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Andreas Plettenberg

Publications and source records attributed to Andreas Plettenberg.

15 recordsLinked to original sources
PubMed2006

Efficacy and safety of a once-daily fixed-dose combination of abacavir/lamivudine compared with abacavir twice daily and lamivudine once daily as separate entities in antiretroviral-experienced HIV-1-infected patients (CAL30001 Study).

BACKGROUND: A one-tablet, once-daily abacavir/lamivudine fixed-dose combination (FDC) has been recently approved to treat HIV-1 infection. METHODS: A randomized, open-label, parallel-group, multicenter study to compare the efficacy and safety of the FDC group to the separate entities (SE) group, in combination with tenofovir and a new protease inhibitor or nonnucleoside reverse transcription inhibitor in antiretroviral-experienced adults experiencing virologic failure (VF). Eligible subjects had viral loads >1000 copies/mL with < or =3 nucleoside reverse transcription inhibitor-associated mutations. The primary efficacy end point was time-average changed from baseline (average area under the curve minus baseline) in plasma HIV-1 RNA over 48 weeks. RESULTS: A total of 186 subjects were enrolled. The average area under the curve minus baseline was -1.65 and -1.83 log10 copies/mL in the FDC and SE groups, respectively (intention to treat; 95% confidence interval: -0.13, 0.38). Patients in the FDC (50%) and SE groups (47%) achieved viral loads <50 copies/mL based on the time to loss of virologic response algorithm. VF was low and similar in both groups (FDC, 16%; SE, 18%). Tolerability was similar between the 2 groups. CONCLUSIONS: The FDC group had noninferior efficacy over 48 weeks to the SE group in treatment-experienced subjects with VF.

Adult↗
PubMed2006

AIDS-associated Burkitt or Burkitt-like lymphoma: short intensive polychemotherapy is feasible and effective.

The objective was to evaluate the feasibility and efficacy of a short-term, multi-agent and dose intensive regimen in AIDS patients with Burkitt or Burkitt-like lymphoma (BL/BLL) and to compare its efficacy with that of a conventional regimen. This was a retrospective, multi-center cohort study of all HIV-1-infected patients diagnosed with BL/BLL between 1990 - 2004. Patients were assigned to two different chemotherapy approaches. Group A received a protocol which was adapted from the German multi-center study group for adult acute lymphoblastic leukemia (GMALL). Group B received a conventional CHOP-based chemotherapy. Fifty-one patients were included in the analysis. In group A (n = 20), significantly more patients achieved complete remission (75% vs 40%, P = 0.02) than in group B (n = 31). One-year survival in group A was 65% compared to 44% in group B (P = 0.17). In a multi-variable Cox regression analysis, treatment according to the GMALL protocol was significantly associated with prolonged survival with a relative hazard rate of 0.13 (95% CI 0.03 - 0.63, P = 0.01). In conclusion, the short and intensive GMALL protocol for B-ALL/NHL is feasible in patients with AIDS-BL/BLL. Outcome may be improved compared to patients treated with CHOP-based regimens. In the era of HAART, more intensive chemotherapy regimens should be considered in patients with highly aggressive lymphomas.

Adult↗
PubMed2006

Pharmacokinetics of enfuvirtide in patients treated in typical routine clinical settings.

Therapeutic drug monitoring (TDM) is gaining importance for improving the success of antiretroviral treatment in human immunodeficiency virus-infected patients. However, enfuvirtide (ENF) concentrations are not regularly determined. The objective of this work was to study the pharmacokinetics (PK) of ENF in patients treated in routine clinical settings, to develop a population PK model describing the concentration-time profile, and to establish PK reference values. A liquid chromatography-tandem mass spectrometry method was developed and applied to serum samples submitted for TDM. A two-compartment model with linear absorption and elimination was fitted to 329 concentrations from 131 patients. The PK model was used for simulations resulting in percentile curves for ENF levels for the full dosing interval. The model predicted that a median concentration of 1,968 ng/ml would be reached 12 h after administration of 90 mg of ENF, and 23% and 58% of patients are expected to have concentrations below 1,000 ng/ml and 2,200 ng/ml, respectively. Both values have been proposed as cutoffs for virological efficacy. The median maximum concentration of drug in serum (Cmax) of 3,943 ng/ml, predicted for 3 h after drug administration, is lower than the Cmax reported previously. We found an enormous interpatient variability at every time point, with concentration spectrums covering >1 log and 52% and 123% interindividual variabilities in the typical clearance and volume of distribution, respectively, in contrast to preexisting PK data. In summary, ENF levels are lower and more variable than expected. Many patients may achieve insufficient concentrations. Further covariate analysis in the population PK model might help to identify factors influencing the variability in ENF concentrations.

