A 12-week multicomponent exercise program enhances frailty by increasing robustness, improves physical performance, and preserves muscle mass in older adults with HIV: MOVIhNG study.

Background: Our aim was to analyze the effects of a multicomponent exercise program (MEP) on frailty and physical performance in older adults with HIV (OAWH) since exercise can reverse frailty in the older population overall, but there is no data for OAWH. Methods: A prospective longitudinal study with intervention and control group was designed. Sedentary adults 50 or over with and without HIV were included. The intervention was a 12-week home-based MEP. Dependent variables were frailty (frailty phenotype), physical performance (Senior Fitness Test), muscle mass (ASMI) by bioimpedance. Pre- and postintervention measurements were analyzed using McNemar's test for categorical variables and the Wilcoxon signed-rank test for quantitative variables. Results: 40 OAWH and 20 OA without HIV. The median age was 56.5 years. 23.3% were women. The prevalence of frailty was 6.6% with no frail HIV-negative participants. Three of the four frail HIV-participants transitioned two (50%) from frail to prefrail and one (25%) to robust after the MEP. In participants with an adherence ≥50%, physical performance was significantly improved [basal vs. 12 week]: upper extremity strength [13 (13-15) vs. 16 (15-19), p = 0.0001], lower extremity strength [13 (11-16) vs. 15 (13-16), p = 0.004], aerobic endurance [62 (55-71) vs. 66 (58-80), p = 0.005]. Participants with low adherence experienced a significant worsening in ASMI [8.35 (7.44-9.26) vs. 7.09 (6.08-8.62), p = 0.03]. Conclusion: A 12-week MEP enhances frailty by increasing robustness in OAWH, and improves physical performance, and preserves muscle mass in older adults with good adherence to the MEP independently of HIV status.

Global DNA methylation and telomere length as markers of accelerated aging in people living with HIV and non-alcoholic fatty liver disease.

Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a comorbidity that generally increases in people living with HIV (PLWH). This condition is usually accompanied by persistent inflammation and premature immune system aging. In this prospective cohort study, we describe a straightforward methodology for quantifying biomarkers of aging, such as DNA methylation and telomere length, in PLWH and in the context of another relevant condition, such as MAFLD. Fifty-seven samples in total, thirty-eight from PLWH and nineteen from non-PLWH participants with or without MAFLD, were obtained and subjected to DNA extraction from peripheral blood mononuclear cells (PBMCs). Global DNA methylation and telomere length quantification were performed using an adapted enzyme-linked immunosorbent assay (ELISA) and qPCR, respectively. The quantification results were analysed and corrected by clinically relevant variables in this context, such as age, sex, and metabolic syndrome. Our results show an increased association of these biomarkers in PLWH regardless of their MAFLD status. Thus, we propose including the quantification of these age-related factors in studies of comorbidities. This will allow a better understanding of the effect of comorbidities of HIV infection and MAFLD and prevent their effects in these populations in the future.

Comparison of the Fecal Bacteriome of HIV-Positive and HIV-Negative Older Adults.

HIV infection is considered a scenario of accelerated aging. Previous studies have suggested a link between aging, frailty, and gut dysbiosis, but there is a knowledge gap regarding the HIV population. Our objective was to compare the fecal bacteriome of older people with HIV (PWH) and non-HIV controls, and to assess potential links between gut dysbiosis and frailty. A total of 36 fecal samples (24 from PWH and 12 from non-HIV controls) were submitted to a metataxonomic analysis targeting the V3-V4 hypervariable region of the 16S rRNA gene. High-quality reads were assembled and classified into operational taxonomic units. Alpha diversity, assessed using the Shannon index, was higher in the control group than in the HIV group (p < 0.05). The relative abundance of the genus Blautia was higher in the HIV group (p < 0.001). The presence of Blautia was also higher in PWH with depression (p = 0.004), whereas the opposite was observed for the genus Bifidobacterium (p = 0.004). Our study shows shifts in the composition of the PWH bacteriome when compared to that of healthy controls. To our knowledge, this is the first study suggesting a potential link between depression and gut dysbiosis in the HIV population.

Effects of frailty, geriatric syndromes, and comorbidity on mortality and quality of life in older adults with HIV.

