Background. As a result of effective combination antiretroviral therapy (cART) and advanced suppo... more Background. As a result of effective combination antiretroviral therapy (cART) and advanced supportive healthcare, a growing number of human immunodeficiency virus (HIV)-infected children survive into adulthood. The period of transition to adult care is often associated with impaired adherence to treatment and discontinuity of care. We aimed to evaluate virological and social outcomes of HIV-infected adolescents and young adults (AYAs) before and after transition, and explore which factors are associated with virological failure. Methods. We included 59 HIV-infected AYAs from the Netherlands who had entered into pediatric care and transitioned from pediatric to adult healthcare. We used HIV RNA load and cART data from the Dutch Stichting HIV Monitoring database (1996-2014), and collected social and treatment data from patients' medical records from all Dutch pediatric HIV treatment centers and 14 Dutch adult treatment centers involved. We evaluated risk factors for virological failure (VF) in a logistic regression model adjusted for repeated measurements. Results. HIV VF occurred frequently during the study period (14%-36%). During the transition period (from 18 to 19 years of age) there was a significant increase in VF compared with the reference group of children aged 12-13 years (odds ratio, 4.26 [95% confidence interval, 1.12-16.28]; P = .03). Characteristics significantly associated with VF were low educational attainment and lack of autonomy regarding medication adherence at transition. Conclusions. HIV-infected AYAs are vulnerable to VF, especially during the transition period. Identification of HIV-infected adolescents at high risk for VF might help to improve treatment success in this group.
With a rising incidence of acute hepatitis C virus (HCV) infection in patients coinfected with th... more With a rising incidence of acute hepatitis C virus (HCV) infection in patients coinfected with the human immunodeficiency virus (HIV), there is a need for evidence-based treatment recommendations. There are no randomised trials available and published studies differ with respect to design, patient characteristics and number of patients included, making a comparison between studies difficult. However, it is critical to standardise treatment for this group of patients in order to optimise the outcome of therapy. The Dutch Society for HIV Physicians proposed to write recommendations for the treatment of acute HCV in HIV -coinfected patients. Combination therapy with pegylated interferon-alpha and ribavirin is the preferred regimen initiated preferably within 12 weeks after the diagnosis of acute HCV. A treatment duration of 24 weeks is recommended in case of a favourable virological response (either achievement of a rapid virological response or a > 2 log10 decrease plus undetectable HCV-RNA at week 12). In all other patients prolonging the duration of therapy to 48 weeks should be considered.
All human immunodeficiency virus type 1 (HIV-1)-infected patients who started to use indinavir (8... more All human immunodeficiency virus type 1 (HIV-1)-infected patients who started to use indinavir (800 mg three times a day) as part of their triple drug regimen were included in a study to determine the importance of low plasma concentrations of indinavir as a cause of virological treatment failure. The indinavir concentration and a number of patient characteristics at baseline were tested as risk factors for virological treatment failure (defined as a viral load above 200 copies/ml after 24 weeks of treatment) in univariate and multivariate analyses; 65 patients were included. Virological treatment failure occurred in 36.9% of the patients. Multivariate analysis showed that a low plasma concentration of indinavir (odds ratio 0.1), a high viral load at baseline (odds ratio 2.6) and pretreatment with another protease inhibitor (odds ratio 10.0) were independent factors related to virological treatment failure. Monitoring of indinavir plasma concentrations may be an important tool for the optimization of triple drug combination therapy.
