A pharmacist’s role in the individualization of treatment of HIV patients

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

• 1 Centers for Disease C. Pneumocystis pneumonia – Los Angeles. MMWR Morb. Mortal. Wkly Rep. 30(21), 250–252 (1981).
  MedlineGoogle Scholar
• 2 Blaylock JM, Wortmann GW. Care of the aging HIV patient. Cleve. Clin. J. Med. 82(7), 445–455 (2015).
  MedlineGoogle Scholar
• 3 Baldwin CE, Sanders RW, Berkhout B. Inhibiting HIV-1 entry with fusion inhibitors. Curr. Med. Chem. 10(17), 1633–1642 (2003).
  Medline CASGoogle Scholar
• 4 Department of Human Health Service (DHHS) Panel on Antiretroviral Guidelines for Adults and Adolescents. Guideline for the use of antiretroviral agents in HIV-1-infected adults and adolescents (2015). http://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf.
  Google Scholar
• 5 Panel de expertos de Gesida y Plan Nacional sobre el Sida. Documento de consenso de Gesida/Plan Nacional sobre el Sida respecto al tratamiento antirretroviral en adultos infectados por el virus de la inmunodeficiencia humana (2015). www.gesida-seimc.org/contenidos/guiasclinicas/2015/gesida-guiasclinicas-2015-tar.pdf.
  Google Scholar
• 6 Fox J, Boffito M, Winston A. The clinical implications of antiretroviral pharmacogenomics. Pharmacogenomics 7(4), 587–596 (2006).
  CASGoogle Scholar
• 7 Gatell JM, Mallolas JM. Guía Práctica Del Sida: Clínica, Diagnóstico y Tratamiento. Antares, Barcelona, Spain (2013).
  Google Scholar
• 8 Clevenbergh P, Mouly S, Sellier P et al. Improving HIV infection management using antiretroviral plasma drug levels monitoring: a clinician's point of view. Curr. HIV Res. 2(4), 309–321 (2004).
  Medline CASGoogle Scholar
• 9 Van Luin M, Kuks PF, Burger DM. Use of therapeutic drug monitoring in HIV disease. Curr. Opin. HIV AIDS 3(3), 266–271 (2008).•• Discussion of the principal arguments in favor of and against therapeutic drug monitoring in patients with HIV infection.
  MedlineGoogle Scholar
• 10 Boffito M, Acosta E, Burger D et al. Current status and future prospects of therapeutic drug monitoring and applied clinical pharmacology in antiretroviral therapy. Antivir. Ther. (Lond.) 10(3), 375–392 (2005).
  Medline CASGoogle Scholar
• 11 Lacasa JM. Farmacocinética y farmacodinámica de los principales antirretrovirales. www.educasida.es/sites/default/files/Farmacocin%C3%A9tica%20y%20farmacodin%C3%A1mica%20de%20los%20principales%20antirretrovirales.pdf
  Google Scholar
• 12 Bangsberg DR, Perry S, Charlebois ED et al. Non-adherence to highly active antiretroviral therapy predicts progression to AIDS. AIDS 15(9), 1181–1183 (2001).
  Medline CASGoogle Scholar
• 13 García De Olalla P, Knobel H, Carmona A, Guelar A, López-Colomés JL, Caylà JA. Impact of adherence and highly active antiretroviral therapy on survival in HIV-infected patients. J. Acquir. Immune Defic. Syndr. 30(1), 105–110 (2002).
  Medline CASGoogle Scholar
• 14 Hogg RS, Heath K, Bangsberg D et al. Intermittent use of triple-combination therapy is predictive of mortality at baseline and after 1 year of follow-up. AIDS 16(7), 1051–1058 (2002).
  MedlineGoogle Scholar
• 15 Back D, Gatti G, Fletcher C et al. Therapeutic drug monitoring in HIV infection: current status and future directions. AIDS 16(Suppl. 1) S5–S37 (2002).
  Medline CASGoogle Scholar
• 16 Aarnoutse RE, Schapiro JM, Boucher CAB, Hekster YA, Burger DM. Therapeutic drug monitoring: an aid to optimising response to antiretroviral drugs? Drugs 63(8), 741–753 (2003).
  Medline CASGoogle Scholar
• 17 Fabbiani M, Di Giambenedetto S, Bracciale L et al. Pharmacokinetic variability of antiretroviral drugs and correlation with virological outcome: 2 years of experience in routine clinical practice. J. Antimicrob. Chemother. 64(1), 109–117 (2009).
