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Biomedical subjects

Hartwig Klinker

Publications and source records attributed to Hartwig Klinker.

11 recordsLinked to original sources
PubMed2006

Extended treatment duration for hepatitis C virus type 1: comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin.

BACKGROUND & AIMS: The treatment of patients infected with hepatitis C virus (HCV) type 1 remains a challenge necessitating innovative strategies to improve treatment outcome. The extension of treatment duration beyond 48 weeks is one possible strategy to address this problem. METHODS: The efficacy and safety of 48 weeks (group A, N = 230) vs 72 weeks (group B, N = 225) of treatment with pegylated-interferon-alfa-2a (180 microg/wk) plus ribavirin (800 mg/day) were studied in treatment-naive patients with HCV type 1 infection. On-treatment and sustained virologic response (SVR) 24 weeks after stopping treatment was assessed by qualitative reverse-transcription polymerase chain reaction (sensitivity 50 IU/mL). RESULTS: Overall, no significant differences could be observed in the treatment outcome between both groups. End-of-treatment and SVR rates in groups A and B were 71% vs 63% and 53% vs 54%, respectively. Patients with undetectable HCV-RNA levels already at weeks 4 and 12 had excellent SVR rates ranging from 76% to 84% regardless of treatment group, whereas patients shown to be still HCV-RNA positive at week 12 achieved significantly higher SVR rates when treated for 72 instead of 48 weeks (29% vs 17%, P = .040). A particular benefit from extended treatment duration was seen in patients with low-level viremia (<6000 IU/mL) at week 12. The frequency and intensity of adverse events was similar between the 2 groups. CONCLUSIONS: Extended treatment duration generally is not recommended in HCV type 1 infection and should be reserved only for patients with slow virologic response defined as HCV-RNA positive at week 12 but negative at week 24.

Adult↗
PubMed2005

No influence of the P-glycoprotein polymorphisms MDR1 G2677T/A and C3435T on the virological and immunological response in treatment naïve HIV-positive patients.

BACKGROUND: In a retrospective study of HIV-infected patients, we investigated the influence of the MDR1 genotype (G2677T/A and C3435T) on the virological and immunological response of treatment naive patients. METHODS: The MDR1 genotype was analysed from 72 patients in whom antiretroviral therapy was initiated between 1998 and 2004. Data were obtained at week 4, 12, 24 and 48 and were analysed by the Kruskal-Wallis test. RESULTS: During the first 48 weeks of antiretroviral therapy, there were no significant differences in the virological and immunological response with respect to the MDR1 2677 and 3435 genotypes and the 2677/3435 haplotype. CONCLUSIONS: In view of different results from several studies concerning the influence of MDR1 polymorphisms on the immunological and virological response to antiretroviral therapy, further studies with larger patient groups and longer follow-up are necessary in order to resolve conflicting issues.

Adult↗
PubMed2005

Comparison of efavirenz and nevirapine in HIV-infected patients (NEEF Cohort).

The non-nucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz (EFV) and nevirapine (NVP) taken in combination with nucleoside reverse transcriptase inhibitors (NRTIs) have both shown to be just as highly effective as protease inhibitors (PIs) in reducing viral load in patients infected with HIV. Our study compares the performance of these two NNRTIs with each other. This was a non-randomized, prospective, two-arm, multi-centre trial. We evaluated all patients with an EFV- or NVP-containing antiretroviral regimen. The primary endpoint was the difference in success rates defined as a viral load of </=50 copies/mL at week 48. chi(2)-tests were used for naïve and pretreated patients using intention-to-treat (ITT) and on-treatment analysis. As secondary endpoints, a viral load of </=500 copies/mL and CD4 count at week 48 for naïve patients were evaluated. A Cox regression was used to adjust for prespecified covariates. We included 662 patients (NVP 337, EFV 325). The difference in success rates in the ITT analysis was 4.5% ( -11.5%, 19.0%), P=0.578. Pretreated patients with a triple therapy show a difference of 10.1 (-0.3, 20.6), P=0.056. Non-significant results appeared for all secondary analyses. In this trial, no difference between EFV and NVP in combination with NRTI backbone therapy can be shown, regarding viral load. Further randomized studies are necessary to evaluate possible differences.