Objectives: We investigated occurrence of and risk factors for severe COVID-19 outcomes in people... more Objectives: We investigated occurrence of and risk factors for severe COVID-19 outcomes in people with HIV (PWH) in the Netherlands. Design: An ongoing prospective nationwide HIV cohort study. Methods: COVID-19 diagnoses and outcomes with other relevant medical information were prospectively collected from electronic medical records in all HIV treatment centers in the Netherlands, from the start of the COVID-19 epidemic until December 31, 2021. Risk factors for COVID-19 related hospitalization and death were investigated using multivariable logistic regression, including demographics, HIV-related factors, and comorbidities. Results: The cohort comprises 21 289 adult PWH, median age 51.2 years, 82% male, 70% were of Western origin, 12.0% were of sub-Saharan African and 12.6% Latin American/Caribbean origin, 96.8% had HIV-RNA less than 200 copies/ml, median CD4+ cell count 690 (IQR 510–908) cells/μl. Primary SARS-CoV-2 infections were registered in 2301 individuals, of whom 157 (6.8%) required hospitalization and 27 (1.2%) ICU admission. Mortality rates were 13 and 0.4% among hospitalized and nonhospitalized individuals, respectively. Independent risk factors for severe outcomes (COVID-19-related hospitalization and death) were higher age, having multiple comorbidities, a CD4+ cell count less than 200 cells/μl, uncontrolled HIV replication, and prior AIDS diagnosis. Migrants from sub-Saharan Africa, Latin America, and the Caribbean were at an increased risk of severe outcomes independently of other risk factors. Conclusion: In our national cohort of PWH, risk of severe COVID-19 outcomes was increased in individuals with uncontrolled HIV replication, low CD4+ cell count, and prior AIDS diagnosis, independently of general risk factors such as higher age, comorbidity burden and migrants originating from non-Western countries.
Nature of double-stranded DNA binding activity in seropositive rheumatoid arthritis: formation of... more Nature of double-stranded DNA binding activity in seropositive rheumatoid arthritis: formation of low avidity DNA/rheumatoid factor/IgG/low density lipoprotein complexes.
An HIV-positive man from Somalia presented with severe malaise, weight loss, relapsing fever, lym... more An HIV-positive man from Somalia presented with severe malaise, weight loss, relapsing fever, lymphadenopathy and splenomegaly. An FDG-PET-scan-guided lymph node biopsy revealed the characteristic histological features of the plasma cell variant of Castleman's disease. A high HHV-8 viral load was detected in the serum (7980 copies/ml). Treatment with HAART, rituximab and vinblastine resulted in a full and rapid recovery and lowered HHV-8 viral load to undetectable levels.
Background: Recent publications have reported superior efficacy of telaprevir- or boceprevir-base... more Background: Recent publications have reported superior efficacy of telaprevir- or boceprevir-based triple therapy over conventional peginterferon-alfa/ribavirin therapy, albeit with varying rates of adverse events and treatment discontinuations in HIV/HCV coinfected patients. Therefore, the aim of this study is to describe the effectiveness of triple therapy in an HIV/HCV coinfection cohort in the Netherlands. Methods: HIV-infected patients with chronic HCV genotype 1 starting triple therapy including either boceprevir or telaprevir were enrolled, 26% had F3-F4 fibrosis. Data were assessed at Week 4, 8, 12, 24, 48 and SVR12 (i.e. absence of detectable plasma HCV RNA 12 weeks after completion of treatment). Failure was defined as discontinuation of treatment due to virological failure, adverse events or loss to follow-up. Results: A total of 53 HIV/HCV coinfected patients started peginterferon-alfa/ribavirin therapy with either boceprevir (n = 29) or telaprevir (n = 24). SVR12 was achieved in 19 (66%) of the boceprevir-treated and 15 (63%) of the telaprevir-treated patients. Both prior relapse and achievement of a rapid virological response were associated with a higher SVR12 rate. Non- response, breakthrough and relapse occurred in 4, 1 and 5 patients on boceprevir and 3, 2, 2 on telaprevir, respectively. One patient was lost to follow-up and one patient died due to progression of liver failure. Except for these two patients, no treatment discontinuations were observed due to adverse events. Conclusion: In HIV/HCV coinfected patients, boceprevir or telaprevir triple therapy was well tolerated and resulted in favourable SVR12 rates comparable with previous publications concerning HCV mono-infected patients.
