Clemens Richter

Radboud University Nijmegen, Nijmegen, Provincie Gelderland, Netherlands

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Publications (35)120.53 Total impact

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    ABSTRACT: Background Adherence to combination antiretroviral therapy (ART) is a key predictor of the success of human immunodeficiency virus (HIV) treatment, and is potentially amenable to intervention. Insight into predictors or correlates of non-adherence to ART may help guide targets for the development of adherence-enhancing interventions. Our objective was to review evidence on predictors/correlates of adherence to ART, and to aggregate findings into quantitative estimates of their impact on adherence.Methods We searched PubMed for original English-language papers, published between 1996 and June 2014, and the reference lists of all relevant articles found. Studies reporting on predictors/correlates of adherence of adults prescribed ART for chronic HIV infection were included without restriction to adherence assessment method, study design or geographical location. Two researchers independently extracted the data from the same papers. Random effects models with inverse variance weights were used to aggregate findings into pooled effects estimates with 95% confidence intervals. The standardized mean difference (SMD) was used as the common effect size. The impact of study design features (adherence assessment method, study design, and the United Nations Human Development Index (HDI) of the country in which the study was set) was investigated using categorical mixed effects meta-regression.ResultsIn total, 207 studies were included. The following predictors/correlates were most strongly associated with adherence: adherence self-efficacy (SMD¿=¿0.603, P¿=¿0.001), current substance use (SMD¿=¿¿0.395, P¿=¿0.001), concerns about ART (SMD¿=¿¿0.388, P¿=¿0.001), beliefs about the necessity/utility of ART (SMD¿=¿0.357, P¿=¿0.001), trust/satisfaction with the HIV care provider (SMD¿=¿0.377, P¿=¿0.001), depressive symptoms (SMD¿=¿¿0.305, P¿=¿0.001), stigma about HIV (SMD¿=¿¿0.282, P¿=¿0.001), and social support (SMD¿=¿0.237, P¿=¿0.001). Smaller but significant associations were observed for the following being prescribed a protease inhibitor-containing regimen (SMD¿=¿¿0.196, P¿=¿0.001), daily dosing frequency (SMD¿=¿¿0.193, P¿=¿0.001), financial constraints (SMD ¿0.187, P¿=¿0.001) and pill burden (SMD¿=¿¿0.124, P¿=¿0.001). Higher trust/satisfaction with the HIV care provider, a lower daily dosing frequency, and fewer depressive symptoms were more strongly related with higher adherence in low and medium HDI countries than in high HDI countries.Conclusions These findings suggest that adherence-enhancing interventions should particularly target psychological factors such as self-efficacy and concerns/beliefs about the efficacy and safety of ART. Moreover, these findings suggest that simplification of regimens might have smaller but significant effects.
    BMC medicine. 08/2014; 12(1):142.
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    ABSTRACT: Yellow fever (YF) 17D vaccine is one of the most successful vaccines ever developed. Since 2001, 56 cases of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) have been published in the peer-reviewed literature. Here, we report a new case suspected for YEL-AVD in the Netherlands. Further research is needed to determine the true incidence of YEL-AVD and to clarify host and vaccine-associated factors in the pathogenesis of YEL-AVD. Because of the potential adverse events, healthcare providers should carefully consider vaccination only in people who are truly at risk for YF infection, especially in primary vaccine recipients.
    Journal of Travel Medicine 06/2014; · 1.68 Impact Factor
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    ABSTRACT: Renal dysfunction is highly prevalent in HIV-infected patients and may require dose adjustment of renally excreted antiretroviral drugs. The Modification of Diet in Renal Disease (MDRD)-4 formula is frequently used in daily practice to estimate patients' renal function. The aim of this systematic review was to assess the validity of the MDRD-4 formula in HIV-infected patients. A systematic search in Pubmed and EMBASE was done to identify studies which compared MDRD-4 with measured glomerular filtration rate (mGFR) in HIV-infected patients. Five studies were included, which provided data from 464 HIV-infected patients with mean mGFR ranging from 87 to 118 ml/min/1.73 m(2). In all studies, results from the MDRD-4 gave an underestimation of the mGFR. Mean bias ((MDRD-4) - mGFR) ranged from -6 to -11 ml/min/1.73 m(2) across studies. The accuracy expressed in terms of P 30 ranged from 64 to 89 %. The MDRD-4 formula is as valid in HIV-positive as in HIV-negative patients. Because the available studies comprised mainly HIV-infected patients with mildly impaired to good renal function (GFR ≥ 60 ml/min/1.73 m(2)), more research is needed to validate the MDRD-4 formula in HIV-infected patients with moderate to severe renal impairment.
