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Niels Obel

Publications and source records attributed to Niels Obel.

32 records · Page 2Linked to original sources
PubMed2004

Tenofovir treatment in an unselected cohort of highly antiretroviral experienced HIV positive patients.

The aim of the present study was to explore the treatment effect of tenofovir as implemented in clinical practice. Data are presented on 34 patients. 11 patients had tenofovir added to a stable anti-retroviral treatment (ART) and 23 patients had drugs other than tenofovir. CD4 counts, HIV-RNA levels and genotypic resistance were determined at baseline and after 3 and 6 months. After initiation of tenofovir treatment, a mean decrease in HIV-RNA for all 34 patients was observed (-0.43 log1o copies/ml (+/- 1.22) and -0.49 log10 copies/ml (+/- 1.36) after 3 and 6 months, respectively, (p = 0.045)). However, the effect of tenofovir on HIV-RNA in the group of patients who had tenofovir added to a stable ART was limited, and the decrease in HIV-RNA was significantly higher in patients who had drugs other than tenofovir changed as well (p = 0.004 and p = 0.03 after 3 and 6 months, respectively). After initiation of tenofovir treatment, no significant increases in CD4 count were observed. All new NRTI-associated mutations could be explained by the background treatment. In conclusion, we observed a significant decrease in HIV-RNA only when tenofovir was prescribed, in conjunction with other anti-retroviral drugs, to patients on a failing highly active antiretroviral drug regimen (HAART).

Adenine↗
PubMed2004

Low effectiveness of highly active antiretroviral therapy and high mortality in the Greenland HIV-infected population.

Greenland is a high-income country with free access to human immunodeficiency virus (HIV) care, including highly active antiretroviral therapy (HAART). We aimed to examine the HIV prevalence, age and gender distribution, and the effectiveness of HAART on CD4 positive cell count, viral load (VL), and mortality in the Greenland HIV-infected population. In this population-based cohort study we collected demographic, clinical and biochemical data on all HIV-infected patients followed in health clinics since 1995. For each case, we identified 100 age- and gender-matched population controls. The HIV cohort included 103 patients of whom 91% were Inuit; 81% were infected heterosexually. Only 40% of the patients had a VL <400 copies/ml at 48 weeks after starting HAART, and patients on HAART had a substantial excess relative mortality compared with the general population (mortality rate ratio [MRR]: 10.6; 95% confidence interval [CI]: 6.9-16.4). After the introduction of HAART, the mortality decreased (MRR: 2.5; 95% CI 0.9-6.8), but remained high with a mortality rate of 62 per 1000 person-years (py) (95% CI 29-129). Our findings underline the difficulties of implementing successful HIV treatment even with unlimited economic resources and free access to health care.

Adult↗
PubMed2003

Low efficacy and high frequency of adverse events in a randomized trial of the triple nucleoside regimen abacavir, stavudine and didanosine.

BACKGROUND: Highly active antiretroviral therapy containing three nucleoside reverse transcriptase inhibitors has been somewhat successful, but the clinical efficacy is unclear. METHODS: Randomized, controlled, open-label trial of 180 antiretroviral drug-naive HIV-infected patients allocated to a regimen of abacavir, stavudine and didanosine (A/S/D, n = 60), ritonavir and saquinavir (R/S 400/400 mg twice daily; n = 60) or nelfinavir and nevirapine (N/N 1250/200 mg twice daily; n = 60); the latter two in combination with lamivudine and zidovudine. The primary endpoint was HIV plasma RNA < or = 20 copies/ml after 48 weeks. RESULTS: At baseline, the median CD4 cell count was 161 x 106 cells/l (range, 0-920) and the HIV RNA was 5.0 log10 copies/ml (range, 2.7-6.7). At 48 weeks, 43% in the A/S/D arm had a HIV RNA < or = 20 copies/ml, compared with 69% in the N/N arm (P < 0.01) and 62% in the R/S arm (P < 0.05). In a multivariate analysis, the A/S/D arm had an odds ratio of obtaining a viral load of < or = 20 copies/ml at week 48 of 0.25 [95% confidence interval (CI) 0.10-0.59] versus N/N and 0.53 (95% CI, 0.33-0.83) versus R/S. The A/S/D arm had a particularly poor outcome in patients with higher viral load and AIDS at baseline: 63% had to discontinue A/S/D (any drug). Side effects were more frequent in the A/S/D arm and included neuropathy 27%, suspicion of hypersensitivity 12%, and increase in lactate accompanied by systemic symptoms 8%. CONCLUSION: The A/S/D regimen had a low efficacy and a high frequency of adverse events and cannot be recommended.