BACKGROUND: To understand the effects of frailty, geriatric syndromes, and comorbidity on quality of life and mortality in older adults with HIV (OAWH). METHODS: Cross-sectional study of the FUNCFRAIL multicenter cohort. The setting was outpatient HIV-Clinic. OAWH, 50 year or over were included. We recorded sociodemographic data, HIV infection-related data, comorbidity, frailty, geriatric syndromes (depression, cognitive impairment, falls and malnutrition), quality of life (QOL) and the estimated risk of all-cause 5-year mortality by VACS Index. Association of frailty with geriatric syndromes and comorbidity was evaluated using the Cochran-Mantel-Haenszel test. RESULTS: Seven hundred ninety six patients were included. 24.7% were women, mean age was 58.2 (6.3). 14.7% were 65 or over. 517 (65%) patients had ≥3 comorbidities, ≥ 1 geriatric syndrome and/or frailty. There were significant differences in the estimated risk of mortality [(frailty 10.8%) vs. (≥ 3 comorbidities 8.2%) vs. (≥ 1 geriatric syndrome 8.2%) vs. (nothing 6.2%); p = 0.01] and in the prevalence of fair or poor QOL [(frailty 71.7%) vs. (≥ 3 comorbidities 52%) vs. (≥ 1 geriatric syndrome 58.4%) vs. (nothing 51%); p = 0.01]. Cognitive impairment was significantly associated to mortality (8.7% vs. 6.2%; p = 0.02) and depression to poor QOL [76.5% vs. 50%; p = 0.01]. CONCLUSIONS: Frailty, geriatric syndromes, and comorbidity had negative effects on mortality and QOL, but frailty had the greatest negative effect out of the three factors. Our results should be a wake-up call to standardize the screening for frailty and geriatric syndromes in OAWH in the clinical practice. TRIAL REGISTRATION: NCT03558438.

HTLV-2 Enhances CD8+ T Cell-Mediated HIV-1 Inhibition and Reduces HIV-1 Integrated Proviral Load in People Living with HIV-1.

People living with HIV-1 and HTLV-2 concomitantly show slower CD4+ T cell depletion and AIDS progression, more frequency of the natural control of HIV-1, and lower mortality rates. A similar beneficial effect of this infection has been reported on HCV coinfection reducing transaminases, increasing the spontaneous clearance of HCV infection and delaying the development of hepatic fibrosis. Given the critical role of CD8+ T cells in controlling HIV-1 infection, we analysed the role of CD8+ T cell-mediated cytotoxic activity in coinfected individuals living with HIV-1. One hundred and twenty-eight individuals living with HIV-1 in four groups were studied: two groups with HTLV-2 infection, including individuals with HCV infection (N = 41) and with a sustained virological response (SVR) after HCV treatment (N = 25); and two groups without HTLV-2 infection, including individuals with HCV infection (N = 25) and with a sustained virological response after treatment (N = 37). We found that CD8+ T cell-mediated HIV-1 inhibition in vitro was higher in individuals with HTLV-2. This inhibition activity was associated with a higher frequency of effector memory CD8+ T cells, higher levels of granzyme A and granzyme B cytolytic enzymes, and perforin. Hence, cellular and soluble cytolytic factors may contribute to the lower HIV-1 pre-ART viral load and the HIV-1 proviral load during ART therapy associated with HTLV-2 infection. Herein, we confirmed and expanded previous findings on the role of HTLV-2 in the beneficial effect on the pathogenesis of HIV-1 in coinfected individuals.

Relationship of Diet to Gut Microbiota and Inflammatory Biomarkers in People with HIV.

While changes in microbiome composition have been associated with HIV, the effect of diet and its potential impact on inflammation remains unclear. Methods: Twenty-seven people living with HIV (PWH) on antiretroviral therapy (ART) were studied. A comprehensive dietary analysis was performed and two types of dietary patterns were determined. We explored the associations of each dietary pattern with gut microbiota and plasma inflammatory biomarkers. Results: We appreciated two dietary patterns, Mediterranean-like (MEL) and one Western-like (WEL). Compared to participants with the WEL pattern, participants with MEL pattern showed higher abundance of Lachnospira (p-value = 0.02) and lower levels of the inflammatory biomarkers D-dimer (p-value = 0.050) and soluble TNF-alpha receptor 2 (sTNFR2) (p-value = 0.049). Men who have sex with men (MSM) with MEL pattern had lower abundance of Erysipelotrichaceae (p-value < 0.001) and lower levels of D-dimer (p-value = 0.026) than MSM with WEL pattern. Conclusion: MEL pattern favours Lachnospira abundance, and protects against Erysipelotrichaceae abundance and higher levels of the inflammatory biomarkers D-dimer and sTNFR2, precursors of inflammatory processes in HIV-infected patients. Our study contributes to understanding the determinants of a healthier diet and its connections with gut microbiota and inflammation.

