Switching to dual/monotherapy determines an increase in CD8+ in HIV-infected individuals: An observational cohort study

Background: The CD4/CD8 ratio has been associated with the risk of AIDS and non-AIDS events. We describe trends in immunological parameters in people who underwent a switch to monotherapy or dual therapy, compared to a control group remaining on triple antiretroviral therapy (ART). Methods: We included patients in Icona who started a three-drug combination ART regimen from an ART-naïve status and achieved a viral load ≤ 50 copies/mL; they were subsequently switched to another triple or to a mono or double regimen. Standard linear regression at fixed points in time (12-24 months after the switch) and linear mixed model analysis with random intercepts and slopes were used to compare CD4 and CD8 counts and their ratio over time according to regimen types (triple vs. dual and vs. mono). Results: A total of 1241 patients were included; 1073 switched to triple regimens, 104 to dual (72 with 1 nucleoside reverse transcriptase inhibitor (NRTI), 32 NRTI-sparing), and 64 to monotherapy. At 12 months after the switch, for the multivariable linear regression the mean change in the log10 CD4/CD8 ratio for patients on dual therapy was -0.03 (95% confidence interval (CI) -0.05, -0.0002), and the mean change in CD8 count was +99 (95% CI +12.1, +186.3), taking those on triple therapy as reference. In contrast, there was no evidence for a difference in CD4 count change. When using all counts, there was evidence for a significant difference in the slope of the ratio and CD8 count between people who were switched to triple (points/year change ratio = +0.056, CD8 = -25.7) and those to dual regimen (ratio = -0.029, CD8 = +110.4). Conclusions: We found an increase in CD8 lymphocytes in people who were switched to dual regimens compared to those who were switched to triple. Patients on monotherapy did not show significant differences. The long-term implications of this difference should be ascertained

Governing Boards and Profound Organizational Change in Hospitals

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69047/2/10.1177_107755878904600204.pd

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

Assenza di correlazione statistica tra eterodimeri diabetogeni HLA-DQ e diabete di tipo 2: Analisi familiare.

Type 2 diabetes is a multifactorial disease with a polygenic inheritance and environmental factors contributing to its clinical expression. The search for the genetic determinants of type 2 diabetes has become possible by comparing in groups of patients and healthy controls from various populations the frequency of the different alleles of polymorphic markers of various candidate genes. Among them, unlike in type 1 diabetes, the role of specific HLA class II genes is not clear. We studied 8 families with high incidence of type 2 diabetes in which at least two probands were affected by the disease. The therapy consisted in a specific diet and the intake of hypoglicemic drugs. Amongst the 8 families 40 subjects were selected. Of these, 5 males and 19 females were affected by type 2 diabetes with no prevalence of type 1 diabetes. HLA-DQA1 and DQB1 alleles were determined with 52 healthy controls by PCRSSO and PCR-SSP techniques respectively. None of their alleles was associated to either susceptibility or protection. In conclusion, unlike in type 1 diabetes there was no statistically significant correlation between susceptible a- f DQ eterodimers and the type 2 diabetes status

Role of apolipoprotein e alleles as risk factors in patients with medium-high level of dementia assessed by an MMSE <24.

Alzheimer\u2019s disease is a dementia characterized by neuronal loss, athrophy, gliosis and clinically by progressive cognitive impairment. The apolipoprotein E type 4 allele is genetically associated with the common late onset familial and sporadic forms of Alzheimer's disease. Aim of this study was to evaluate and compare genotypic and allelic polymorphism of APO-E gene in a sample caucasoid AD patients with Mini Mental State Examination <24 and cognitively - normal control individuals

Role of the genetic polymorphism of inflammatory cytokines in patients with Alzheimer's disease.