Adult↗
PubMed2003

Randomized trial to evaluate indinavir/ritonavir versus saquinavir/ritonavir in human immunodeficiency virus type 1-infected patients: the MaxCmin1 Trial.

This trial assessed the rate of virological failure at 48 weeks in adult human immunodeficiency virus (HIV) type 1-infected patients assigned indinavir/ritonavir (Idv/Rtv; 800/100 mg 2 times daily) or saquinavir/ritonavir (Sqv/Rtv; 1000/100 mg 2 times daily) in an open-label, randomized (1:1), multicenter, phase 4 design. Three hundred six patients began the assigned treatment. At 48 weeks, virological failure was seen in 43 (27%) of 158 and 37 (25%) of 148 patients in the Idv/Rtv and Sqv/Rtv arms, respectively. The time to virological failure did not differ between study arms (P=.76). When switching from randomized treatment was counted as failure, this was seen in 78 of 158 patients in the Idv/Rtv arm, versus 51 of 148 patients in the Sqv/Rtv arm (P=.009). A switch from the randomized treatment occurred in 64 (41%) of 158 patients in the Idv/Rtv arm, versus 40 (27%) of 148 patients in the Sqv/Rtv arm (P=.013). Sixty-four percent of the switches occurred because of adverse events. A greater number of treatment-limiting adverse events were observed in the Idv/Rtv arm, relative to the Sqv/Rtv arm. In conclusion, Rtv-boosed Sqv and Idv were found to have comparable antiretroviral effects in the doses studied.

Adult↗
PubMed2003

Use of the protease inhibitor saquinavir hard gel in human immunodeficiency virus-infected patients in the early period of highly active antiretroviral therapy: does it affect long-term treatment outcome?

Saquinavir hard gel capsule (hgc), the first human immunodeficiency virus (HIV) protease inhibitor (PI) used in clinical practice, has been shown to have insufficient effectiveness. A population-based cohort study assessed the long-term consequences of using saquinavir hgc as initial PI in HIV-infected patients pre-exposed to nucleoside reverse transcriptase inhibitors. 121 patients starting a regimen with saquinavir hgc were compared with 91 starting with non-boosted indinavir (n = 72) or ritonavir (n = 19). Median follow-up time was 4.6 and 4.7 y for the 2 groups. Starting with saquinavir hgc was associated with a lower overall probability of achieving an undetectable viral load [risk ratio (RR) = 0.41, 95%, confidence interval (95% CI) 0.30-0.56]. However, the lower probability of having undetectable viral load during follow-up declined over time with odds ratios (OR) = 0.27 (95%, CI 0.14-0.54), 0.35 (951% CI 0.19-0.66), 0.47 (95% CI 0.24-0.91) and 0.73 (95% CI 0.34-1.55) at 60, 120, 180 and 240 weeks, respectively, after starting HAART. Starting with saquinavir hgc was correlated with a higher risk of having the initial PI discontinued (RR = 1.89, 95% CI 1.39-2.58). The insufficient suppression of viral load in patients starting with saquinavir hgc subsided during follow-up, probably owing to the earlier discontinuation of saquinavir hcg in favour of newer and more potent HAART regimens.

Adult↗
PubMed2003

Prevalence of drug resistance mutations and non-B subtypes in newly diagnosed HIV-1 patients in Denmark.

The aim of this study was to monitor the prevalence of drug resistance mutations in newly diagnosed HIV-1 positive individuals in Denmark. In addition we assessed the prevalence of non-B subtypes based on phylogenetic analysis of the pol gene. Plasma samples from 104 newly diagnosed HIV-1 positive patients were obtained in the year 2000. The entire protease gene and 320 amino acids of the reverse transcriptase gene were genotyped. Sequences were obtained from 97 patients. No subjects displayed primary resistance mutations in the protease gene, whereas all carried 1 or more secondary mutations. Resistance mutations in the RT-gene associated with NRTI-resistance were found in 1 patient, who was infected with zidovudine resistant HIV-1 harbouring the M41L mutation in combination with T215S and L210S. The T215S mutation has been showed to be associated with reversion of zidovudine resistance. The T215S mutation was found in 1 additional patient. The subtype distribution was subtype B 59%, C 18%, A 8%, CRF02_AG 5%, CRF01_AE 4%, D 3% and G 2%. We found 2 patients (2%) with mutations associated with resistance in the RT-gene and none in the protease gene indicating a low prevalence of resistant HIV-1 in Denmark in the year 2000.

