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Biomedical subjects

J R Bogner

Publications and source records attributed to J R Bogner.

At least 19 recordsLinked to original sources
PubMed2006

Highly active antiretroviral therapy (HAART) improves survival in HIV-associated Hodgkin's disease: results of a multicenter study.

BACKGROUND: The purpose of the study was to evaluate the outcome of Hodgkin's disease (HD) in patients infected with the human immunodeficiency virus (HIV) with respect to the use of highly active antiretroviral therapy (HAART). MATERIALS AND METHODS: This cohort study included patients with HIV-HD diagnosed from June 1984 to February 2004. Patients treated in the pre-HAART era (1984-1996) were compared with those belonging to the HAART era (1997-2004). RESULTS: Of 66 patients with HIV-HD, 47 (71%) presented with stage III/IV disease and 38 patients (58%) with an AIDS-defining illness. Fifty-nine of 66 patients (89.4%) underwent curative intended chemotherapy. Patients receiving HAART (n = 34) had a significantly better 2-year overall survival (OS) than those not receiving HAART (74% versus 30%, P <0.001). The 2-year OS of HAART-responders was 88% compared with 19% in patients without HAART-response (P = 0.0002). By multivariate analysis patients without HAART had a 5.6-fold higher risk for 3-year mortality [HR 5.6, 95% confidence interval (CI) 2.20-14.26]. Three-year mortality was significantly higher in patients without complete remission (HR 4.40, CI 1.77-10.99), with stage III/IV HD (HR 4.64, CI 1.31-16.49) and with CD4 cells <200/microl (HR 2.69, CI 0.99-7.33). CONCLUSIONS: Use of HAART significantly improved the overall survival in patients with HIV-HD.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Endogenous endophthalmitis with azole-resistant Candida albicans--Case report and review of the literature.

Candida endophthalmitis accounts for the majority of fungal endophthalmitis. Despite its clinical relevance there are no controlled trials on different treatment regimens. We report a case of endogenous endophthalmitis caused by azole-resistant Candida albicans following abdominal surgery in an otherwise healthy woman, and review the literature concerning treatment recommendations. In consideration of the serious outcome with loss of sight in insufficiently treated endophthalmitis we like to increase awareness to this disease entity and the possibility of azole-resistance, even in treatment-naive patients.

Antifungal Agents↗
PubMed2005

[Recurring disseminated Mycobacterium avium infections in an HIV-negative patient].

HISTORY AND ADMISSION FINDINGS: A 64 year old man complained about progressive pain in his right upper leg and pelvis since 4 weeks without any history of trauma. He noticed a reduced general health status for several months with weight loss and subfebrile temperatures. The patient's medical history revealed several malignant tumours and recurrent infections with atypical mycobacteria and herpes viruses. INVESTIGATIONS: Laboratory findings showed signs of chronic inflammation. Multiple disseminated osteolytic bone lesions, hepatosplenomegaly, lymphadenopathy and multiple splenic lesions were detected by CT scan. Mycobacterium avium was isolated from an osteolytic lesion of the pelvic bone. Malignant disease and acquired immunodeficiency syndrome were excluded. Lymphocyte counts showed lymphocytopenia with reduced T cells, B cells and a reduced CD4-/CD8-ratio. Interferon-gamma-pathway defects as described in patients with susceptibility to atypical mycobacteria could not be identified. TREATMENT AND COURSE: Clinical and immunologic findings indicated a link between recurrent Mycobacterium avium infections and an idiopathic CD-4 T-cell lymphopenia (low CD4 syndrome). Antimycobacterial treatment at standard doses was started according to the resistance test obtained from microbiological culture. Medical and radiological checkup after 3 months of therapy showed signs of progressive disease. CONCLUSIONS: Osteolytic lesions can be caused by mycobacterium avium infection. Disseminated atypical mycobacteriosis is an opportunistic disease in patients with congenital or acquired immunodeficiency syndrome.

B-Lymphocytes↗
PubMed2005

Treatment of acute hepatitis C infection in HIV-infected patients: a retrospective analysis of eleven cases.

