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Biomedical subjects

Göran Bratt

Publications and source records attributed to Göran Bratt.

14 recordsLinked to original sources
PubMed2007

Factors associated with suboptimal antiretroviral therapy adherence to dose, schedule, and dietary instructions.

The purpose of this study was to assess the degree of suboptimal antiretroviral therapy adherence to dose, schedule, and dietary instructions and to examine the effects of extra-personal, intra-personal, and inter-personal factors on suboptimal adherence across the three types of instructions. Self-report and clinical data were collected from 193 sexually infected Swedish patients receiving ART. Effects of extra-personal, intra-personal, and inter-personal factors on suboptimal adherence were examined using multivariate logistic regression models. Suboptimal adherence to dose instructions was recorded in 12% of patients. Equivalent percentage for suboptimal adherence to schedule instructions was 37% and for suboptimal adherence to dietary instructions 58%. Anxiety was the only risk factor for suboptimal adherence to dose. Heavy pill burden was a risk factor for suboptimal adherence to schedule. Older age and HIV-related post-traumatic stress disorder (PTSD) symptoms decreased the risk of suboptimal adherence to schedule. No factors investigated had an effect on suboptimal adherence to dietary instructions. To improve adherence to dose and schedule instructions, clinicians caring for patients with HIV should assess and treat anxiety and be alert to HIV-related PTSD symptoms.

Adult↗
PubMed2006

A nonsense mutation (428G-->A) in the fucosyltransferase FUT2 gene affects the progression of HIV-1 infection.

BACKGROUND: The human FUT2 gene encodes the alpha(1,2)fucosyltransferase that determines secretor status. Homozygous for the nonsense mutation are called non-secretors and are unable to express histo-blood group antigens in secretions and on mucosal surfaces. In this study we have investigated the importance of the FUT2 fucosyltransferase activity on the progress of HIV-1 infection. METHODS: Swedish blood donors (n = 276), 15 long-term non-progressors (LTNP) and 19 progressors were genotyped with respect to the nonsense mutation 428G-->A in the FUT2 gene. In addition 265/276 blood donors and 19 progressors with rapid or expected progression rate were Delta32 CCR5 genotyped. RESULTS: Of 276 blood donors 218 (79%) were found to be secretor positive (se+), either homozygous (se+/+) wild type (30%) or heterozygous (se+/-) (49%) and 58 (21%) were homozygous non-secretors (se-/-). Five LTNP (33%) were found to be secretor-positive (se+/+, se+/-) and 10 (67%) se-/-. Of the 19 individuals with normal HIV-1 progression 15 (79 %) were found to be secretor positive and four (21%) were non-secretors. No frequency differences were found in the Delta32 CCR5 allele among the groups studied. CONCLUSION: Strong association (P < 0.001) was observed between the nonsense mutation 428G-->A in the FUT2 gene and a slow disease progression of HIV-1 infection.

Adult↗
PubMed2006

Human immunodeficiency virus-type 1 specific cellular immunity in chronic infected patients on prolonged highly active antiretroviral treatment and on structured treatment interruption.

We have followed 15 HIV-1 chronically infected patients during prolonged highly active antiretroviral treatment (HAART) and subsequent long term structured treatment interruption (STI). We analyzed Nef, Tat, and p24 specific cellular immunity using IFN-gamma enzyme-linked immunospot assays and T cell proliferation assays. Eight HAART patients showed IFN-gamma responses to at least one antigen, but no positive responses were seen during STI. We observed retained or increased p24 specific IFN-gamma responses in most patients during HAART with viral suppression. These results showed persisting HIV-1 specific cellular immunity during HAART; however, in prolonged STI with viral rebound this immunity declined.

Anti-HIV Agents↗
PubMed2005

CD4 cell-monitored treatment interruption in patients with a CD4 cell count > 500 x 106 cells/l.

