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1. Virological responses to lamivudine or emtricitabine when combined with tenofovir and a protease inhibitor in treatment-naïve HIV-1-infected patients in the Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort

Author

Rokx, C., Gras, L., van de Vijver, D. A M C, Verbon, A., Rijnders, B. J A, Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., van der Meer, J. T M, Wit, F. W M N, Godfried, M. H., Reiss, P., van der Poll, T., Nellen, F. J B, Lange, J. M A, Geerlings, S. E., van Vugt, M., Pajkrt, D., Bos, J. C., van der Valk, M, Wiersinga, W. J., Goorhuis, A., Hovius, J. W R, Lowe, S., Oude Lashof, A., Posthouwer, D., Pronk, M. J H, Ammerlaan, H. S M, van der Ende, M. E., de Vries-Sluijs, T. E M S, Schurink, C. A M, Nouwen, J. L., van Gorp, E. C M, van der Feltz, M., Driessen, G. J A, van Rossum, A. M C, Branger, J., Schippers, E. F., van Nieuwkoop, C., van Elzakker, E. P., Groeneveld, P. H P, Bouwhuis, J. W., Soetekouw, R., ten Kate, R. W., Kroon, F. P., van Dissel, J. T., Arend, S. M., de Boer, M. G J, Jolink, H., Vollaard, A. M., Bauer, M. P., den Hollander, J. G., Pogany, K., van Twillert, G., Kortmann, W., Cohen Stuart, J. W T, Diederen, B. M W, Leyten, E. M S, Gelinck, L. B S, Kootstra, G. J., Delsing, C. E., Brinkman, K., Blok, W. L., Frissen, P. H J, Schouten, W. E M, van den Berk, G. E L, van Kasteren, M. E E, Brouwer, A.E., Veenstra, J., Lettinga, K. D., Mulder, J. W., Vrouenraets, S. M E, Lauw, F. N., van Eeden, A., Verhagen, D. W M, Sprenger, H. G., Scholvinck, E. H., van Assen, S., Bierman, W. F W, Wilting, K. R., Stienstra, Y., Koopmans, P. P., Keuter, M., van der Ven, A. J A M, ter Hofstede, H. J M, Dofferhoff, A. S M, Warris, A., van Crevel, R., Hoepelman, A. I M, Mudrikova, T., Schneider, M. M E, Ellerbroek, P. M., Oosterheert, J. J., Arends, J. E., Wassenberg, M. W M, Barth, R. E., van Agtmael, M. A., Perenboom, R. M., Claessen, F. A P, Bomers, M., Peters, E.J.G., Geelen, S. P M, Wolfs, T. F W, Bont, L. J., Richter, C., van der Berg, J. P., Gisolf, E. H., van den Berge, M., Stegeman, A., van Vonderen, M. G A, van Houte, D. P F, Weijer, S., el Moussaoui, R., Winkel, C., Muskiet, F., Durand, A., Voigt, R., Rokx, C., Gras, L., van de Vijver, D. A M C, Verbon, A., Rijnders, B. J A, Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., van der Meer, J. T M, Wit, F. W M N, Godfried, M. H., Reiss, P., van der Poll, T., Nellen, F. J B, Lange, J. M A, Geerlings, S. E., van Vugt, M., Pajkrt, D., Bos, J. C., van der Valk, M, Wiersinga, W. J., Goorhuis, A., Hovius, J. W R, Lowe, S., Oude Lashof, A., Posthouwer, D., Pronk, M. J H, Ammerlaan, H. S M, van der Ende, M. E., de Vries-Sluijs, T. E M S, Schurink, C. A M, Nouwen, J. L., van Gorp, E. C M, van der Feltz, M., Driessen, G. J A, van Rossum, A. M C, Branger, J., Schippers, E. F., van Nieuwkoop, C., van Elzakker, E. P., Groeneveld, P. H P, Bouwhuis, J. W., Soetekouw, R., ten Kate, R. W., Kroon, F. P., van Dissel, J. T., Arend, S. M., de Boer, M. G J, Jolink, H., Vollaard, A. M., Bauer, M. P., den Hollander, J. G., Pogany, K., van Twillert, G., Kortmann, W., Cohen Stuart, J. W T, Diederen, B. M W, Leyten, E. M S, Gelinck, L. B S, Kootstra, G. J., Delsing, C. E., Brinkman, K., Blok, W. L., Frissen, P. H J, Schouten, W. E M, van den Berk, G. E L, van Kasteren, M. E E, Brouwer, A.E., Veenstra, J., Lettinga, K. D., Mulder, J. W., Vrouenraets, S. M E, Lauw, F. N., van Eeden, A., Verhagen, D. W M, Sprenger, H. G., Scholvinck, E. H., van Assen, S., Bierman, W. F W, Wilting, K. R., Stienstra, Y., Koopmans, P. P., Keuter, M., van der Ven, A. J A M, ter Hofstede, H. J M, Dofferhoff, A. S M, Warris, A., van Crevel, R., Hoepelman, A. I M, Mudrikova, T., Schneider, M. M E, Ellerbroek, P. M., Oosterheert, J. J., Arends, J. E., Wassenberg, M. W M, Barth, R. E., van Agtmael, M. A., Perenboom, R. M., Claessen, F. A P, Bomers, M., Peters, E.J.G., Geelen, S. P M, Wolfs, T. F W, Bont, L. J., Richter, C., van der Berg, J. P., Gisolf, E. H., van den Berge, M., Stegeman, A., van Vonderen, M. G A, van Houte, D. P F, Weijer, S., el Moussaoui, R., Winkel, C., Muskiet, F., Durand, A., and Voigt, R.