    Journal of nephrology 02/2014; 27(1):11-8. · 2.02 Impact Factor
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    ABSTRACT: Single drug class regimens with nucleotide reverse transcriptase inhibitors (NRTIs) are generally not recommended as initial therapy, because they were inferior compared to therapy with 2 NRTIs plus efavirenz. However triple-NRTI combinations can be useful in specific circumstances such as in tuberculosis co-infection, pregnancy, or dyslipidemia. Here, we review the potential of such combinations to maintain viral suppression after induction of suppression by standard combination antiretroviral therapy (cART), and to evaluate the trade-off of NRTI-only regimens for metabolic control. We conducted a systematic search of the literature in two databases from 1 January, 1998, up to 1 March, 2013: Medline through the search engine PubMed, and Embase. A total of 11 randomized controlled trials (RCTs) with 2105 patients, and 3 observational studies with 2639 patients were included. Studies including patients with mono- or dual-NRTI treatment before start of effective cART, showed a tendency to higher failure rate due to resistance based on archived viral mutations. In studies with ART-naive subjects before start of cART, triple-NRTI combination showed virologic activity comparable to two NRTIs plus a protease inhibitor, or a nonnucleoside reverse transcriptase inhibitor in all RCTs, but not in one cohort study. Switching improved serum lipids significantly. Of the studied triple-NRTI combinations only abacavir/lamivudine/zidovudine was sufficiently potent. Triple-NRTI maintenance after successful induction with two-class cART appeared successful in treatment-naive subjects, and remains a useful option in specific circumstances, especially when other drugs are not available or drug interactions are an issue.
    Antiviral therapy 01/2014; · 3.07 Impact Factor
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    ABSTRACT: The aim of the study was to investigate the effect of a simplified regimen, in terms of reducing pill burden, dietary requirements and possible adverse effects, on patients' adherence, treatment satisfaction and quality of life (QoL). Antiretroviral-naïve patients who achieved a viral load < 50 HIV-1 RNA copies/ml after induction therapy with twice-daily (bid) lopinavir/ritonavir (LPV/r) and fixed-dose zidovudine (ZDV)/lamivudine (3TC) (CBV) were randomly assigned to continue CBV/LPV/r or switch to fixed-dose ZDV/3TC/abacavir (TZV). Patients completed standardized questionnaires on adherence, treatment satisfaction and QoL at randomization (between weeks 12 and 24) and at weeks 48, 72 and 96. Patients on CBV/LPV/r were more likely to have skipped medicines in the last week (P = 0.035) and during the preceding weekend (P = 0.027) than patients on TZV. Patients on CBV/LPV/r were significantly less satisfied with the convenience of their treatment (P = 0.004) and tended to be less satisfied with the side effects of their treatment (P = 0.091) and continuation of their present treatment (P = 0.056) than patients on TZV. Patients on CBV/LPV/r reported significantly lower levels of role functioning (P = 0.013) than patients on TZV. In this randomized controlled trial, simplification of therapy to fixed-dose TZV among patients with suppressed HIV RNA was perceived to be more convenient, and resulted in improved adherence and better role functioning, than continuing treatment with CBV/LPV/r.
    HIV Medicine 11/2013; · 3.16 Impact Factor
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    ABSTRACT: OBJECTIVES: To evaluate the use of raltegravir with unboosted atazanavir in combination with one nucleoside reverse transcriptase inhibitor (NRTI) (lamivudine or emtricitabine) as a potentially well-tolerated once-daily (qd) maintenance regimen. METHODS: We compared the pharmacokinetics of raltegravir 400 mg twice daily (bid) with raltegravir 800 mg qd in HIV-infected patients (n = 17) on unboosted atazanavir (600 mg qd) in combination with lamivudine or emtricitabine. RESULTS: The area under the plasma concentration vs. time curve for a dose interval t (AUC0 -t ) of 800 mg qd divided by 2 was not significantly different from the AUC0 -t of 400 mg bid (P = 0.664) but the minimum concentration (Cmin ) was 72% lower with the qd regimen (P = 0.002). The regimen was well tolerated and the viral load remained undetectable in all patients during the 6 weeks of the study follow-up. CONCLUSIONS: A qd regimen of raltegravir 800 mg, atazanavir 600 mg and lamivudine or emtricitabine resulted in favourable pharmacokinetic profiles and good short-term safety and efficacy data. Larger phase IIb studies are needed to explore this novel regimen.