Autonomous sensory meridian response (ASMR) is a warm tingling sensation which is often accompani... more Autonomous sensory meridian response (ASMR) is a warm tingling sensation which is often accompanied by feelings of calmness and relaxation. The present study examined the effects of an ASMR video on mood, attention, heart rate (HR), electrodermal activity (EDA), electroencephalography (EEG) and the interaction with personality factors in 38 young adults (33 females and 5 males). Based on the ASMR-checklist responses of having tingles during watching the ASMR video 15 participants out of 38 were classified as ASMR-experiencers. Mood, attention and personality characteristics were measured by the Profile of Mood States, the Flanker task and HEXACO. EEG, HR and EDA were recorded during the ASMR and control videos. Depressive feelings decreased after watching the ASMR video in individuals experiencing tingles relative to those not experiencing tingles. Furthermore, in all participants, irrespective of experiencing tingles, a decrease of HR during watching the ASMR video was found. In ASMR-experiencers scoring low on Conscientiousness EDA tended to increase and HR tended-relatively to the group not experiencing tingles-to decrease during watching the ASMR video. EEG recordings indicated that watching the ASMR video was associated with decreased alpha power in ASMR-sensitive participants and decreased theta as well as increased beta power in the whole group of participants. The observed ASMR-induced decrease of alpha and theta power and increase of beta power and (only in low conscientious participants) EDA may reflect that, apart from relaxation, ASMR is related to arousal and focused attention.
International Journal of Infectious Diseases, Dec 1, 2020
Take-down policy If you believe that this document breaches copyright please contact us providing... more Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
Objectives A decrease of both diffusion capacity (DLCO) and Quality of Life (QoL) was reported af... more Objectives A decrease of both diffusion capacity (DLCO) and Quality of Life (QoL) was reported after discharge in hospitalized COVID-19 pneumonia survivors. We studied three and 6 month outcomes in hospitalized and non-hospitalized patients. Methods COVID-19 pneumonia survivors ( n = 317) were categorized into non-hospitalized “moderate” cases ( n = 59), hospitalized “severe” cases ( n = 180) and ICU-admitted “critical” cases ( n = 39). We studied DLCO and QoL (Short Form SF-36 health survey) 3 and 6 months after discharge. Data were analyzed using (repeated measures) ANOVA, Kruskal-Wallis or Chi-square test ( p < .05). Results At 3 months DLCO was decreased in 44% of moderate-, 56% of severe- and 82% of critical cases ( p < .003). Mean DLCO in critical cases (64±14%) was lower compared to severe (76 ± 17%) and moderate (81±15%) cases ( p < .001). A total of 159/278 patients had a decreased DLCO (<80%), of whom the DLCO improved after 6 months in 45% (71/159). However th...
Due to the introduction of combination antiretroviral therapy (cART) 20 years ago, HIV infection ... more Due to the introduction of combination antiretroviral therapy (cART) 20 years ago, HIV infection in the Netherlands has changed from a fatal disease to a chronic condition with a near normalized life expectancy. The average age of HIV-positive patients continues to increase, as does the prevalence of non-HIV-related comorbidity. The number of new HIV diagnoses seems to be decreasing in the Netherlands, which is partly due to increased testing, earlier diagnosis, prompt cART initiation, and achievement of high levels of viral suppression, resulting in a reduced likelihood of onward transmission. In order to further curb the epidemic, it is important that as yet undiagnosed people living with HIV are identified as soon as possible. All practicing physicians in the Netherlands can contribute to this goal
BACKGROUND Successful treatment of chronic hepatitis C with direct-acting antiviral agents (DAAs)... more BACKGROUND Successful treatment of chronic hepatitis C with direct-acting antiviral agents (DAAs) is expected to lead to improvement in liver fibrosis in most of the patients. However, limited data are available on the improvement of advanced liver fibrosis and cirrhosis, measured by transient elastography after treatment. This study assessed the change in liver stiffness measurements after successful treatment with DAAs in patients with pre-treatment advanced fibrosis or cirrhosis. METHODS This observational retrospective cohort study included 514 mono-infected chronic hepatitis C patients, treated with all possible DAA-regimes in the Amsterdam region, the Netherlands. Liver stiffness was measured using FibroScan® at baseline and during follow-up. Cut-off values for staging liver fibrosis were ≥ 9.5 kPa for advanced fibrosis (F3) and ≥ 14.6 kPa for cirrhosis (F4). RESULTS Liver stiffness decreased significantly from a median of 15.6 kPa (IQR 11.4-25.4) to 9.4 kPa (IQR 6.2-17.0) in ...
