• 1
    Mocroft A, Ledergerber B, Katlama C et al. Decline in the AIDS and death rates in the EuroSIDA study: an observational study. Lancet 2003; 362: 2229.
  • 2
    Centers for Disease Control and P. HIV/AIDS Surveillance Report, 2009. 2011.
  • 3
    Mussini C, Manzardo C, Johnson M et al. Patients presenting with AIDS in the HAART era: a collaborative cohort analysis. AIDS 2008; 22: 24612469.
  • 4
    Silverberg MJ, Leyden W, Horberg MA, DeLorenze GN, Klein D, Quesenberry CP, Jr. Older Age and the Response to and Tolerability of Antiretroviral Therapy. 2007. 684691.
  • 5
    The Collaboration of Observational HIVEREsg. Response to combination antiretroviral therapy: variation by age. AIDS 2008; 22: 14631473.
  • 6
    Goetz MB, Boscardin WJ, Wiley D, Alkasspooles S. Decreased recovery of CD4 lymphocytes in older HIV-infected patients beginning highly active antiretroviral therapy. AIDS 2001; 15: 15761579.
  • 7
    Kaufmann GR, Furrer H, Ledergerber B et al. Characteristics, determinants, and clinical relevance of CD4 T cell recovery to < 500 cells/microL in HIV type 1-infected individuals receiving potent antiretroviral therapy. Clin Infect Dis 2005; 41: 361372.
  • 8
    Greenblatt DJ, Shader RI, Harmatz JS. Implications of altered drug disposition in the elderly: studies of benzodiazepines. J Clin Pharmacol 1989; 29: 866872.
  • 9
    Klotz U. Pharmacokinetics and drug metabolism in the elderly. Drug Metab Rev 2009; 41: 6776.
  • 10
    Rea IM, McNerlan SE, Alexander HD. CD69, CD25, and HLA-DR activation antigen expression on CD3+ lymphocytes and relationship to serum TNF-[alpha], IFN-[gamma], and sIL-2R levels in aging. Exp Gerontol 1999; 34: 7993.
  • 11
    Anderson PL, Kakuda TN, Lichtenstein KA. The cellular pharmacology of nucleoside- and nucleotide-analogue reverse-transcriptase inhibitors and its relationship to clinical toxicities. Clin Infect Dis 2004; 38: 743753.
  • 12
    Fletcher CV, Kawle SP, Kakuda TN et al. Zidovudine triphosphate and lamivudine triphosphate concentration-response relationships in HIV-infected persons. AIDS 2000; 14: 21372144.
  • 13
    Vourvahis M, Tappouni HL, Patterson KB et al. The pharmacokinetics and viral activity of tenofovir in the male genital tract. J Acquir Immune Defic Syndr 2008; 47: 329333.
  • 14
    Wang LH, Begley J, St. Claire RL, Harris J, Wakeford C, Rousseau FS. Pharmacokinetic and pharmacodynamic characteristics of emtricitabine support its once daily dosing for the treatment of HIV infection. 2004. 11731182.
  • 15
    Fried LP, Tangen CM, Walston J et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001; 56: M146M157.
  • 16
    Corso DMPF, DeLeo JM, Calis KA, Gallelli JF. Development of a questionnaire for detecting potential adverse drug reactions. Ann Pharmacother 1992; 26: 890896.
  • 17
    Rezk NL, Crutchley RD, Kashuba ADM. Simultaneous quantification of emtricitabine and tenofovir in human plasma using high-performance liquid chromatography after solid phase extraction. J Chromatogr B 2005; 822: 201208.
  • 18
    Rezk NL, Tidwell RR, Kashuba ADM. High-performance liquid chromatography assay for the quantification of HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors in human plasma. J Chromatogr B. 2004; 805: 241247.
  • 19
    US DHHS FaC. Guidance for industry: bioanalytical method validation. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Veterinary Medicine, 2001. Available at (accessed 10 May 2012).
  • 20
    Kiser JJ, Carten ML, Aquilante CL et al. The effect of lopinavir//ritonavir on the renal clearance of tenofovir in HIV-infected patients. Clin Pharmacol Ther 2007; 83: 265272.
  • 21
    Rousseau FS, Kahn JO, Thompson M et al. Prototype trial design for rapid dose selection of antiretroviral drugs: an example using emtricitabine (Coviracil). J Antimicrob Chemother 2001; 48: 507513.
  • 22
    Bristol-Myers Squibb Company. Sustiva (efavirenz) full U.S. prescribing information. Princeton, NJ. 2009.
  • 23
    Taburet A-M, Piketty C, Chazallon C et al. Interactions between Atazanavir-Ritonavir and Tenofovir in Heavily Pretreated Human Immunodeficiency Virus-Infected Patients. Antimicrob Agents Chemother 2004; 48: 20912096.