Different profiles among older adults with HIV according to their chronological age and the year of HIV diagnosis: The FUNCFRAIL cohort study (GeSIDA 9817).

BACKGROUND: People in their fifties with HIV are considered older adults, but they appear not to be a homogeneous group. OBJECTIVE: To evaluate the differences among older adults with HIV according to their chronological age and the year of HIV diagnosis. METHODS: Cross-sectional study of the FUNCFRAIL cohort. Patients 50 or over with HIV were included and were stratified by both chronological age and the year of HIV diagnosis: before 1996 (long-term HIV survivors [LTHS]) and after 1996. We recorded sociodemographic data, HIV-related factors, comorbidities, frailty, physical function, other geriatric syndromes, and quality of life (QOL). RESULTS: We evaluated 801 patients. Of these, 24.7% were women, 47.0% were LTHS, and 14.7% were 65 or over. Of the 65 or over patients, 73% were diagnosed after 1996. Higher rates of comorbidities among LTHS were found, being the more prevalent: COPD, history of cancer, osteoarthritis, depression, and other psychiatric disorders while the more prevalent among the 65 or over patients were: hypertension, diabetes, dyslipidemia, cancer, and osteoarthritis. LTHS showed a significantly worse QOL. There were no differences by the year of HIV diagnosis regarding frailty and functional impairment (SPPB <10) but they were more than twice as prevalent in the 65 or over patients compared to the other chronological age groups. CONCLUSIONS: A LTHS and a 65 or over person are both "older adults with HIV," but their characteristics and requirements differ markedly. It is mandatory to design specific approaches focused on the real needs of the different profiles.

Fecal microbiota transplantation in HIV: A pilot placebo-controlled study.

Changes in the microbiota have been linked to persistent inflammation during treated HIV infection. In this pilot double-blind study, we study 30 HIV-infected subjects on antiretroviral therapy (ART) with a CD4/CD8 ratio < 1 randomized to either weekly fecal microbiota capsules or placebo for 8 weeks. Stool donors were rationally selected based on their microbiota signatures. We report that fecal microbiota transplantation (FMT) is safe, not related to severe adverse events, and attenuates HIV-associated dysbiosis. FMT elicits changes in gut microbiota structure, including significant increases in alpha diversity, and a mild and transient engraftment of donor's microbiota during the treatment period. The greater engraftment seems to be achieved by recent antibiotic use before FMT. The Lachnospiraceae and Ruminococcaceae families, which are typically depleted in people with HIV, are the taxa more robustly engrafted across time-points. In exploratory analyses, we describe a significant amelioration in the FMT group in intestinal fatty acid-binding protein (IFABP), a biomarker of intestinal damage that independently predicts mortality. Gut microbiota manipulation using a non-invasive and safe strategy of FMT delivery is feasible and deserves further investigation. Trial number: NCT03008941.

Cryptococcal infection in HIV-infected patients with CD4+ T-cell counts under 100/µL diagnosed in a high-income country: a multicentre cohort study.

OBJECTIVES: The World Health Organization recommends routinely screening HIV-infected patients with CD4+ T-cell counts <100/µL for cryptococcal infection to prevent cryptococcal meningitis (CM), based on studies in Sub-Saharan Africa where the prevalence of positive cryptococcal antigen (CrAg+) is ≥ 3% in this subgroup. Data about such prevalence in Spain are unavailable and rare in other European countries. Thus, the Spanish AIDS Study Group guidelines do not recommend routinely screening. We aim to determine the prevalence and outcomes of cryptococcal infection in this subgroup of patients in Spain. METHODS: We determined CrAg using a lateral flow assay in banked plasma from participants in the cohort of the Spanish AIDS Research Network. Eligible patients had CD4+ T-cell counts ≤100/µL at the time of plasma collection and a follow-up >4 weeks, unless they died. RESULTS: We included 576 patients from June 2004 to December 2017. Of these, 43 were CrAg+ for an overall prevalence of 7.5%. There were no differences depending on birthplace. The CrAg+ was independently associated with a higher mortality at eight weeks (hazard ratio (HR) 5.36, 95% confidence interval (CI) 1.46-19.56) and 6 months (HR 3.12, 95% CI 1.19-8.21). CM was reported in 10 of the 43 CrAg+ patients. There were no cases among negatives. Five patients had CM when the plasma was collected and five developed it during the follow-up. The number of subjects needed to screen to anticipate the diagnosis of one CM case was 114. CONCLUSIONS: The CrAg+ prevalence among HIV-infected patients with CD4+ T-cell counts ≤100/µL diagnosed in Spain, both immigrants and native-born Spanish, is >7%. Consequently, the Spanish AIDS Study Group guidelines have to be updated and recommend routine screening for cryptococcal infection in these patients. Future studies should explore whether this recommendation could be firmly applied to other European populations.