  Medline CASGoogle Scholar
• 18 Fletcher CV, Anderson PL, Kakuda TN et al. Concentration-controlled compared with conventional antiretroviral therapy for HIV infection. AIDS 16(4), 551–560 (2002).• Establishes the viability of implementing therapeutic drug monitoring of various antiretroviral agents in clinical practice and compares the virological responses and safety of this strategy with conventional fixed-dose therapy.
  MedlineGoogle Scholar
• 19 Levy G. Genesis of clinical pharmacokinetic/pharmacodynamic concepts: E.K. Marshall, Jr.'s role. Ann. Pharmacother. 28(11), 1300–1302 (1994).
  Medline CASGoogle Scholar
• 20 Cabrera S, Valverde MP, García MJ, Sánchez A, González MC. Intervención farmacéutica en el seguimiento de la terapia antirretroviral. An. R. Acad. Nac. Farm. 75, 43–62 (2009).
  Google Scholar
• 21 Moltó J, Blanco A, Miranda C et al. Variability in non-nucleoside reverse transcriptase and protease inhibitors concentrations among HIV-infected adults in routine clinical practice. Br. J. Clin. Pharmacol. 63(6), 715–721 (2007).
  Medline CASGoogle Scholar
• 22 British HIV Association (BHIVA) Expert Panel. British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2012. HIV Med. 15(Suppl. 1), 1–85 (2014).
  Google Scholar
• 23 LaPorte CJL, Back BJ, Blaschke T et al. Updated guidelines to perform therapeutic drug monitoring for antiretroviral agents. Rev. Antivir. Ther. 3, 4–14 (2006).
  Google Scholar
• 24 Acosta EP. The promise of therapeutic drug monitoring in HIV infection, Medscape. www.medscape.com/viewarticle/715530
  Google Scholar
• 25 Duval X, Mentré F, Rey E et al. Benefit of therapeutic drug monitoring of protease inhibitors in HIV-infected patients depends on PI used in HAART regimen – ANRS 111 trial. Fundam. Clin. Pharmacol. 23(4), 491–500 (2009).
  Medline CASGoogle Scholar
• 26 Schoenenberger JA, Aragones AM, Cano SM et al. The advantages of therapeutic drug monitoring in patients receiving antiretroviral treatment and experiencing medication-related problems. Ther. Drug Monit. 35(1), 71–77 (2013).
  Medline CASGoogle Scholar
• 27 Barrail-Tran A, Taburet A-M, Poirier J-M, Groupe Suivi Therapeutique Pharmacologique De La Societe Francaise De Pharmacologie Et De T. Evidence-based therapeutic drug monitoring of lopinavir. Therapie 66(3), 231–238 (2011).
  MedlineGoogle Scholar
• 28 Yang S-P, Liu W-C, Lee K-Y et al. Effectiveness of a reduced dose of efavirenz plus 2 NRTIs as maintenance antiretroviral therapy with the guidance of therapeutic drug monitoring. J. Int. AIDS Soc. 17(4 Suppl. 3), 19524 (2014).
  MedlineGoogle Scholar
• 29 Fayet Mello A, Buclin T, Decosterd LA et al. Successful efavirenz dose reduction guided by therapeutic drug monitoring. Antivir. Ther. (Lond.) 16(2), 189–197 (2011).
  MedlineGoogle Scholar
• 30 Van Luin M, Gras L, Richter C et al. Efavirenz dose reduction is safe in patients with high plasma concentrations and may prevent efavirenz discontinuations. J. Acquir. Immune Defic. Syndr. 52(2), 240–245 (2009).
  Medline CASGoogle Scholar
• 31 Gatanaga H, Hayashida T, Tsuchiya K et al. Successful efavirenz dose reduction in HIV type 1-infected individuals with cytochrome P450 2B6 *6 and *26. Clin. Infect. Dis. 45(9), 1230–1237 (2007).•• Establishes that dose reduction of efavirenz in carriers of the genotypes CYP2B6*6/*6 and *6/*26 can reduce adverse effects involving the CNS.
  Medline CASGoogle Scholar
• 32 McFayden L, Jacqmin P, Wade J et al. Maraviroc exposure response analysis: Phase 3 antiviral efficacy in treatment experienced HIV+ patients. Presented at: 16th Population Approach Group in Europe Meeting. Kobenhavn, Denmark, 13–15 June 2007 (Abstract P4–13).