Published
2016

2. Virological responses to lamivudine or emtricitabine when combined with tenofovir and a protease inhibitor in treatment-naïve HIV-1-infected patients in the Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort

Author

Epidemiology & Health Economics, MMB, MS Infectieziekten, Circulatory Health, Infection & Immunity, MS Interne Geneeskunde, Directie Raad van Bestuur, MMB Medische Staf, Infectieziekten patientenzorg, Other research (not in main researchprogram), Onderwijssecretariaat, Divisieleiding O&O, Child Health, CTI Bont, Infectieziekten onderzoek1 (Bont), Rokx, C., Gras, L., van de Vijver, D. A M C, Verbon, A., Rijnders, B. J A, Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., van der Meer, J. T M, Wit, F. W M N, Godfried, M. H., Reiss, P., van der Poll, T., Nellen, F. J B, Lange, J. M A, Geerlings, S. E., van Vugt, M., Pajkrt, D., Bos, J. C., van der Valk, M, Wiersinga, W. J., Goorhuis, A., Hovius, J. W R, Lowe, S., Oude Lashof, A., Posthouwer, D., Pronk, M. J H, Ammerlaan, H. S M, van der Ende, M. E., de Vries-Sluijs, T. E M S, Schurink, C. A M, Nouwen, J. L., van Gorp, E. C M, van der Feltz, M., Driessen, G. J A, van Rossum, A. M C, Branger, J., Schippers, E. F., van Nieuwkoop, C., van Elzakker, E. P., Groeneveld, P. H P, Bouwhuis, J. W., Soetekouw, R., ten Kate, R. W., Kroon, F. P., van Dissel, J. T., Arend, S. M., de Boer, M. G J, Jolink, H., Vollaard, A. M., Bauer, M. P., den Hollander, J. G., Pogany, K., van Twillert, G., Kortmann, W., Cohen Stuart, J. W T, Diederen, B. M W, Leyten, E. M S, Gelinck, L. B S, Kootstra, G. J., Delsing, C. E., Brinkman, K., Blok, W. L., Frissen, P. H J, Schouten, W. E M, van den Berk, G. E L, van Kasteren, M. E E, Brouwer, A.E., Veenstra, J., Lettinga, K. D., Mulder, J. W., Vrouenraets, S. M E, Lauw, F. N., van Eeden, A., Verhagen, D. W M, Sprenger, H. G., Scholvinck, E. H., van Assen, S., Bierman, W. F W, Wilting, K. R., Stienstra, Y., Koopmans, P. P., Keuter, M., van der Ven, A. J A M, ter Hofstede, H. J M, Dofferhoff, A. S M, Warris, A., van Crevel, R., Hoepelman, A. I M, Mudrikova, T., Schneider, M. M E, Ellerbroek, P. M., Oosterheert, J. J., Arends, J. E., Wassenberg, M. W M, Barth, R. E., van Agtmael, M. A., Perenboom, R. M., Claessen, F. A P, Bomers, M., Peters, E.J.G., Geelen, S. P M, Wolfs, T. F W, Bont, L. J., Richter, C., van der Berg, J. P., Gisolf, E. H., van den Berge, M., Stegeman, A., van