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Robert Zangerle

Publications and source records attributed to Robert Zangerle.

7 recordsLinked to original sources
PubMed2003

Tuberculosis risk varies with the duration of HIV infection: a prospective study of European drug users with known date of HIV seroconversion.

BACKGROUND: It is not known whether the risk of active tuberculosis disease varies with the length of time that individuals are infected with HIV. OBJECTIVE: To study how, independently of CD4 T cell count, the risk of tuberculosis varies with the duration of HIV infection. METHODS: Using Poisson regression analysis, the incidence of and risk factors for tuberculosis were studied in 683 injecting drug users (IDU) with a documented date of HIV seroconversion followed in seven cohorts in six European countries until 1998. RESULTS: Overall incidence was 11.5/1000 person-years. Adjusted for CD4 T cell count and geographic region, the risk ratio (RR) for tuberculosis (both pulmonary and extrapulmonary), compared with the first 3 years of HIV infection, was 2.8 for years 4 to 6 of HIV infection [95% confidence interval (CI), 1.3-6.3], 1.2 for year 7 to 9 (95% CI, 0.3-4.2) and 4.6 after 9 years (95% CI, 1.4-15.0). The adjusted RR for geographic region was 13.1 (95% CI, 4.3-40.0) for Amsterdam and 15.8 (95% CI, 4.8-52.0) for the Valencian region of Spain compared with all other sites combined. CONCLUSION: The risk of tuberculosis is increased relatively early in HIV infection (year 4 to 6) and also later (after year 9) with possibly a relatively silent period between. As expected, IDU in Southern Europe have a substantially higher risk of tuberculosis than IDU in Northern and Central Europe. Amsterdam forms an exception for Northern Europe, with very high incidence rates.

AIDS-Related Opportunistic Infections↗
PubMed2003

High prevalence of high risk human papillomavirus-capsid antibodies in human immunodeficiency virus-seropositive men: a serological study.

BACKGROUND: Serological study of human papillomavirus (HPV)-antibodies in order to estimate the HPV-prevalence as risk factor for the development of HPV-associated malignancies in human immunodeficiency virus (HIV)-positive men. METHODS: Sera from 168 HIV-positive men and 330 HIV-negative individuals (including 198 controls) were tested using a direct HPV-ELISA specific to HPV-6, -11, -16, -18, -31 and bovine PV-1 L1-virus-like particles. Serological results were correlated with the presence of HPV-associated lesions, the history of other sexually transmitted diseases (STD) and HIV classification groups. RESULTS: In HIV-negative men low risk HPV-antibodies were prevailing and associated with condylomatous warts (25.4%). Strikingly, HIV-positive men were more likely to have antibodies to the high-risk HPV types -16, -18, -31, and low risk antibodies were not increased in a comparable range. Even those HIV-positive heterosexual individuals without any HPV-associated lesions exhibited preferentially antibody responses to the oncogenic HPV-types (cumulative 31.1%). The highest antibody detection rate (88,8%) was observed within the subgroup of nine HIV-positive homosexual men with anogenital warts. Three HIV-positive patients had HPV-associated carcinomas, in all of them HPV-16 antibodies were detected. Drug use and mean CD4-cell counts on the day of serologic testing had no influence on HPV-IgG antibody prevalence, as had prior antiretroviral therapy or clinical category of HIV-disease. CONCLUSION: High risk HPV-antibodies in HIV-infected and homosexual men suggest a continuous exposure to HPV-proteins throughout the course of their HIV infection, reflecting the known increased risk for anogenital malignancies in these populations. The extensive increase of high risk antibodies (compared to low risk antibodies) in HIV-positive patients cannot be explained by differences in exposure history alone, but suggests defects of the immunological control of oncogenic HPV-types. HPV-serology is economic and can detect past or present HPV-infection, independently of an anatomical region. Therefore HPV-serology could help to better understand the natural history of anogenital HPV-infection in HIV-positive men in the era of antiretroviral therapy.

Antibodies, Viral↗
PubMed2003

Acute hepatic failure and lactate acidosis associated with antiretroviral treatment for HIV.