  Google Scholar
• 33 Burger D, Krens S, Robijns K, Aarnoutse R, Brüggemann R, Touw D. Poor performance of laboratories assaying newly developed antiretroviral agents: results for darunavir, etravirine, and raltegravir from the international quality control program for therapeutic drug monitoring of antiretroviral drugs in human plasma/serum. Ther. Drug Monit. 36(6), 824–827 (2014).
  Medline CASGoogle Scholar
• 34 Siccardi M, D’Avolio A, Rodriguez-Novoa S et al. Intrapatient and interpatient pharmacokinetic variability of raltegravir in the clinical setting. Ther. Drug Monit. 34(2), 232–235 (2012).
  Medline CASGoogle Scholar
• 35 Back D, Gibbons S, Khoo S. An update on therapeutic drug monitoring for antiretroviral drugs. Ther. Drug Monit. 28(3), 468–473 (2006).
  MedlineGoogle Scholar
• 36 Sadler BM, Gillotin C, Lou Y, Stein DS. Pharmacokinetic and pharmacodynamic study of the human immunodeficiency virus protease inhibitor amprenavir after multiple oral dosing. Antimicrob. Agents Chemother. 45(1), 30–37 (2001).
  Medline CASGoogle Scholar
• 37 Hsu A, Zolopa A, Shulman N et al. Final analysis of ritonavir (RTV) intensification in indinavir (IDV) recipients with detectable HIV RNA levels. Presented at: 8th Conference on Retroviruses and Opportunistic Infection. Chicago, IL, USA, 4–8 February 2001 (Abstract 337).
  Google Scholar
• 38 Núñez M, González De Requena D, Gallego L, Jiménez-Nácher I, González-Lahoz J, Soriano V. Higher efavirenz plasma levels correlate with development of insomnia. J. Acquir. Immune Defic. Syndr. 28(4), 399–400 (2001).
  Medline CASGoogle Scholar
• 39 Dieleman JP, Gyssens IC, Van Der Ende ME, De Marie S, Burger DM. Urological complaints in relation to indinavir plasma concentrations in HIV-infected patients. AIDS 13(4), 473–478 (1999).
  Medline CASGoogle Scholar
• 40 Gatti G, Di Biagio A, Casazza R et al. The relationship between ritonavir plasma levels and side-effects: implications for therapeutic drug monitoring. AIDS 13(15), 2083–2089 (1999).
  Medline CASGoogle Scholar
• 41 Anderson PL, Brundage RC, Bushman L, Kakuda TN, Remmel RP, Fletcher CV. Indinavir plasma protein binding in HIV-1-infected adults. AIDS 14(15), 2293–2297 (2000).
  Medline CASGoogle Scholar
• 42 González de Requena D. Monitorización de concentraciones plasmaticas (MCP) y farmacogenética del tratamiento antirretroviral. 2o seminario de atención farmacéutica. Grupo VIH de la SEFH, Madrid (2002). www.sefh.es/bibliotecavirtual/2_AF_VIH_2002/4_monitorizacion_concentraciones_plasmaticas.pdf.
  Google Scholar
• 43 Liverpool HIV Pharmacology Group. HIV-drug interactions. www.hiv-druginteractions.org/FactSheets.aspx.• Periodic update by the Liverpool HIV Pharmacology Group of the principal pharmacokinetic parameters of the antiretroviral classes.
  Google Scholar
• 44 Acosta EP, Gerber JG, Adult Pharmacology Committee of the ACTG. Position paper on therapeutic drug monitoring of antiretroviral agents. AIDS Res. Hum. Retroviruses 18(12), 825–834 (2002).
  Medline CASGoogle Scholar
• 45 Rodríguez J. Estudio de la variabilidad poblacional en farmacocinética y farmacodinamia (I). Conceptos generales Cienc. Pharm. 6, 96–106 (1996).
  Google Scholar
• 46 Snedecor SJ, Khachatryan A, Nedrow K et al. The prevalence of transmitted resistance to first-generation non-nucleoside reverse transcriptase inhibitors and its potential economic impact in HIV-infected patients. PLoS ONE 8(8), e72784 (2013).
  Medline CASGoogle Scholar
• 47 Hoetelmans RMW. Exploiting pharmacokinetics to optimize antiretroviral therapy. www.medscape.org/viewarticle/416455
  Google Scholar
• 48 Kakuda TN, Brochot A, Tomaka FL, Vangeneugden T, Van De Casteele T, Hoetelmans RMW. Pharmacokinetics and pharmacodynamics of boosted once-daily darunavir. J. Antimicrob. Chemother. 69(10), 2591–2605 (2014).
