• 1

    Mocroft A, Ledergerber B, Katlama C, Kirk O, Reiss P, d’Arminio Monforte A, Knysz B, Dietrich M, Phillips AN, Lundgren JD, 2003. Decline in the AIDS and death rates in the EuroSIDA study: an observational study. Lancet 362 :22–29.

    • Search Google Scholar
    • Export Citation
  • 2

    Mocroft A, Vella S, Benfield TL, Chiesi A, Miller V, Gargalianos P, d’Arminio Monforte A, Yust I, Bruun JN, Phillips AN, Lundgren JD, 1998. Changing patterns of mortality across Europe in patients infected with HIV-1. EuroSIDA Study Group. Lancet 352 :1725–1730.

    • Search Google Scholar
    • Export Citation
  • 3

    Braitstein P, Brinkhof MW, Dabis F, Schechter M, Boulle A, Miotti P, Wood R, Laurent C, Sprinz E, Seyler C, Bangsberg DR, Balestre E, Sterne JA, May M, Egger M, 2006. Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries. Lancet 367 :817–824.

    • Search Google Scholar
    • Export Citation
  • 4

    Lawn SD, Wood R, 2006. How can earlier entry of patients into antiretroviral programs in low-income countries be promoted? Clin Infect Dis 42 :431–432.

    • Search Google Scholar
    • Export Citation
  • 5

    Etard JF, Ndiaye I, Thierry-Mieg M, Gueye NF, Gueye PM, Laniece I, Dieng AB, Diouf A, Laurent C, Mboup S, Sow PS, Delaporte E, 2006. Mortality and causes of death in adults receiving highly active antiretroviral therapy in Senegal: a 7-year cohort study. AIDS 20 :1181–1189.

    • Search Google Scholar
    • Export Citation
  • 6

    Lawn SD, Myer L, Orrell C, Bekker LG, Wood R, 2005. Early mortality among adults accessing a community-based antiretroviral service in South Africa: implications for programme design. AIDS 19 :2141–2148.

    • Search Google Scholar
    • Export Citation
  • 7

    Mezzaroma I, Carlesimo M, Pinter E, 1999. Long-term evaluation of T-cell subsets and T-cell function after HAART in advanced stage of HIV-1 disease. AIDS 13 :1187–1193.

    • Search Google Scholar
    • Export Citation
  • 8

    Pakker NG, Notermans DW, de Boer RJ, Roos MT, de Wolf F, Hill A, Leonard JM, Danner SA, Miedema F, Schellekens PT, 1998. Biphasic kinetics of peripheral blood T cells after triple combination therapy in HIV-1 infection: a composite of redistribution and proliferation. Nat Med 4 :208–214.

    • Search Google Scholar
    • Export Citation
  • 9

    Powderly WG, Landay A, Lederman MM, 1998. Recovery of the immune system with antiretroviral therapy: the end of opportunism? JAMA 280 :72–77.

    • Search Google Scholar
    • Export Citation
  • 10

    Shelburne SA, Montes M, Hamill RJ, 2006. Immune reconstitution inflammatory syndrome: more answers, more questions. J Antimicrob Chemother 57 :167–170.

    • Search Google Scholar
    • Export Citation
  • 11

    Hunt PW, Deeks SG, Rodriguez B, Valdez H, Shade SB, Abrams DI, Kitahata MM, Krone M, Neilands TB, Brand RJ, Lederman MM, Martin JN, 2003. Continued CD4 cell count increases in HIV-infected adults experiencing 4 years of viral suppression on antiretroviral therapy. AIDS 17 :1907–1915.

    • Search Google Scholar
    • Export Citation
  • 12

    Smith CJ, Sabin CA, Lampe FC, Kinloch-de-Loes S, Gumley H, Carroll A, Prinz B, Youle M, Johnson MA, Phillips AN, 2003. The potential for CD4 cell increases in HIV-positive individuals who control viraemia with highly active antiretroviral therapy. AIDS 17 :963–969.

    • Search Google Scholar
    • Export Citation
  • 13

    Binquet C, Chene G, Jacqmin-Gadda H, Journot V, Saves M, Lacoste D, Dabis F, 2001. Modeling changes in CD4-positive T-lymphocyte counts after the start of highly active antiretroviral therapy and the relation with risk of opportunistic infections: the Aquitaine Cohort, 1996–1997. Am J Epidemiol 153 :386–393.

    • Search Google Scholar
    • Export Citation
  • 14

    Pakker N, Kroon E, Roos M, 1999. Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy. AIDS 13 :203–212.

