Clinical outcomes and prognostic factors after HCV clearance with DAA in HIV/HCV-coinfected patients with advanced fibrosis/cirrhosis.

BACKGROUND AND AIMS: We assessed long-term clinical outcomes and prognostic factors for liver disease progression after sustained viral response with direct-acting antivirals in patients coinfected with HIV/HCV with advanced fibrosis or cirrhosis. APPROACH AND RESULTS: A total of 1300 patients who achieved sustained viral response with direct-acting antivirals from 2014 to 2017 in Spain were included: 1145 with compensated advanced chronic liver disease (384 advanced fibrosis and 761 compensated cirrhosis) and 155 with decompensated cirrhosis. The median follow-up was 40.9 months. Overall, 85 deaths occurred, 61 due to non-liver non-AIDS-related causes that were the leading cause of death across all stages of liver disease. The incidence (95% CI) of decompensation per 100 person-years (py) was 0 in patients with advanced fibrosis, 1.01 (0.68-1.51) in patients with compensated cirrhosis, and 8.35 (6.05-11.53) in patients with decompensated cirrhosis. The incidence (95% CI) of HCC per 100 py was 0.34 (0.13-0.91) in patients with advanced fibrosis, 0.73 (0.45-1.18) in patients with compensated cirrhosis, and 1.92 (1.00-3.70) per 100 py in patients with decompensated cirrhosis. Prognostic factors for decompensation in patients with compensated advanced chronic liver disease included serum albumin, liver stiffness measurement (LSM), and fibrosis 4. In this population, LSM and LSM-based posttreatment risk stratification models showed their predictive ability for decompensation and HCC. CONCLUSIONS: Non-liver non-AIDS-related events were the leading causes of morbidity and mortality after direct-acting antiviral cure among coinfected patients with advanced fibrosis/cirrhosis. Among those with compensated advanced chronic liver disease, baseline LSM and posttreatment LSM-based models helped to assess decompensation and HCC risk.

Waist circumference and cardiometabolic parameters in people of African/Caribbean ancestry with HIV in South London (CKD-AFRICA study).

BACKGROUND: There are no validated waist circumference (WC) cut-offs to define metabolic syndrome in Black people with HIV. METHODS: Cross-sectional analyses within the CKD-AFRICA study. We used Pearson correlation coefficients and receiver operating characteristic (ROC) curves to describe the relationship between WC and cardiometabolic parameters including triglycerides, cholesterol, glucose, glycated haemoglobin (HbA1c), and homeostatic model assessment for insulin resistance (HOMA-IR), and to identify optimal WC cut-offs for each of these outcomes. RESULTS: We included 383 participants (55% female, median age 52 years) with generally well controlled HIV. Female and male participants had similar WC (median 98 vs. 97 cm, p = .16). Generally weak correlations (r2 < 0.2) between WC and other cardiometabolic parameters were observed, with low (<0.7) areas under the ROC curves. The optimal WC cut-offs for constituents of the metabolic syndrome, HbA1c and HOMA-IR ranged from 92 to 101 cm in women and 89-98 cm in men, respectively; these cut-offs had variable sensitivity (52%-100%) and generally poor specificity (28%-72%). CONCLUSIONS: In this cohort of Black people with HIV, WC cut-offs for cardiometabolic risk factors in male participants were in line with the recommended value of 94 cm while in female participants they vastly exceeded the recommended 80 cm for white women.

Associations between social determinants of health and comorbidity and multimorbidity in people of black ethnicities with HIV.

OBJECTIVE: Social determinants of health (SDH) are important determinants of long-term conditions and multimorbidity in the general population. The intersecting relationship between SDH and multimorbidity in people with HIV remains poorly studied. DESIGN: A cross-sectional study investigating the relationships between eight socio-economic parameters and prevalent comorbidities of clinical significance and multimorbidity in adults of African ancestry with HIV aged 18-65 years in South London, UK. METHODS: Multivariable logistic regression analysis was used to evaluate associations between SDH and comorbidities and multimorbidity. RESULTS: Between September 2020 and January 2022, 398 participants (median age 52 years, 55% women) were enrolled; 85% reported at least one SDH and 72% had at least one comorbidity. There were no associations between SDH and diabetes mellitus or kidney disease, few associations between SDH (job and food insecurity) and cardiovascular or lung disease, and multiple associations between SDH (financial, food, housing and job insecurity, low educational level, social isolation, and discrimination) and poor mental health or chronic pain. Associations between SDH and multimorbidity mirrored those for constituent comorbidities. CONCLUSION: We demonstrate strong associations between SDH and poor mental health, chronic pain and multimorbidity in people of black ethnicities living with HIV in the UK. These findings highlight the likely impact of enduring socioeconomic hardship in these communities and underlines the importance of holistic health and social care for people with HIV to address these adverse psychosocial conditions.