Adult↗
PubMed2005

Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1.

We assessed the efficacy and safety of 10-d monotherapy with the orally administered CCR5 antagonist maraviroc in 63 HIV-1-positive individuals prescreened for the absence of CXCR4-using virus. Maximum reduction in viral load occurred at a median of 10-15 d, with a mean reduction of >or=1.6 log(10) copies/ml at all twice daily doses >or=100 mg. These results provide proof of concept that CCR5 antagonism is a viable antiretroviral therapeutic approach.

Anti-HIV Agents↗
PubMed2005

AIDS-related B-cell lymphoma (ARL): correlation of prognosis with differentiation profiles assessed by immunophenotyping.

This study was undertaken to analyze the differentiation profiles assessed by immunophenotyping in AIDS-related B-cell lymphoma (ARL) and their relation to the clinical course. Paraffin-embedded sections of 89 ARL cases during 1989 to 2004 were stained immunohistochemically with antibodies to CD3, CD10, CD20, CD38, CD138/Syndecan-1 (Syn-1), multiple myeloma-1/interferon regulatory factor-4 (MUM1/IRF4), B-cell lymphoma protein-2 (BCL-2), BCL-6, latent membrane protein-1 (LMP-1), and Ki-67. Expression of CD10 and CD20 were associated with better overall survival (OS; P = .009 and P = .04, respectively). Expression of CD20 was associated with longer disease-free survival (DFS; P = .03), whereas expression of CD138/Syn-1 was associated with shorter DFS (P = .03). OS and DFS were worse in patients with immunophenotypic profiles related to post-germinal center (GC) differentiation (BCL-6 and CD10 negative, MUM1/IRF4 and/or CD138/Syn-1 positive) when compared with GC differentiation (P = .01). When controlled for age-adjusted International Prognostic Index (IPI), prior AIDS-defining illness (ADI), and year of ARL diagnosis, a post-GC differentiation remained significantly associated with poor OS and DFS. Expression of CD10 was associated with a preserved immunocompetence, whereas CD20 was less frequent in patients developing ARL while on highly active antiretroviral therapy (P = .04). In summary, lack of CD20 or CD10 expression and a post-germinal center signature are associated with a worse prognosis in ARL.

Adult↗
PubMed2004

Epidemiology of HHV-8 infection in HIV-positive patients with and without Kaposi sarcoma: diagnostic relevance of serology and PCR.

BACKGROUND: Kaposi's sarcoma (KS) remains the most common neoplasm in HIV-infected patients. Human herpesvirus 8 (HHV-8) infection is etiologically associated with KS. Diagnostic procedures with regard to HHV-8 infection are not routinely performed in HIV-infected patients; diagnostic and prognostic value of HHV-8 serology or PCR are unknown in this setting. Epidemiological data concerning HHV-8 infection of HIV-infected patients in Germany are rare. OBJECTIVES: To assess prevalence of HHV-8 infection in a cohort of HIV-infected patients with and without KS in Germany and to correlate this to manifestations and clinical course of KS. STUDY DESIGN: HHV-8 serology was performed in 483 patients in routine care for HIV-infection in northern Germany. HHV-8 DNA was analyzed by PCR in peripheral blood mononuclear cells (PBMC) of 293 patients; in a subgroup multiple samples were analyzed. History and manifestations of KS were recorded. RESULTS: HHV-8 antibodies were detected using IFT in 91% of 33 patients with KS and 52% of 398 patients without KS. In 36 of 293 (12.3%) patients HHV-8 DNA was detected in PBMC. In general, HHV-8 DNA was not continuously detected when multiple samples from the same patient were analyzed. Patients with KS history were more likely to be PCR positive than those without (45.5% versus 7.8%). In patients with active KS HHV-8 DNA was detected more frequently than in patients with disease remission. HHV-8 DNA was not detected in serologically negative patients. However, three patients with KS history in full remission for several years were seronegative. CONCLUSIONS: HIV-infected patients were frequently found to be positive for HHV-8 antibodies. The number of patients positive for viral DNA in PBMC was much smaller. Single PCR-examinations were of little value for prognosis, but repeated detection of HHV-8 DNA represents an increased risk of disease activity.