BACKGROUND: Little is known about CD4 cell count changes in patients with high CD4 cell counts who interrupt antiretroviral therapy, especially in those with a nadir of 250-350 x 10 cells/l. METHODS: Data derived from 139 patients from seven prospective cohorts who had > 12 months highly active antiretroviral therapy (HAART), CD4 cell count nadir of > 250 x 10 cells/l and at pre-interruption of > 500 x 10 cells/l. Endpoint was time to CD4 cell count < 350 x 10 cells/l or reinitiation of treatment. RESULTS: At interruption, the median CD4 cell count was 800 x 10 cells/l, median viral load was 1.7 log10 copies/ml. At the time of analysis, 63 (45.3%) had resumed therapy or experienced < 350 x 10 cells/l CD4 cells over a median interruption of 75 weeks. Of these, 33 (52.4%) experienced a decline to < 350 x 10 cells/l and 30 (47.6%) restarted therapy before their CD4 cell count had fallen below this level. In 43 patients with CD4 cell nadir of 251-350 x 10 cells/l, median time to therapy resumption or CD4 cell count < 350 x 10 cells/l was 61 weeks. Higher CD4 cell count nadir, longer duration of viral load suppression on therapy, and higher viral load level at interruption were independently associated with longer time to restart therapy. The risk of clinical events was 5 per 1000 person-years of follow-up. CONCLUSIONS: Patients who started therapy with CD4 cell count of 250-350 x 10 cells/l and who later interrupted therapy appear able to remain off therapy with a CD4 cell count > 350 x 10 cells/l for a substantial period of time.

Adult↗
PubMed2005

Coreceptor usage of primary HIV type 1 isolates obtained from different lymph node subsets.

Biological characteristics of virus quantitatively rescued from different cell types present in lymph nodes of HIV-1-infected individuals in various stages of their disease were determined, not including patients with AIDS defining illness. Viruses were obtained by cocultivation with donor monocyte-derived macrophages and T-lymphocytes and their biological phenotype compared to viruses obtained from the peripheral blood mononuclear cells of the same patient. The biological phenotype was determined on established cell lines (U937-2, CEM, and MT-2) and on the U87.CD4 coreceptor indicator cell lines and variable region 3 (V3) of the envelope was subjected to direct sequencing. All isolates obtained from lymph node subsets used CCR5 as coreceptor. Furthermore, these viruses were also sensitive to inhibition by beta-chemokines as analyzed for viruses of one patient. All 12 V3 regions showed a unique sequence indicating compartmentalization within each patient. The biological phenotype of CCR5-dependent (R5) HIV-1 isolates obtained from PBMC resembles the phenotype of viruses isolated from different lymph node cell subsets.

Amino Acid Sequence↗
PubMed2004

Long-term persistence of vaccination and HAART to human immunodeficiency virus (HIV).

The aim of this study was to monitor the immune responses in HIV-infected patients previously immunized with gp160 or DNA vaccines to analyze whether the introduction of highly active antiretroviral treatment (HAART) would affect the persistence of immunity. The immune responses were evaluated in patients who had participated in randomized trials of therapeutic vaccination. Immunization in conjunction with antiretroviral therapy was effective in inducing HIV-specific T-cell responses. Therapeutic immunizations with recombinant gp160 had a modest effect on CD4-cell counts, the treatment alone lead to a transient clinical benefit in the form of an improved survival after two years of immunization. Immunizations with HIV DNA during HAART treatment permitted persistence or development of innate (NK), CD4+ and/or CD8+ immune responses. HIV specific T-helper cell responses induced by immunization with gp160 were maintained at high levels up to 7 years after the last injection. Cells with HIV-specific interferon-gamma (IFN-gamma) production were retained or increased in long-term HAART treated patients. The impact of a single structured therapy interruption (STI) was analyzed in a small group of patients showing no obvious increase or decrease in the HIV-specific immune response during or after STI. The possibility to induce very long-term strong and persistent immune responses in HIV-infected individuals raises hopes that vaccination preceding therapy interruption might prolong the symptom-free period without HAART.