Alzheimer\u2019s disease (AD) is a dementia characterized by neuronal loss, atrophy, gliosis and clinically by progressive cognitive impairment. In the last years several experimental evidences both \u201cin vitro\u201d and \u201cin vivo\u201d have suggested a possible involvement of the immune system in the pathogenesis and/or in the progression of the disease. Considering the relative low quantity of studies about multiple cytokine gene polymorphisms in AD, we were prompted to studying the panel polymorphism of related cytokine genes in an AD group of patients and in a control healthy group. In a case control, using a unified method of genotyping (PCR\u2013SSP methodology), we have examined 22 polymorphisms in 13 cytokine genes in 63 caucasian AD patients with medium\u2013high level of dementia (Mini Mental State Examination MMSE <24) and 65 normal controls belonging to the same ethnic group matched by age and gender affected by non inflammatory neuropsychiatric diseases. The patients and the control group did not shown any symptoms or signs of inflammatory process. Polymorphisms in the genes for IL-1A, IL-1\u3b2, IL-2, IL-4, IL-6, IL-10, IL-12, IFN-\u3b3, TGF-\u3b2, TNF-\u3b1 and for the cytokine receptors IL-1R, IL-1RA, IL-4RA were investigated. Angiotensin I-converting enzyme (ACE) gene polymorphism was carried out only in the group of patients to evaluate a possible association with known genetic risk factors for AD and cerebrovascular diseases. Our analysis showed an highly significant presence in AD patients when compared to controls of some alleles belonging to the anti-inflammatory cytokine gene IL-4 (C allele for the -590 promoter and T allele for the -1098, p <0.0006 and p <0.0005, respectively). Statistically no difference was evident for the D allele of the ACE gene in the group of demented patients. Although our observations suggest the presence of a pro-inflammatory environment in AD patients with MMSE <24, which is sustained by a low expression of anti-inflammatory cytokine genes, it is important to underline that these results could not apply to AD patients belonging to different ethnic groups, as the ethnic characteristics can influence the study of polymorphisms. Large cohort studies are necessary in order to assess the true association of some cytokine alleles or extended haplotypes with AD

HLA polymorphism in Lombardy defined by high-resolution typing methods

Background - Population data on the HLA system are important to several areas of medicine and science. HLA-A*, B*, C*, DRB1* and DQB1* allele and haplotype frequencies in 105 unrelated healthy Italian individuals from Lombardy were estimated. Methods - Commercial kits with sequence-specific primers designed to match single alleles were used for specific primer polymerase chain reactions (PCR-SSP) to determine HLA class I (HLA-A*, B* and C* loci) and class II (HLA-DRB1*, DQB1* loci) alleles. For HLA-DRB1* single allele-specific amplification and sequencing was also used separately, using a Protrans S4 commercial kit. Results - A total of 16 HLA-A*, 22 HLA-B*, 14 HLA-C*, 20 DRB1* and 12 DQB1* alleles showing a frequency >1% were identified at the four-digit level in the population. The highest frequency alleles included A*02:01 (13.3%), B*51:01 (9.5%), C*04:01 (20.5%), DRB1* 11:01 (13.8%) and DQB1*03:01 (33.8%). The most frequent extensive haplotype was A*01:01-C*07:01 B*08:01-DRB1*03:01-DQB1*02:01 with a haplotype frequency of 2.4%. Conclusions - The present findings could be useful to elucidate the genetic background of the population, and to provide data for HLA matching in clinical transplantation, information on the distribution of HLA genotypes in different populations for the development of peptidebased vaccines, and information for paternity diagnosis and on evolutionary factors such as genetic drift, migration and selection

HLA-DRB1* frequencies in Lombardy and Trentino valleys defined by high resolution typing methods

Population data on the HLA system are important to several areas of medicine and science. HLA-DRB1* allele frequencies found in 105 and 242 unrelated Italian healthy individuals from Lombardy and Trentino Valleys (from Alto Garda, Val di Ledro, Valli Giudicarie, Val Rendena, Val di Sole, Val di Non, Trento, Val di Fiemme, Val di Fassa, Valsugana, Vallagarina) were estimated, respectively. Sequencing Protrans S4 commercial kit and sequence-specific primers designed to match single alleles were used for specific primer polymerase chain reactions (PCR-SSP) to determine HLA-DRB1* alleles. A total of 30 DRB1* and 37 DRB1* alleles were identified at the 4-digit level in the Lombardy (LRP) and Trentino Valleys population (TrVP) respectively. A comparison between the allelic frequencies of DRB1* locus of the two populations shows that most of these frequencies are shared. One exception is the frequency of DRB1*11:04 allele in the TrVP characterized by a statistically significant lower frequency (3.09% vs. 14.3%, p <0.0138 ) than the LRP. Our data demonstrate that two populations are not genetically different for the DRB1* locus. The present findings as well as being useful for elucidating the genetic background of the populations, can also provide data for HLA matching in clinical transplantation, information about the distribution of HLA genotypes in different populations for the development of peptide-based vaccines and also for paternity diagnosis and evolutionary factors such as genetic drift, migration and selection