  Medline CASGoogle Scholar
• 49 Havlir DV, O'marro SD. Atazanavir: new option for treatment of HIV infection. Clin. Infect. Dis. 38(11), 1599–1604 (2004).
  Medline CASGoogle Scholar
• 50 Curran A, Pérez-Valero I, Moltó J. Rezolsta^® (darunavir/cobicistat): first boosted protease inhibitor co-formulated with cobicistat. AIDS Rev. 17(2), 114–120 (2015).
  MedlineGoogle Scholar
• 51 Mcdonald CK, Martorell C, Ramgopal M et al. Cobicistat-boosted protease inhibitors in HIV-infected patients with mild to moderate renal impairment. HIV Clin. Trials 15(6), 269–273 (2014).
  Medline CASGoogle Scholar
• 52 Min S, Song I, Borland J et al. Pharmacokinetics and safety of S/GSK1349572, a next-generation HIV integrase inhibitor, in healthy volunteers. Antimicrob. Agents Chemother. 54(1), 254–258 (2010).
  Medline CASGoogle Scholar
• 53 Min S, Sloan L, Dejesus E et al. Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of dolutegravir as 10-day monotherapy in HIV-1-infected adults. AIDS 25(14), 1737–1745 (2011).
  Medline CASGoogle Scholar
• 54 Margolis DA, Brinson CC, Smith GHR et al. Cabotegravir plus rilpivirine, once a day, after induction with cabotegravir plus nucleoside reverse transcriptase inhibitors in antiretroviral-naive adults with HIV-1 infection (LATTE): a randomised, Phase 2b, dose-ranging trial. Lancet Infect. Dis. doi:10.1016/S1473-3099(15)00152-8 (2015) (Epub ahead of print).
  MedlineGoogle Scholar
• 55 Abel S, Van Der Ryst E, Rosario MC et al. Assessment of the pharmacokinetics, safety and tolerability of maraviroc, a novel CCR5 antagonist, in healthy volunteers. Br. J. Clin. Pharmacol. 65(Suppl. 1), 5–18 (2008).
  Medline CASGoogle Scholar
• 56 Birkett D. Farmacocinética Fácil (1st Edition). McGraw-Hill Interamericana, Spain (2005).
  Google Scholar
• 57 Marzolini C, Telenti A, Decosterd LA, Greub G, Biollaz J, Buclin T. Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1-infected patients. AIDS 15(1), 71–75 (2001).
  Medline CASGoogle Scholar
• 58 Langmann P, Zilly M, Weissbrich B, Desch S, Väth T, Klinker H. Therapeutic drug monitoring of indinavir in HIV-infected patients undergoing HAART. Infection 30(1), 13–16 (2002).
  Medline CASGoogle Scholar
• 59 De Vries-Sluijs TEMS, Dieleman JP, Arts D et al. Low nevirapine plasma concentrations predict virological failure in an unselected HIV-1-infected population. Clin. Pharmacokinet. 42(6), 599–605 (2003).
  Medline CASGoogle Scholar
• 60 Rayner C, Dooley M, Nation R. Antivirals for HIV. In: Applied Pharmacokinetics & Pharmacodynamics: Principles of Therapeutic Drug Monitoring. Burton M, Schentag J, Shaw L, Evans W (Eds). Lippincott Williams & Wilkins, Baltimore, MD, USA, 355–409 (2006).
  Google Scholar
• 61 Higgins N, Tseng A, Sheehan NL, La Porte CJL. Antiretroviral therapeutic drug monitoring in Canada: current status and recommendations for clinical practice. Can. J. Hosp. Pharm. 62(6), 500–509 (2009).
  MedlineGoogle Scholar
• 62 Barrail-Tran A, Taburet A-M, Poirier J-M, Groupe Suivi Therapeutique Pharmacologique De La Societe Francaise De Pharmacologie Et De T. Evidence-based therapeutic drug monitoring for indinavir. Therapie 66(3), 239–246 (2011).
  MedlineGoogle Scholar
• 63 Liu X, Ma Q, Zhang F. Therapeutic drug monitoring in highly active antiretroviral therapy. Expert Opin. Drug Saf. 9(5), 743–758 (2010).