Base Sequence↗
PubMed2004

[Oral candidiasis].

Explore the source record for details and available documents.

Antifungal Agents↗
PubMed2004

Strong impact of highly active antiretroviral therapy on survival in patients with human immunodeficiency virus-associated Hodgkin's disease.

Hodgkin's disease (HD) is the most common non-acquired immunodeficiency syndrome (AIDS)-defining malignancy in human immunodeficiency virus (HIV)-infected patients. We analysed the outcome of patients with HIV-associated HD (HIV-HD) with respect to the use and efficacy of highly active antiretroviral therapy (HAART) and other prognostic factors. To evaluate the effects of several variables on overall survival (OS), Kaplan-Meier statistics and extended Cox regression analysis were performed. Response to HAART was used as a time-dependent variable and was defined as an increase of >0.1 x 10(9) CD4 cells/l and/or at least one viral load <500 copies/ml during the first 2 years following diagnosis of HIV-HD. Fifty-seven patients with HIV-HD diagnosed between 1990 and 2002 were included in the study. In the Cox model, the only factors independently associated with OS were HAART response [relative hazard (RH) 0.19; 95% confidence interval (CI) 0.06-0.60], complete remission (RH 0.30, 95% CI 0.13-0.72), and age <or=45 years (RH 0.23; 95% CI 0.09-0.60). Median survival time in patients without HAART response was 18.6 months, whereas the median survival time in patients with HAART response was not reached (89% OS at 24 months). In this cohort, a significant improvement in survival was found in patients with HIV-HD who responded to HAART.

Adult↗
PubMed2004

[Dramatic increase in lymphogranuloma venereum among homosexual men in Hamburg].

Classical sexually transmitted diseases, including syphilis and gonorrhea, have recently increased significantly among homosexual men in Hamburg. During the last year we also observed an increase in patients with lymphogranuloma venereum (LGV) at the ifi-institute in Hamburg. In 2003, we identified 4 homosexual patients with LGV in different clinical stages. None of the patients has traveled outside Germany. Three of these patients were HIV-infected. In all cases Chlamydia trachomatis was identified by SDA (strand displacement amplification) in genital swabs or lymph node aspirates. In three cases sequencing of ompA PCR products was performed and in each instance revealed the C. trachomatis serovar L2. Other important genital pathogens were excluded by specific PCR tests, bacteriological and serological tests. LGV should be included in the differential diagnosis of anogenital and oral erosions, especially in homosexual patients and HIV-infected patients. Novel nucleic acid amplification tests can be used for the rapid and reliable diagnosis of LGV by identifying Chlamydia trachomatis.

Adult↗
PubMed2003

Response to highly active antiretroviral therapy strongly predicts outcome in patients with AIDS-related lymphoma.