AIDS Vaccines↗
PubMed2004

Autologous cytotoxicity of natural killer cells derived from HIV-infected patients.

NK cells recognize target cells with reduced expression of MHC class I molecules. Human immunodeficiency virus (HIV) infection decreases MHC class I on the cell membrane. The aim of this study was to directly evaluate the role and conditions of NK cell effects in HIV seropositive patients ex vivo. Autologous HIV-infected CD4+ T cells were exposed to NK cells recognition. We discovered an increased lysis of the target cells after infection with human immunodeficiency virus-1 (HIV-1). The expression of the HIV-1 nef gene or the combined expression of nef and tat confers NK susceptibility to autologous CD4+ targets. Downregulation of MHC class I but not HLA-C or CD4 correlated with increased recognition by NK cells. The specific recognition is correlated with downregulation of MHC class I molecules on the infected target cells.

CD4 Antigens↗
PubMed2004

The reverse transcriptase (RT) mutation V118I is associated with virologic failure on abacavir-based antiretroviral treatment (ART) in HIV-1 infection.

Antiviral efficacy and serum lipids were investigated following a switch from long-term successful protease inhibitor based antiretroviral treatment (PI-ART) to abacavir-based ART in 29 patients who have been followed for 28 months thereafter. Virologic failure occurred within 3 months in 21% (6/29) of the patients, and abacavir hypersensitivity in 1 individual. The remaining 22 patients continue to have HIV RNA < 50 copies/ml after 28 months with a CD4 increase from 605 +/- 265 x 10(6)/l to 798 +/- 366 x 10(6)/l (p < 0.001). All virologic failing patients had been on long-term unsuccessful nucleoside reverse transcriptase inhibitor (NRTI) therapy before PI-ART as compared to 32% (7/22) of the virologic non-failing patients (p < 0.01). The viral strains from the virologic failing patients harboured 3-6 reverse transcriptase (RT) mutations, including the V118I mutation in 5/6 cases prior to PI-ART or at viral rebound. Only the V118I RT mutation was statistically more common among virologic failing than non-failing NRTI pretreated patients (p < 0.05). Stepwise multiple regression analysis for viral failure resulted in a model with only the V118I RT mutation entering the model (p < 0.01). The LDL cholesterol and triglyceride values decreased and the HDL cholesterol increased after the switch to abacavir-based ART (p < 0.01, p < 0.05, p < 0.05, respectively). In conclusion, viral failure was associated with prior mono- or dual-NRTI treatment and the occurrence of the V1181 RT mutation, persisting despite long term viral control. The selection process for patients suitable for treatment simplification to abacavir-based ART should contain a detailed antiretroviral treatment history.

Adult↗
PubMed2003

Antiretroviral treatment of human immunodeficiency virus infection: Swedish recommendations.

The Swedish guidelines (SwG) for treatment of human immunodeficiency virus (HIV) infection have several important roles. A major task involves the promotion of a uniformly high standard of care in all HIV treatment clinics in Sweden and the identification of strengths, weaknesses and relevance of recent research findings. CD4+ T-cell counts < 200 cells/microl are clear indications for the initiation of treatment, whereas high viral loads serve as an indication for increased vigilance rather than a criterion for therapy. It is recommended that the first regimen consists of 2 nucleoside reverse transcriptase inhibitors in combination with 1 protease inhibitor or 1 non-nucleoside reverse transcriptase inhibitor. The definition of treatment failure is rigorous. Treatment change should be considered if the viral load has not fallen by at least 1.5 log in 4 weeks or is undetectable within 3-4 months. Resistance testing is endorsed at primary infection, in the event of treatment failure and in pregnant women. Interaction with experts in HIV resistance testing is emphasized. Therapeutic drug monitoring is advocated. Patients with treatment failure should be handled individually and the decision on therapeutic strategy should be based on treatment history, resistance testing and other clinical facts. The SwG do not give recommendations for some important issues such as prolonged drug holidays and preferences in initial treatment regimens. More scientific data are likely to be available soon and the SwG will be refined accordingly. The present guidelines are translated from Swedish; they are published on the Medical Products Agency (MPA) and Swedish Reference Group for Antiviral Therapy (RAV) websites (www.mpa.se and www.rav.nu.se), including 7 separate papers based on a thorough literature search. A complete reference list is available on request from the MPA.