Studies on hepatitis C virus (HCV) monoinfected patients suggest high sustained treatment response rates of up to 98% when interferon monotherapy is administered during the acute phase of HCV-infection. To clarify whether early treatment of acute hepatitis C is similarly efficient in human immunodeficiency virus (HIV) positive patients, we conducted a retrospective survey of HIV-positive patients with acute HCV infection. Eleven HIV-positive patients who had been treated with interferon or interferon/ribavirin were identified at eight HIV-specialty outpatient clinics. The patients had been treated over a median 25 weeks with standard interferon (two patients), pegylated interferon (four patients) and pegylated interferon in combination with ribavirin (five patients). A post-treatment response (negative serum HCV-RNA at the end of treatment) was seen in 10 of 11 patients and HCV-RNA remained undetectable 24 weeks after the end of treatment in all the 10 responders. Alanine aminotransferase (ALT) normalized in eight patients while two virological responders and one nonresponder showed persistent mild ALT elevations. In conclusion, early treatment of acute hepatitis C seems to achieve high sustained virological treatment response rates also in patients with HIV-infection.

AIDS-Related Opportunistic Infections↗
PubMed2004

Association of highly active antiretroviral therapy failure with chemokine receptor 5 wild type.

OBJECTIVES: Approximately 10% of HIV-infected patients fail to respond properly to highly active antiretroviral therapy (HAART). Among other factors, genetic variants of chemokine receptors have been shown to modify the course and outcome of HIV infection. Our objective was to investigate whether a failure of virological response is associated with polymorphisms of the chemokine receptors or cofactors. METHODS: A total of 256 HIV-infected patients receiving HAART and 221 healthy controls were analysed for the chemokine receptor 5 (CCR5)-Delta32-bp, stromal derived factor 1 (SDF1)-3'A and chemokine receptor 2 (CCR2)-64I polymorphisms. Treatment failure was defined as failure to lower the viral load below 50 HIV-1 RNA copies/mL within the first year of treatment despite good adherence. Genomic DNA was extracted from peripheral blood lymphocytes (PBL) and amplified by polymerase chain reaction (PCR). RESULTS: Successful treatment was associated with heterozygosity for the CCR5-Delta32-bp variant found in 24 of 184 responders (13%) vs. one of 72 nonresponders (1.4%; P=0.004). Eighty-four of 184 responders (45.7%) vs. 25 of 72 nonresponders (34.7%) were heterozygous for the SDF1-3'A allele (P=0.073). The CCR2-64I polymorphism was rare in both groups: 4.9% in responders vs. 1.4% in nonresponders (P=0.175). The odds ratio for successful treatment was 4.7 for individuals who tested positive for at least one variant allele of the three polymorphisms. Comparison of genotype frequencies between HIV-infected and healthy individuals showed highly significant differences (P<0.001). CONCLUSIONS: Chemokine receptor polymorphisms have a modifying effect on the virological response to HAART. Multivariate analysis demonstrated that heterozygosity for the CCR5-Delta32-bp variant is an independent prognostic factor for treatment outcome.

Adult↗
PubMed2004

Kinetics of lactate metabolism after submaximal ergometric exercise in HIV-infected patients.

OBJECTIVES: It is unknown whether high levels of lactate result from enhanced production or decreased degradation. We therefore investigated differences in the kinetics of plasma lactic acid in HIV-infected patients receiving or not receiving highly active antiretroviral therapy (HAART) and in uninfected controls after submaximal ergometric exercise. METHODS: Ten healthy controls, 11 HIV-infected therapy-naïve patients, 15 HIV-infected patients on HAART with normal baseline lactate levels, and nine HIV-infected patients on HAART with elevated baseline lactate levels >2 mmol/L performed 10 min of ergometric exercise, with a heart rate of 200 beats/min minus age. Lactate levels were measured at baseline, at the end of exercise and 15, 30, 45, 60 and 120 min thereafter. RESULTS: Mean baseline lactate levels were 1.4, 1.5, 1.5 and 2.8 mmol/L in the controls, the therapy-naïve patients, the patients on HAART with normal lactate levels and the patients on HAART with elevated lactate levels, respectively. Maximum lactate levels after exercise were similar in all groups (9.7, 9.4, 9.0 and 10.1 mmol/L, respectively). Significant differences were found in the slope of lactate decline between controls and untreated individuals (P=0.038) and between patients on HAART with normal baseline lactate and patients on HAART with elevated baseline lactate (P=0.028). CONCLUSIONS: Differences in lactate metabolism do exist between healthy controls and HIV-infected therapy-naïve individuals. Thus, HIV infection in itself may influence lactate levels. Elevated baseline lactate levels are associated with a delayed decline of lactate after exercise. These results could be explained by impaired lactate clearance. Lactate production upon exercise does not seem to be affected by baseline lactate levels.