    • Search Google Scholar
    • Export Citation
  • 15

    Bennett KK, DeGruttola VG, Marschner IC, Havlir DV, Richman DD, 2002. Baseline predictors of CD4 T-lymphocyte recovery with combination antiretroviral therapy. J Acquir Immune Defic Syndr 31 :20–26.

    • Search Google Scholar
    • Export Citation
  • 16

    Bosch RJ, Wang R, Vaida F, Lederman MM, Albrecht MA, 2006. Changes in the slope of the CD4 cell count increase after initiation of potent antiretroviral treatment. J Acquir Immune Defic Syndr 43 :433–435.

    • Search Google Scholar
    • Export Citation
  • 17

    Autran B, Carcelain G, Li TS, Blanc C, Mathez D, Tubiana R, Katlama C, Debre P, Leibowitch J, 1997. Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science 277 :112–116.

    • Search Google Scholar
    • Export Citation
  • 18

    Kaufmann GR, Bloch M, Zaunders JJ, Smith D, Cooper DA, 2000. Long-term immunological response in HIV-1-infected subjects receiving potent antiretroviral therapy. AIDS 14 :959–969.

    • Search Google Scholar
    • Export Citation
  • 19

    Kaufmann GR, Bloch M, Finlayson R, Zaunders J, Smith D, Cooper DA, 2002. The extent of HIV-1-related immunodeficiency and age predict the long-term CD4 T lymphocyte response to potent antiretroviral therapy. AIDS 16 :359–367.

    • Search Google Scholar
    • Export Citation
  • 20

    Garcia F, de Lazzari E, Plana M, Castro P, Mestre G, Nomdedeu M, Fumero E, Martinez E, Mallolas J, Blanco JL, Miro JM, Pumarola T, Gallart T, Gatell JM, 2004. Long-term CD4+ T-cell response to highly active antiretroviral therapy according to baseline CD4+ T-cell count. J Acquir Immune Defic Syndr 36 :702–713.

    • Search Google Scholar
    • Export Citation
  • 21

    Tarwater PM, Margolick JB, Jin J, Phair JP, Detels R, Rinaldo C, Giorgi J, Munoz A, 2001. Increase and plateau of CD4 T-cell counts in the 3(1/2) years after initiation of potent antiretroviral therapy. J Acquir Immune Defic Syndr 27 :168–175.

    • Search Google Scholar
    • Export Citation
  • 22

    Moore RD, Keruly JC, 2007. CD4+ cell count 6 years after commencement of highly active antiretroviral therapy in persons with sustained virologic suppression. Clin Infect Dis 44 :441–446.

    • Search Google Scholar
    • Export Citation
  • 23

    Lederman HM, Williams PL, Wu JW, Evans TG, Cohn SE, McCutchan JA, Koletar SL, Hafner R, Connick E, Valentine FT, McElrath MJ, Roberts NJ Jr, Currier JS, 2003. Incomplete immune reconstitution after initiation of highly active antiretroviral therapy in human immunodeficiency virus-infected patients with severe CD4+ cell depletion. J Infect Dis 188 :1794–1803.

    • Search Google Scholar
    • Export Citation
  • 24

    Lange CG, Lederman MM, Medvik K, Asaad R, Wild M, Kalayjian R, Valdez H, 2003. Nadir CD4+ T-cell count and numbers of CD28+ CD4+ T-cells predict functional responses to immunizations in chronic HIV-1 infection. AIDS 17 :2015–2023.

    • Search Google Scholar
    • Export Citation
  • 25

    Staszewski S, Miller V, Sabin C, Schlecht C, Gute P, Stamm S, Leder T, Berger A, Weidemann E, Hill A, Phillips A, 1999. Determinants of sustainable CD4 lymphocyte count increases in response to antiretroviral therapy. AIDS 13 :951–956.

    • Search Google Scholar
    • Export Citation
  • 26

    Piketty C, Castiel P, Belec L, Batisse D, Si Mohamed A, Gilquin J, Gonzalez-Canali G, Jayle D, Karmochkine M, Weiss L, Aboulker JP, Kazatchkine MD, 1998. Discrepant responses to triple combination antiretroviral therapy in advanced HIV disease. AIDS 12 :745–750.

    • Search Google Scholar
    • Export Citation
  • 27

    Le Moing V, Thiebaut R, Chene G, Leport C, Cailleton V, Michelet C, Fleury H, Herson S, Raffi F, 2002. Predictors of long-term increase in CD4(+) cell counts in human immunodeficiency virus-infected patients receiving a protease inhibitor-containing antiretroviral regimen. J Infect Dis 185 :471–480.

