide fumarate (EVG/c/FTC/TAF) are currently available for HIV patients. This study evaluated the modifications in the lipid profile of patients who received these treatments in the last three years at our institution. A retrospective observational study in HIV‐infected patients who received EVG/c/FTC/TDF or EVG/c/FTC/TAF from January 2015 to January 2018 at a reference hospital in northwestern Spain was carried out. Epidemiological, clinical and immunovirological data were recorded. A statistical analysis was performed using SPSS software. A total of 384 EVG/c‐based therapies were initiated during the study period, 151 EVG/c/FTC/TDF and 233 EVG/c/FTC/TAF. A significantly negative influence in all the lipid profile parameters in experienced patients and total cholesterol (TC), and LDL‐C in naïve patients were observed after 48 weeks of treatment with EVG/c/FTC/TAF, while these parameters remained stable in the EVG/c/FTC/TDF group. During follow‐up, a greater proportion of patients had lipid levels above the normal range (63.1% TC, 56.2% LDL‐C) and new lipid‐modifying drugs were prescribed (11.9%) in the EVG/c/FTC/TAF group. The number of cardiovascular risk factors (OR 1.66 [95% CI 1.01‐2.72]; P = 0.043) was recognised as an independent predictor of lipid‐lowering prescription for patients treated with both EVG/c/FTC/TDF and EVG/c/FTC/TAF. For patients treated with EVG/c/FTC/TAF, the mean total cholesterol to HDL ratio in the first 48 weeks of the study treatment was associated with a higher likelihood of lipid‐lowering prescription in multivariate analysis (OR 1.6 [95% CI 1.12‐2.52]; P = 0.011). Significant changes in lipid profile have been observed in patients who have received EVG/c/FTC/TAF. It was necessary to prescribe almost twice the number of lipid‐lowering drugs to patients who received EVG/c/FTC/TAF (11.9%) vs EVG/c/FTC/TDF (4.7%).

"Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM", Objectives: We aimed to assess the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and factors associated with seropositivity and asymptomatic coronavirus disease 2019 (COVID-19) among people with HIV (PWH). Methods: This was a cross-sectional study carried out within the cohort of the Spanish HIV Research Network. Participants were consecutive PWH with plasma collected from 1st April to 30th September 2020. We determined SARS-CoV-2 antibodies (Abs) in plasma. Illness severity (NIH criteria) was assessed by a review of medical records and, if needed, participant interviews. Multivariable logistic regression analysis was used to identify predictors of seropositivity among the following variables: sex, age, country of birth, education level, comorbidities (hypertension, chronic heart disease, diabetes mellitus, non-AIDS-related cancer, chronic kidney disease, cirrhosis), route of HIV acquisition, prior AIDS, CD4+ cell count, HIV viral load, nucleoside/nucleotide reverse transcriptase inhibitor (N [t]RTI) backbone, type of third antiretroviral drug, and month of sample collection. Results: Of 1076 PWH (88.0% males, median age 43 years, 97.7% on antiretroviral therapy, median CD4+ 688 cells/mm3, 91.4% undetectable HIV viral load), SARS-CoV-2 Abs were detected in 91 PWH, a seroprevalence of 8.5% (95%CI 6.9–10.3%). Forty-five infections (45.0%) were asymptomatic. Variables independently associated with SARS-CoV-2 seropositivity were birth in Latin American countries versus Spain (adjusted odds ratio (aOR) 2.30, 95%CI 1.41–3.76, p 0.001), and therapy with tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC) versus tenofovir alafenamide (TAF)/FTC as the N(t)RTI backbone (aOR 0.49, 95%CI 0.26–0.94, p 0.031). Conclusions: Many SARS-CoV-2 infections among PWH were asymptomatic, and birth in Latin American countries increased the risk of SARS-CoV-2 seropositivity. Our analysis, adjusted by comorbidities and other variables, suggests that TDF/FTC may prevent SARS-CoV-2 infection among PWH., This work was supported by the Instituto de Salud Carlos III (ISCII) (grant number COV20/00108) and the Spanish AIDS Research Network (RD16/0025), which is included in the Spanish I þ D þ I Plan and is co-funded by ISCIII-Subdirección General de Evaluacion and European Funding for Regional Development (FEDER).