Adolescent↗
PubMed2003

K65R with and without S68: a new resistance profile in vivo detected in most patients failing abacavir, didanosine and stavudine.

Antiretroviral treatment with three nucleoside reverse transcriptase inhibitors (NRTIs) is widely used, but the combination of abacavir, didanosine and stavudine has never been investigated. We describe the surprising and consistent genotypic and phenotypic outcome in patients failing this combination. As part of a Danish multicentre study, 60 antiretroviral-naive patients were randomized to treatment with abacavir, didanosine and stavudine. Failure was defined as one HIV-1 RNA >400 copies/ml. Genotyping was performed using TrueGene HIV-1 assay (Visible Genetics, London, UK). Phenotypic susceptibilities were determined with the Virco Antivirogram assay. Eight patients failed treatment with a median viral load of 2.980 copies/ml (range 478-5.950). At baseline, five patients were wild-type. Three patients harboured nucleoside excision mutations (NEMs), but phenotypic susceptibilities were within normal range. All five patients with wild-type virus developed K65R and four of these patients also acquired the S68G mutation. Phenotypic susceptibility decreased towards abacavir (median 8.9-fold) and didanosine (median 3.2-fold), while susceptibility towards stavudine was unchanged (median 0.8-fold). Susceptibility towards lamivudine and tenofovir decreased median 14.2- and 4.0-fold, respectively. In two patients with baseline resistance mutations, further accumulation of NEMs and V75T or L74V was observed. One patient developed Q151M. Failure of a triple NRTI regimen is possible and frequent with only the K65R mutation. Under adequate selection pressure K65R can easily emerge in vivo and may compromise several future treatment options including newer NRTIs. The unexpected high incidence of S68G suggests a functional role of this mutation in viruses harbouring K65R.

Anti-HIV Agents↗
PubMed2003

A randomized trial comparing initial HAART regimens of nelfinavir/nevirapine and ritonavir/saquinavir in combination with two nucleoside reverse transcriptase inhibitors.

BACKGROUND: A triple-class HAART regimen may be associated with a better virological effect than conventional regimens, but may also lead to toxicity and more profound resistance. METHODS: Randomized, controlled, open-label trial of 233 protease inhibitor- and non-nucleoside reverse transcriptase inhibitor-naive HIV-infected patients allocated to a regimen of nelfinavir and nevirapine (1250/200 mg twice daily; n = 118) or ritonavir and saquinavir (400/400 mg twice daily; n = 115), both in combination with two nucleoside reverse transcriptase inhibitors. The primary end-point was HIV RNA < or = 20 copies/ml after 48 weeks (missing value = failure). Patients remained under follow-up also in case of switch from the randomized therapy. RESULTS: At baseline, the median CD4 cell counts were 126 (range: 0-942) (nelfinavir/nevirapine) and 150 (0-642) (ritonavir/saquinavir) cells/mm3, and HIV RNA measurements 5.0 copies/ml (1.3-6.4) in both groups. A total of 102 (86%) and 101 (88%) were antiretroviral-naive. 44% discontinued randomized therapy; P = 0.13. Of these, 80 and 73% switched therapy due to adverse events; P = 0.99. At week 48, 69 and 56%, respectively, had a HIV RNA < or = 20 copies/ml; P = 0.037. CONCLUSION: A regimen of nelfinavir/nevirapine had a favourable virological effect and tolerability over a 48-week period compared with ritonavir/saquinavir, when administered in combination with two nucleoside reverse transcriptase inhibitors. However, more extensive follow-up is required to determine the long-term consequences of triple class HAART regimens, including the development of broad drug resistance.

Adult↗
PubMed2002

The effect of race/ethnicity on the outcome of highly active antiretroviral therapy for human immunodeficiency virus type 1-infected patients.

We performed a population-based cohort study to assess the impact of nonwhite origin on the outcome of highly active antiretroviral therapy (HAART) for a Danish cohort of human immunodeficiency virus (HIV)-infected patients. A total of 389 whites and 135 nonwhites started receiving HAART before 1 April 2001. After 1 year of treatment, 78% of nonwhites and 76% of whites achieved a virus load of <500 HIV RNA copies/mL. No major differences were found between the 2 groups with respect to achievement of a virus load of <500 copies/mL (relative risk [RR], 0.94; 95% confidence interval [CI], 0.74-1.18), risk of clinical progression (RR, 0.63; 95% CI, 0.32-1.24), or response measured by total CD4+ cell count. One year after fulfilling Danish recommendations for initiation of HAART, 91% of nonwhites and 93% of whites had started receiving HAART. Race and ethnic origin play no major role in the outcome associated with HAART if access to health care is free.