Adult↗
PubMed2003

Is anal carcinoma a HAART-related problem?

BACKGROUND: There is evidence that frequency of AIN/AC rises in HIV+ individuals treated with HAART whilst frequency of most other opportunistic neoplasms declines with immune reconstitution. METHOD: 1472 patients were screened 3655 times for ACA as a strong risk factor for AIN/AC. The periods 1985 to 1995 (before introduction of PI in Germany) and 1996 to 2001 were compared. In addition, 10 cases of AC are described. Time between HIV-infection and AC as well as time between ACA and AC is assessed, pre-treatment with HAART, age, CD4-cell count and CDC-stage at timepoint of diagnosis of AC is mentioned. RESULTS: There are significantly higher numbers of ACA+ screens in the years after 1996 (p<0.001) independent of number of CD4+ T-lymphocytes. AIN/AC occurs more often in HIV+ individuals, preferably in advanced disease stages, at younger age and within a shorter time after first signs of ACA than in HIV-negative population. AC occurs more likely in patients pretreated with HAART, AC tumor stage is ACIS in most cases. - CONCLUSION: Analogical to AIN/AC, frequency of ACA seems to rise under HAART (regimen including PI) although risk for opportunistic diseases usually decreases under HAART. Similarity of AC to ICC in HIV+ women is striking and AC could become part of the list of AIDS-indicator diseases. According to pre-existing cost-effectiveness calculations [6], screening for AC (including physical examination, proctoscopy, cytology and biopsy of all suspect lesions) should be performed every 2-3 years in patients with CD4+ T-lymphocytes >500/microl and yearly in patients with CD4+ T-lymphocytes <500/microl. Existing ACA should be treated thoroughly. The role of serum HIV load in development and progression of ACA [20], and in consequence of AIN/AC needs further investigation.

Adult↗
PubMed2003

Amprenavir in pre-treated patients: virological and immunological response in a cohort of 45 patients.

Treatment failure after preceding protease inhibitors (PI) is often due to resistance mutations. Our objective was to evaluate amprenavir (APV) in pre-treated patients and to correlate it with pre-existing mutations. - Fourty five patients were entered in an open label prospective study (6/99-12/2000). Pre-treatment was 6.2 years +/- 2.4 (2-11.3) and included a mean of 4.13 nucleosides (RTIs) and 2.73 PIs. Genotypic resistance testing was performed prior to the switch. APV dose was 1200 mg/d in combination with ritonavir (RTV) boosting (2 x 100mg) and 2 x 1200 mg/d in 6 patients without RTV. Co-medication was selected based on treatment history and results of genotypic testing. - The median duration of treatment at analysis was 34 weeks. Plasma viral load (VL) average at baseline was 4.6 log subset 10 +/- 08. After 24 weeks the mean VL reduction was 1.4 log subset 10 +/- 1.2 3.86-0.40s). A VL reduction of >1.5 log subset 10 was found in 16/45 patients (36%), 21/45 (47%) patients achieved a VL <400 cp/ml, and 12/45 (27%) a VL < 50 cp/ml. CD4 cells increased from a mean baseline of 208/microl +/- 185 to 318/microl +/- 253. Fourty percent (18/45) of patients had a CD4 gain of more than 100 cells/microl. Genotypic resistance determination showed PI mutations in 87% of patients tested. The average number of mutated codons was 4.54. Three of 4 patients with I84V mutation did not achieve an undetectable VL. - Our findings demonstrate that APV and APV/RTV plus two additional antiretrovirals has a good virological and immunological success rate in pre-treated patients. Presence of more than two APV resistance mutations was associated with treatment failure.

Anti-HIV Agents↗
PubMed2001

Improvement of HAART-associated insulin resistance and dyslipidemia after replacement of protease inhibitors with abacavir.