Background To estimate the prevalence and severity of menopausal symptoms and anxiety/depression and to assess the differences according to menopausal status among women living with HIV aged 45–60 years from the cohort of Spanish HIV/AIDS Research Network (CoRIS). Methods Women were interviewed by phone between September 2017 and December 2018 to determine whether they had experienced menopausal symptoms and anxiety/depression. The Menopause Rating Scale was used to evaluate the prevalence and severity of symptoms related to menopause in three subscales: somatic, psychologic and urogenital; and the 4-item Patient Health Questionnaire was used for anxiety/depression. Logistic regression models were used to estimate odds ratios (ORs) of association between menopausal status, and other potential risk factors, the presence and severity of somatic, psychological and urogenital symptoms and of anxiety/depression. Results Of 251 women included, 137 (54.6%) were post-, 70 (27.9%) peri- and 44 (17.5%) pre-menopausal, respectively. Median age of onset menopause was 48 years (IQR 45–50). The proportions of pre-, peri- and post-menopausal women who had experienced any menopausal symptoms were 45.5%, 60.0% and 66.4%, respectively. Both peri- and post-menopause were associated with a higher likelihood of having somatic symptoms (aOR 3.01; 95% CI 1.38–6.55 and 2.63; 1.44–4.81, respectively), while post-menopause increased the likelihood of having psychological (2.16; 1.13–4.14) and urogenital symptoms (2.54; 1.42–4.85). By other hand, post-menopausal women had a statistically significant five-fold increase in the likelihood of presenting severe urogenital symptoms than pre-menopausal women (4.90; 1.74–13.84). No significant differences by menopausal status were found for anxiety/depression. Joint/muscle problems, exhaustion and sleeping disorders were the most commonly reported symptoms among all women. Differences in the prevalences of vaginal dryness (p = 0.002), joint/muscle complaints (p = 0.032), and sweating/flush (p = 0.032) were found among the three groups. Conclusions Women living with HIV experienced a wide variety of menopausal symptoms, some of them initiated before women had any menstrual irregularity. We found a higher likelihood of somatic symptoms in peri- and post-menopausal women, while a higher likelihood of psychological and urogenital symptoms was found in post-menopausal women. Most somatic symptoms were of low or moderate severity, probably due to the good clinical and immunological situation of these women.

Background There are limited data to help guide implementation of differentiated HIV service delivery (DSD) in resource-limited settings in sub-Saharan Africa. Objectives This pre-implementation study sought to assess the proportion of patients eligible for DSD and HIV services utilization, as well as risk factor analysis of virologic failure in Sierra Leone. Methods We conducted a retrospective study of adult HIV-infected patients aged 18 years and older receiving care at the largest HIV treatment center in Sierra Leone 2019–2020. Multiple logistic regression was used to identify predictors of virologic failure. Results Of 586 unique patients reviewed, 210 (35.8%) qualified as ‘stable’ for antiretroviral therapy (ART) delivery. There was high utilization of certain HIV service programs (e.g. HIV status disclosure to partners (83%) and treatment ‘buddy’ program participation (62.8%)), while other service programs (e.g. partner testing and community HIV support group participation) had low utilization (

ObjectivesWe compared 48 week effectiveness and safety of first-line antiretroviral regimens.MethodsWe 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 0.4 and >1); (iv) CD4 percentage normalization (>29%); (v) multiple T-cell marker recovery (MTMR: CD4 > 500 cells/mm3 plus CD4 percentage >29% plus CD4/CD8 > 1); (vi) lipid, creatinine and transaminase changes; and (vii) discontinuations due to adverse events (AE).ResultsAmong 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.ConclusionsThe significantly greater immunological response and safety of some combinations may be useful for making decisions when initiating treatment.