Adult↗
PubMed2002

[Meningitis caused by herpes simplex virus type 2].

Herpes simplex virus type 1 (HSV-1) is well-known as a cause of orolabial ulcers, whereas HSV-2 predominantly causes genital infections. Furthermore, HSV can lead to severe infections in the central nervous system (CNS). In adults, HSV encephalitis is predominantly caused by HSV-1, whereas HSV-2 mainly leads to aseptic meningitis, the symptoms of which are seen with or without concurrent genital ulcers. We describe four cases of HSV-2-associated aseptic meningitis. One of the patients had a primary HSV infection, and another had recurrent aseptic meningitis. All the patients recovered without neurological sequelae.

Adult↗
PubMed2002

[HIV in Western Denmark. Demographic data from a population-based cohort study].

INTRODUCTION: The course of HIV infection has changed since the introduction of highly active anti-retroviral treatment. MATERIAL AND METHODS: We present demographic data from an observational database on HIV and AIDS in the Western part of Denmark, a region representing 2,935,156 individuals, or 55.1% of the population in Denmark (1 January 2000). Five centres in the region treat HIV positive adults; all patients attached to these centres since 1995 are included. Altogether 749 adult HIV-infected individuals were enrolled as of 31 December 1999. Estimates of the prevalence and incidence of HIV infection in the area were 25.8/100,000 and 2.6/100,000 respectively, which are lower than the average for the country. RESULTS: The number of newly diagnosed HIV-infected patients remained constant in the period 1995-1999 with an average of 62 diagnoses per year. The number of HIV-related deaths declined from 43 in 1995 to 15 in 1999. DISCUSSION: There seems to be a shift in the HIV epidemic over the last few years, with a higher proportion of newly diagnosed HIV-patients who have contracted the infection through heterosexual contact, and a higher proportion who are immigrants from less developed countries.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Serum level of YKL-40 is elevated in patients with Streptococcus pneumoniae bacteremia and is associated with the outcome of the disease.

YKL40 is secreted by activated macrophages and neutrophils. Elevated serum concentrations of YKL40 are found in patients with diseases characterized by inflammation or ongoing fibrosis. The aim of this study was to evaluate serum YKL-40 levels in patients with Streptococcus pneumoniae bacteremia and to correlate these levels with clinical findings and outcomes. YKL40 was determined by ELISA and 89 patients were included in the study. Serum YKL-40 levels were significantly higher in patients with S. pneumoniae bacteremia (median 342 microg/l; range 20-20,400 microg/l) than in age-matched healthy subjects (44 microg/l; 20-184; p < 0.001). Serum YKL-40 levels were related to the severity of the infection, with significantly higher serum YKL-40 levels being observed in patients who needed hemodialysis (p < 0.001), pharmacological treatment of hypotension (p < 0.001) and mechanical ventilation (p = 0.003) compared to those in patients who did not need this supportive treatment. Nineteen patients died and these patients had significantly higher serum YKL-40 levels (980 microg/l; 88-20,400 microg/l) than those of survivors (256 microg/l; 20-9,100 microg/l; p < 0.001). Serum YKL40 level was an independent prognostic factor of survival in logistic multivariate regression analysis (p = 0.002). In conclusion, high serum levels of YKL40 indicated a poorer prognosis for patients with S. pneumoniae bacteremia.

Adipokines↗
PubMed2002

Trends in the use of highly active antiretroviral therapy in western Denmark 1996-2000.

New antiretroviral drugs, expanding knowledge of their long-term toxic effects and the large number of patients with treatment failure have increased the demand for new strategies in the antiretroviral treatment of HIV-infected patients. The present study was conducted as part of the HIV Cohort Study in western Denmark to reveal trends in the use of antiretrovirals in the region. The cohort includes all patients attached to those centers treating HIV patients in western Denmark. A total of 537 patients who started highly active antiretroviral therapy (HAART) were included. The number of patients receiving HAART increased dramatically in 1996 and 1997 before leveling off, with 45-75 patients initiating treatment annually thereafter. Median follow-up time after initiation of HAART was 151 weeks. An estimated 45.1% of patients had the initial HAART regimen modified during the first year of follow-up. Side-effects and treatment failure were the main reasons for treatment modifications. Major new strategies implemented in the region in 1999 and 2000 included treatment with boosted protease inhibitors and non-nucleoside reverse transcriptase inhibitors.

Adult↗