Miositis aguda asociada a infección por virus influenza. Serie de casos en un hospital pediátrico

La miositis aguda benigna asociada a influenza es una complicación esporádica. En Argentina, en el año 2022, hubo un aumento temprano de la circulación de influenza y del número total de las notificaciones, con la aparición de miositis secundarias. Serie clínica retrospectiva de nueve pacientes pediátricos que consultaron por dolor e impotencia funcional de extremidades inferiores, y enzimas musculares elevadas, en el hospital Pedro de Elizalde de la Ciudad Autónoma de Buenos Aires, entre agosto y octubre del 2022. En todos se detectó infección por virus influenza y se recuperaron sin secuelas. La miositis aguda benigna es una entidad infrecuente en la infancia, cuyo diagnóstico es predominantemente clínico y de recuperación ad integrum. Debe ser sospechada en pacientes con clínica compatible en contexto de alta circulación viral. La vigilancia epidemiológica aporta herramientas para identificar los virus circulantes y sus posibles complicaciones.

Benign acute myositis associated with influenza is a sporadic complication. In Argentina, in 2022, there was an early increase in influenza circulation and the total number of notifications, with the appearance of secondary myositis. Retrospective clinical series of nine pediatric patients who consulted for pain and functional impotence of the lower extremities, and elevated muscle enzymes, at the Pedro de Elizalde hospital in the Autonomous City of Buenos Aires, between August and October 2022. In all of them, infection by influenza virus and recovered without sequelae. Benign acute myositis is a rare entity in childhood, whose diagnosis is predominantly clinical and recovery ad integrum. It should be suspected in patients with compatible symptoms in a context of high viral circulation. Epidemiological surveillance provides tools to identify circulating viruses and their possible complications.

MicroRNA signature from extracellular vesicles of HCV/HIV co-infected individuals differs from HCV mono-infected.

Hepatitis C virus (HCV) coinfection with human immunodeficiency virus (HIV) has a detrimental impact on disease progression. Increasing evidence points to extracellular vesicles (EVs) as important players of the host-viral cross-talk. The microRNAs (miRNAs), as essential components of EVs cargo, are key regulators of normal cellular processes and also promote viral replication, viral pathogenesis, and disease progression. We aimed to characterize the plasma-derived EVs miRNA signature of chronic HCV infected and HIV coinfected patients to unravel the molecular mechanisms of coinfection. EVs were purified and characterized from 50 plasma samples (21 HCV mono- and 29 HCV/HIV co-infected). EV-derived small RNAs were isolated and analyzed by massive sequencing. Known and de novo miRNAs were identified with miRDeep2. Significant differentially expressed (SDE) miRNA identification was performed with generalized linear models and their putative dysregulated biological pathways were evaluated. Study groups were similar for most clinical and epidemiological characteristics. No differences were observed in EVs size or concentration between groups. Therefore, HCV/HIV co-infection condition did not affect the concentration or size of EVs but produced a disturbance in plasma-derived EVs miRNA cargo. Thus, a total of 149 miRNAs were identified (143 known and 6 de novo) leading to 37 SDE miRNAs of which 15 were upregulated and 22 downregulated in HCV/HIV co-infected patients. SDE miRNAs regulate genes involved in inflammation, fibrosis, and cancer, modulating different biological pathways related to HCV and HIV pathogenesis. These findings may help to develop new generation biomarkers and treatment strategies, in addition to elucidate the mechanisms underlying virus-host interaction. KEY MESSAGES: HCV and HCV/HIV displayed similar plasma-EV size and concentration. EVs- derived miRNA profile was characterized by NGS. 37 SDE miRNAs between HCV and HCV/HIV were observed. SDE miRNAs regulate genes involved in inflammation, fibrosis and cancer.