Background. As a result of effective combination antiretroviral therapy (cART) and advanced suppo... more Background. As a result of effective combination antiretroviral therapy (cART) and advanced supportive healthcare, a growing number of human immunodeficiency virus (HIV)-infected children survive into adulthood. The period of transition to adult care is often associated with impaired adherence to treatment and discontinuity of care. We aimed to evaluate virological and social outcomes of HIV-infected adolescents and young adults (AYAs) before and after transition, and explore which factors are associated with virological failure. Methods. We included 59 HIV-infected AYAs from the Netherlands who had entered into pediatric care and transitioned from pediatric to adult healthcare. We used HIV RNA load and cART data from the Dutch Stichting HIV Monitoring database (1996-2014), and collected social and treatment data from patients' medical records from all Dutch pediatric HIV treatment centers and 14 Dutch adult treatment centers involved. We evaluated risk factors for virological failure (VF) in a logistic regression model adjusted for repeated measurements. Results. HIV VF occurred frequently during the study period (14%-36%). During the transition period (from 18 to 19 years of age) there was a significant increase in VF compared with the reference group of children aged 12-13 years (odds ratio, 4.26 [95% confidence interval, 1.12-16.28]; P = .03). Characteristics significantly associated with VF were low educational attainment and lack of autonomy regarding medication adherence at transition. Conclusions. HIV-infected AYAs are vulnerable to VF, especially during the transition period. Identification of HIV-infected adolescents at high risk for VF might help to improve treatment success in this group.
With a rising incidence of acute hepatitis C virus (HCV) infection in patients coinfected with th... more With a rising incidence of acute hepatitis C virus (HCV) infection in patients coinfected with the human immunodeficiency virus (HIV), there is a need for evidence-based treatment recommendations. There are no randomised trials available and published studies differ with respect to design, patient characteristics and number of patients included, making a comparison between studies difficult. However, it is critical to standardise treatment for this group of patients in order to optimise the outcome of therapy. The Dutch Society for HIV Physicians proposed to write recommendations for the treatment of acute HCV in HIV -coinfected patients. Combination therapy with pegylated interferon-alpha and ribavirin is the preferred regimen initiated preferably within 12 weeks after the diagnosis of acute HCV. A treatment duration of 24 weeks is recommended in case of a favourable virological response (either achievement of a rapid virological response or a > 2 log10 decrease plus undetectable HCV-RNA at week 12). In all other patients prolonging the duration of therapy to 48 weeks should be considered.
All human immunodeficiency virus type 1 (HIV-1)-infected patients who started to use indinavir (8... more All human immunodeficiency virus type 1 (HIV-1)-infected patients who started to use indinavir (800 mg three times a day) as part of their triple drug regimen were included in a study to determine the importance of low plasma concentrations of indinavir as a cause of virological treatment failure. The indinavir concentration and a number of patient characteristics at baseline were tested as risk factors for virological treatment failure (defined as a viral load above 200 copies/ml after 24 weeks of treatment) in univariate and multivariate analyses; 65 patients were included. Virological treatment failure occurred in 36.9% of the patients. Multivariate analysis showed that a low plasma concentration of indinavir (odds ratio 0.1), a high viral load at baseline (odds ratio 2.6) and pretreatment with another protease inhibitor (odds ratio 10.0) were independent factors related to virological treatment failure. Monitoring of indinavir plasma concentrations may be an important tool for the optimization of triple drug combination therapy.
