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Background. The effect of peginterferon alpha/ribavirin (PEG-IFN/RBV) and hepatitis C virus (HCV) clearance on lipid and insulin resistance (IR) profiles in HCV/human immunodeficiency virus (HIV) coinfection is unknown. Methods. We measured fasting total cholesterol (TC), low-density lipoprotein (LDL-C), high-density lipoproteins (HDL-C), triglycerides (TG), glucose, and insulin at defined intervals in the A5178 study (N = 329), a prospective treatment trial in HCV/HIV coinfection. Changes from baseline and the relation between baseline values of these variables to sustained virologic response (SVR) were determined. Results. Of 182 subjects with metabolic data, 98 achieved early virologic response (EVR) and continued PEG-IFN/RBV. Among those, median pretreatment HCV RNA was 6.6 log10 IU/mL; 73% had HCV genotype 1. Median pretreatment TC was 176 mg/dL (interquartile range [IQR],150–205]; median LDL-C was 99 mg/dL (IQR, 79–123); median HDL-C was 40 mg/dL (IQR, 31–47); and median TG was 147 mg/dL (IQR, 101–221). Median homeostasis model assessment of IR (HOMA-IR) was 3.3 (IQR, 1.7–5.3). The EVRs demonstrated a decline in TC, LDL-C, and HDL-C, whereas TG increased on treatment but returned to near baseline 24 weeks after end of treatment (EOT). The HOMA-IR decline from entry to 24 weeks after EOT was significant among non—sustained virologic responders and nonsignificant among sustained virologic responders; this difference was offset after adjusting for higher HOMA-IR at baseline among the former. Among all 182 subjects, entry LDL-C was associated with SVR in a joint logistic model adjusted for HCV genotype, race, and prior IFN (odds ratio, 1.17 per 10 mg/dL increase; 95% confidence interval, 1.03–1.32), but TC, HDL, TG, and IR were not. Conclusions. Peginterferon alpha and RBV can significantly affect lipid profile and IR in HCV/HIV—coinfected persons. Although the lipid profile returns to near pretreatment levels after completion of treatment, our data suggest persistent modest improvement in IR with treatment. Clinical Trials Registration. NCT00078403.

HIV-infected persons are at risk for HBV co-infection which is associated with increased morbidity and mortality. Unfortunately, protective immunity following HBV vaccination in HIV-infected persons is poor. This randomized, phase II, open-label study aimed to evaluate efficacy and safety of 40 mcg HBV vaccine with or without 250 mcg GM-CSF administered at day 0, weeks 4 and 12. HIV-infected individuals ≥18 years of age, CD4 count ≥200 cells/mm 3, seronegative for HBV and HCV, and naïve to HBV vaccination were eligible. Primary endpoints were quantitative HBsAb titers and adverse events. The study enrolled 48 subjects. Median age and baseline CD4 were 41 years and 446 cells/mm 3, 37 were on ART, and 26 subjects had undetectable VL. Vaccination was well tolerated. Seven subjects in the GM-CSF arm reported transient grade ≥2 signs/symptoms (six grade 2, one grade 3), mostly aches and nausea. GM-CSF had no significant effect on VL or CD4. Four weeks after vaccination, 26 subjects (59%) developed a protective antibody response (HBsAb ≥10 mIU/mL; 52% in the GM-CSF arm and 65% in the control arm) without improved Ab titer in the GM-CSF vs. control arm (median 11 mIU/mL vs. 92 mIU/mL, respectively). Response was more frequent in those with CD4 ≥350 cells/mm 3 (64%) than with CD4 <350 cells/mm 3 (50%), though not statistically significant. GM-CSF as an adjuvant did not improve the Ab titer or the development of protective immunity to HBV vaccination in those receiving an accelerated vaccine schedule. Given the common routes of transmission for HIV and HBV, additional HBV vaccine research is warranted.

We evaluated immunologic predictors of response to HBV vaccine administered in the presence or absence of GM-CSF in HIV infected individuals. We measured peripheral blood hematopoietic progenitor, monocyte and myeloid-derived suppressor cell (MDSC) frequencies, and expression of GMCSF receptor on monocytes and MDSCs, at baseline and 4weeks after immunization in relation to antibody response. We observed higher baseline progenitor and lower monocyte frequencies among week 16 antibody responders. Week 4 decline in MDSC frequency was associated with week 16 antibody response, while administration of GM-CSF was associated with preservation of these cells. No significant differences in GM-CSF receptor expression were observed in the presence vs. absence of GM-CSF. These findings are consistent with a positive role of progenitor cells and a potential negative role of monocytes in vaccine response. Additionally, GM-CSF augmented the preservation of peripheral blood MDSC, which may contribute to the lack of improved vaccine responses.