BACKGROUND: AIDS-related lymphoma (ARL) remains a frequent complication of HIV infection. We analyzed the outcome of patients with ARL with respect to the use and efficacy of highly active antiretroviral therapy (HAART) and to potential prognostic factors. METHODS: This multicenter cohort study included patients with systemic ARL diagnosed between 1990-2001. We evaluated overall survival and the effects of several variables on overall survival using the Kaplan-Meier method and the extended Cox proportional hazards model. Response to HAART was used as a time-dependent variable and was defined as a CD4 cell count increase of >/= 100 x 106 cells/l and/or at least one viral load < 500 copies/ml during the first 2 years following diagnosis of ARL. RESULTS: Among 203 patients with ARL, median overall survival was 9.0 months [95% confidence interval (CI), 7.6-12.4 months]. In the univariate analyses, age < 60 years, no previous AIDS, CD4 cell counts >/= 200 x 106 cells/l, hemoglobin > 11 g/dl, Ann Arbor stages I-II and A, no extranodal lesion, response to HAART, and complete remission showed statistically significant association with prolonged overall survival. In the multivariate Cox model, the only factors independently associated with overall survival were response to HAART [relative hazard (RH), 0.32; 95% CI, 0.16-0.62], complete remission (RH, 0.24; 95% CI, 0.15-0.36), previous AIDS (RH, 1.92; 95%CI, 1.23-3.01) and extranodal involvement (RH, 2.85; 95% CI, 1.47-5.51). CONCLUSIONS: Efficacy of HAART was independently associated with prolonged survival in this large cohort of patients with ARL. Information on patient's response to HAART is crucial for the evaluation of future treatment strategies.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Remission of a cutaneous Mycosis fungoides after topical 5-ALA sensitisation and photodynamic therapy in a patient with advanced HIV-infection.

BACKGROUND: Treatment of Mycosis fungoides (MF) in HIV-infected patients is controversially discoursed. Photodynamic therapy (PDT) after topical sensitization with 5-aminolevulinic acid (5-ALA) is a new and effective modality for treatment of skin malignancies. OBJECTIVE: In this report we describe, what is, to our knowledge, the first case of a patient with MF through advanced HIV-infection, successfully experiencing topical 5-ALA sensitization and PDT. METHODS: 5-ALA ointment was applied to plaques and held in occlusion for 4 hours. PDT was applied using the PDT 1200 irradiation source (Waldmann Medizintechnik System) with 180 J/cm superset 2. RESULTS: Complete remission of MF was achieved, after two completed cycles of photodynamic therapy. CONCLUSION: MF lesions in the presended case showed a high response to 5-ALA sensitization and PDT. This modality appeared to be very effective in treatment of MF in a HIV-infected patient and could be a valuable treatment option for cutaneous T-cell lymphoma in HIV-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Reappearance of HIV multidrug-resistance in plasma and circulating lymphocytes after reintroduction of antiretroviral therapy.

BACKGROUND: After the discontinuation of antiretroviral therapy in HIV-infected patients with highly resistant virus, the detectability of viral resistance mutations quickly decreases. To which extent this represents a true loss of resistance or rather a detectability phenomenon remains unclear. OBJECTIVES: To monitor virologic response and resistance pattern during a non-strategic treatment interruption in the presence of highly drug-resistant viral strains. STUDY DESIGN: We performed serial genotypic resistance analyses on viral DNA isolated from a patient with a multidrug-resistant human immunodeficiency virus infection who discontinued and later on reintroduced antiretroviral therapy. Sequencing was performed on viral DNA from plasma as well as DNA from circulating leukocytes. RESULTS: While under combination antiretroviral therapy with two nucleosidic reverse transcriptase inhibitors, a non-nucleosidic reverse transcriptase inhibitor and a protease inhibitor, the viral load of the patient was around five logs. Genotypic resistance to all available agents was detected during this time. Antiretroviral therapy was then interrupted, and 14 weeks later an almost complete reversion of the virus to wild type was observed. After introduction of a new antiretroviral therapy regimen, the reappearance of nearly all of the formerly present resistance mutations had to be noted within 6 weeks, including mutations without known relation to any of the drugs in the new regimen. CONCLUSIONS: We obviously observed not the de novo appearance of a complex resistance pattern under just 6 weeks of potent antiretroviral therapy, but a reappearing archival strain of the virus. This finding provides evidence for subdetectable persistence of resistant variants during treatment interruptions. Therefore, resistance analyses from peripheral blood performed in times of treatment interruptions should be interpreted with caution as they may provide incomplete information about the resistance profile soon after reintroduction of therapy.

Adult↗