    HIV Medicine 03/2013; · 3.16 Impact Factor
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    ABSTRACT: Background. The kinetics of hepatitis B surface antigen (HBsAg) are predictive in HBV-infected patients treated with pegylated interferon. Knowledge about the value of HBsAg levels in patients coinfected with HBV and human immunodeficiency virus (HIV) is lacking. Methods. We quantified serum HBsAg in a Dutch multicenter cohort of 104 patients coinfected with HIV and HBV who were treated with tenofovir disoproxil fumarate (TDF) as part of highly active antiretroviral therapy. The median duration of therapy was 57 months (interquartile range, 34-72 months). Results. Hepatitis B e antigen (HBeAg)-positive patients achieved a decline of 2.2 log IU/mL in HBsAg, whereas HBeAg-negative patients only achieved a decline of 0.6 log IU/mL during 6 years of TDF therapy. Declines in HBsAg at months 6 and 12 correlated with CD4 cell count for HBeAg-positive patients. Five HBeAg-positive patients (8%) and 3 HBeAg-negative patients (8%) cleared HBsAg. HBeAg-negative patients who cleared HBsAg had lower baseline HBsAg as compared to patients who remained HBsAg positive. The majority of patients who cleared HBsAg achieved this end point within the first year. In HBeAg-positive patients, decline in HBsAg at month 6 was predictive of achieving HBsAg seroclearance. Conclusions. Receipt of TDF therapy by HIV/HBV-coinfected patients for up to 6 years led to a significant decrease in HBsAg in the HBeAg-positive population. HBsAg kinetics early during treatment were predictive of HBsAg seroclearance and correlated with an increased CD4 cell count, underlining the importance of immune restoration in HBV clearance.
    The Journal of Infectious Diseases 07/2012; 206(6):974-80. · 5.85 Impact Factor
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    ABSTRACT: Several studies reported an association between immunodeficiency and non-AIDS-defining diseases. We investigated whether nonstructured treatment interruptions and episodes of viremia during suppressive combination antiretroviral therapy were independently associated with non-AIDS diseases. Six thousand four hundred forty patients with viral suppression (<50 copies/mL) within 48 weeks of starting combination antiretroviral therapy were selected from the Dutch ATHENA cohort. In proportional hazards models, associations between treatment interruptions, viral suppression, low-level (50-400 copies/mL), and high-level viremia (>400), and serious non-AIDS diseases (cardiovascular disease, chronic renal failure, liver fibrosis/cirrhosis) were investigated by including time-updated cumulative exposure to either viremia and interruptions or HIV RNA >400 copies per milliliter. During 24,603 person-years, of which 88.5% occurred during viral suppression, 102 patients developed cardiovascular disease, 54 chronic renal failure, and 70 liver fibrosis/cirrhosis. Overall incidence of non-AIDS diseases ranged from 1.41 (95% confidence interval: 0.73 to 2.46) per 100 person-years for CD4 counts <200 to 0.71 (0.49 to 1.00) for CD4 ≥500 cells per cubic millimeter. Compared with viral suppression, high-level viremia was associated only with cardiovascular disease (relative hazard: 1.37, 1.04 to 1.81 per year longer), whereas interruptions and low-level viremia were not associated with non-AIDS diseases. Relative hazards for cumulative exposure to RNA >400 versus ≤400 copies per milliliter were 1.32 (1.01 to 1.73) for cardiovascular disease, 1.13 (0.66 to 1.92) for renal failure, and 0.86 (0.51 to 1.44) for fibrosis/cirrhosis. Lower CD4 counts are associated with increased risk of non-AIDS diseases, whereas high-level viremia seems to be independently associated with cardiovascular disease. However, the power to detect associations with viremia or interruptions may have been limited as most events occurred during viral suppression.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2012; 60(3):265-72. · 4.65 Impact Factor
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    ABSTRACT: Hepatitis C virus infection is a serious health threat in today's society. Improved identification strategies have increased the number of patients undergoing the expensive treatment with ribavirin and peg-interferon, inducing a substantial economic burden. In a retrospective cohort study in three treatment centres in the Netherlands, files of patients treated between 2001 and 2010 were systematically searched for all cost-inducing treatment details. Costs of treatment resulting in sustained viral response (SVR), relapse, non-response and the costs per cured patient were specified for genotype and treatment setting. Determinants of costs were determined by multivariate linear regression. The mean 'real-life' treatment costs excluding side effects for genotype 1/4 and genotype 2/3 were approximately € 12,900 and € 9900 for all patients, € 15,500 and € 10,100 for treatment resulting in SVR and € 16,800 and € 12,100 for relapse, respectively. Costs per cured patient were € 28,500 and € 15,400 respectively. The costs of non-response were approximately € 8000 for all genotypes. Costs of side effects can be high and are mainly caused by incidental treatment for neutropenia. Medication is the main component of treatment costs. Treatment costs were higher in the academic setting due to longer duration and higher costs of side effects. Regression analysis confirms duration as the main determinant of treatment costs excluding side effects. The 'real-life' costs of treatment are mainly determined by treatment duration, medication costs and costs of side effects. The costs of unsuccessful treatment are considerable as are the costs of side effects. Therefore, future research should aim at increasing SVR rates, reducing treatment duration and preventing side effects.