HCV spontaneous clearers showed low senescence profile in people living with HIV under long ART.

Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) increases immune activation, inflammation, and oxidative stress that could lead to premature senescence. Different HCV infections, either acute or chronic infection, could lead to distinct premature cellular senescence in people living with HIV (PLWHIV). Observational study in 116 PLWHIV under antiretroviral treatment with different HCV status: (i) n = 45 chronically infected with HCV (CHC); (ii) n = 36 individuals who spontaneously clarify HCV (SC); (iii) n = 35 HIV controls. Oxidative stress biomarkers were analyzed at lipid, DNA, protein, and nitrates levels, as well as antioxidant capacity and glutathione reductase enzyme. Replicative senescence was evaluated by relative telomere length (RTL) measurement. Additionally, 26 markers of Senescence-Associated Secretory Phenotype (SASP) were analyzed by multiplex immunoassays (Luminex xMAP technology). Differences were evaluated by generalized linear model (GLMs) adjusted by most significant covariates. The SC group had a senescence signature similar to the HIV control group and slightly lower SASP levels. However, significant differences were observed with respect to the CHC group, where an increase in the nitrate concentration [adjusted arithmetic mean ratio, aAMR = 1.73 (1.27-2.35), p < 0.001, q = 0.009] and the secretion of 13 SASP-associated factors [granulocyte macrophage colony-stimulating factor (GM-CSF), interferon-ß, interleukin (IL)-1ß, IL-2, IL-8, IL-13, tumor necrosis factor (TNF)-α, IL-1α, IL-1RA, IL-7, IL-15, C-X-C motif chemokine ligand 10 (IP-10), stem cell factor (SCF); q < 0.1)] was detected. The CHC group also showed higher values of IL-1α, IP-10, and placental growth factor 1 (PIGF-1) than HIV controls. The SC group showed a slightly lower senescence profile than the HIV group, which could indicate a more efficient control of viral-induced senescence due to their immune strengths. Chronic HCV infection in PLWHIV led to an increase in nitrate and elevated SASP biomarkers favoring the establishment of viral persistence.

Dynamics of cellular senescence markers after HCV elimination spontaneously or by DAAs in people living with HIV.

BACKGROUND: We identified that acute or chronic Hepatitis C (HCV) infection in people living with HIV (PLWHIV) results in different senescence profiles. However, variations in these profiles after HCV elimination, spontaneously or with direct-acting antivirals (DAAs), remain unclear. METHODS: Longitudinal observational study (48 weeks) in 70 PLWHIV: 23 PLWHIV with active HCV-chronic infection (CHC) before and after HCV eradication with DAAs, 12 PLWHIV who spontaneously clarify the HCV (SC), and 35 controls (HIV). Oxidative stress was quantified at DNA, lipid, protein, and nitrate levels, as well as the antioxidant capacity and glutathione enzyme. The replicative senescence was evaluated by relative telomere length measurement by PCR and twenty-six factors related to Senescence-Associated Secretory Phenotype (SASP) were characterized by Luminex. Differences in senescence markers was evaluated by generalized linear models. RESULTS: During follow-up, the SC group achieved a significant improvement in glutathione enzyme and lipid peroxidation. The secretion of SASP markers increased but was still lower than that of the HIV group. Overall, the CHC group reduced the levels of oxidative stress and SASP markers to levels like those of the HIV group. No significant differences in telomere shortening were observed between groups. CONCLUSIONS: As the time since spontaneous resolution of HCV infection increased, patients had an improved senescence profile compared to the HIV group. Elimination of chronic HCV infection by DAAs led to a partial improvement of the senescent profile by restoring oxidative stress levels. However, although some SASP markers reached levels like those of the HIV group, others remained altered.

PrEP for women in Europe: a systematic literature review.