Anti-HIV Agents↗
PubMed2003

Sildenafil does not alter nelfinavir pharmacokinetics.

The objective of this study was to investigate if sildenafil influences the pharmacokinetics of nelfinavir. Five HIV-infected patients on steady-state nelfinavir-containing therapy were subject to pharmacokinetic sampling for nelfinavir concentration twice: without sildenafil and with sildenafil 25 mg as a single dose. There were no differences in the AUC, T(max), or C(max) of nelfinavir. In a similar design, two patients on indinavir and two patients on ritonavir combined with saquinavir were studied. In accordance with the literature, neither of these two treatments was affected. It is concluded that nelfinavir pharmacokinetics were unaffected by concomitant intake of a single dose of sildenafil.

Adult↗
PubMed2002

Hypofibrinolytic state in HIV-1-infected patients treated with protease inhibitor-containing highly active antiretroviral therapy.

Decreased insulin sensitivity, hyperlipidemia, and body fat changes are considered as risk factors for coronary heart disease (CHD). A clustering of such factors (metabolic syndrome [MSDR]) exponentially increases the risk. Impaired fibrinolysis and increased coagulation are additional independent risk factors for CHD. We studied the effects of protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) on metabolic and hemostatic parameters in 363 HIV-infected individuals, of whom 266 were receiving PI-containing HAART and 97 were treatment naive. The fasting plasma levels of insulin, glucose, triglycerides, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, plasminogen activator inhibitor type 1 (PAI-1), and fibrinogen were evaluated together with the areas of visceral adipose tissue and the visceral adipose tissue/subcutaneous adipose tissue area ratio. The levels of insulin, triglycerides, cholesterol, and low-density lipoprotein cholesterol; visceral adipose tissue area; low-density lipoprotein/high-density lipoprotein ratio; and visceral adipose tissue/subcutaneous adipose tissue area ratio were significantly increased in patients receiving PI-containing HAART compared with treatment-naive patients. The levels of PAI-1 and fibrinogen were significantly higher in patients receiving PI-containing HAART. PAI-1 levels were higher in individuals with MSDR but also in patients without MSDR who were receiving PI-containing HAART. PAI-1 was independently correlated to use of PI-containing HAART, triglyceride level, insulin level, and body mass index (p <.001). These findings suggest that patients receiving PI-containing HAART have decreased fibrinolysis and increased coagulability, which may thus represent additional risk factors for cardiovascular disease in this patient group.

Adipose Tissue↗
PubMed2002

DNA mucosal HIV vaccine in humans.

This is a demonstration of immune activation by delivery of genetic vaccines in human mucosa. We analyzed the local and systemic responses in HIV-1 infected individuals following intraoral jet-injections of HIV-1 DNA constructs encoding the nef, rev, and tat regulatory genes. The immunological responses of the oral mucosa may be representative of other mucosal sites and was therefore selected for induction of mucosal reactivity by DNA immunization. The oral and intramuscular routes induced specific systemic T cell proliferative responses. Immunohistochemical analysis of oral biopsies 2 days after immunization revealed increased levels of granulocytes and T cells as well as expression of HLA-DR. T cell markers for CD3 +, CD4 + and CD8 + were significantly increased in the vaccinated mucosa. Vaccine-specific local and systemic antibodies were present during the immunization. However, increases were neither seen in the local or systemic titer nor in the B-cell accumulation in response to the immunizations. The presence of HIV-1 plasmid DNA was observed in mucosal biopsies as well as local proinflammatory T lymphocyte immune responses with predominantly IL-2 expression in the oral mucosal transudate.

AIDS Vaccines↗