Alkynes↗
PubMed2004

Drug monitoring of pyrimethamine during maintenance therapy of toxoplasmic encephalitis in patients with advanced HIV infection during HAART.

BACKGROUND: Prophylaxis of toxoplasmic encephalitis was performed with pyrimethamine in 6 patients with advanced HIV infection during combination therapy with protease inhibitors. MATERIAL/METHODS: Steady-state plasma pyrimethamine (PYR) levels were measured by gas chromatography. Protease inhibitor plasma concentrations were analyzed trough concentration by high pressure liquid chromatography. During a treatment period of 22I13 months a total of 93 samples from 6 patients were investigated, containing pyrimethamine and protease inhibitors. RESULTS: The mean pyrimethamine concentration was 1,108+/-459 ng/ml with a dosage of 37.5 mg/d and 1, 685+/-665 ng/ml with 50 mg/d. With the simultaneous use of indinavir (IDV), a mean pyrimethamine concentration of 2,165+/-273 ng/ml was found, significantly higher than in combination with saquinavir (SQV) and ritonavir (RTV) (1,192+/-178 ng/ml) or saquinavir and nelfinavir (NLV) (1,117+/-173 ng/ml). This effect was not considered clinically significant. Drug monitoring of protease inhibitors revealed a wide range of protease inhibitor levels. CONCLUSIONS: The statistically significant lower PYR concentrations with the SQV + RTV or SQV + NLV comedication in comparison to comedication with IDV were not considered clinically significant. Therapeutic drug monitoring of PYR and PI plasma levels can be recommended in patients during therapy with both PYR and PI, especially during therapy with a double PI regimen.

Adult↗
PubMed2004

Osteomyelitis and skin ulcers caused by Mycobacterium szulgai in an AIDS patient.

Mycobacterium szulgai is a ubiquitious non-tuberculous mycobacterium causing infection in immunocompetent and immunocompromized patients. Clinically mimicking pulmonary tuberculosis in most cases described, rarely other manifestations occur. Here we report the case of an AIDS patient with osteomyelitis of the hand and toe, accompanied by multiple cutaneous ulcers of the chest and forearm. The case highlights the unusual combination of osteomyelitis and skin ulcers without pulmonary infection and describes the likely cutaneous route of infection in a patient who keeps tropical fish.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Highly sensitive gas chromatographic determination of ethanol in human urine samples.

In order to evaluate recent alcohol consumption, a very sensitive and specific gas chromatographic method for ethanol determination in human urine samples was developed. The non-invasive method was performed without any pretreatment and carried out on a Stabilwax capillary column, 30 m x 0.53 mm x 1.0 microm film thickness. Helium was used as carrier gas with a constant inlet pressure of 27.72 kPa (0.277 bar) and a flame ionization detector (FID). Quantification was performed with the use of acetonitrile as an internal standard (IS). The calibration curve was linear throughout the concentration range from 0.5 to 500 mg/l. The calculated intra- and inter-day coefficients of variation were below 8%. A clear chromatographic separation of ethanol from methanol, acetone, 1-propanol and 2-propanol was achieved.

Chromatography, Gas↗
PubMed2002

Rapid determination of nevirapine in human plasma by gas chromatography.

A sensitive and rapid gas chromatographic method has been developed to determine the levels of the HIV-1 non-nucleoside reverse transcriptase inhibitor nevirapine in human plasma. Quantitative recovery following liquid-liquid-extraction with diethylether from 500 microl of human plasma was achieved. Subsequently, the assay was performed with a CP-Sil 5CB capillary column, 15 m x 0.32 mm x 1.0 microm film thickness with a nitrogen-phosphorous-detector (NPD), Helium 5.0 was used as carrier gas with a constant inlet pressure of 7 p.s.i. Linear standard curves were obtained for concentrations ranging from 10 to 20 000 ng/ml. The calculated intra- and inter-day coefficients of variation were below 8%.

Chromatography, Gas↗