BACKGROUND: Prevention of HIV transmission is fundamental to ending the HIV epidemic. Pre-exposure prophylaxis (PrEP) with oral tenofovir-emtricitabine (TDF-FTC) is an established HIV-prevention method; however, most PrEP services in Europe have been targeted at men who have sex with men (MSM). A survey in 2021 by Women Against Viruses in Europe (WAVE) showed considerable variation in PrEP access and guidance for women throughout Europe. WAVE therefore commissioned this systematic review to provide insight into PrEP provision and barriers to uptake for women in Europe. METHODS: PubMed, Embase, and Scopus were searched for studies (January 2013-May 2021) that reported on actual (e.g., efficacy and safety) or hypothetical (e.g., awareness, barriers, PrEP impact models) use of oral PrEP involving women (including cis, transgender, pregnant, migrant, and breastfeeding women). Search terms included HIV, pre-exposure prophylaxis (specifically TDF-FTC), and women. Studies performed outside of the World Health Organization European region were excluded. RESULTS: The search identified 4716 unique citations, and 45 peer-reviewed articles (44 studies) were included. The majority of these studies (34/44 [77%]) included recipients or potential recipients of PrEP, representing 4699 women (243 transgender women). However, few studies were women focused (4/34 [12%]) or took place outside of Western Europe (3/34 [9%]). Across the three clinical studies that reported women-specific outcomes (60 transgender women, 13 pregnant, and 19 cis women), no breakthrough infections were recorded during the use of PrEP. Lack of awareness of PrEP, low self-estimation of HIV acquisition risk, concerns about stigma, lack of protection against other sexually transmitted infections, and PrEP interaction with hormones (for transgender women) were identified as barriers to use. The remaining studies examined healthcare professionals' perceptions of PrEP (9/44 [20%]), asked for public opinion (2/44 [5%]), or modelled the potential of PrEP for HIV prevention (1/44 [2%]). CONCLUSIONS: This review revealed a notable lack of literature on PrEP for cis and transgender women in Europe. This is synonymous with a lack of PrEP provision for women in this region. Barriers to PrEP uptake are complex and rooted in institutional and societal stigma, which must be addressed at policy level. HIV prevention with PrEP is not 'one size fits all' and requires a nuanced gender-responsive approach. Further research into the use of PrEP in cis, pregnant, breastfeeding, and transgender women is essential if we are to stop HIV transmission by 2030.

Association between ten-eleven methylcytosine dioxygenase 2 genetic variation and viral load in people with HIV.

INTRODUCTION: Identifying genetic factors that influence HIV-pathogenesis is critical for understanding disease pathways. Previous studies have suggested a role for the human gene ten-eleven methylcytosine dioxygenase 2 (TET2) in modulating HIV-pathogenesis. METHODS: We assessed whether genetic variation in TET2 was associated with markers of HIV-pathogenesis using both gene level and single nucleotide polymorphism (SNP) level association in 8512 HIV-positive persons across five clinical trial cohorts. RESULTS: Variation at both the gene and SNP-level of TET2 was found to be associated with levels of HIV viral load (HIV-VL) consistently in the two cohorts that recruited antiretroviral-naïve participants. The SNPs occurred in two clusters of high linkage disequilibrium (LD), one associated with high HIV-VL and the other low HIV-VL, and were predominantly found in Black participants. CONCLUSION: Genetic variation in TET2 was associated with HIV-VL in two large antiretroviral therapy (ART)-naive clinical trial cohorts. The role of TET2 in HIV-pathogenesis warrants further investigation.

Takayasu's arteritis in an adolescent with fever of unknown origin: the contribution of PET-CT in the diagnosis.

Finding the cause of fever of unknown origin can sometimes be a real challenge. We present an adolescent whose diagnosis was achieved after 4 months of fever onset by performing a positron emission tomography (PET)-CT. A young woman presented with prolonged, intermittent fever along with inflammatory and iron deficiency anaemia, loss of weight and abdominal and chest pain. First investigational studies showed high-titre positive antinuclear antibodies, extractable nuclear antibodies and anti-Sjögren's-syndrome-related antigen a autoantibodies (anti-SSA), and mild pericardial effusion and aortic regurgitation, but without meeting criteria for systemic lupus erythematosus. She had maxillary sinusitis that did not resolve with antibiotics. Further study displayed elevated calprotectin in faeces. After normal abdominal ultrasound and CT, an intestinal MRI showed thickening of the terminal ileum, orienting towards an inflammatory bowel disease. A colonoscopy showed only minor macroscopic changes. A PET-CT scan was finally requested, which exhibited a diffuse increase in metabolism in the wall of the thoracic and abdominal aortas, suggesting Takayasu's arteritis.