Objectives: We investigated occurrence of and risk factors for severe COVID-19 outcomes in people... more Objectives: We investigated occurrence of and risk factors for severe COVID-19 outcomes in people with HIV (PWH) in the Netherlands. Design: An ongoing prospective nationwide HIV cohort study. Methods: COVID-19 diagnoses and outcomes with other relevant medical information were prospectively collected from electronic medical records in all HIV treatment centers in the Netherlands, from the start of the COVID-19 epidemic until December 31, 2021. Risk factors for COVID-19 related hospitalization and death were investigated using multivariable logistic regression, including demographics, HIV-related factors, and comorbidities. Results: The cohort comprises 21 289 adult PWH, median age 51.2 years, 82% male, 70% were of Western origin, 12.0% were of sub-Saharan African and 12.6% Latin American/Caribbean origin, 96.8% had HIV-RNA less than 200 copies/ml, median CD4+ cell count 690 (IQR 510–908) cells/μl. Primary SARS-CoV-2 infections were registered in 2301 individuals, of whom 157 (6.8%) required hospitalization and 27 (1.2%) ICU admission. Mortality rates were 13 and 0.4% among hospitalized and nonhospitalized individuals, respectively. Independent risk factors for severe outcomes (COVID-19-related hospitalization and death) were higher age, having multiple comorbidities, a CD4+ cell count less than 200 cells/μl, uncontrolled HIV replication, and prior AIDS diagnosis. Migrants from sub-Saharan Africa, Latin America, and the Caribbean were at an increased risk of severe outcomes independently of other risk factors. Conclusion: In our national cohort of PWH, risk of severe COVID-19 outcomes was increased in individuals with uncontrolled HIV replication, low CD4+ cell count, and prior AIDS diagnosis, independently of general risk factors such as higher age, comorbidity burden and migrants originating from non-Western countries.
Nature of double-stranded DNA binding activity in seropositive rheumatoid arthritis: formation of... more Nature of double-stranded DNA binding activity in seropositive rheumatoid arthritis: formation of low avidity DNA/rheumatoid factor/IgG/low density lipoprotein complexes.
An HIV-positive man from Somalia presented with severe malaise, weight loss, relapsing fever, lym... more An HIV-positive man from Somalia presented with severe malaise, weight loss, relapsing fever, lymphadenopathy and splenomegaly. An FDG-PET-scan-guided lymph node biopsy revealed the characteristic histological features of the plasma cell variant of Castleman&#39;s disease. A high HHV-8 viral load was detected in the serum (7980 copies/ml). Treatment with HAART, rituximab and vinblastine resulted in a full and rapid recovery and lowered HHV-8 viral load to undetectable levels.
Background: Recent publications have reported superior efficacy of telaprevir- or boceprevir-base... more Background: Recent publications have reported superior efficacy of telaprevir- or boceprevir-based triple therapy over conventional peginterferon-alfa/ribavirin therapy, albeit with varying rates of adverse events and treatment discontinuations in HIV/HCV coinfected patients. Therefore, the aim of this study is to describe the effectiveness of triple therapy in an HIV/HCV coinfection cohort in the Netherlands. Methods: HIV-infected patients with chronic HCV genotype 1 starting triple therapy including either boceprevir or telaprevir were enrolled, 26% had F3-F4 fibrosis. Data were assessed at Week 4, 8, 12, 24, 48 and SVR12 (i.e. absence of detectable plasma HCV RNA 12 weeks after completion of treatment). Failure was defined as discontinuation of treatment due to virological failure, adverse events or loss to follow-up. Results: A total of 53 HIV/HCV coinfected patients started peginterferon-alfa/ribavirin therapy with either boceprevir (n = 29) or telaprevir (n = 24). SVR12 was achieved in 19 (66%) of the boceprevir-treated and 15 (63%) of the telaprevir-treated patients. Both prior relapse and achievement of a rapid virological response were associated with a higher SVR12 rate. Non- response, breakthrough and relapse occurred in 4, 1 and 5 patients on boceprevir and 3, 2, 2 on telaprevir, respectively. One patient was lost to follow-up and one patient died due to progression of liver failure. Except for these two patients, no treatment discontinuations were observed due to adverse events. Conclusion: In HIV/HCV coinfected patients, boceprevir or telaprevir triple therapy was well tolerated and resulted in favourable SVR12 rates comparable with previous publications concerning HCV mono-infected patients.