  Medline CASGoogle Scholar
• 64 Burugula L, Pilli NR, Makula A, Lodagala DS, Kandhagatla R. Liquid chromatography-tandem mass spectrometric assay for the non-nucleoside reverse transcriptase inhibitor rilpivirine in human plasma. Biomed. Chromatogr. 27(2), 172–178 (2013).
  Medline CASGoogle Scholar
• 65 Aouri M, Calmy A, Hirschel B et al. A validated assay by liquid chromatography-tandem mass spectrometry for the simultaneous quantification of elvitegravir and rilpivirine in HIV positive patients. J. Mass Spectrom. 48(5), 616–625 (2013).
  Medline CASGoogle Scholar
• 66 Martin AM, Nolan D, Gaudieri S, Phillips E, Mallal S. Pharmacogenetics of antiretroviral therapy: genetic variation of response and toxicity. Pharmacogenomics 5(6), 643–655 (2004).
  CASGoogle Scholar
• 67 Feero WG, Guttmacher AE, Collins FS. Genomic medicine – an updated primer. N. Engl. J. Med. 362(21), 2001–2011 (2010).
  Medline CASGoogle Scholar
• 68 Genomes Project C, Abecasis GR, Altshuler D et al. A map of human genome variation from population-scale sequencing. Nature 467(7319), 1061–1073 (2010).
  MedlineGoogle Scholar
• 69 The Single Nucleotide Polymorphism database. www.ncbi.nlm.nih.gov/snp
  Google Scholar
• 70 Mhandire D, Lacerda M, Castel S et al. Effects of CYP2B6 and CYP1A2 genetic variation on nevirapine plasma concentration and pharmacodynamics as measured by CD4 cell count in Zimbabwean HIV-infected patients. OMICS 19(9), 553–562 (2015).
  Medline CASGoogle Scholar
• 71 Sukasem C, Chamnanphon M, Koomdee N et al. Pharmacogenetics and clinical biomarkers for subtherapeutic plasma efavirenz concentration in HIV-1 infected Thai adults. Drug Metab. Pharmacokinet. 29(4), 289–295 (2014).
  Medline CASGoogle Scholar
• 72 Haas DW, Smeaton LM, Shafer RW et al. Pharmacogenetics of long-term responses to antiretroviral regimens containing efavirenz and/or nelfinavir: an adult AIDS Clinical Trials Group Study. J. Infect. Dis. 192(11), 1931–1942 (2005).
  Medline CASGoogle Scholar
• 73 Mouly SJ, Matheny C, Paine MF et al. Variation in oral clearance of saquinavir is predicted by CYP3A5*1 genotype but not by enterocyte content of cytochrome P450 3A5. Clin. Pharmacol. Ther. 78(6), 605–618 (2005).
  Medline CASGoogle Scholar
• 74 Lubomirov R, Arab-Alameddine M, Rotger M et al. Pharmacogenetics-based population pharmacokinetic analysis of etravirine in HIV-1 infected individuals. Pharmacogenet. Genomics 23(1), 9–18 (2013).
  Medline CASGoogle Scholar
• 75 Fellay J, Marzolini C, Meaden ER et al. Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study. Lancet 359(9300), 30–36 (2002).
  Medline CASGoogle Scholar
• 76 Kwara A, Lartey M, Sagoe KW, Rzek NL, Court MH. CYP2B6 (c.516G→T) and CYP2A6 (*9B and/or *17) polymorphisms are independent predictors of efavirenz plasma concentrations in HIV-infected patients. Br. J. Clin. Pharmacol. 67(4), 427–436 (2009).
  Medline CASGoogle Scholar
• 77 Ribaudo HJ, Liu H, Schwab M et al. Effect of CYP2B6, ABCB1, and CYP3A5 polymorphisms on efavirenz pharmacokinetics and treatment response: an AIDS Clinical Trials Group study. J. Infect. Dis. 202(5), 717–722 (2010).• Establishes the association between efavirenz slow metabolizer genotypes (516/983) and an increase in CNS events among whites, as well as a decrease in virological failure among blacks.
  Medline CASGoogle Scholar
• 78 Rotger M, Taffe P, Bleiber G et al. Gilbert syndrome and the development of antiretroviral therapy-associated hyperbilirubinemia. J. Infect. Dis. 192(8), 1381–1386 (2005).
  Medline CASGoogle Scholar
• 79 Haas DW, Kwara A, Richardson DM et al. Secondary metabolism pathway polymorphisms and plasma efavirenz concentrations in HIV-infected adults with CYP2B6 slow metabolizer genotypes. J. Antimicrob. Chemother. 69(8), 2175–2182 (2014).