Low CD4/CD8 ratio is associated with increased morbidity and mortality in late and non-late presenters: results from a multicentre cohort study, 2004-2018.

BACKGROUND: To study whether the association between the CD4/CD8 ratio variation over time and the development of clinical outcomes vary in late presenters (CD4 count < 350/µL or AIDS event at enrolment) or advanced presenters (CD4 count < 200/µL or AIDS event at enrolment). METHODS: We included ART-naïve adults from the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) enrolled between January 2004 up to November 2018 and with at least 6 months of follow-up. We used extended Cox proportional hazard models to estimate the hazard ratios (HRs) for the association between CD4/CD8 ratio over time and a composite endpoint of the occurrence of the first AIDS event, first serious non-AIDS event or overall mortality occurring from 6 months after enrolment. HRs in non-late, late and advanced presenters were obtained by including an interaction term between late presentation status and CD4/CD8 ratio over time. RESULTS: Of 10,018 participants, 55.6% were late presenters and 26.5% were advanced presenters. Compared with CD4/CD8 ratio > 0.4, CD4/CD8 ratio ≤ 0.4 over time was associated with an increased risk of experiencing the composite endpoint in non-late (HR 1.90; 95%CI 1.48, 2.43), late (HR 1.94; 1.46, 2.57) and advanced presenters (HR 1.72; 1.26, 2.34). Similarly, CD4/CD8 ratio ≤ 0.4 over time was associated with a higher risk of developing an AIDS event (HR 3.31; 2.23, 4.93 in non-late; HR 2.75; 1.78, 4.27 in late and HR 2.25; 1.34, 3.76 in advanced presenters) or serious non-AIDS event (HR 1.39; 0.96, 2.02 in non-late, HR 1.62; 1.10, 2.40 in late and HR 1.49; 0.97, 2.29 in advanced presenters) as well as with a higher risk of overall mortality (HR 1.49; 0.92, 2.41 in non-late, HR 1.80; 1.04, 3.11 in late and HR 1.61; 0.92, 2.83 in advanced presenters) compared to CD4/CD8 > 0.4, regardless of the late presentation status. CONCLUSIONS: A low CD4/CD8 measured over time is associated with increased risk of morbidity and mortality in people living with HIV independently of their late presentation status. These data support the prognostic role of CD4/CD8 over time and can help defining a subgroup of patients who need closer monitoring to avoid comorbidities.

Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019.

OBJECTIVES: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. METHODS: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. RESULTS: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). CONCLUSIONS: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population.

Different HCV Exposure Drives Specific miRNA Profile in PBMCs of HIV Patients.

Micro RNAs (miRNAs) are essential players in HIV and HCV infections, as both viruses modulate cellular miRNAs and interact with the miRNA-mediated host response. We aim to analyze the miRNA profile of HIV patients with different exposure to HCV to explore specific signatures in the miRNA profile of PBMCs for each type of infection. We massively sequenced small RNAs of PBMCs from 117 HIV+ infected patients: 45 HIV+ patients chronically infected with HCV (HIV/HCV+), 36 HIV+ that spontaneously clarified HCV after acute infection (HIV/HCV-) and 36 HIV+ patients without previous HCV infection (HIV). Thirty-two healthy patients were used as healthy controls (HC). Differential expression analysis showed significantly differentially expressed (SDE) miRNAs in HIV/HCV+ (n = 153), HIV/HCV- (n = 169) and HIV (n = 153) patients. We found putative dysregulated pathways, such as infectious-related and PI3K signaling pathways, common in all contrasts. Specifically, putatively targeted genes involved in antifolate resistance (HIV/HV+), cancer-related pathways (HIV/HCV-) and HIF-signaling (HIV) were identified, among others. Our findings revealed that HCV strongly influences the expression profile of PBMCs from HIV patients through the disruption of its miRNome. Thus, different HCV exposure can be identified by specific miRNA signatures in PBMCs.

Detection of archived lamivudine-associated resistance mutations in virologically suppressed, lamivudine-experienced HIV-infected adults by different genotyping techniques (GEN-PRO study).