    • Search Google Scholar
    • Export Citation
  • 28

    Tumbarello M, Rabagliati R, de Gaetano Donati K, Bertagnolio S, Montuori E, Tamburrini E, Tacconelli E, Cauda R, 2004. Older age does not influence CD4 cell recovery in HIV-1 infected patients receiving highly active antiretroviral therapy. BMC Infect Dis 4 :46.

    • Search Google Scholar
    • Export Citation
  • 29

    Sloand EM, Kumar PN, Kim S, Chaudhuri A, Weichold FF, Young NS, 1999. Human immunodeficiency virus type 1 protease inhibitor modulates activation of peripheral blood CD4(+) T cells and decreases their susceptibility to apoptosis in vitro and in vivo. Blood 94 :1021–1027.

    • Search Google Scholar
    • Export Citation
  • 30

    Jaffar S, Grant AD, Whitworth J, Smith PG, Whittle H, 2004. The natural history of HIV-1 and HIV-2 infections in adults in Africa: a literature review. Bull World Health Organ 82 :462–469.

    • Search Google Scholar
    • Export Citation
  • 31

    Laurent C, Diakhate N, Gueye NF, Toure MA, Sow PS, Faye MA, Gueye M, Laniece I, Toure Kane C, Liegeois F, Vergne L, Mboup S, Badiane S, Ndoye I, Delaporte E, 2002. The Senegalese government’s highly active antiretroviral therapy initiative: an 18-month follow-up study. AIDS 16 :1363–1370.

    • Search Google Scholar
    • Export Citation
  • 32

    Laird NM, Ware JH, 1982. Random-effects models for longitudinal data. Biometrics 38 :963–974.

  • 33

    Diggle P, Heagerty P, Liang K, Zeger S, 2002. Analysis of Longitudinal Data. Second edition. Oxford: University Press.

  • 34

    Pinheiro J, Bates D, 2000. Mixed-Effects Models in S and S-Plus. New York: Springer.

  • 35

    Potvin C, Lechowicz MJ, Tardif S, 1990. The statistical analysis of ecophysiological response curves obtained from experiments involving repeated measures. Ecology 71 :1389–1400.

    • Search Google Scholar
    • Export Citation
  • 36

    Etard JF, Lanièce I, Fall MB, Cilote V, Blazejewski L, Diop K, Desclaux A, Ecochard R, Ndoye I, Delaporte E; ANRS 1215/1290 Study Group, 2007. A 84-month follow up of adherence to HAART in a cohort of adult Senegalese patients. Trop Med Int Health 12 :1191–1198.

    • Search Google Scholar
    • Export Citation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 

 

 

Modeling CD4+ Cell Count Increase Over a Six-Year Period in HIV-1–Infected Patients on Highly Active Antiretroviral Therapy in Senegal

View More View Less
  • 1 Hospices Civils de Lyon, Service de Biostatistique, Lyon, F-69003, France; Université de Lyon, F-69000, Lyon; Université Lyon I, Villeurbanne, F-69100, France; CNRS; UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique Santé, Pierre-Bénite, F-69310, France; UMR 145, Institut de Recherche pour le Développement (IRD), Montpellier, France; Regional Research and Training Centre for HIV/AIDS, Fann University Teaching Hospital, Dakar, Senegal; Infectious Diseases Department, Fann University Teaching Hospital, Dakar, Senegal; Ambulatory Care Unit, Fann University Teaching Hospital, Dakar, Senegal; Military Hospital of Dakar, Dakar, Senegal; Laboratory of Bacteriology and Virology, Le Dantec Teaching Hospital, Dakar, Senegal; CNLS, Ministry of Health, Dakar, Senegal
Restricted access

To assess the extents and determinants of long-term CD4 cell increases after initiation of antiretroviral therapy (ART), changes in CD4 cell counts were analyzed in a cohort of HIV-1–infected Senegalese using a mixed-effects model. After a median follow-up of 54 months, an average of 483 CD4 cells/mm3 (95% confidence interval [CI] = 331; 680) was reached. The average asymptote level was ~421 cells/mm3 (95% CI = 390; 454) in patients with < 200 cells/mm3 at baseline and ~500 cells/mm3 in patients with > 200 cells/mm3. The independent predictors of long-term CD4 cell reconstitution were the baseline CD4 cell count and the monthly average viral load over the entire follow-up. This good long-term immune reconstitution, optimal in subjects with low average viral loads and > 200 CD4 cells/mm3 at baseline, argues in favor of the earliest possible access to ART and underlines the importance of strict compliance with the treatment.

Author Notes

Reprint requests: Pierre de Beaudrap, IRD, UMR 145, 911 Avenue Agropolis, BP 64501, F-34394 Montpellier, France, E-mail: pierre.debeaudrap@ird.fr.
Save