OBJECTIVE: To assess the effect of replacing protease inhibitors (PIs) with abacavir on insulin sensitivity and plasma lipids. - DESIGN: Pilot study including 31 patients with sustained virological control on their first PI-containing HAART regimen. 16 patients were switched from PIs to abacavir (ABC group), 15 patients continued on PIs (PI group). In all patients, nucleoside-analogue reverse transcriptase inhibitors were continued. METHODS: Insulin sensitivity (using an intravenous insulin tolerance test) and fasting total cholesterol and triglycerides were determined at baseline, month 3, 6, 9 and 12. RESULTS: In the ABC group, there was a significant increase in median insulin sensitivity from baseline within 6 months (+ 49 micromol/l/min), and a significant decrease in both triglycerides (-41mg/dl) and cholesterol (-40mg/dl) at month 3. These changes were sustained through month 12. In addition, a reversal of baseline insulin resistance, hypercholesterolemia and hypertriglyceridemia was observed in the majority of patients. In the PI group, no significant changes in insulin sensitivity, triglycerides and cholesterol were observed. There was a significant correlation between the changes in insulin sensitivity, triglycerides and cholesterol. INTERPRETATION: Switching from PIs to abacavir is associated with an improvement of insulin sensitivity and a decrease of cholesterol and triglycerides in the majority of patients with HAART-associated metabolic alterations and therefore might be an alternative for patients to PI-containing HAART regimens.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Stavudine versus zidovudine and the development of lipodystrophy.

The pathogenesis of some components of the lipodystrophy (LD) syndrome might be linked to the use of nucleosides. Earlier reports did not compare treatment regimens according to the nucleoside backbone. We studied a cohort of individuals who did not switch between stavudine and zidovudine. LD was defined to be present if one of three criteria was met: self-report by the patient, observation by an investigator who had known the patient since commencement of highly active antiretroviral therapy (HAART), or examination by a physician masked to therapy. The mean duration of therapy was 101 weeks (range: 26-234 weeks). Overall prevalence of LD was 48.7%. Lipoatrophy and lipohypertrophy occurred in 33.9% and 28.7% of patients, respectively. Logistic regression showed four parameters to be significantly associated with lipoatrophy: HAART longer than 2 years (p =.002, odds ratio [OR] = 4.4, 95% confidence interval [CI]: 1.608-11.965), baseline viral load >100,000 copies/ml (p =.004, OR = 4.3, CI: 1.726-11.197), age >40 years (p =.016, OR = 3.2, CI: 1.247-8.373), and white ethnicity (p =.041, OR = 5.4, CI: 1.070-28.184). Cholesterol levels of >200 mg/dl at baseline were associated with a risk reduction (p =.047, OR = 0.36, CI: 0.130-0.987). Use of lipohypertrophy as a dependent variable resulted in a significant association with HAART duration (p = 0.028, OR = 2.7, CI: 1.2-6.5) and protease inhibitor use (p =.014, OR = 3.8, CI: 1.3-11.2). LD prevalence is similar with both backbones using stavudine or zidovudine. This is the first time that baseline cholesterol was shown to be significantly associated with lipoatrophy.

Adult↗
PubMed2001

Phase I/II dose escalation and randomized withdrawal study with add-on azodicarbonamide in patients failing on current antiretroviral therapy.

BACKGROUND: Azodicarbonamide (ADA), a HIV-1 zinc finger inhibitor, targets a new step in viral replication and cell infectivity. OBJECTIVE: A first phase I/II clinical study of ADA. METHODS: ADA was administered at escalating doses concomitantly with current antiviral therapy during a 3-month open-label period in patients with advanced AIDS and documented virological failure. After 3 months, patients were randomized in a double-blind placebo-controlled withdrawal, ADA being given at the highest tolerated dosage. RESULTS: Fifteen patients with advanced disease failing on combined antiretroviral therapy, 75% of them with proven phenotypic resistance, had a median baseline CD4 cell count of 85 x 10(6) cells/l, CD4/CD8 cell ratio of 0.09 and median plasma RNA viral load of 4.2 log10 copies/ml. Tolerance to ADA was dose dependent and some patients developed nephrolithiasis, glucose intolerance or showed an ADA-related cytotoxicity towards CD4 cells at higher dosages. No patient died during the study period. ADA increased CD4 cell percentage, increased the CD4/CD8 cell ratio and decreased plasma RNA viral load from baseline. At the end of the double-blind period, the ADA group, but not the placebo group, showed a significant response (P < 0.05). No phenotypic resistance to ADA was observed. Overall, 3/11 patients (27%) had consistent viral load reductions > 0.5 log10 copies/ml compared with baseline and 5/ 11 (45%) showed a CD4 cell recovery from baseline > 33%. In responders, ADA induced a median peak increase in CD4 cell percentage change from baseline of 65% (range 47-243%), and viral load decrease of 1.04 log10 copies/ml (range 0.52-1.23). CONCLUSIONS: The maximal tolerated dosage of ADA appears to be 2 g (three times daily). This study provides safety results that will allow larger clinical trials to confirm the preliminary efficacy data.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Kaposi's sarcoma-associated herpesvirus serology in Europe and Uganda: multicentre study with multiple and novel assays.