BACKGROUND: Previously selected lamivudine resistance-associated mutations (RAMs) may remain archived within the proviral HIV-DNA. OBJECTIVES: To evaluate the ability of proviral DNA genotyping to detect lamivudine RAMs in HIV-1 virologically suppressed participants; the correlation between Sanger and next generation sequencing (NGS); and predictive factors for detection of lamivudine RAMs in proviral DNA. METHODS: Cross-sectional study of participants on stable antiretroviral therapy and suppressed for ≥1 year. Analysis of proviral DNA was performed by Sanger sequencing in whole blood and by NGS in PBMCs. RESULTS: We analysed samples from 102 subjects (52 with and 50 without lamivudine RAMs in historical plasma RNA-genotypes). Among participants with previous lamivudine resistance, Sanger sequencing detected RAMs in 26.9%. Detection rates significantly increased using NGS: 47.9%, 64.6%, 75% and 87.5% with the 20%, 10%, 5% and 1% thresholds, respectively. As for participants without historical lamivudine resistance, Sanger detected the RAMs in 1/49 (2%), and NGS (5% threshold) in 8/45 (17.8%). Multivariate models fitted to the whole population revealed that having a history of lamivudine resistance was a risk factor for detection of lamivudine RAMs by NGS. Among participants with historical lamivudine resistance, multivariate analysis showed that a longer time since HIV diagnosis was associated with persistence of archived mutations by NGS at thresholds of >10% [OR 1.10 (95% CI: 1.00-1.24)] and >5% [OR 1.16 (95% CI: 1.02-1.32)]. CONCLUSIONS: Proviral DNA Sanger sequencing does not detect the majority of historical lamivudine RAMs. NGS increases the sensitivity of detection at lower thresholds, although the relevance of these minority populations with lamivudine RAMs needs further evaluation.

Hepatocellular carcinoma risk in hepatitis C stage-3 fibrosis after sustained virological response with direct-acting antivirals.

BACKGROUND & AIMS: Patients with chronic hepatitis C and stage 3 fibrosis are thought to remain at risk of hepatocellular carcinoma after sustained virological response. We investigated this risk in a large cohort of patients with well-defined stage 3 fibrosis. METHODS: We performed a multicentre, ambispective, observational study of chronic hepatitis C patients with sustained virological response after treatment with direct-acting antivirals started between January and December 2015. Baseline stage 3 was defined in a two-step procedure: we selected patients with transient elastography values of 9.5-14.5 kPa and subsequently excluded those with nodular liver surface, splenomegaly, ascites or collaterals on imaging, thrombopenia or esophago-gastric varices. Patients were screened twice-yearly using ultrasound. RESULTS: The final sample comprised 506 patients (median age, 57.4 years; males, 59.9%; diabetes, 17.2%; overweight, 44.1%; genotype 3, 8.9%; HIV coinfection, 18.4%; altered liver values, 15.2%). Median follow-up was 33.7 (22.1-39.1) months. Five hepatocellular carcinomas and 1 cholangiocarcinoma were detected after a median of 29.4 months (95% CI: 26.8-39.3), with an incidence of 0.47/100 patients/year (95% CI: 0.17-1.01). In the multivariate analysis, only males older than 55 years had a significant higher risk (hazard ratio 7.2 [95% CI: 1.2-41.7; P = .029]) with an incidence of 1.1/100 patients/year (95% CI: 0.3-2.8). CONCLUSIONS: In a large, well-defined cohort of patients with baseline hepatitis C stage-3 fibrosis, the incidence of primary liver tumours was low after sustained virological response and far from the threshold for cost-effectiveness of screening, except in males older than 55 years.

Late presentation for HIV remains a major health issue in Spain: Results from a multicenter cohort study, 2004-2018.