Vonderen, M. G A, van Houte, D. P F, Weijer, S., el Moussaoui, R., Winkel, C., Muskiet, F., Durand, A., Voigt, R., Epidemiology & Health Economics, MMB, MS Infectieziekten, Circulatory Health, Infection & Immunity, MS Interne Geneeskunde, Directie Raad van Bestuur, MMB Medische Staf, Infectieziekten patientenzorg, Other research (not in main researchprogram), Onderwijssecretariaat, Divisieleiding O&O, Child Health, CTI Bont, Infectieziekten onderzoek1 (Bont), Rokx, C., Gras, L., van de Vijver, D. A M C, Verbon, A., Rijnders, B. J A, Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., van der Meer, J. T M, Wit, F. W M N, Godfried, M. H., Reiss, P., van der Poll, T., Nellen, F. J B, Lange, J. M A, Geerlings, S. E., van Vugt, M., Pajkrt, D., Bos, J. C., van der Valk, M, Wiersinga, W. J., Goorhuis, A., Hovius, J. W R, Lowe, S., Oude Lashof, A., Posthouwer, D., Pronk, M. J H, Ammerlaan, H. S M, van der Ende, M. E., de Vries-Sluijs, T. E M S, Schurink, C. A M, Nouwen, J. L., van Gorp, E. C M, van der Feltz, M., Driessen, G. J A, van Rossum, A. M C, Branger, J., Schippers, E. F., van Nieuwkoop, C., van Elzakker, E. P., Groeneveld, P. H P, Bouwhuis, J. W., Soetekouw, R., ten Kate, R. W., Kroon, F. P., van Dissel, J. T., Arend, S. M., de Boer, M. G J, Jolink, H., Vollaard, A. M., Bauer, M. P., den Hollander, J. G., Pogany, K., van Twillert, G., Kortmann, W., Cohen Stuart, J. W T, Diederen, B. M W, Leyten, E. M S, Gelinck, L. B S, Kootstra, G. J., Delsing, C. E., Brinkman, K., Blok, W. L., Frissen, P. H J, Schouten, W. E M, van den Berk, G. E L, van Kasteren, M. E E, Brouwer, A.E., Veenstra, J., Lettinga, K. D., Mulder, J. W., Vrouenraets, S. M E, Lauw, F. N., van Eeden, A., Verhagen, D. W M, Sprenger, H. G., Scholvinck, E. H., van Assen, S., Bierman, W. F W, Wilting, K. R., Stienstra, Y., Koopmans, P. P., Keuter, M., van der Ven, A. J A M, ter Hofstede, H. J M, Dofferhoff, A. S M, Warris, A., van Crevel, R., Hoepelman, A. I M, Mudrikova, T., Schneider, M. M E, Ellerbroek, P. M., Oosterheert, J. J., Arends, J. E., Wassenberg, M. W M, Barth, R. E., van Agtmael, M. A., Perenboom, R. M., Claessen, F. A P, Bomers, M., Peters, E.J.G., Geelen, S. P M, Wolfs, T. F W, Bont, L. J., Richter, C., van der Berg, J. P., Gisolf, E. H., van den Berge, M., Stegeman, A., van Vonderen, M. G A, van Houte, D. P F, Weijer, S., el Moussaoui, R., Winkel, C., Muskiet, F., Durand, A., and Voigt, R.