A multicentre study was undertaken to define novel assays with increased inter-assay concordance, sensitivity, specificity and predictive value for serological diagnosis of human herpesvirus type 8 (HHV-8) infection. A total of 562 sera from European and Ugandan human immunodeficiency virus (HIV)-infected or uninfected individuals with or without Kaposi's sarcoma (KS) and blood donors were examined under code by 18 different assays in seven European laboratories. Sera from KS patients and all non-KS sera found positive by at least 70%, 80%, or 90% of the assays were considered "true positive." The validity of the assays was then evaluated by univariate logistic regression analysis. Two immunofluorescence assays (IFA) for detection of antibodies against HHV-8 lytic (Rlyt) or latent (LLANA) antigens and two enzyme-linked-immunosorbent assays (ELISA) (M2, EK8.1) for detection of antibodies against HHV-8 structural proteins were found to be highly concordant, specific, and sensitive, with odds ratios that indicated a high predictive value. When used together, the two IFA (Rlyt-LLANA) showed the best combination of sensitivity (89.1%) and specificity (94.9%). The performance of these assays indicate that they may be used for the clinical management of individuals at risk of developing HHV-8 associated tumours such as allograft recipients.

AIDS-Related Opportunistic Infections↗
PubMed2000

Expansion of CD60 helper lymphocytes detected in peripheral lymphocytes of HIV-1 infected individuals is not paralleled in lymph nodes.

BACKGROUND AND OBJECTIVE: A significant expansion of CD8 cells with capability of Th2 type helper function had been observed in hemophiliacs with HIV infection. These cells were characterised by the surface co-expression of CD8 and CD60 antigen. Our objective was to investigate this lymphocyte subset in relation to other subsets in homosexuals and drug users in two compartments: blood and lymph nodes. Blood and lymph nodes from not HIV-infected persons served as control. RESULTS: CD8+CD60+ cells were expanded in perpheral blood of HIV - infected patients as compared to age matched controls (10.0 versus 4.1%, p <0.05). This difference was not observed in lymph node cell suspensions (6.2 vs. 4.3% of all lymph node cells; p = n.s.). The CD 4/CD8 ratio was significantly less impaired in lymph nodes than in blood (2.27 vs. 0.83; p <0.05). Cytotoxic T cells were more abundant in the lymph nodes of patients with early stage HIV disease when compared two late stage patients (4.3 vs 2.1%; p <0.05). Immunohistochemistry on frozen lymph node cuts showed presence of CD60 cells mainly in the interfollicular and paracortical area. In 3 of 10 HIV infected patients these cells were also found in the germinal centers. In controls no CD60 cells were detected in the follicles. Numbers and percentages of CD60 cellls and CD8+CD60+ cells in blood and in lymph nodes did not correlate with HIV - stage, CD4 count or plasma viral load. No correlation with lymph node viral load was seen. CONCLUSIONS: Our data confirm that like in hemophiliacs expansion of CD8+CD60+ is also found in the blood of other HIV risk groups and seems not to be specific for hemophiliacs. However, the higher percentage in peripheral blood is not paralleled in lymph nodes. Redistribution phenomena seem to be the most plausible explanation. According to these data, a major impact of CD8+CD60+ cells in the immunopathogenesis of HIV infection does not seem likely.

Antigens, CD↗