OBJECTIVES: With the purpose of reducing the well-known negative impact of late presentation (LP) on people living with HIV (PLWH), guidelines on early HIV diagnosis were published in 2014 in Spain, but since then no data on LP prevalence have been published. To estimate prevalence and risk factors of LP and to evaluate their impact on the development of clinical outcomes in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) during 2004-2018. METHODS: CoRIS is an open prospective multicenter cohort of PLWH, adults, naive to ART at entry. LP was defined as HIV diagnosis with CD4 count ≤350 cells/µL or an AIDS defining event (ADE). Multivariable Poisson regression models were used to estimate both prevalence ratios (PR) for the association of potential risk factors with LP and Incidence rate ratios (IRRs) for its impact on the development of the composite endpoint (first ADE, first serious non-AIDS event [SNAE] or overall mortality). RESULTS: 14,876 individuals were included. Overall, LP prevalence in 2004-2018 was 44.6%. Risk factors for LP included older age, having been infected through injection drug use or heterosexual intercourse, low educational level and originating from non-European countries. LP was associated with an increased risk of the composite endpoint (IRR: 1.34; 95%CI 1.20, 1.50), ADE (1.39; 1.18, 1.64), SNAE (1.22; 1.01, 1.47) and mortality (1.71; 1.41, 2.08). CONCLUSIONS: LP remains a health problem in Spain, mainly among certain populations, and is associated with greater morbidity and mortality. Public policies should be implemented to expand screening and early diagnosis of HIV infection, for a focus on those at greatest risk of LP.

Late presentation for HIV impairs immunological but not virological response to antiretroviral treatment.

OBJECTIVES: The aim of this study was to examine the impact of late presentation (CD4+ cell count <350 cells/µl or an AIDS-defining event) on effectiveness and safety of initial antiretroviral therapy (ART) and to evaluate whether treatment response depends on first-line ART regimen in late presenters. DESIGN: ART-naive adults from the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) starting triple ART between 2010 and 2018. METHODS: We used multivariable models to assess differences in viral suppression (viral load <50 copies/ml), immunological response (change in CD4+ cell count, CD4% (>29%) and CD4/CD8 normalization (>0.4 and >1) multiple T-cell marker recovery (MTMR): CD4+ cell count more than 500 cells/µl and CD4% >29% and CD4/CD8 >1), and treatment discontinuation due to adverse events (TDAE) at 48 weeks from ART initiation. RESULTS: Out of 8002 participants, 48.7% were late presenters. Of them, 45.8% initiated ART with a NNRTI- (mostly TDF/FTC/EFV), 33.9% with a protease inhibitor (mostly TDF/FTC+boosted DRV) and 20.3% with an INI-based regimen (mostly ABC/3TC/DTG). At 48 weeks, late presenters had similar viral suppression, but worse immunological response, than non-late presenters with no difference on TDAE. Late presenters initiating with NNRTI-based regimens were more likely to achieve viral suppression than those starting with INI-based, due to the higher chance of achieving viral suppression observed with TDF/FTC/RPV compared to ABC/3TC/DTG. Initial treatment with NNRTI or protease inhibitor based showed similar immunological response than the INI-based regimens, which showed lower rates of TDAE than NNRTI- and protease inhibitor based regimens. CONCLUSION: Despite safety and effectiveness of initial ART in terms of viral suppression, late presenters may not experience complete immunological response. In late presenters, effectiveness and safety depends on both the class and the specific first-line ART regimen.

Long-term efficacy of dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: Week 96 results of ART-PRO pilot study.

BACKGROUND: In the ART-PRO pilot trial there were no virological failures through 48 weeks of treatment with dolutegravir plus lamivudine in suppressed individuals with and without archived lamivudine resistance-associated mutations (RAMs) detected through next-generation sequencing (NGS) but without evidence of lamivudine RAMs in baseline proviral DNA population sequencing. OBJECTIVES: To present 96 week results from ART-PRO. METHODS: Open-label, single-arm pilot trial. At baseline, all participants switched to dolutegravir plus lamivudine. Participants were excluded if proviral DNA population genotyping detected lamivudine RAMs. To detect resistance minority variants, proviral DNA NGS was retrospectively performed from baseline samples. For this analysis the efficacy endpoint was the proportion of participants with <50 HIV-1 RNA copies/mL at week 96. Safety and tolerability outcomes were incidence of adverse events and treatment discontinuations. RESULTS: Forty-one participants were included, 21 with lamivudine RAMs in historical plasma RNA genotypes. Baseline proviral DNA NGS detected lamivudine RAMs (M184V/I and/or K65R/E/N) above a 5% threshold in 71.4% (15/21) and 15% (3/20) of participants with and without history of lamivudine resistance, respectively. At 96 weeks, 90.2% of participants achieved the efficacy endpoint. Between week 48 and 96 there was one discontinuation due to consent withdrawal and no discontinuations related to adverse events. Two participants had a transient viral rebound, both re-suppressed on dolutegravir plus lamivudine. Through week 96, there were no virological failures. CONCLUSIONS: In this pilot trial, dolutegravir plus lamivudine maintained virological suppression at 96 weeks despite historical lamivudine resistance and persisting archived minority lamivudine RAMs.

