Luuk Gras

Senior statistician
I’m working as a statistician at the Stichting HIV Monitoring (SHM), partly supporting other researchers with their analyses, partly doing my own research which focuses on comparing statistical methods in the analysis of HIV observational data.

Changing virulence of HIV over time
Recent published research suggests that in the Netherlands and other countries the viral load in plasma shortly after HIV infection (at the so-called viral set-point) is higher in patients infected in more recent calendar years compared to patients infected 10 years ago. Likewise CD4 cell counts at viral set-point (a marker of the functioning of the immune system) are lower in patients infected in more recent calendar year. This suggests that the virulence of HIV-1 has increased over time.

A good marker of virulence of HIV is the rate of CD4 cell decline in untreated HIV infection, which is the focus of my current research. Has this also changed over time, similar to the observed changes in plasma viral load and CD4 cell counts at viral set-point? This analysis is complicated by the fact that patients with a more rapid immunological decline are more likely to start on antiretroviral therapy. It is therefore important to model CD4 cell decline and timing of antiretroviral therapy initiation simultaneously.

Selected publications

• The Efficacy of Combination Antiretroviral Therapy in HIV Type 1-Infected Patients Treated in Curaçao Compared with Antillean, Surinam, and Dutch HIV Type 1-Infected Patients Treated in The Netherlands.
  Hermanides HS, Gras L, Winkel CN, Gerstenbluth I, van Sighem A, de Wolf F, Duits AJ. AIDS Res Hum Retroviruses. 2010 Dec 14.

• Life expectancy of recently diagnosed asymptomatic HIV-infected patients approaches that of uninfected individuals.
  van Sighem AI, Gras LA, Reiss P, Brinkman K, de Wolf F; ATHENA national observational cohort study. AIDS. 2010 Jun 19;24(10):1527-35.

• Immune restoration and onset of new AIDS-defining events with combination antiretroviral therapy in HIV type-1-infected immigrants in the Netherlands.
  Kesselring AM, Gras L, Wit FW, Smit C, Geerlings SE, Mulder JW, Schreij G, Sprenger HG, Reiss P, de Wolf F. Antivir Ther. 2010;15(6):871-9.

• Clinical significance of transient HIV type-1 viraemia and treatment interruptions during suppressive antiretroviral treatment.
  Zhang S, van Sighem A, Gras L, Reiss P, Smit C, Kroon F, Jurriaans S, Prins J, Lange J, de Wolf F. Antivir Ther. 2010;15(4):555-62.

• Viral load levels measured at set-point have risen over the last decade of the HIV epidemic in the Netherlands.
  Gras L, Jurriaans S, Bakker M, van Sighem A, Bezemer D, Fraser C, Lange J, Prins JM, Berkhout B, de Wolf F; ATHENA National Observational Cohort Study. PLoS One. 2009 Oct 7;4(10):e7365.

• Efavirenz dose reduction is safe in patients with high plasma concentrations and may prevent efavirenz discontinuations.
  van Luin M, Gras L, Richter C, van der Ende ME, Prins JM, de Wolf F, Burger DM, Wit FW. J Acquir Immune Defic Syndr. 2009 Oct 1;52(2):240-5.

• Baseline lipid levels rather than the presence of reported body shape changes determine the degree of improvement in lipid levels after switching to atazanavir.
  van Vonderen MG, Gras L, Wit F, Brinkman K, van der Ende ME, Hoepelman AI, de Wolf F, Reiss P. HIV Clin Trials. 2009 May-Jun;10(3):168-80.

• Which method of adherence measurement is most suitable for daily use to predict virological failure among immigrant and non-immigrant HIV-1 infected patients?
  Nellen JF, Nieuwkerk PT, Burger DM, Wibaut M, Gras LA, Prins JM. AIDS Care. 2009 Jul;21(7):842-50.

• Clinical experience with the combined use of lopinavir/ritonavir and rifampicin.
  L'homme RF, Nijland HM, Gras L, Aarnoutse RE, van Crevel R, Boeree M, Brinkman, K, Prins JM, Juttmann JR, Burger DM. AIDS. 2009 Apr 27;23(7):863-5.

• A resurgent HIV-1 epidemic among men who have sex with men in the era of potent antiretroviral therapy.
  Bezemer D, de Wolf F, Boerlijst MC, van Sighem A, Hollingsworth TD, Prins M, Geskus RB, Gras L, Coutinho RA, Fraser C. AIDS. 2008 May 31;22(9):1071-7.

• Immunologic, virologic, and clinical consequences of episodes of transient viremia during suppressive combination antiretroviral therapy.
  van Sighem A, Zhang S, Reiss P, Gras L, van der Ende M, Kroon F, Prins J, de Wolf F. J Acquir Immune Defic Syndr. 2008 May 1;48(1):104-8.