Published
2016

3. A randomized controlled trial of single-class maintenance therapy with abacavir/lamivudine/zidovudine after standard triple antiretroviral induction therapy : Final 96-week results from the FREE study

Author

Sprenger, H. G., Langebeek, N., Mulder, P. G H, ten Napel, C. H H, Vriesendorp, R., Hoepelman, A. I M, Legrand, J. C., Koopmans, P. P., Bravenboer, B., ten Kate, R. W., Groeneveld, P. H P, Bierman, W. F W, van der Werf, T. S., Gisolf, E. H., Richter, C., Sprenger, H. G., Langebeek, N., Mulder, P. G H, ten Napel, C. H H, Vriesendorp, R., Hoepelman, A. I M, Legrand, J. C., Koopmans, P. P., Bravenboer, B., ten Kate, R. W., Groeneveld, P. H P, Bierman, W. F W, van der Werf, T. S., Gisolf, E. H., and Richter, C.

Published
2015

4. A randomized controlled trial of single-class maintenance therapy with abacavir/lamivudine/zidovudine after standard triple antiretroviral induction therapy: Final 96-week results from the FREE study

Author

MS Infectieziekten, Infection & Immunity, Sprenger, H. G., Langebeek, N., Mulder, P. G H, ten Napel, C. H H, Vriesendorp, R., Hoepelman, A. I M, Legrand, J. C., Koopmans, P. P., Bravenboer, B., ten Kate, R. W., Groeneveld, P. H P, Bierman, W. F W, van der Werf, T. S., Gisolf, E. H., Richter, C., MS Infectieziekten, Infection & Immunity, Sprenger, H. G., Langebeek, N., Mulder, P. G H, ten Napel, C. H H, Vriesendorp, R., Hoepelman, A. I M, Legrand, J. C., Koopmans, P. P., Bravenboer, B., ten Kate, R. W., Groeneveld, P. H P, Bierman, W. F W, van der Werf, T. S., Gisolf, E. H., and Richter, C.

Published
2015

5. Drought stress-induced changes in starch yield and physiological traits in potato.

Author

Rudack, K., Seddig, S., Sprenger, H., Köhl, K., Uptmoor, R., and Ordon, F.

Subjects
POTATOES, AGRICULTURAL climatology, DROUGHT tolerance, STARCH, GENOTYPES, PHYSIOLOGY
Abstract

Drought stress is an important limitation for potato ( Solanum tuberosum L.) production as potato depends on appropriate water availability for high yields of good quality. Therefore, especially in the background of climate change, it is an important goal in potato breeding to improve drought stress tolerance. In this study, 34 European starch potato cultivars were evaluated for drought stress tolerance by growing under well-watered and long-term drought stress conditions in rainout shelters in 2 years' pot trials. Besides yield, six physiological traits, that is free proline content, osmolality, total soluble sugar content, chlorophyll content ( SPAD), cell membrane stability and crude protein content, were determined in leaves sampled during vegetative growth and during flowering to investigate their association with drought tolerance. ANOVA revealed significant treatment effects for all physiological traits and increased genotypic effects at flowering. The sensitivity of physiological traits to drought was significantly higher during flowering than during vegetative growth. Drought stress decreased starch yield significantly ( p < .001), on average by 55%. Starch yield was significantly influenced by genotype and genotype × treatment interactions. Stress tolerance index ( STI) calculated from starch yield ranged from 0.26 (sensitive) to 0.76 (tolerant) with significant genotype effects ( p ≤ .001). STI correlated positively with cell membrane stability ( r = .59) and crude protein content ( r = .38) and negatively with osmolality ( r = −.57) and total soluble sugar content ( r = −.71). These contrary correlations suggest a dual adaptation strategy in potato under long-term drought stress conditions including increased membrane stability combined with an increased osmolality due to an increased soluble sugar content. [ABSTRACT FROM AUTHOR]

Published
2017
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6. Abacavir Pharmacokinetics During Chronic Therapy in HIV-1-Infected Adolescents and Young Adults.

Author

Sleasman, J. W., Robbins, B. L., Cross, S. J., Lindsey, J. C., Kraimer, J. M., Heckman, B. E., Sprenger, H. L., Tustin, N. B., Rose, C. H., Poston, P. A., Neal, E. F., Pakes, G. E., Nikanjam, M., and Capparelli, E. V.