In a trial involving participants with HIV infection receiving antiretroviral therapy, the use of pitavastatin resulted in a lower risk of a major adverse cardiac event than placebo at a median of 5.1 years.

Background. Women infected with human immunodeficiency virus (HIV) are disproportionately affected by human papillomavirus (HPV)–related anogenital disease, particularly with increased immunosuppressions. AIDS Clinical Trials Group protocol A5240 was a trial of 319 HIV-infected women in the United States, Brazil, and South Africa to determine immunogenicity and safety of the quadrivalent HPV vaccine in 3 strata based on screening CD4 count: >350 (stratum A), 201–350 (stratum B), and ≤200 cells/μL (stratum C). Methods. Safety and serostatus of HPV types 6, 11, 16, and 18 were examined. HPV serological testing was performed using competitive Luminex immunoassay (HPV-4 cLIA). HPV type-specific seroconversion analysis was done for participants who were seronegative for the given type at baseline. Results. Median age of patients was 36 years; 11% were white, 56% black, and 31% Hispanic. Median CD4 count was 310 cells/μL, and 40% had undetectable HIV-1 load. No safety issues were identified. Seroconversion proportions among women at week 28 for HPV types 6, 11,16, and 18 were 96%, 98%, 99%, and 91%, respectively, for stratum A; 100%, 98%, 98%, and 85%, respectively, for stratum B, and 84%, 92%, 93%, and 75%, respectively, for stratum C. Conclusions. The quadrivalent HPV vaccine targeted at types 6, 11, 16, and 18 was safe and immunogenic in HIV-infected women aged 13–45 years. Women with HIV RNA load > 10 000 copies/mL and/or CD4 count <200 cells/μL had lower rates of seroconversion rates. Clinical Trials Registration. NCT00604175.

Among human immunodeficiency virus-infected individuals with mild-to-moderate Kaposi sarcoma initiating antiretroviral therapy, immediate oral etoposide chemotherapy provided no substantial clinical benefit by 48 weeks compared to delayed, as-needed therapy. Mortality and poor tumor response were common. Abstract Background Mild-to-moderate AIDS-associated Kaposi sarcoma (KS) often responds to antiretroviral therapy (ART) alone; the role of chemotherapy is unclear. We assessed the impact of immediate vs as-needed oral etoposide (ET) among human immunodeficiency virus (HIV)-infected individuals with mild-to-moderate KS initiating ART. Methods Chemotherapy-naive, HIV type 1-infected adults with mild-to-moderate KS initiating ART in Africa and South America were randomized to ART (tenofovir/emtricitabine/efavirenz) alone (chemotherapy \"as-needed\" arm) vs ART plus up to 8 cycles of oral ET (immediate arm). Participants with KS progression on ART alone received ET as part of the as-needed strategy. Primary outcome was ordinal as follows: failure, stable, and response at 48 weeks. Secondary outcomes included time to initial KS progression, KS-associated immune reconstitution inflammatory syndrome (KS-IRIS), and KS response. Results Of 190 randomized participants (as-needed = 94, immediate = 96), the majority were men (71%) and African (93%). Failure (53.8% vs 56.6%), stable (16.3% vs 10.8%), and response (30% vs 32.5%) did not differ between arms (as-needed vs immediate) among those with week 48 data potential (N = 163, P = .91). Time to KS progression (P = .021), KS-IRIS (P = .003), and KS response (P = .003) favored the immediate arm. Twenty-five participants died (13%). Mortality, adverse events, CD4+ T-cell changes, and HIV RNA suppression were similar at 48 weeks. Conclusions Among HIV-infected adults with mild-to-moderate KS, immediate ET provided early, nondurable clinical benefits. By 48 weeks, no clinical benefit was observed compared to use of ET as needed. Mortality was high and tumor response was low. Clinical Trials Registration NCT01352117.