    The Netherlands Journal of Medicine 04/2012; 70(3):145-53. · 2.38 Impact Factor
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    ABSTRACT: Background: Adherence to treatment is the key to the success of combination antiretroviral therapy (cART) for HIV infection. It is generally assumed that simplification of cART will lead to better adherence, higher treatment satisfaction, and quality of life (QoL), but randomized studies demonstrating such advantages of simplified regimens are scarce. Methods: Antiretroviral-naïve patients who achieved viral load <50 c/ml in two consecutive samples between 12-24 weeks after commencing induction therapy with bid lopinavir/ritonavir (LPV/r) and fixed-dose combination AZT/3TC (Combivir(®)) were randomly assigned to either continue LPV/r/Combivir(®) or switch to simplified therapy with bid fixed-dose AZT/3TC/abacavir (Trizivir(®)). Both arms yielded similar antiviral efficacy after 48 weeks as reported previously [1]. Patients completed standardized questionnaires on adherence (Simplified Medication Adherence Questionnaire (SMAQ)), treatment satisfaction (HIVTSQ) and QoL (MOS-HIV) at randomization and at weeks 48, 72 and 96. Adherence data were analyzed using generalized estimating equations, and satisfaction and QoL using mixed linear models. Results: Patients in the Trizivir(®)-group (n=30) tended to skip fewer doses both during the preceding 7 days (p=0.055) and during the preceding weekend (p=0.09) than patients in the LPV/r-group (n=20). Moreover, patients in the Trizivir(®)-group found their regimen significantly more convenient (p=0.022) than patients in the LPV/r-group. However, patients in the LPV/r-group reported a better QoL than patients in the Trizivir(®)-group in the domains measuring cognitive functioning (p=0.003), energy/fatigue (p=0.046) and social functioning (p=0.074). Conclusions: In this randomized trial simplification of therapy to fixed-dose Trizivir(®) was perceived to be more convenient, and tended to result in improved adherence, but at the expense of a lower level of QoL. Our findings suggest that the choice for simplified regimens should be individualized and may involve a trade-off between convenience and QoL.
    Journal of the International AIDS Society 01/2012; 15(6):18091. · 3.94 Impact Factor
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    ABSTRACT: Therapeutic drug monitoring (TDM) is recommended in several international HIV treatment guidelines. The adherence of clinicians to these recommendations is unknown. The authors evaluated the adherence to the Dutch TDM guideline of 2005. From the ATHENA cohort study, three scenarios were selected for which the guideline recommended TDM: 1) start of a combination of lopinavir/ritonavir + efavirenz or nevirapine (drug-drug interaction); 2) start of efavirenz (routine TDM); and 3) use of nelfinavir during pregnancy. For each scenario, we determined the proportion of patients for whom TDM was performed. Multivariable logistic regression modeling was used to identify determinants for the use of TDM. The adherence to the TDM guideline was 46.7% in patients who started lopinavir/ritonavir plus efavirenz or nevirapine; 9.5% for patients who started efavirenz; and 58.5% for patients who used nelfinavir during pregnancy. Patients treated in clinics that had a TDM assay available locally and patients treated in academic clinics were more likely to receive TDM. A higher baseline HIV viral load was another significant predictor for the performing TDM. The adherence of clinicians to the Dutch TDM guidelines varied from low to moderate for the three investigated TDM scenarios. This study identifies several determinants for the use of TDM, which may be useful information for those responsible for generating TDM guidelines.