Description of COVID-19 in HIV-infected individuals: a single-centre, prospective cohort.

BACKGROUND: Information about incidence, clinical characteristics, and outcomes of HIV-infected individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is scarce. We characterised individuals with COVID-19 among a cohort of HIV-infected adults in Madrid. METHODS: In this observational prospective study, we included all consecutive HIV-infected individuals (aged ≥18 years) who had suspected or confirmed COVID-19 as of April 30, 2020, at the Hospital Universitario Ramón y Cajal (Madrid, Spain). We compared the characteristics of HIV-infected individuals with COVID-19 with a sample of HIV-infected individuals assessed before the COVID-19 pandemic, and described the outcomes of individuals with COVID-19. FINDINGS: 51 HIV-infected individuals were diagnosed with COVID-19 (incidence 1·8%, 95% CI 1·3-2·3). Mean age of patients was 53·3 years (SD 9·5); eight (16%) were women, and 43 (84%) men. 35 (69%) cases of co-infection had laboratory confirmed COVID-19, and 28 (55%) required hospital admission. Age and CD4 cell counts in 51 patients diagnosed with COVID-19 were similar to those in 1288 HIV-infected individuals without; however, 32 (63%) with COVID-19 had at least one comorbidity (mostly hypertension and diabetes) compared with 495 (38%) without COVID-19 (p=0·00059). 37 (73%) patients had received tenofovir before COVID-19 diagnosis compared with 487 (38%) of those without COVID-19 (p=0·0036); 11 (22%) in the COVID-19 group had previous protease inhibitor use (mostly darunavir) compared with 175 (14%; p=0·578). Clinical, analytical, and radiological presentation of COVID-19 in HIV-infected individuals was similar to that described in the general population. Six (12%) individuals were critically ill, two of whom had CD4 counts of less than 200 cells per µL, and two (4%) died. SARS-CoV-2 RT-PCR remained positive after a median of 40 days from symptoms onset in six (32%) individuals, four of whom had severe disease or low nadir CD4 cell counts. INTERPRETATION: HIV-infected individuals should not be considered to be protected from SARS-CoV-2 infection or to have lower risk of severe disease. Generally, they should receive the same treatment approach applied to the general population. FUNDING: None.

CD4+:CD8+ T-cell ratio changes in people with HIV receiving antiretroviral treatment.

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.

Risk, Diagnostic and Predictor Factors for Classical Hodgkin Lymphoma in HIV-1-Infected Individuals: Role of Plasma Exosome-Derived miR-20a and miR-21.