  Medline CASGoogle Scholar
• 80 Mahungu TW, Nair D, Smith CJ et al. The relationships of ABCB1 3435C>T and CYP2B6 516G>T with high-density lipoprotein cholesterol in HIV-infected patients receiving Efavirenz. Clin. Pharmacol. Ther. 86(2), 204–211 (2009).
  Medline CASGoogle Scholar
• 81 Gupta SK, Rosenkranz SL, Cramer YS et al. The pharmacokinetics and pharmacogenomics of efavirenz and lopinavir/ritonavir in HIV-infected persons requiring hemodialysis. AIDS 22(15), 1919–1927 (2008).
  Medline CASGoogle Scholar
• 82 Kiser JJ, Aquilante CL, Anderson PL, King TM, Carten ML, Fletcher CV. Clinical and genetic determinants of intracellular tenofovir diphosphate concentrations in HIV-infected patients. J. Acquir. Immune Defic. Syndr. 47(3), 298–303 (2008).
  Medline CASGoogle Scholar
• 83 ThePharmacogenetics and Pharmacogenomics Knowledge Base. www.pharmgkb.org/
  Google Scholar
• 84 Álvarez Barco E, Rodríguez Novoa S. The pharmacogenetics of HIV treatment: a practical clinical approach. J. Pharmacogenomics Pharmacoproteomics 4(116), 1–10 (2013).
  Google Scholar
• 85 Illing PT, Vivian JP, Dudek NL et al. Immune self-reactivity triggered by drug-modified HLA-peptide repertoire. Nature 486(7404), 554–558 (2012).
  Medline CASGoogle Scholar
• 86 Allele*Frequencies in Worldwide Populations. www.allelefrequencies.net.
  Google Scholar
• 87 Rodríguez-Nóvoa S, Martín-Carbonero L, Barreiro P et al. Genetic factors influencing atazanavir plasma concentrations and the risk of severe hyperbilirubinemia. AIDS 21(1), 41–46 (2007).
  Medline CASGoogle Scholar
• 88 Farley J, Hines S, Musk A, Ferrus S, Tepper V. Assessment of adherence to antiviral therapy in HIV-infected children using the Medication Event Monitoring System, pharmacy refill, provider assessment, caregiver self-report, and appointment keeping. J. Acquir. Immune Defic. Syndr. 33(2), 211–218 (2003).
  MedlineGoogle Scholar
• 89 Rodríguez Nóvoa S, Barreiro P, Rendón A et al. Plasma levels of atazanavir and the risk of hyperbilirubinemia are predicted by the 3435C–>T polymorphism at the multidrug resistance gene 1. Clin. Infect. Dis. 42(2), 291–295 (2006).
  MedlineGoogle Scholar
• 90 Soranzo N, Cavalleri GL, Weale ME et al. Identifying candidate causal variants responsible for altered activity of the ABCB1 multidrug resistance gene. Genome Res. 14(7), 1333–1344 (2004).
  Medline CASGoogle Scholar
• 91 Siccardi M, D'Avolio A, Baietto L et al. Association of a single-nucleotide polymorphism in the pregnane X receptor (PXR 63396C–>T) with reduced concentrations of unboosted atazanavir. Clin. Infect. Dis. 47(9), 1222–1225 (2008).
  Medline CASGoogle Scholar
• 92 Schipani A, Siccardi M, D'Avolio A et al. Population pharmacokinetic modeling of the association between 63396C–>T pregnane X receptor polymorphism and unboosted atazanavir clearance. Antimicrob. Agents Chemother. 54(12), 5242–5250 (2010).
  Medline CASGoogle Scholar
• 93 Smith NF, Figg WD, Sparreboom A. Role of the liver-specific transporters OATP1B1 and OATP1B3 in governing drug elimination. Expert Opin. Drug Metab. Toxicol. 1(3), 429–445 (2005).
  Medline CASGoogle Scholar
• 94 Schipani A, Egan D, Dickinson L et al. Estimation of the effect of SLCO1B1 polymorphisms on lopinavir plasma concentration in HIV-infected adults. Antivir. Ther. (Lond.) 17(5), 861–868 (2012).
  Medline CASGoogle Scholar
• 95 Hartkoorn RC, Kwan WS, Shallcross V et al. HIV protease inhibitors are substrates for OATP1A2, OATP1B1 and OATP1B3 and lopinavir plasma concentrations are influenced by SLCO1B1 polymorphisms. Pharmacogenet. Genomics 20(2), 112–120 (2010).