Abstract Background Among people with HIV (PWH), COVID-19 is common and potentially severe. We leveraged REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) to assess the effects of statin therapy for cardiovascular disease prevention on COVID-19 outcomes (incidence and serious cases) among a global cohort of PWH. Methods COVID-19 data collection was implemented April 2020 to capture events from January 2020. COVID-19 was defined by positive test result or clinical diagnosis and serious COVID-19 according to the International Conference on Harmonisation definition. Among participants in follow-up on 1 January 2020, Cox proportional hazards modeling was used to estimate the hazard ratio (HR) of COVID-19 (pitavastatin/placebo), stratified by Global Burden of Disease region. Modification of statin effect following COVID-19 vaccination was evaluated via interaction with time-updated vaccination status. Results Among 6905 PWH, 32% were natal female and 41% were Black or African American. The median age was 53 years and the 10-year atherosclerotic cardiovascular disease risk score 4.5%. Statin therapy did not reduce COVID-19 incidence (HR, 1.05; 95% CI, .95–1.15) but appeared to reduce incidence of serious COVID-19 (HR, 0.75; 95% CI, .52–1.09). Among 1701 PWH with COVID-19, the relative risk (pitavastatin/placebo) for serious COVID-19 was 0.73 (95% CI, .52–1.03). The treatment effect size for serious COVID-19 fell within the hypothesized range, but the 95% CI crossed 1 given fewer-than-anticipated cases (117 vs 200). Furthermore, 83% reported COVID-19 vaccination by end of study, with a strong protective effect on serious COVID-19 (HR, 0.27; 95% CI, .14–.53; P < .0001). A protective statin effect was observed prior to vaccination. Conclusions Among PWH, statin therapy had no effect on COVID-19 incidence but showed potential to reduce risk of serious COVID-19 prior to COVID-19 vaccination. Clinical Trials Registration NCT02344290 (ClinicalTrials.gov). In a global cohort of people with HIV with low to moderate traditional atherosclerotic cardiovascular disease risk, statin therapy had no effect on COVID-19 incidence but showed potential to reduce the risk of serious COVID-19 prior to COVID-19 vaccination.

Aims: To investigate variations in smoking and associated factors on individual and aggregate level among adolescents in Tallinn (Estonia), Helsinki (Finland) and Moscow (the Russian Federation). Methods: The data was collected in Tallinn (N=1268 in Estonian and N=901 in Russian schools), in Helsinki (N=1396) and in Moscow (N=618) from pupils aged 13-18 by self-administered questionnaire. Multilevel analysis was used to estimate the possible effects of background characteristics, of the proximity of other smokers and the school context on the tobacco use of pupils. Results: The prevalence rate of smoking among girls in Russian schools in Tallinn (34.6%), among girls in Helsinki (39.5%), and in Moscow (32.1%) was higher than that among girls in Estonian schools in Tallinn (17.6%). Smoking was slightly less prevalent among boys in Helsinki (27.5%), compared to boys in Estonian (33.6%) and Russian (35.6%) schools in Tallinn, and to boys in Moscow (32.8%). Smoking increased with age. Multilevel analysis showed that smoking differed by school among pupils. Individual determinants of smoking as study site, grade, friends', siblings' and parental smoking behaved differently depending upon school. Friends and siblings' smoking showed interaction with study site to the smoking among girls. Conclusions: Strategies aimed at influencing smoking behaviour need to be directed not only towards the individual but also towards the influences within the child's school environment.

This paper presents an unsupervised feature selection method for multi-dimensional histogram-valued data. We define a multi-role measure, called the compactness, based on the concept size of given objects and/or clusters described using a fixed number of equal probability bin-rectangles. In each step of clustering, we agglomerate objects and/or clusters so as to minimize the compactness for the generated cluster. This means that the compactness plays the role of a similarity measure between objects and/or clusters to be merged. Minimizing the compactness is equivalent to maximizing the dis-similarity of the generated cluster, i.e., concept, against the whole concept in each step. In this sense, the compactness plays the role of cluster quality. We also show that the average compactness of each feature with respect to objects and/or clusters in several clustering steps is useful as a feature effectiveness criterion. Features having small average compactness are mutually covariate and are able to detect a geometrically thin structure embedded in the given multi-dimensional histogram-valued data. We obtain thorough understandings of the given data via visualization using dendrograms and scatter diagrams with respect to the selected informative features. We illustrate the effectiveness of the proposed method by using an artificial data set and real histogram-valued data sets.

Based on a simple example, it is explained how the homological analysis may be used for modeling of the electric circuits. The homological branch, mesh and nodal analyses are presented. Geometrical interpretations are given.