Valores de riesgo vascular de indicadores metabólicos en adolescentes y ancianos de La Habana / Vascular Risk Values of Metabolic Indicators in Adolescents and Elderlies from Havana

Introducción: Durante el ciclo de vida de los individuos son imprescindibles intervenciones para detectar y reducir el riesgo y las complicaciones de las enfermedades crónicas. Objetivo: Determinar la prevalencia de valores de riesgo vascular de los principales indicadores del metabolismo glucídico y lipídico en adolescentes y ancianos de La Habana. Métodos: Se realizó un estudio transversal en una muestra conformada por adolescentes (469 de 12-16 años) aparentemente sanos y ancianos (395 de 65-100 años) sin diagnóstico de enfermedades asociadas a la alteración marcada del estado nutricional y metabólico. Ambas poblaciones fueron evaluadas para glucosa, triglicéridos, colesterol total, colesterol de lipoproteinas de alta densidad y colesterol de lipoproteínas de baja densidad, séricos, mediante métodos enzimáticos convencionales. Se usaron rangos de riesgo referentes. Los resultados se analizaron mediante estadística descriptiva. Resultados: En los adolescentes evaluados, los triglicéridos (35,6 por ciento) y el colesterol total (23,9 por ciento) mostraron las mayores frecuencias de valores de riesgo. En las hembras ambos marcadores se mantuvieron como los más elevados en ese orden, mientras que, en los varones, la glucosa (25,5 por ciento) secundó a los triglicéridos como indicadores más alterados. En ancianos, al colesterol de lipoproteínas de baja densidad (58,2 por ciento) y al colesterol total (48,6 por ciento) correspondieron las mayores frecuencias de cifras de riesgo, patrón que se repitió en cada sexo. Los valores promedio de los indicadores fueron marcadamente superiores en ancianos que, en adolescentes, excepto para glucosa y colesterol de lipoproteínas de alta densidad. Conclusiones: Los resultados obtenidos muestran una elevada prevalencia de valores de riesgo vascular de varios indicadores metabólicos evaluados en adolescentes y ancianos, lo que sugiere la necesidad de monitorear los indicadores analizados e implementar intervenciones modificadoras de sus valores hacia la reducción del riesgo asociado, desde etapas tempranas, como las previas a la adolescencia(AU)

Introduction: During the life cycle of individuals, interventions are essential to detect and reduce the risk and complications of chronic diseases. Objective: To determine the prevalence of vascular risk values of the main indicators of carbohydrate and lipid metabolism in adolescents and elderlies in Havana. Methods: A cross-sectional study was carried out with a sample made up of apparently healthy adolescents (469; aged 12-16 years) and elderlies (395 aged 65-100 years) without a diagnosis of diseases associated with marked alteration of nutritional and metabolic status. Both populations were evaluated regarding serum glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol using conventional enzymatic methods. Reference risk ranges were used. The results were analyzed using descriptive statistics. Results: In the evaluated adolescents, triglycerides (35.6 percent) and total cholesterol (23.9 percent) showed the highest frequencies of risk values. In females, both markers remained the highest in that aspect; while in males, glucose (25.5 percent) accounted second after triglycerides as the most altered indicators. In the elderlies, low-density lipoprotein cholesterol (58.2 percent) and total cholesterol (48.6 percent) corresponded to the highest frequencies of risk values, a pattern that was repeated in each sex. The average values of the indicators were markedly higher in the elderlies than in adolescents, except for glucose and high-density lipoprotein cholesterol. Conclusions: The results obtained show high prevalence of vascular risk values of several metabolic indicators evaluated in adolescents and elderlies, which suggests the need to monitor the analyzed indicators and implement interventions to modify such values, in view of reducing the associated risk, from stages early, such as the pre-adolescence stage(AU)