Effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide in HIV late presenters.

OBJECTIVES: The efficacy of BIC/FTC/TAF in HIV late presenters initiating antiretroviral therapy (ART) has not been sufficiently evaluated. METHODS: The aim of this study was to assess the effectiveness and tolerability of BIC/FTC/TAF compared to other first-line antiretroviral regimens in treatment-naïve adult individuals from the CoRIS Cohort starting ART with CD4 counts <200 cells/mm3 and/or AIDS-defining conditions between January 1st 2019 and November 30th 2020. Logistic regression models were used to estimate odds ratios (ORs) of association between initial regimen and achievement of viral suppression (VS) (primary objective), defined as HIV RNA <50 cop/mL, and immunological recovery (IR) (secondary objective), defined as CD4 count >200 cells/mm3, at weeks 24 and 48 after initiation of ART. RESULTS: We evaluated 314 individuals (84.7% men, median age 40 years). Of them, 158 initiated with BIC/FTC/TAF. At inclusion, 117 had an AIDS-defining condition. In multivariable analyses, individuals with AIDS-defining conditions initiating ART with BIC/FTC/TAF achieved higher rates of VS at 24 weeks than other regimens (aOR: 0.2; 95% CI: 0.06-0.64) and, at 48 weeks, than DTG/ABC/3TC (aOR: 0.06; 95% CI: 0.01-0.76) and DTG + TDF/3TC (aOR: 0.2; 95% CI: 0.47-0.9). No other differences in VS or IR were observed. At 24 and 48 weeks after ART initiation, treatment discontinuations were lower with BIC/FTC/TAF than with other regimens (3.2% and 7.6% vs. 24.4% and 37.8%, respectively; P < 0.005). CONCLUSION: Our results suggest that BIC/FTC/TAF could be a preferred regimen as initial therapy in HIV late presenters because of its high effectiveness and good tolerability.

Prognostic value of acute delirium recovery in older adults.

AIM: To analyze the prognostic impact of short-term changes in the intensity of delirium in association or not with sepsis. We also aimed to analyze if s100B, a serum protein derived from astrocytes related to cerebral damage, could be a marker of delirium or sepsis. METHODS: We included 47 patients with acute delirium and sepsis, 36 with delirium and no evidence of infection, and 36 patients with sepsis without delirium. The diagnosis of delirium was established by the Confusion Assessment Method. To evaluate delirium, we recorded the following characteristics on the first and third day after admission: level of consciousness, orientation, attention, hallucinations, psychomotor activity, language and disorganized thinking. RESULTS: In 53 patients, delirium improved during hospitalization with 3.8% of mortality, whereas in the 30 patients in which delirium did not improve or worsened, 50% died during hospitalization. The improvement on the third day of consciousness, orientation, attention and disorganized thinking was related to a better long-term survival. s100B and inflammatory markers tumor necrosis factor-α, interleukin-6, interleukin-10 and interferon-γ were increased in patients with sepsis and confusion when compared with control participants; furthermore, s100B, interleukin-6 and interferon-γ were increased in septic patients without confusion, but also in delirious patients without sepsis. CONCLUSIONS: The main factor related to mortality was the recovery from delirium during hospitalization. We found increased s100B serum levels in patients with delirium, but also in septic patients without delirium. This increase was not related to mortality. Geriatr Gerontol Int 2017; 17: 1161-1167.

Most HIV type 1 non-B infections in the Spanish cohort of antiretroviral treatment-naïve HIV-infected patients (CoRIS) are due to recombinant viruses.

HIV-1 group M is classified into 9 subtypes, as well as recombinants favored by coinfection and superinfection events with different variants. Although HIV-1 subtype B is predominant in Europe, intersubtype recombinants are increasing in prevalence and complexity. In this study, phylogenetic analyses of pol sequences were performed to detect the HIV-1 circulating and unique recombinant forms (CRFs and URFs, respectively) in a Spanish cohort of antiretroviral treatment-naïve HIV-infected patients included in the Research Network on HIV/AIDS (CoRIS). Bootscanning and other methods were used to define complex recombinants not assigned to any subtype or CRF. A total of 670 available HIV-1 pol sequences from different patients were collected, of which 588 (87.8%) were assigned to HIV-1 subtype B and 82 (12.2%) to HIV-1 non-B variants. Recombinants caused the majority (71.9%) of HIV-1 non-B infections and were found in 8.8% of CoRIS patients. Eleven URFs (accounting for 13.4% of HIV-1 non-B infections), presenting complex mosaic patterns, were detected. Among them, 10 harbored subtype B fragments. Four of the 11 URFs were found in Spanish natives. A cluster of three B/CRF02_AG recombinants was detected. We conclude that complex variants, including unique recombinant forms, are being introduced into Spain through both immigrants and natives. An increase in the frequency of mosaic viruses, reflecting the increasing heterogeneity of the HIV epidemic in our country, is expected.