Severe hepatotoxicity is a rare but potentially life-threatening side effect of antiretroviral therapy. In this case report we describe an HIV-positive patient who was admitted to our clinic with evidence of severe acute pancreatitis 18 months after the introduction of antiretroviral treatment, which included stavudine and didanosine. Shortly afterwards, she developed lactate acidosis and acute hepatic failure associated with renal failure. Renal support (hemofiltration) was required for three days. The patient subsequently developed grade III encephalopathy, as well as a large pleural effusion and ascites. Although the reported outcome of patients with liver failure due to antiretroviral treatment is poor, with a high mortality rate, our patient fully recovered after intensive supportive care and cessation of the antiretroviral agents. Liver biopsy revealed microvesicular steatosis and giant mitochondria, which are the typical hallmarks of mitochondrial damage, the presumed mechanism of antiretroviral drug toxicity. More than three years later the patient has an excellent clinical status with a stable HIV infection and no need for antiretroviral treatment. This case report indicates the need for increased awareness of the potential hepatotoxicity of an antiretroviral therapy, as severe side effects may occur more frequently with increasing use of such treatment.

Acidosis, Lactic↗
PubMed2003

Increase of haemoglobin levels by anti-retroviral therapy is associated with a decrease in immune activation.

DESIGN: We evaluated whether an increase in haemoglobin levels in the first 6 months of effective anti-retroviral therapy (ART) is associated with a decrease in immune activation. To reduce confounding factors only men (n = 35) and patients not receiving agents known to enhance haematopoiesis or patients without diseases that might suppress haematopoiesis were included. Simultaneously parameters of iron metabolism and cofactors for haematopoiesis were analysed. RESULTS: A median baseline haemoglobin level of 139 g L-1 increased to 149 g L-1 at month 6 of ART (P < 0.001). At baseline low haemoglobin levels were strongly associated with high neopterin concentrations (r = - 0.64, P < 0.001), and much less correlated to high HIV-1 RNA levels (r = - 0.41, P < 0.05) and to a lower CD4+ cell count (r = 0.33, P < 0.05). The change of neopterin levels during the study period correlated with the relative change in haemoglobin levels, r = - 0.35, P = 0.03, whereas no such correlations were found for the change of HIV-1 RNA levels and the CD4 cell count. A logistic regression analysis revealed that the change of neopterin and soluble transferrin receptors concentrations are independently associated with an increase of haemoglobin levels of more than 15 g L-1. CONCLUSION: Our study supports a cause-effect relationship between immune activation and anaemia in HIV-infected patients. Treatment of patients with ART decreases virus load, which may thereby result in silencing of immune effector activity thus ameliorating anaemia by reversing the anti-proliferative effects of cytokines towards erythroid progenitors and the iron withdrawal strategy of the immune system.

Adult↗
PubMed2002

Effective antiretroviral therapy reduces degradation of tryptophan in patients with HIV-1 infection.

Antiretroviral therapy (ART) has a significant impact on HIV-1 RNA levels, the CD4 cell count, and immune activation. We examined whether these changes are associated with a change in the rate of tryptophan degradation (expressed as the kynurenine to tryptophan ratio, kyn/trp) as an estimate for the activity of interferon-gamma inducible enzyme indoleamine (, )-dioxygenase (IDO). Plasma levels of tryptophan, kynurenine, and neopterin were measured pretherapy and 6 months postinitiation of therapy in 45 patients with HIV-1 RNA levels of less than 1000 copies/ml 6 months after initiation of ART. Before ART, the patients had decreased tryptophan and increased kynurenine concentrations compared to healthy controls. During ART, average tryptophan levels increased; in the same time kynurenine and kyn/trp decreased (P < 0.001), although not to normal levels. Since pretherapy tryptophan concentrations correlated inversely with neopterin, and kynurenine correlated with viral load and neopterin but not with CD4 cell count, the data support the view that HIV production may induce immune activation and consequently tryptophan is degraded at a higher rate. In agreement, kyn/trp positively correlated with neopterin (r(s) = 0.60, P < 0.001), with virus load (r(s) = 0.37, P = 0.013), and very weakly with CD4(+) cells counts (r(s) = 0.30, P = 0.049). The change in the kyn/trp ratio during ART correlated more strongly with the change in neopterin levels (r(s) = 0.49, P = 0.001) than with the change in HIV RNA levels and weakly with the CD4 cell count. The data underscore the fact that both neopterin production and tryptophan degradation are triggered by immune activation. Tryptophan degradation is increased in HIV infection and partially reversed under ART. The data agree with the concept that immune activation is the common background of IDO activation which may be an important factor underlying T-cell hyporesponsiveness.

Acquired Immunodeficiency Syndrome↗