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Biomedical subjects

M Battegay

Publications and source records attributed to M Battegay.

At least 91 records · Page 5Linked to original sources
PubMed1999

General and specific immunosuppression caused by antiviral T-cell responses.

Immunosuppression caused by the non-cytopathic lymphocytic choriomeningitis virus (LCMV) (an RNA virus) is mediated by antiviral cytotoxic T cells that destroy LCMV-infected cells, also of the immune system. While this immunopathological destruction of antigen-presenting cells, macrophages and follicular dendritic cells and of some CD4+ T cells causes general immunosuppression and impairs immune response to third party antigens, it also enhances exhaustion/deletion of LCMV-specific CD8+ T-cell responses. LCMV seems in addition to infect neutralizing antibody-producing B cells via the specific receptor; immunopathological LCMV specific CD8+ T-cell-mediated elimination of these infected B cells (but not of uninfected internal virus antigen-specific B cells) causes a highly specific immunosuppression that delays neutralizing antibody responses and thereby enhances virus persistence. Both generalized and specific immunosuppression by CD8+ T-cell-mediated immunopathology may be involved in human infections with HIV, hepatitis B virus or hepatitis C virus.

Animals↗
PubMed1999

Is there a relation between risk groups or initial CD4 T cell counts and prevalence of seborrheic dermatitis in HIV-infected patients?

OBJECTIVES: (i) To investigate whether there is a difference in the prevalence of seborrheic dermatitis (SD) between homo- or bisexual HIV-infected patients and HIV-infected intravenous drug users, (ii) to study whether the initial CD4 T cell count at the first positive HIV test is of any significance for the prevalence of SD and furthermore to analyze whether (iii) antiretroviral treatment influences the prevalence and time course of SD. PATIENTS AND METHODS: Since 1992 we have been following, within the scope of the Swiss HIV Cohort Study, a group of individuals with proven HIV infection. In this study all HIV-infected patients belonging either to the risk group of homo- or bisexuals or that of intravenous drug users were included for further analysis. RESULTS: We included 226 men and 51 women. The ages ranged from 17 to 68 years (mean 30.1). One hundred and forty-four were homo- or bisexual men and 133 (82 men and 51 women) were intravenous drug users. Out of these 277 HIV-infected patients, 66 (23.8%) had SD at baseline and 7 (2.5%) developed SD during the observation period (male:female = 68:5). CONCLUSION: In our study we found that (i) the risk group influences the prevalence and time course of SD, yet that (ii) neither the initial CD4 T cell count nor (iii) antiretroviral treatment is of any significance.

Adolescent↗
PubMed1999

Salvage treatment against human immunodeficiency virus.

Despite dramatic declines in human immunodeficiency virus (HIV)-associated morbidity and mortality as a result of highly active antiretroviral combination therapies, including protease inhibitors, treatment failure occurs at such high rates as 20-50%. As drug regimens are very demanding, even short decreases of drug concentrations may trigger resistance. Viral loads can be decreased to very low concentrations, and there is no strict cut-off regarding the definition of treatment failure. Nevertheless, continuous detection of HIV of more than 50 copies per mL blood plasma is a predictor of increasing viral loads and of a suboptimal response to therapy. From a theoretical point of view, treatment changes should be made at low HIV RNA levels, but fewer options often dictate a more conservative approach. Drug susceptibility testing will be of increasing value, especially in patients experiencing drug failure for the first time. Success of salvage therapies is closely connected with the use of new compounds including new drug classes. As drugs susceptible to a multi-drug-resistant HIV are not yet available, regimens with more than three or even with five to nine drugs are used in clinical trials. Salvage therapies often fail in virological terms, ie in 50-80% of patients, depending primarily on the treatment history, but immunological and clinical stability can often be achieved.

Anti-HIV Agents↗
PubMed1998

[Quality aspects in internal medicine--from anamnesis to meta-analysis].

Quality aspects get more important in internal medicine due to novel technical developments and economic constraints. In spite of an extensive research activity in clinical medicine some research aspects of quality control are new. Among these are investigations about symptoms and complaints as well as risk factors. Too much evidence might also blur the view when the necessary data might already be available from existing studies but conclusions have not been drawn to improve quality of patient care. An instrument to this end is metaanalysis compounding the results of single studies to a more meaningful result. Thus further unnecessary trials can be avoided. Finally quality control is characterized by readiness to self-criticism. Its aim is to avoid mistakes and intends to optimize medical actions whenever possible.