The incidence of classical Hodgkin lymphoma (cHL) in the HIV-1 setting has increased 5-25-fold compared to that observed in the general population. This study aimed to determine whether selected micro RNAs (miRs) and other soluble biomarkers and cellular subsets are dysregulated in cHL and could be used as biomarkers. This was a retrospective and longitudinal matched case-control study of 111 Caucasian, HIV-1-infected adult individuals, including 37 individuals with cHL and 74 with no type of cancer. Immunovirological data, plasma exosome-derived miR-16, miR-20a, miR-21, miR-221, miR-223, miR-106a, miR-185, miR-23, miR-30d, miR-222, miR-146a and miR-324, plasma IL-6, sCD14, sCD27, sCD30, sIL-2R, TNFR1, and cell phenotyping of T and B lymphocytes and natural killer (NK) cells were analyzed. Before cHL diagnosis, miR-20a, miR-21, and sCD30 were higher in cHL (p = 0.008, p = 0.009 and p = 0.042, respectively), while miR-16 was down-regulated (p = 0.040). miR-20a and miR-21 were independently associated with cHL (p = 0.049 and p = 0.035, respectively). The combination of miR-20a and miR-21 showed a good AUC value of 0.832 with a moderate likelihood ratio positive (LR+) value of 5.6 and a slight likelihood ratio negative (LR-) value of 0.23. At cHL diagnosis, miR-20a, miR-21 and miR-324 were overexpressed in cHL (p = 0.005, p = 0.024, and p = 0.001, respectively), while miR-223, miR-16, miR-185 and miR-106a were down regulated (p = 0.042, p = 0.007, p = 0.006, and p = 0.002, respectively). In addition, sCD14, sCD27, sCD30 and IL2R levels were higher in these individuals (p = 0.038, p = 0.010, p = 0.030, p = 0.006, respectively). miR-20a was independently associated with cHL (p = 0.011). The diagnostic value of miR-20a showed good AUC value of 0.754 (p = 0.074) with a slight LR+ value of 2 and a slight LR- of 0.25. After chemotherapy, miR-20a was higher in those individuals who had an adverse outcome (p < 0.001), while sCD14 and sCD30 were higher (p < 0.001). A specific signature of miRs and cytokines associated with a subsequent cHL diagnosis was found in this study, especially miR-20a and miR-21. Also, another biomarker signature was found at cHL diagnosis, with a relevant discriminant disease value for miR-20a. Of note, miR-20a expression was higher in those individuals who had an adverse clinical outcome after chemotherapy.

Cervical cancer risk in women living with HIV across four continents: A multicohort study.

We compared invasive cervical cancer (ICC) incidence rates in Europe, South Africa, Latin and North America among women living with HIV who initiated antiretroviral therapy (ART) between 1996 and 2014. We analyzed cohort data from the International Epidemiology Databases to Evaluate AIDS (IeDEA) and the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord. We used flexible parametric survival models to determine regional ICC rates and risk factors for incident ICC. We included 64,231 women from 45 countries. During 320,141 person-years (pys), 356 incident ICC cases were diagnosed (Europe 164, South Africa 156, North America 19 and Latin America 17). Raw ICC incidence rates per 100,000 pys were 447 in South Africa (95% confidence interval [CI]: 382-523), 136 in Latin America (95% CI: 85-219), 76 in North America (95% CI: 48-119) and 66 in Europe (95% CI: 57-77). Compared to European women ICC rates at 5 years after ART initiation were more than double in Latin America (adjusted hazard ratio [aHR]: 2.43, 95% CI: 1.27-4.68) and 11 times higher in South Africa (aHR: 10.66, 95% CI: 6.73-16.88), but similar in North America (aHR: 0.79, 95% CI: 0.37-1.71). Overall, ICC rates increased with age (>50 years vs. 16-30 years, aHR: 1.57, 95% CI: 1.03-2.40) and lower CD4 cell counts at ART initiation (per 100 cell/µl decrease, aHR: 1.25, 95% CI: 1.15-1.36). Improving access to early ART initiation and effective cervical cancer screening in women living with HIV should be key parts of global efforts to reduce cancer-related health inequities.

Impact of a structured HIV testing program in a hospital emergency department and a primary care center.

INTRODUCTION: HIV testing guidelines are poorly implemented in most clinical settings. The best screening strategy and healthcare scenario are still unknown. The aim of our study is to evaluate the impact of a structured HIV testing intervention (DRIVE), compared to HIV testing as routinely performed in clinical practice, in two different clinical settings: a primary care center and an emergency department. METHODS: Prospective evaluation of an HIV testing strategy in two clinical settings from the same healthcare area. The DRIVE program included trained nurse practitioners to perform the screening, a questionnaire to assess the risk of exposure and HIV indicator conditions (RE&IC), and rapid HIV tests. The main variables between the DRIVE program and clinical practice were the absolute number of newly diagnosed HIV infections and testing coverage. RESULTS: The DRIVE program included 5,329 participants, of which 51.2% reported at least one positive answer in the questionnaire. The estimated HIV testing coverage was significantly higher in the DRIVE program than in the routine clinical practice (7.17% vs. 0.96%, p < 0.001), and was better in the primary care center than in the emergency department with the two strategies. Twenty-two HIV-positive people were identified, with a rate of 8.6‰ in the emergency department vs. 2.2‰ in the primary care center (p = 0.001). A higher rate of new HIV diagnoses was found in the DRIVE program compared to routine clinical practice (29.6 vs. 3.1 per 100,000 patients attended; p < 0.001). CONCLUSIONS: An easy-to-implement, structured intervention increased the absolute number of new HIV diagnoses and HIV tests, compared to routine clinical practice.