© The Author(s) 2020., [Background]: 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), [Results]: We included 39 patients (12.8% women). At baseline, 10 (25.6%) patients had VL, [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., The RIS cohort (CoRIS) is supported by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en Sida (RD06/006, RD12/0017/0018 and RD16/0002/0006) as part of the Plan Nacional I+D+i and cofnanced by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER)”.

ObjectivesTo assess the attitudes and opinions about generic antiretroviral drugs (ARVs) and single-tablet regimen (STR) de-simplification among physicians prescribing HIV treatment in the cohort of the Spanish HIV/AIDS Research Network (CoRIS).MethodsAn online questionnaire with 27 structured questions was sent to all physicians (n = 199) who prescribed ARVs among the 45 centres participating in the cohort.ResultsA total of 169 (84.9%) physicians answered the questionnaire. Only 4.1% of the physicians would never prescribe generic ARVs, but 53.3% would not prescribe them if the number of pills per day increased and 89.3% would not prescribe them if the number of doses per day increased. However, 84.0% of the physicians agreed to prescribe generic ARVs if doing so would decrease costs for the public healthcare system. The percentages of physicians stating that generic ARVs (compared with branded ones) would be associated with worse adherence, more adverse effects or more probability of virological failure, provided that the number of pills and doses per day would not change, were low: 0.6%, 7.7% and 3.6%, respectively. However, these percentages were much higher if the generic ARV entailed breaking an STR: 63.9%, 18.9% and 42.0%, respectively. Most physicians stated that they needed more information about the effectiveness and safety of generic ARVs and the price difference compared with their branded equivalents.ConclusionsAlthough most physicians were confident about prescribing generic ARVs, the majority had strong concerns about de-simplifying STR, and they also needed more information about generic drugs.

Antiretroviral therapy (ART) is recommended for all patients infected by HIV-1. The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should be based on a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors (tenofovir in either of its two formulations plus emtricitabine or abacavir plus lamivudine) and another drug from a different family. Four of the recommended regimens, all of which have an integrase inhibitor as the third drug (dolutegravir, elvitegravir boosted with cobicistat or raltegravir), are considered preferential, whereas a further 3 regimens (based on elvitegravir/cobicistat, rilpivirine, or darunavir boosted with cobicistat or ritonavir) are considered alternatives. We present the reasons and criteria for switching ART in patients with an undetectable PVL and in those who present virological failure, in which case salvage ART should include 3 (or at least 2) drugs that are fully active against HIV. We also update the criteria for ART in specific situations (acute infection, HIV-2 infection, pregnancy) and comorbidities (tuberculosis or other opportunistic infections, kidney disease, liver disease and cancer).

Since hepatitis C virus (HCV) and human T-lymphotropic virus (HTLV) share transmission routes, dual infection could be frequent. In Spain, HTLV underdiagnosis is highlighted by the high proportion of patients presenting either with tropical spastic paraparesis or adult T cell leukemia at first diagnosis. We examined whether the renewed efforts for expanding HCV testing may provide a sentinel population that might selectively be targeted to unveil asymptomatic HTLV carriers. The presence of anti-HTLV antibodies was examined in 3,838 consecutive individuals with reactive HCV serology attended during the last 3 years at 13 hospitals distributed across the Spanish geography. Overall 71% were male, and the median age was 41 years old. Foreigners represented 9% of the study population. A total of 50 individuals (1.3%) were seroreactive for HTLV, being 30 confirmed as HTLV-2 and 2 as HTLV-1 (0.12%). The remaining 18 had indeterminate Western blot patterns. Most individuals with HTLV-2 and HTLV indetermi...