Diagnosis↗
PubMed1998

Highly active antiretroviral therapy during early HIV infection reverses T-cell activation and maturation abnormalities. Swiss HIV Cohort Study.

OBJECTIVES: To evaluate the impact of early initiation of highly active antiretroviral therapy (HAART) on disease-induced T-cell activation and maturation abnormalities during asymptomatic HIV infection. DESIGN: A prospective open-label trial of zidovudine, lamivudine and ritonavir in treatment-naive asymptomatic HIV-infected individuals with CD4 cells > or = 400 x 10(6)/l. METHODS: Peripheral blood CD4+ and CD8+ T cells derived from 15 asymptomatic HIV-infected individuals (median baseline CD4+ cells, 608 x 10(6)/l; CD8+ cells, 894 x 10(6)/l; plasma HIV RNA, 3.93 log10 copies/ml) undergoing therapy with zidovudine (300 mg twice daily), lamivudine (150 mg twice daily), and ritonavir (600 mg twice daily) were assessed for changes in expression of phenotypic markers of T-cell activation (HLA-DR and CD38) and maturation (CD45RA and CD45RO). At weeks 0, 2, 4, 8, 12, 16, 20 and 24, T-cell subsets were quantified by flow cytometry and plasma HIV viral loads determined using reverse transcription PCR. RESULTS: HAART-induced decrease in plasma HIV RNA levels coincided with a significant reduction in numbers of activated CD4+/HLA-DR+ (maximum change, -36%; P < or = 0.05), CD8+/HLA-DR+ (maximum change, -66%; P < or = 0.005) and CD8+/CD38+ (maximum change, -51%; P < or = 0.01) T cells. A concomitant significant increase in numbers of naive CD4+/CD45RA+ (maximum change, +12%; P < or = 0.005) and memory CD4+/CD45RO+ (maximum change, +6%; P < or = 0.05) T cells was also evident, which contrasted with a significant decrease in memory CD8+/CD45RO+ cells (maximum change, -42%; P < or = 0.005). CONCLUSION: The observed ability of HAART during early asymptomatic HIV infection to initiate rapid reversal of disease-induced T-cell activation and maturation abnormalities, while preserving pretherapy levels of immune function, supports the concept that therapeutic advantage is to be gained by commencing early aggressive antiretroviral therapy.

ADP-ribosyl Cyclase↗
PubMed1998

[Anti-retroviral therapy and antiepileptics. Case report and discussion].

Therapy of HIV infection is changing rapidly as new drugs are introduced. Many patients with HIV infection require anticonvulsants for therapy or prophylaxis of seizures. Antiretroviral drugs, above all protease inhibitors, and anticonvulsants may cause interactions since they are metabolised through common hepatic pathways and may substantially modulate the activity of numerous cytochrome P450 isoenzymes. We describe known interactions between anticonvulsants and antiretroviral drugs and advise on possible combinations.

Adult↗
PubMed1998

Interferon-alpha activates signal transducers and activators of transcription 5 and 6 in Daudi cells.

In most cells studied so far, interferon-alpha (IFN-alpha) activates signal transducer and activator of transcription (Stat1), Stat2 and Stat3, whereas interferon-gamma (IFN-gamma) induces Stat1 only. In general, each of the several dozens of cytokines, growth factors and hormones that signal through the Janus kinases-signal transducers and activators of transcription (Jak-STAT) pathway activates a distinct subset of STATs, and this selectivity is thought to be essential for the specificity of the cellular responses toward these ligands. Here, we have studied the pattern of STAT activation in the human lymphoblastoid cell line Daudi in response to IFN-alpha. In addition to Stat1, Stat2 and Stat3 activation, IFN-alpha was found to directly induce activation of Stat5 and Stat6. Cell-type-specific activation of additional STATs could be responsible for cell-type-specific responses to IFN-alpha.

Base Sequence↗
PubMed1998

Does pregnancy influence the course of HIV infection? Evidence from two large Swiss cohort studies.