Serum leptin levels in community acquired pneumonia (CAP) are related to nutritional status and not to acute phase reaction.

To determine whether leptin in patients with CAP acts as a nutritional or as an inflammatory marker and whether leptin plays any role regarding survival, we included 222 patients diagnosed of CAP, 142 men and 80 women, median age 74 years. We did not find significant differences in serum leptin levels between CAP patients and healthy controls, even after adjusting by BMI. Serum leptin levels were directly related with BMI, body fat and muscle mass and inversely related with inflammatory markers, including pro- and anti-inflammatory cytokines. Patients with positive blood cultures showed lower serum leptin and raised inflammatory markers. Although patients who died showed lower values of serum leptin, multivariate analysis showed that the prognostic value of low serum leptin levels depends on impaired nutritional status. In conclusion, we suggest that in CAP patients, leptin does not act as an inflammatory reactant but as a nutritional marker.

Low serum leptin levels and malnutrition in chronic alcohol misusers hospitalized by somatic complications.

AIMS: Leptin is a peptide produced by fat cells which regulates fat mass by decreasing food intake and increasing resting energy expenditure, so an increase of serum leptin could be an indicator of malnutrition. Our objective was to determine serum leptin levels (at admission and on the 15th day) in 79 male alcohol misusers, hospitalized by somatic complications, who drink more than 80 g ethanol/day, and to analyse its relationships with nutritional status assessed by anthropometry and dual-energy X-ray absortiometry (DEXA), insulin-like growth factor (IGF-1) and its binding protein (IGF1BP-3); acute phase reaction assessed by C-reactive protein (CRP), interleukin-6 (IL-6) and type II soluble receptor of tumour necrosis factor (TNF) (sTNFRII); serum oestradiol and testosterone; and the amount and duration of ethanol intake, the smoking habit and the presence of liver cirrhosis. METHODS: Patients were admitted through the emergency room, and blood for the above-mentioned determinations was taken at 08.00 on the following day, so none of the patients was acutely intoxicated at this time. The control group was composed of 32 healthy male (age-matched) subjects. RESULTS: Malnutrition was frequent among alcoholics. Serum leptin levels were closely related to total fat both in controls and in alcoholics. Serum leptin levels were decreased in alcoholics, even after adjusting for the amount of fat. Those alcoholics who reported anorexia and weight loss showed decreased leptin levels. After 15 days of hospitalization, serum leptin did not increase, in contrast with LDL cholesterol, serum albumin, prealbumin, IGF-1, IGF1BP-3 and testosterone which increased, whereas oestradiol and acute phase reactants, such as CRP, IL-6 and sTNFRII, were decreased. Serum leptin was not related to gonadal hormones at admission, but on day 15 we found a negative correlation between leptin and testosterone, and a positive one with oestradiol. CONCLUSIONS: Serum leptin levels are related to many factors, e.g. fat mass, age, smoking, serum testosterone and oestradiol levels, growth factors such as IGF-1 and CRP, and cytokines, such as IL-6 and sTNFRII. The most important of these is fat mass, as shown by multivariate analysis. Since serum leptin levels are decreased in alcohol misusers, we consider this decrease to be a consequence of a low fat mass.

Leptin role in advanced lung cancer. A mediator of the acute phase response or a marker of the status of nutrition?

Leptin is an anorexia inductor peptide produced by adipocytes and related to fat mass. Leptin is also produced by fat under proinflammatory cytokine action. Our objective is to study serum leptin levels in relation to nutritional status and acute phase response in advanced-stage non-small cell lung cancer.Seventy-six patients newly diagnosed of non surgical non-small cell lung cancer before chemotherapy treatment and 30 healthy controls were included. BMI, serum leptin and cholesterol levels and lymphocyte count were decreased in lung cancer patients. Cytokine IL-6, TNF-alpha, sTNF-RII, sIL-2R, IL-12, IL-10 and IFN-gamma, and other acute phase reactants as alpha1 antitrypsin, ferritin, CRP and platelets were all raised in patients, whereas the IL-2 was decreased. We found a direct relationship between leptin and other indicators of the status of nutrition, especially total fat mass. We also found a close relationship between the status of nutrition and the performance status (Karnofsky index). However, serum leptin and nutritional status were inversely correlated with acute phase proteins and proinflammatory cytokines, suggesting a stress-type malnutrition. Although serum leptin levels, nutritional status and Karnofsky index are related to survival, at multivariate analysis they all were displaced by the acute phase reaction markers. These results suggest that cancer anorexia and cachexia are not due to a dysregulation of leptin production. Circulating leptin concentrations are not elevated in weight-losing cancer patients and are inversely related to the intensity of the inflammatory response. In advanced lung cancer patients serum leptin concentrations only depend on the total amount of fat.