ObjectivesDirect-acting antiviral agents (DAAs) have provided an ultimate treatment duration of 12 weeks for most hepatitis C virus (HCV)-infected patients. The opportunity to reduce treatment duration to 6 or 8 weeks is being evaluated. Here, the HCV viral dynamics at short times during HCV therapi

[Abstract] Background. New patterns in epidemiological characteristics of people living with HIV infection (PLWH) and the introduction of Highly Active Antiretroviral Therapy (HAART) have changed the profile of hospital admissions in this population. The aim of this study was to evaluate trends in hospital admissions, re-admissions, and mortality rates in HIV patients and to analyze the role of HCV co-infection. Methods. A retrospective cohort study conducted on all hospital admissions of HIV patients between 1993 and 2013. The study time was divided in two periods (1993–2002 and 2003–2013) to be compared by conducting a comparative cross-sectional analysis. Results. A total of 22,901 patient-years were included in the analysis, with 6917 hospital admissions, corresponding to 1937 subjects (75% male, mean age 36 ± 11 years, 37% HIV/HCV co-infected patients). The median length of hospital stay was 8 days (5–16), and the 30-day hospital re-admission rate was 20.1%. A significant decrease in hospital admissions related with infectious and psychiatric diseases was observed in the last period (2003–2013), but there was an increase in those related with malignancies, cardiovascular, gastrointestinal, and chronic respiratory diseases. In-hospital mortality remained high (6.8% in the first period vs. 6.3% in the second one), with a progressive increase of non-AIDS-defining illness deaths (37.9% vs. 68.3%, P < .001). The admission rate significantly dropped after 1996 (4.9% yearly), but it was less pronounced in HCV co-infected patients (1.7% yearly). Conclusions. Hospital admissions due to infectious and psychiatric disorders have decreased, with a significant increase in non-AIDS-defining malignancies, cardiovascular, and chronic respiratory diseases. In-hospital mortality is currently still high, but mainly because of non-AIDS-defining illnesses. HCV co-infection increased the hospital stay and re-admissions during the study period. [Resumen] Introducción. Los cambios en las características epidemiológicas de los pacientes con infección por el VIH, y la introducción del tratamiento antirretroviral de alta eficacia, han modificado el perfil de las hospitalizaciones en esta población. El objetivo del estudio fue evaluar las tendencias en hospitalización, reingreso y mortalidad en pacientes VIH, y analizar el papel de la coinfección por el VHC. Métodos. Estudio de cohortes retrospectivo, que incluyó todas las hospitalizaciones de pacientes VIH entre 1993-2013. El estudio fue dividido en 2 periodos (1993-2002 y 2003-2013) para ser comparados mediante un análisis transversal. Resultados. Se analizaron 22.901 pacientes/años, que presentaron 6.917 hospitalizaciones que correspondieron a 1.937 pacientes (75% varones, edad media 36 ± 11 años, 37% coinfectados VIH/VHC). La mediana de estancia hospitalaria fue de 8 días (5-16), y la tasa de reingreso a los 30 días del 20,1%. Se observó un descenso significativo en el segundo periodo (2003-2013) de las hospitalizaciones motivadas por enfermedades infecciosas y trastornos psiquiátricos, y un incremento de aquellas relacionadas con neoplasias, enfermedad cardiovascular, gastrointestinal y enfermedades respiratorias crónicas. La mortalidad intrahospitalaria permanece elevada (6,8% en el primer periodo vs. 6,3% en el segundo), con un aumento progresivo de las muertes por enfermedades no definitorias de sida (37,9 vs. 68,3%; p < 0,001). La tasa de hospitalización disminuyó de manera significativa después de 1996 (4,9% anual), pero este descenso fue menos acusado en los pacientes coinfectados VIH/VHC (1,7% anual). Conclusiones. Las hospitalizaciones motivadas por enfermedades infecciosas y trastornos psiquiátricos han descendido; por el contrario, se observó un aumento significativo de aquellas relacionadas con neoplasias no definitorias de sida, enfermedad cardiovascular y enfermedades respiratorias crónicas. La mortalidad intrahospitalaria permanece a día de hoy elevada, pero a expensas fundamentalmente de enfermedades no definitorias de sida. La coinfección VIH/VHC incrementó los días de hospitalización y los reingresos durante el periodo de estudio. Instituto de Salud Carlos III; CPII14/00014 Instituto de Salud Carlos III; PI10/02166 Instituto de Salud Carlos III; PI13/02266 Instituto de Salud Carlos III; CM13/00328