The question whether the natural history of HIV infection in women is affected by pregnancy has not so far been convincingly answered. We used prospective cohort data to compare pregnant and nonpregnant HIV-infected women during follow-up within the Swiss HIV Cohort Study (SHCS) and the Swiss Collaborative HIV and Pregnancy Study (SCHPS). Pregnant women were eligible if a CD4 cell count had been made before conception had taken place. Additional inclusion criteria were a pregnancy completed to delivery during follow-up and an observation period of at least 6 months after delivery. Thirty-two women who fulfilled these criteria were compared with 416 controls, matched for age and CD4 cell count at entry, who had not been pregnant during follow-up. Mean follow-up time was 4.8 years for pregnant women and 3.6 years for controls. The rate of any AIDS-defining event was higher in pregnant women (rate ratio [RR] from Cox regression, 1.92; 95% confidence interval [CI], 0.80-4.64) but this did not reach statistical significance (p = .15). A statistically significant difference (p = .008) emerged only for one AIDS-defining event, recurrent bacterial pneumonia (RR, 7.98; 95% CI, 1.73-36.8). The rate of death was similar in the two groups (RR, 1.14; 95% CI, 0.48-2.72; p = .8). Our results thus indicate that, after taking CD4 cell counts before conception into account, acceleration of disease progression is inconsistent among HIV-infected women who become pregnant during follow-up.

AIDS-Related Opportunistic Infections↗
PubMed1998

Genotype distribution of hepatitis C virus infection in Greece: correlation with different risk factors and response to interferon therapy.

The aim of this study was to investigate the prevalence of HCV genotypes among Greek patients with chronic hepatitis C and to assess the influence of genotypes and quasi-species populations on efficacy of interferon therapy. Genotypes were determined in 65 patients (18 patients after kidney transplantation, 16 with thalassemia and 31 with no known risk factor) with elevated ALT for more than 6 months and histologically proven chronic hepatitis, using the Inno-Lipa strip assay. The quasi-species were determined using the fluorescence single-strand conformational polymorphism method. Most patients were infected with genotype 3a, namely 61% of patients with kidney transplants (n = 18), 50% of patients with thalassemia (n = 16) and 48% of patients without known risk factors (n = 31). Other genotypes were found including coinfection with different genotypes. In all patients with mixed infection, genotype 3a was present. Thirty-six patients from the last two groups received interferon (3Mio U 3x week) for 1 year. Biochemical and/or virological and histological responses were found in 11/19 patients with genotype 3a (58%), 3/5 with mixed infection, 2/4 with genotype 1b, 2/5 with genotype 2a, 1/4 with genotype 1a and 1/1 with genotype 4. The virus found in non-responders with genotype 3a was genetically more heterogeneous than in responders. These data indicate that (1) the genotype 3a is prevalent in Greek patients (68% of all patients), (2) there is no significant difference regarding genotypes among patients with different risk factors and (3) although based on a small number of patients, the genotype 3a seems to respond better to interferon therapy. Finally, the number of quasi-species may be a factor predictive of response.

Adult↗
PubMed1998

[Emergencies in HIV infection].

Emergencies in HIV-infected patients are a common complication which may occur at any stage of the disease. Opportunistic infections may lead to irreversible damages of organs such as the brain, the eye or the lung. With the widely use of antiretroviral therapy side effects of reverse transcriptease inhibitors and proteinase inhibitors and drug interactions are frequent causes of severe symptoms such as nausea and diarrhoea or of complications such as anaemia or leucopenia. As with Non-HIV-associated emergencies empiric therapy may be necessary to treat patients to prevent severe organ damage.

AIDS-Related Opportunistic Infections↗
PubMed1998

[Clinically significant drug interactions in HIV-infected patients].

In recent years the availability of highly active antiretroviral therapies and prophylaxis and treatment of opportunistic infections in patients with HIV-disease have reduced morbidity and mortality. Many different drugs may be prescribed in a patient simultaneously. Therefore, the potential for interactions between different substances is increased. The possible mechanisms of drug interaction concern pharmakokinetics (absorption, metabolism, elimination) and pharmakodynamics. They can lead to significant changes in plasma concentrations and may affect efficacy and toxicity of a drug. One of the most important mechanisms of interaction is the inhibition or induction of the hepatic cytochrome P-450 enzyme system. All protease-inhibitors are metabolized by CYP450, mostly by the subunit 3A4. Proteinase-inhibitors are themselves very potent inhibitors of CYP4503A4 and increase the concentration of drugs metabolized this way. This article summarises the most important mechanisms of drug interactions and demonstrates the most frequent and clinical significant consequences.

AIDS-Related Opportunistic Infections↗
PubMed1998

Early participation in an HIV cohort study slows disease progression and improves survival. The Swiss HIV Cohort Study.