  Medline CASGoogle Scholar
• 96 Kohlrausch FB, De Cássia Estrela R, Barroso PF, Suarez-Kurtz G. The impact of SLCO1B1 polymorphisms on the plasma concentration of lopinavir and ritonavir in HIV-infected men. Br. J. Clin. Pharmacol. 69(1), 95–98 (2010).
  Medline CASGoogle Scholar
• 97 Hughes CA, Foisy MM, Dewhurst N et al. Abacavir hypersensitivity reaction: an update. Ann. Pharmacother. 42(3), 387–396 (2008).•• Establishes that carriers of the allele HLA-B*5701 have a greater risk of hypersensitivity reactions to abacavir; therefore, the presence of HLA-B*5701 should be evaluated in all patients prior to initiating antiretroviral treatment that includes abacavir.
  Medline CASGoogle Scholar
• 98 Hetherington S, Hughes AR, Mosteller M et al. Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Lancet 359(9312), 1121–1122 (2002).
  Medline CASGoogle Scholar
• 99 Colombo S, Rauch A, Rotger M et al. The HCP5 single-nucleotide polymorphism: a simple screening tool for prediction of hypersensitivity reaction to abacavir. J. Infect. Dis. 198(6), 864–867 (2008).
  Medline CASGoogle Scholar
• 100 Sanchez-Giron F, Villegas-Torres B, Jaramillo-Villafuerte K et al. Association of the genetic marker for abacavir hypersensitivity HLA-B*5701 with HCP5 rs2395029 in Mexican Mestizos. Pharmacogenomics 12(6), 809–814 (2011).
  CASGoogle Scholar
• 101 Galván CA, Elbarcha OC, Fernández EJ, Beltramo DM, Soria NW. Rapid HCP5 single-nucleotide polymorphism genotyping: a simple allele-specific PCR method for prediction of hypersensitivity reaction to abacavir. Clin. Chim. Acta 412(15–16), 1382–1384 (2011).
  Medline CASGoogle Scholar
• 102 Ribaudo HJ, Haas DW, Tierney C et al. Pharmacogenetics of plasma efavirenz exposure after treatment discontinuation: an Adult AIDS Clinical Trials Group Study. Clin. Infect. Dis. 42(3), 401–407 (2006).
  Medline CASGoogle Scholar
• 103 Rodríguez-Nóvoa S, Cuenca L, Morello J et al. Use of the HCP5 single nucleotide polymorphism to predict hypersensitivity reactions to abacavir: correlation with HLA-B*5701. J. Antimicrob. Chemother. 65(8), 1567–1569 (2010).
  Medline CASGoogle Scholar
• 104 Johnson DH, Venuto C, Ritchie MD et al. Genomewide association study of atazanavir pharmacokinetics and hyperbilirubinemia in AIDS Clinical Trials Group protocol A5202. Pharmacogenet. Genomics 24(4), 195–203 (2014).
  Medline CASGoogle Scholar
• 105 Martín AS, Gómez AI, García-Berrocal B et al. Dose reduction of efavirenz: an observational study describing cost–effectiveness, pharmacokinetics and pharmacogenetics. Pharmacogenomics 15(7), 997–1006 (2014).
  CASGoogle Scholar
• 106 Rotger M, Colombo S, Furrer H et al. Influence of CYP2B6 polymorphism on plasma and intracellular concentrations and toxicity of efavirenz and nevirapine in HIV-infected patients. Pharmacogenet. Genomics 15(1), 1–5 (2005).
  Medline CASGoogle Scholar
• 107 Haas DW, Ribaudo HJ, Kim RB et al. Pharmacogenetics of efavirenz and central nervous system side effects: an Adult AIDS Clinical Trials Group study. AIDS 18(18), 2391–2400 (2004).
  Medline CASGoogle Scholar
• 108 Rodríguez-Nóvoa S, Labarga P, Soriano V et al. Predictors of kidney tubular dysfunction in HIV-infected patients treated with tenofovir: a pharmacogenetic study. Clin. Infect. Dis. 48(11), e108–e116 (2009).
  Medline CASGoogle Scholar
• 109 Wang J, Sönnerborg A, Rane A et al. Identification of a novel specific CYP2B6 allele in Africans causing impaired metabolism of the HIV drug efavirenz. Pharmacogenet. Genomics 16(3), 191–198 (2006).