Autonomous sensory meridian response (ASMR) is a warm tingling sensation which is often accompani... more Autonomous sensory meridian response (ASMR) is a warm tingling sensation which is often accompanied by feelings of calmness and relaxation. The present study examined the effects of an ASMR video on mood, attention, heart rate (HR), electrodermal activity (EDA), electroencephalography (EEG) and the interaction with personality factors in 38 young adults (33 females and 5 males). Based on the ASMR-checklist responses of having tingles during watching the ASMR video 15 participants out of 38 were classified as ASMR-experiencers. Mood, attention and personality characteristics were measured by the Profile of Mood States, the Flanker task and HEXACO. EEG, HR and EDA were recorded during the ASMR and control videos. Depressive feelings decreased after watching the ASMR video in individuals experiencing tingles relative to those not experiencing tingles. Furthermore, in all participants, irrespective of experiencing tingles, a decrease of HR during watching the ASMR video was found. In ASMR-experiencers scoring low on Conscientiousness EDA tended to increase and HR tended-relatively to the group not experiencing tingles-to decrease during watching the ASMR video. EEG recordings indicated that watching the ASMR video was associated with decreased alpha power in ASMR-sensitive participants and decreased theta as well as increased beta power in the whole group of participants. The observed ASMR-induced decrease of alpha and theta power and increase of beta power and (only in low conscientious participants) EDA may reflect that, apart from relaxation, ASMR is related to arousal and focused attention.
International Journal of Infectious Diseases, Dec 1, 2020
Take-down policy If you believe that this document breaches copyright please contact us providing... more Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
Objectives A decrease of both diffusion capacity (DLCO) and Quality of Life (QoL) was reported af... more Objectives A decrease of both diffusion capacity (DLCO) and Quality of Life (QoL) was reported after discharge in hospitalized COVID-19 pneumonia survivors. We studied three and 6 month outcomes in hospitalized and non-hospitalized patients. Methods COVID-19 pneumonia survivors ( n = 317) were categorized into non-hospitalized “moderate” cases ( n = 59), hospitalized “severe” cases ( n = 180) and ICU-admitted “critical” cases ( n = 39). We studied DLCO and QoL (Short Form SF-36 health survey) 3 and 6 months after discharge. Data were analyzed using (repeated measures) ANOVA, Kruskal-Wallis or Chi-square test ( p < .05). Results At 3 months DLCO was decreased in 44% of moderate-, 56% of severe- and 82% of critical cases ( p < .003). Mean DLCO in critical cases (64±14%) was lower compared to severe (76 ± 17%) and moderate (81±15%) cases ( p < .001). A total of 159/278 patients had a decreased DLCO (<80%), of whom the DLCO improved after 6 months in 45% (71/159). However th...
Due to the introduction of combination antiretroviral therapy (cART) 20 years ago, HIV infection ... more Due to the introduction of combination antiretroviral therapy (cART) 20 years ago, HIV infection in the Netherlands has changed from a fatal disease to a chronic condition with a near normalized life expectancy. The average age of HIV-positive patients continues to increase, as does the prevalence of non-HIV-related comorbidity. The number of new HIV diagnoses seems to be decreasing in the Netherlands, which is partly due to increased testing, earlier diagnosis, prompt cART initiation, and achievement of high levels of viral suppression, resulting in a reduced likelihood of onward transmission. In order to further curb the epidemic, it is important that as yet undiagnosed people living with HIV are identified as soon as possible. All practicing physicians in the Netherlands can contribute to this goal
BACKGROUND Successful treatment of chronic hepatitis C with direct-acting antiviral agents (DAAs)... more BACKGROUND Successful treatment of chronic hepatitis C with direct-acting antiviral agents (DAAs) is expected to lead to improvement in liver fibrosis in most of the patients. However, limited data are available on the improvement of advanced liver fibrosis and cirrhosis, measured by transient elastography after treatment. This study assessed the change in liver stiffness measurements after successful treatment with DAAs in patients with pre-treatment advanced fibrosis or cirrhosis. METHODS This observational retrospective cohort study included 514 mono-infected chronic hepatitis C patients, treated with all possible DAA-regimes in the Amsterdam region, the Netherlands. Liver stiffness was measured using FibroScan® at baseline and during follow-up. Cut-off values for staging liver fibrosis were ≥ 9.5 kPa for advanced fibrosis (F3) and ≥ 14.6 kPa for cirrhosis (F4). RESULTS Liver stiffness decreased significantly from a median of 15.6 kPa (IQR 11.4-25.4) to 9.4 kPa (IQR 6.2-17.0) in ...
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Papers by Kees Brinkman