BACKGROUND: Different levels of experience of physicians caring for patients with HIV infection have been found to be associated with differences in survival amongst their patients. We examined whether early participation in the Swiss HIV Cohort Study (SHCS), an ongoing prospective study with regular follow-up visits at specialized clinics, improved survival of HIV-infected patients. METHODS: We studied 3553 HIV-infected individuals who joined the Swiss HIV Cohort Study (SHCS) with different levels of immunosuppression: mild (CD4 count above 500 x 106 cells L-1; n x 2038); severe (100-199 cells; n = 960); and very severe (50-99 cells; n = 555). Characteristics at different CD4 cell levels were compared and Cox proportional hazards regression was used to examine the mortality experience during a total of 16 201 person-years of follow-up. RESULTS: Participants joining the cohort early with mild immunodeficiency were younger, more likely to be female, and more likely to have a history of intravenous drug use. At CD4 cell counts below 200 x 106 cells L-1, they were less likely to have a history of Pneumocystis carinii pneumonia or AIDS, more likely to be on prophylaxis against P. carinii and more likely to be on antiretroviral therapy than those joining with severe or very severe immunodeficiency. For example, at the time of the first CD4 cell count in the range of 50-99 x 106 cells L-1, 8.9, 15.0 and 21.6% of participants who joined with mild, severe and very severe immunodeficiency had suffered an episode of P. carinii pneumonia. In Cox models adjusted for CD4 cell count at entry and other relevant baseline differences, mortality was increased amongst participants who joined with severe and very severe immunodeficiency. Hazard ratios (95% confidence intervals (CI)) were 1.71 (1.21-2.42) for participants with severe immunodeficiency at entry and 2.61 (1.70-4. 01) for those with very severe immunodeficiency, compared with 1.0 for those with mild immunodeficiency at entry. CONCLUSIONS: Individuals who were seen regularly at specialized HIV units from early stages of the infection onwards were, at comparable levels of immunodeficiency, less likely to progress to AIDS, and mortality during subsequent follow-up was reduced. This is likely to be explained by better access to prophylactic regimens and antiretroviral therapy.

Adult↗
PubMed1997

Impact of new antiretroviral combination therapies in HIV infected patients in Switzerland: prospective multicentre study. Swiss HIV Cohort Study.

OBJECTIVES: To examine trends in disease progression and survival among patients enrolled in the Swiss HIV cohort study during 1988-96 and to assess the influence of new antiretroviral combination therapies. DESIGN: Prospective multicentre study, with follow up visits planned at six monthly intervals. SETTING: Seven HIV units at university centres and cantonal hospitals in Switzerland. PATIENTS: 3785 men (mean age 35.0 years) and 1391 women (30.3 years) infected with HIV. 2023 participants had a history of intravenous drug misuse; 1764 were men who had sex with men; 1261 were infected heterosexually; and 164 had other or unknown modes of transmission. 601 participants had had an AIDS defining illness. RESULTS: During more than 15,000 years of follow up, there were 1456 first AIDS defining diagnoses and 1903 deaths. Compared with those enrolled during 1988-90, the risk of progression to a first AIDS diagnosis was reduced by 18% (relative risk 0.82 (95% confidence interval 0.73 to 0.93)) among participants enrolled in 1991-2, by 23% (0.77 (0.65 to 0.91)) among those enrolled in 1993-4, and by 73% (0.27 (0.18 to 0.39)) among those enrolled in 1995-6. Mortality was reduced by 19% (0.81 (0.73 to 0.90)), 26% (0.74 (0.63 to 0.87)), and 62% (0.38 (0.25 to 0.97)) respectively. Compared with no antiretroviral treatment, the risk of an initial AIDS diagnosis after CD4 lymphocyte counts fell to < 200 cells x 10(6)/1 was reduced by 16% (0.84 (0.73 to 0.97)) with monotherapy, 24% (0.76 (0.63 to 0.91)) with dual therapy, and 42% (0.58 (0.37 to 0.92)) with triple therapy. Mortality was reduced by 23% (0.77 (0.68 to 0.88)), 31% (0.69 (0.60 to 0.80)), and 65% (0.35 (0.20 to 0.60)) respectively. CONCLUSIONS: The introduction of antiretroviral combination therapies outside the selected patient groups included in clinical trials has led to comparable reductions in disease progression and mortality.

Acquired Immunodeficiency Syndrome↗