• Discontinuation of nevirapine because of hypersensitivity reactions in patients with prior treatment experience, compared with treatment-naive patients: the ATHENA cohort study.
  Wit FW, Kesselring AM, Gras L, Richter C, van der Ende ME, Brinkman K, Lange JM, de Wolf F, Reiss P.. Clin Infect Dis. 2008 Mar 15;46(6):933-40.

• Therapeutic drug monitoring of the HIV protease inhibitor atazanavir in clinical practice.
  Cleijsen RM, van de Ende ME, Kroon FP, Lunel FV, Koopmans PP, Gras L, de Wolf F, Burger DM. J Antimicrob Chemother. 2007 Oct;60(4):897-900.

• CD4 cell counts of 800 cells/mm3 or greater after 7 years of highly active antiretroviral therapy are feasible in most patients starting with 350 cells/mm3 or greater.
  Gras L, Kesselring AM, Griffin JT, van Sighem AI, Fraser C, Ghani AC, Miedema, F, Reiss P, Lange JM, de Wolf F; ATHENA, Netherlands National Observational Cohort Study. J Acquir Immune Defic Syndr. 2007 Jun 1;45(2):183-92.

• Biases in observational studies of the effect of prenatal treatment for congenital toxoplasmosis.
  Thiébaut R, Leroy V, Alioum A, Binquet C, Poizat G, Salmi LR, Gras L, Salamon R, Gilbert R, Chêne G. Eur J Obstet Gynecol Reprod Biol. 2006 Jan 1;124(1):3-9.

• The genotypic inhibitory quotient and the (cumulative) number of mutations predict the response to lopinavir therapy.
  Hoefnagel JG, van der Lee MJ, Koopmans PP, Schuurman R, Jurriaans S, van Sighem AI, Gras L, de Wolf F, Galama JM, Burger DM. AIDS. 2006 Apr 24;20(7):1069-71.

• The effect on treatment comparisons of different measurement frequencies in human immunodeficiency virus observational databases.
  Griffin JT, Fraser C, Gras L, de Wolf F, Ghani AC. Am J Epidemiol. 2006 Apr 1;163(7):676-83.

• Mortality in patients with successful initial response to highly active antiretroviral therapy is still higher than in non-HIV-infected individuals.
  van Sighem A, Danner S, Ghani AC, Gras L, Anderson RM, de Wolf F; ATHENA National Observational Cohort Study. J Acquir Immune Defic Syndr. 2005 Oct 1;40(2):212-8.

• Prediction of congenital toxoplasmosis by polymerase chain reaction analysis of amniotic fluid.
  Thalib L, Gras L, Romand S, Prusa A, Bessieres MH, Petersen E, Gilbert RE.
  BJOG. 2005 May;112(5):567-74.

• Association between prenatal treatment and clinical manifestations of congenital toxoplasmosis in infancy: a cohort study in 13 European centres.
  Gras L, Wallon M, Pollak A, Cortina-Borja M, Evengard B, Hayde M, Petersen E, Gilbert R; European Multicenter Study on Congenital Toxoplasmosis Acta Paediatr. 2005 Dec;94(12):1721-31.

• Duration of the IgM response in women acquiring Toxoplasma gondii during pregnancy: implications for clinical practice and cross-sectional incidence studies.
  Gras L, Gilbert RE, Wallon M, Peyron F, Cortina-Borja M. Epidemiol Infect. 2004 Jun;132(3):541-8.

• Effect of timing and type of treatment on the risk of mother to child transmission of Toxoplasma gondii.
  Gilbert R, Gras L; European Multicentre Study on Congenital Toxoplasmosis. BJOG. 2003 Feb;110(2):112-20.

• Reliability of expert interpretation of retinal photographs for the diagnosis of toxoplasma retinochoroiditis.
  Stanford MR, Gras L, Wade A, Gilbert RE. Br J Ophthalmol. 2002 Jun;86(6):636-9.

• Effect of prenatal treatment on the risk of intracranial and ocular lesions in children with congenital toxoplasmosis.
  Gras L, Gilbert RE, Ades AE, Dunn DT. Int J Epidemiol. 2001 Dec;30(6):1309-13.

• Effect of prenatal treatment on mother to child transmission of Toxoplasma gondii: retrospective cohort study of 554 mother-child pairs in Lyon, France.
  Gilbert RE, Gras L, Wallon M, Peyron F, Ades AE, Dunn DT. Int J Epidemiol. 2001 Dec;30(6):1303-8.