  • 24
    Kiser JJP, Aquilante CLP, Anderson PLP, King TMBS, Carten MLMD, Fletcher CVP. Clinical and Genetic Determinants of Intracellular Tenofovir Diphosphate Concentrations in HIV-Infected Patients. J Acquir Immune Defic Syndr 2008; 47: 298303.
  • 25
    Panel on antiretroviral guidelines for adults and adolescents, in Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services, 2012. Available at (accessed 10 May 2012).
  • 26
    Greenblatt D, Divoll M, Abernethy D, Ochs H, Harmatz J, Shader R. Age and gender effects on chlordiazepoxide kinetics: relation to antipyrine disposition. Pharmacology 1989; 38: 327334.
  • 27
    Sotaniemi EAAA, Pelkonen O, Pasanen M. Age and cytochrome P450-linked drug metabolism in humans: an analysis of 226 subjects with equal histopathologic conditions. Clin Pharmacol Ther 1997; 61: 331339.
  • 28
    Vestal RENA, Tobin JD, Cohen BH, Shock NW, Andres R. Antipyrine metabolism in man: influence of age, alcohol, caffeine, and smoking. Clin Pharmacol Ther 1975; 18: 425432.
  • 29
    Tommasi C, Nicastri E, Gallo A. Pharmacological evaluation of new antiretroviral drugs in the elderly HIV-1 infected people. 11th International Workshop on Clinical Pharmacology and HIV Therapy; April 7–9, 2010; Sorrento, Italy. 2010.
  • 30
    Bristol-Myers Squibb Company. Reyataz (atazanavir) Full U.S. Prescribing Information. Princeton, NJ. 2009.
  • 31
    Dobson PD, Kell DB. Carrier-mediated cellular uptake of pharmaceutical drugs: an exception or the rule? Nat Rev Drug Discov 2008; 7: 205220.
  • 32
    International Transporter Consortium, Giacomini KM, Huang SM, Tweedie DJ et al. Membrane transporters in drug development. Nat Rev Drug Discov 2010; 9: 215236.
  • 33
    Fu ZD, Csanaky IL, Klaassen CD. Effects of aging on mRNA Profiles for drug-metabolizing enzymes and transporters in livers of male and female mice. Drug Metab Dispos 2012; 40: 12161225.
  • 34
    Gao W, Agbaria R, Driscoll J, Mitsuya H. Divergent anti-human immunodeficiency virus activity and anabolic phosphorylation of 2′,3′-dideoxynucleoside analogs in resting and activated human cells. J Biol Chem 1994; 269: 1263312638.
  • 35
    Shirasaka T, Chokekijchai S, Yamada A, Gosselin G, Imbach J, Mitsuya H. Comparative analysis of anti-human immunodeficiency virus type 1 activities of dideoxynucleoside analogs in resting and activated peripheral blood mononuclear cells. Antimicrob Agents Chemother 1995; 39: 25552559.
  • 36
    Desquilbet L, Jacobson LP, Fried LP et al. HIV-1 infection is associated with an earlier occurrence of a phenotype related to frailty. J Gerontol A Biol Sci Med Sci 2007; 62: 12791286.
  • 37
    Margolick J, Li X, Detels R et al. Earlier occurrence of the frailty phenotype in HIV+ men than in HIV– men: the MACS cohort. 18th Conference on Retroviruses and Opportunistic Infections. Boston, MA, February 2011 [Abstract #794].
  • 38
    Wynne HA, Cope LH, Herd B, Rawlins MD, James OFW, Woodhouse KW. The association of age and frailty with paracetamol conjugation in man. 1990. p. 419424.
  • 39
    Wynne HA, Yelland C, Cope LH, Boddy A, Woodhouse KW, Bateman DN. The association of age and frailty with the pharmacokinetics and pharmacodynamics of metoclopramide. Age Ageing 1993; v22 (n5): p354(6).
  • 40
    Groen KHM, Roberts NA, Gulati RS et al. vBC. The relationship between phenazone (antipyrine) metabolite formation and theophylline metabolism in healthy and frail elderly women. Clin Pharmacokinet 1993; 25: 136144.
  • 41
    Renton KW. Cytochrome P450 regulation and drug biotransformation during inflammation and infection. Curr Drug Metab 2004; 5: 235243.
  • 42
    Project HaAC. Recommended treatment strategies for clinicians managing older patients with HIV. Available at (accessed 1 July 2012).
  • 43
    Powell JR, Gobburu JVS. Pharmacometrics at FDA: evolution and impact on decisions. Clin Pharmacol Ther 2007; 82: 97102.
  • 44
    Cockcroft D, Gault M. Prediction of creatinine clearance from serum creatinine. Nephron. 1976; 16: 3141.