    Therapeutic drug monitoring 02/2011; 33(1):32-9. · 2.43 Impact Factor
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    ABSTRACT: Ribavirin is an essential component in the treatment of chronic hepatitis C (HCV) infection. Although ribavirin dose is weight-based, data in the literature suggest large between-patient variability in plasma ribavirin concentrations. Recent studies indicate that higher ribavirin exposure results in higher sustained viral response rates. Monitoring ribavirin concentration is suggested in the literature, but it is unclear at what time point during treatment plasma ribavirin concentrations should be monitored. To investigate the association between early plasma ribavirin concentrations and ribavirin dosing with steady-state (Css) concentration and the between- and within-patient variability in plasma ribavirin concentration in clinical practice. We performed a prospective observational cohort study in patients with HCV who received pegylated interferon in combination with oral weight-based ribavirin (12-15 mg/kg) twice daily. Trough plasma ribavirin concentrations at Weeks 1, 2, 4, 8, 12, 16, 20, and 24 were studied using a validated high-performance liquid chromatography assay. In total, 53 patients (37 male, 16 female) with a mean age of 51 years (range, 26-68 years) were included and 209 samples were collected. There was a significant correlation between Week 2 as well as Week 4 and plasma ribavirin Css (r = 0.589 and r = 0.714, P < 0.05, respectively). Ribavirin Css was reached at Week 8 of HCV treatment. There was no correlation between dose in mg/kg and Css (r = 0.181, P = 0.263). The between- and within-patient coefficients of variation of plasma ribavirin concentrations at Week 8 and beyond were 43% and 13%, respectively. In HCV-infected patients, ribavirin steady-state concentrations can be predicted by measurement of concentrations made early after the start of therapy.
    Therapeutic drug monitoring 02/2011; 33(1):40-4. · 2.43 Impact Factor
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    ABSTRACT: 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.
    The Netherlands Journal of Medicine 01/2011; 69(1):43-9. · 2.38 Impact Factor
  • European Journal of Pharmacology - EUR J PHARMACOL. 01/2011; 668.
  • European Journal of Pharmacology - EUR J PHARMACOL. 01/2011; 668.
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    ABSTRACT: We investigated the long-term efficacy and renal safety of tenofovir disoproxil fumarate (TDF), administered to patients co-infected with human immunodeficiency virus and hepatitis B virus (HBV) as part of an antiretroviral therapy. We performed a multicenter, prospective cohort study of 102 patients co-infected with human immunodeficiency virus and HBV who were treated with TDF. At baseline, 80% of patients had a detectable viral load (HBV DNA >20 IU/mL). Among patients positive for hepatitis B e antigen (HBeAg) (n = 67), 92% had a virologic response (HBV DNA <20 IU/mL) after 5 years of treatment. There was no difference between patients with or without lamivudine resistance at baseline (P = .39). Loss rates of HBeAg and hepatitis B s antigen (HBsAg) were 46% and 12%, respectively. Among HBeAg-negative patients (n = 15), 100% had a virologic response after 4 years of treatment and 2 (13%) lost HBsAg. Twenty subjects (20%, all HBeAg-negative) had undetectable HBV DNA at baseline; during a median follow-up period of 52 months (interquartile range, 41-63 mo), 19 (95%) maintained a virologic response and 2 (10%) lost HBsAg. Overall, one patient acquired a combination of resistance mutations for anti-HBV drugs and experienced a virologic breakthrough. Three (3%) patients discontinued TDF because of increased serum creatinine levels. The estimated decrease in renal function after 5 years of TDF therapy was 9.8 mL/min/1.73 m(2), which was most pronounced shortly after TDF therapy was initiated. TDF, administered as part of antiretroviral therapy, is a potent anti-HBV agent with a good resistance profile throughout 5 years of therapy. Only small nonprogressive decreases in renal function were observed.