Subjects
HIV infections, THERAPEUTICS, PHARMACOKINETICS, CHEMICAL kinetics, PHARMACOLOGY, CLINICAL medicine, DRUG metabolism, HIV-positive persons
Abstract

The pharmacokinetics of abacavir and its metabolites were investigated in 30 human immunodeficiency virus (HIV)-infected adolescents and young adults 13–25 years of age, equally divided into two groups: <18 years of age and ≥18 years of age. All the subjects received the recommended adult dose of 300 mg twice daily. The area under the plasma concentration–time curve (AUC) and half-life of abacavir did not differ significantly between the age groups or by gender or race, and there were only modest associations of age with apparent abacavir clearance and with volume of distribution. There were no significant correlations of carboxylate or glucuronide metabolite levels with age or gender, although glucuronide AUC was higher in Hispanic subjects than in African-American subjects. Zidovudine and lamivudine concentration profiles were also similar in the two age groups. A novel aspect of the study included an assessment of intracellular carbovir, zidovudine, and lamivudine triphosphate levels, and these were found to be similar in the two age-based groups. Overall, these findings suggest that current recommendations relating to adult dosages are appropriate for adolescents and young adults.Clinical Pharmacology & Therapeutics (2009); 85, 4, 394–401 doi:10.1038/clpt.2008.236 [ABSTRACT FROM AUTHOR]

Published
2009
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7. Estimation and prediction of the HIV-AIDS-epidemic under conditions of HAART using mixtures of incubation time distributions.

Author

Heisterkamp, S. H., de Vries, R., Sprenger, H. G., Hubben, G. A. A., and Postma, M. J.

Abstract

The estimation of the HIV-AIDS epidemic by means of back-calculation (BC) has been difficult since the introduction of highly active anti-retroviral therapy (HAART) because the incubation time distributions needed for BC were poorly known. Moreover, it has been assumed that if the general public is aware that effective treatments are available then the majority of infected people would be known, and therefore a hidden epidemic was assumed not to exist. Nevertheless, it was suspected that not every infected person would come to the attention of health-care providers, and therefore estimates independent of the patients' registration were necessary. In this paper, the incubation time distributions for HIV treated with the HAART regimen are derived from a cohort study. By using estimates of the proportion treated according to the HAART regimen and the incubation time distributions estimated in the era before the implementation of HAART (pre-HAART), new marginal population incubation time distributions for each of the three risk groups (homosexuals, drug users and others) were constructed. The BC was performed using an empirical Bayesian approach based on the latter incubation time distribution. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Published
2008
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17. Yield of annually performed routine physical examinations of HIV patients with stable disease.

Author

Amsterdam, M, Assen, S, Sprenger, H, Wilting, K, Stienstra, Y, and Bierman, W

Subjects
HIV-positive persons, PERIODIC health examinations, CD4 antigen, LYMPHADENITIS, SEXUALLY transmitted disease diagnosis, DISEASES
Abstract

Background Adequate follow-up of HIV patients is essential in the cART era. Current guidelines advise regular assessment of the patient, yet the exact content and frequency are less clear and practices vary amongst different hospitals. The objective of this study was to determine the value of performing routine physical examination of patients with normal or near normal immune function, as part of adequate follow-up. Methods In a cohort of 300 HIV-1-infected patients monitored in a large teaching hospital we retrospectively analysed the outcome of routine physical examinations performed at annual check-ups in 2010. Only stable patients were eligible for inclusion (CD4 count >350 cells/mm3 if not using cART, CD4 count >100 cells/mm3 if using cART). Data was collected from the medical records. It was recorded whether or not the physical examination per se was the basis for establishing a new diagnosis. Results Of 300 stable HIV-1-infected patients (81% males) with a median age of 47 years old (range 21-79) 216 patients (72%) had physical abnormalities. Lipodystrophy (30%), lymphadenopathy (16%) and hypertension (8.3%) were the most common findings. Two-thirds of all findings were already known from the past medical history or could be related to current complaints. In 24 patients (8.0%), the physical examination was the basis for establishing a new diagnosis: 6/24 patients (25%) - all men who have sex with men (MSM) - had a concurrent sexually transmitted disease, 8/24 patients (33%) had hypertension. The other 10/24 (42%) patients had a large variety of diagnoses, of which a bradycardia due to a total atrioventricular block was clinically the most relevant diagnosis. Factors associated with the yield of the physical examination could not be identified. Conclusion Routine physical examination per se was the basis for establishing new diagnoses in only 8% of stable HIV infected patients. However, most diagnoses were of little clinical relevance, suggesting that the additional value of routine physical examination in stable HIV patients is limited. Based on our findings, the regular standard assessment could be restricted to measuring blood pressure and the performance of anogenital examination in MSM. [ABSTRACT FROM AUTHOR]