Hypermucoviscous Klebsiella pneumoniae: A challenge in community acquired infection.

In 1986, a new syndrome was described in Taiwan secondary to hypervirulent K. pneumoniae (hvKP), and its main feature was the ability to cause severe infection in young and immunocompetent hosts. Their virulence is explained by the efficient acquisition of iron and an increase in capsule production, which confer the characteristic hypermucoviscous phenotype. Most of these cases have been described in Asia and subsequently spread to America and Europe, where their prevalence is much lower. We present four cases of bacteremia and liver abscesses secondary to hypervirulent K. pneumoniae, two of them associated with endophthalmitis. K. pneumoniae isolates recovered from two of the patients belonged to capsular serotype K1 (genes wzx_K1 and magA), while the other two were K2 (gene wzy_K2). Both of the K1 isolates were classified into a ST23, and isolates of serotype K2 belonged to the ST375 and ST881 clones. In Europe, hvKP isolates are less frequently recovered, mostly associated with Asian citizens or travelers, which was not the case in our patients. K1 capsular serotype is a major cause of primary liver abscess and secondary septic embolus, and K2 is associated with secondary liver abscess. Although these hypervirulent variants usually affect immunocompetent patients as in our cases, diabetes mellitus is a major risk factor for the most invasive cases, with concomitant poor prognosis. Identification of hypervirulent K. pneumoniae serotypes K1 and K2 should be considered as part of the microbiological diagnosis of community-acquired liver abscess due to their clinical implications.

High CD8 T cell percentage and HCV replication control are common features in HIV-1 controllers and HTLV-2-co-infected patients with a history of injection drug use.

HTLV-2/HIV-1-coinfected patients and HIV-infected patients with natural HIV-1 control show an immune capacity that allows some control of viral infections. These two groups of patients have showed an immune capacity that allows them to have some control over viral infections, very strong control of HIV-1 replication in the case of HIV-1 controllers. The purpose of this retrospective cross-sectional study was to compare viral and immunologic parameters between three cohorts of Caucasian adult HIV-1-infected patients, including HIV-1 controllers (29 patients), HTLV-2/HIV-1 chronic progressors (56 patients), and HIV-1 chronic progressors (101 patients), followed in two different tertiary University Hospitals in Spain. Demographic parameters, nadir CD4 T cell count, CD4 and CD8 T cell counts and percentage, anti-HCV antibodies, HCV RNA load, HCV genotype, HIV-1 RNA loads, and anti-HTLV-2 antibodies were analyzed. HIV-1 controllers and HTLV-2/HIV-1 chronic progressors were younger and with shorter time since HIV-1 diagnosis compared to HIV-1 chronic progressors. HIV-1 controllers and HTLV-2/HIV-1 chronic progressors had significantly higher CD8 T cell percentage (p = 0.002 and p = 0.016, respectively) and lower levels of HCV RNA loads (0.015 and 0.007, respectively) compared to that of HIV-1 chronic progressors. Multivariate analyses showed that gender and HTLV-2 infection were independently associated to HCV RNA load, while only HTLV-2 infection was independently associated to CD8 T cell percentage. The implication of HTLV-2 infection in the control of HIV-1 and HCV infections is worth being further analyze.

Frailty phenotype: a clinical marker of age acceleration in the older HIV-infected population.

AIM: To evaluate the association between DNA methylation and frailty in the HIV-infected population and to investigate the usefulness of assessing frailty as a clinical marker to identify age acceleration. METHODS: Frailty was assessed according to Fried's frailty phenotype. DNA methylation was analyzed in 10 frail patients, and compared with 10 robust control patients, all with HIV. Predicted age was inferred using the Weidner's formula. Age acceleration was assessed using the difference between predicted and chronological age. RESULTS: HIV-infected frail patients had significantly higher biological predicted ages than chronological ages (mean acceleration: 10.3 years; p = 0.012). CONCLUSIONS: We link age acceleration and frailty in an older HIV population. Frailty could be used in this population for implementing specific clinical approaches.