    Gastroenterology 12/2010; 139(6):1934-41. · 12.82 Impact Factor
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    ABSTRACT: Maintenance with a triple nucleoside reverse transcriptase Inhibitor (NRTI) regimen after successful induction with a dual NRTI/protease inhibitor (PI) combination may be advantageous, because of low pill burden, favorable lipids, and less drug interactions. This strategy to become free of PI-related problems without losing viral efficacy has not been formally tested. We performed a randomized, open-label, multicenter, 96-week comparative study in antiretroviral therapy (ART)-naïve patients with CD4 <or=350 cells/mm(3) and HIV-1 RNA concentrations (viral load [VL]) greater than 30,000 copies per milliliter. Patients were randomized after reaching VL less than 50 copies per milliliter on two consecutive occasions between 12 and 24 weeks after start of zidovudine/lamuvidine and lopinavir/ritonavir combination. Eligible subjects switched to abacavir/lamivudine/zidovudine (TZV) or continued the PI-containing regimen. Here we present the 48-week data with virologic success rate (failure: VL > 50 copies per milliliter). Two hundred seven patients had similar baseline (BL) characteristics: median CD4 180 cells/mm(3), median VL 5.19 log(10) copies per milliliter. One hundred twenty subjects (58%) met randomization criteria. Baseline VL differed significantly between dropouts and randomized subjects (median 5.41 versus 5.06 log(10) copies per milliliter, p = 0.017), as did CD4 cells (median 160 and 200 cells/mm(3), p = 0.044). Sixty-one subjects received TZV and 59 subjects continued NRTIs/PI. At week 48, 2 patients in the TZV group and 5 in the PI group did not have a sustained virologic suppression (log rank test; p = 0.379). CD4 counts increased significantly in both arms. In ART-naïve patients, TZV maintenance had similar antiviral efficacy compared to continued standard ART at 48 weeks after baseline. Patients on successful standard ART can be safely switched to a NRTI-only regimen, at least for the tested time period.
    AIDS patient care and STDs 06/2010; 24(6):361-6. · 2.68 Impact Factor
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    ABSTRACT: HIV-infected travellers frequently use atovaquone/proguanil as malaria prophylaxis. We compared atovaquone/proguanil pharmacokinetics between healthy volunteers and HIV-infected patients taking efavirenz, lopinavir/ritonavir or atazanavir/ritonavir. The geometric mean ratio (95% confidence interval) area under the curve (AUC)0-->t for atovaquone relative to the healthy volunteers was 0.25 (0.16-0.38), 0.26 (0.17-0.41) and 0.54 (0.35-0.83) for patients on efavirenz, lopinavir/ritonavir and atazanavir/ritonavir, respectively. Proguanil plasma concentrations were also significantly lower (38-43%). Physicians should be alert for atovaquone/proguanil prophylaxis failures in patients taking efavirenz, lopinavir/ritonavir or atazanavir/ritonavir.
    AIDS (London, England) 03/2010; 24(8):1223-6. · 4.91 Impact Factor
  • Clinical Nutrition Supplements 01/2010; 5(2):149-149.
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    ABSTRACT: To establish whether efavirenz dose reduction in patients with high plasma concentrations prevents toxicity-induced efavirenz discontinuations. HIV-infected patients with a high efavirenz plasma concentration (>or=4.0 mg/L) while using efavirenz 600 mg once daily as part of their highly active antiretroviral therapy regimen were selected from the AIDS Therapy Evaluation in The Netherlands cohort study. These patients were classified into 2 groups. The reduced-dose group contained all patients who underwent dose reduction after the high plasma concentration measurement; the standard-dose group consisted of patients who had no dose reduction. Kaplan-Meier and Cox proportional hazards analysis were used to assess the impact of dose reduction on toxicity-induced efavirenz discontinuations. One hundred eighty patients with high plasma efavirenz levels were included, 47 of them subsequently had their efavirenz dose reduced from 600 mg to 400 mg once-daily, which resulted in a 41% decrease in the median efavirenz plasma concentration. At week 48, the Kaplan-Meier estimated cumulative incidence of toxicity-induced efavirenz discontinuations was 11.5% in patients who continued the standard dose versus 2.3% in patients who had a dose reduction; P = 0.066 (log-rank test). Dose reduction was not associated with loss of virological suppression. Dose reduction may prevent toxicity-induced discontinuations in patients with high efavirenz plasma concentrations, whereas not compromising virological efficacy.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 07/2009; 52(2):240-5. · 4.65 Impact Factor

Publication Stats

434 Citations
120.53 Total Impact Points


  • 2011
    • Radboud University Nijmegen
      • Department of Gastroenterology and Hepatology
      Nijmegen, Provincie Gelderland, Netherlands
  • 2010–2011
    • Radboud University Medical Centre (Radboudumc)
      • Department of Human Genetics
      Nymegen, Gelderland, Netherlands
    • University of Groningen
      • Department of Internal Medicine
      Groningen, Province of Groningen, Netherlands
  • 2002–2011
    • Rijnstate Hospital
      Arnheim, Gelderland, Netherlands