Published
2012
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21. Interpatient variability in the pharmacokinetics of the HIV non-nucleoside reverse transcriptase inhibitor efavirenz: the effect of gender, race, and CYP2B6 polymorphism.

Author

Burger D, van der Heiden I, la Porte C, van der Ende M, Groeneveld P, Richter C, Koopmans P, Kroon F, Sprenger H, Lindemans J, Schenk P, and van Schaik R

Subjects
Adult, Alkynes, Anthropometry, Benzoxazines, Cyclopropanes, Cytochrome P-450 CYP2B6, Female, HIV Reverse Transcriptase antagonists & inhibitors, Humans, Male, Middle Aged, Pharmacogenetics, Sex Characteristics, Anti-HIV Agents blood, Aryl Hydrocarbon Hydroxylases genetics, Oxazines blood, Oxidoreductases, N-Demethylating genetics, Polymorphism, Single Nucleotide, Racial Groups genetics, Reverse Transcriptase Inhibitors blood
Abstract

Aims: To characterize the demographic and pharmacogenetic factors that influence interpatient variability in the plasma concentrations of the HIV non-nucleoside reverse transcriptase inhibitor efavirenz., Methods: Data from all samples analyzed for efavirenz in our TDM service in 2002 and 2003 were reviewed. Information on gender, age, body weight, height, race, hormonal contraceptive use (in a subset of patients), and time between sampling and last intake was recorded. PCR-restriction fragment length polymorphism analysis was performed to detect the cytochrome P450 2B6 (CYP2B6) C1459T variant (present in CYP2B6*6 and CYP2B6*7) which is associated with low CYP2B6 activity., Results: A total of 255 patients were included in this analysis. The median plasma efavirenz concentration was 2.50 (interquartile range: 1.85-3.55) mg l(-1). Eight patients (3.1%) were considered to have a subtherapeutic plasma concentration (<1.0 mg l(-1)) and 48 (18.9%) a toxic efavirenz concentration (>4.0 mg l(-1)). Gender, time after last intake, and race were the only factors that were significantly related to plasma efavirenz concentration in a multivariate analysis. No influence was observed for body weight, hormonal contraceptive use, and the presence of the CYP2B6 C1459T polymorphism., Conclusions: Gender and race are important factors in determining interpatient variability in plasma efavirenz concentrations which were unaffected by the presence of the CYP2B6 C1459T polymorphism. Physicians should be particularly alert for signs of efavirenz-induced toxicity in females and non-Caucasian patients.

Published
2006
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22. Nontropical pyomyositis as a cause of subacute, multifocal myalgia in the acquired immunodeficiency syndrome.

Author

Wolf RF, Sprenger HG, Mooyaart EL, Tamsma JT, Kengen RA, and Weits J

Subjects
Adult, Gallium Radioisotopes, Humans, Magnetic Resonance Imaging, Male, Mycobacterium avium-intracellulare Infection diagnosis, Myositis diagnosis, Staphylococcal Infections diagnosis, Acquired Immunodeficiency Syndrome complications, Mycobacterium avium-intracellulare Infection physiopathology, Myositis physiopathology, Pain etiology, Staphylococcal Infections physiopathology
Abstract

We report a case of nontropical pyomyositis in a patient with acquired immunodeficiency syndrome and disseminated Mycobacterium avium infection, in which severe myalgia was the presenting symptom over several weeks. Multifocal muscle lesions were identified by gallium scanning and magnetic resonance imaging techniques. The epidemiology, possible pathogenesis, clinical features, diagnostic imaging, and therapy are reviewed. Early suspicion of nontropical pyomyositis in severely immunocompromised patients with "cryptic" myalgia is recommended.

Published
1990
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