  MedlineGoogle Scholar
• 110 Tsuchiya K, Gatanaga H, Tachikawa N et al. Homozygous CYP2B6*6 (Q172H and K262R) correlates with high plasma efavirenz concentrations in HIV-1 patients treated with standard efavirenz-containing regimens. Biochem. Biophys. Res. Commun. 319(4), 1322–1326 (2004).
  Medline CASGoogle Scholar
• 111 Klein K, Lang T, Saussele T et al. Genetic variability of CYP2B6 in populations of African and Asian origin: allele frequencies, novel functional variants, and possible implications for anti-HIV therapy with efavirenz. Pharmacogenet. Genomics 15(12), 861–873 (2005).
  Medline CASGoogle Scholar
• 112 Wyen C, Hendra H, Vogel M et al. Impact of CYP2B6 983T>C polymorphism on non-nucleoside reverse transcriptase inhibitor plasma concentrations in HIV-infected patients. J. Antimicrob. Chemother. 61(4), 914–918 (2008).
  Medline CASGoogle Scholar
• 113 Manosuthi W, Sukasem C, Lueangniyomkul A et al. Impact of pharmacogenetic markers of CYP2B6, clinical factors, and drug-drug interaction on efavirenz concentrations in HIV/tuberculosis-coinfected patients. Antimicrob. Agents Chemother. 57(2), 1019–1024 (2013).
  Medline CASGoogle Scholar
• 114 Heil SG, Van Der Ende ME, Schenk PW et al. Associations between ABCB1, CYP2A6, CYP2B6, CYP2D6, and CYP3A5 alleles in relation to efavirenz and nevirapine pharmacokinetics in HIV-infected individuals. Ther. Drug Monit. 34(2), 153–159 (2012).
  Medline CASGoogle Scholar
• 115 Sánchez A, Cabrera S, Santos D et al. Population pharmacokinetic/pharmacogenetic model for optimization of efavirenz therapy in Caucasian HIV-infected patients. Antimicrob. Agents Chemother. 55(11), 5314–5324 (2011).
  MedlineGoogle Scholar
• 116 Winzer R, Langmann P, Zilly M et al. No influence of the P-glycoprotein genotype (MDR1 C3435T) on plasma levels of lopinavir and efavirenz during antiretroviral treatment. Eur. J. Med. Res. 8(12), 531–534 (2003).
  Medline CASGoogle Scholar
• 117 Arnedo M, Taffé P, Sahli R et al. Contribution of 20 single nucleotide polymorphisms of 13 genes to dyslipidemia associated with antiretroviral therapy. Pharmacogenet. Genomics 17(9), 755–764 (2007).
  Medline CASGoogle Scholar
• 118 Yuan J, Guo S, Hall D et al. Toxicogenomics of nevirapine-associated cutaneous and hepatic adverse events among populations of African, Asian, and European descent. AIDS 25(10), 1271–1280 (2011).
  Medline CASGoogle Scholar
• 119 Erickson DA, Mather G, Trager WF, Levy RH, Keirns JJ. Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitor nevirapine by human hepatic cytochromes P-450. Drug Metab. Dispos. 27(12), 1488–1495 (1999).
  Medline CASGoogle Scholar
• 120 Mahungu T, Smith C, Turner F et al. Cytochrome P450 2B6 516G-->T is associated with plasma concentrations of nevirapine at both 200 mg twice daily and 400 mg once daily in an ethnically diverse population. HIV Med. 10(5), 310–317 (2009).
  Medline CASGoogle Scholar
• 121 Schipani A, Wyen C, Mahungu T et al. Integration of population pharmacokinetics and pharmacogenetics: an aid to optimal nevirapine dose selection in HIV-infected individuals. J. Antimicrob. Chemother. 66(6), 1332–1339 (2011).
  Medline CASGoogle Scholar
• 122 Carr DF, Chaponda M, Cornejo Castro EM et al. CYP2B6 c.983T>C polymorphism is associated with nevirapine hypersensitivity in Malawian and Ugandan HIV populations. J. Antimicrob. Chemother. 69(12), 3329–3334 (2014).
  Medline CASGoogle Scholar
• 123 Ritchie MD, Haas DW, Motsinger AA et al. Drug transporter and metabolizing enzyme gene variants and nonnucleoside reverse-transcriptase inhibitor hepatotoxicity. Clin. Infect. Dis. 43(6), 779–782 (2006).
  Medline CASGoogle Scholar
• 124 Ciccacci C, Borgiani P, Ceffa S et al. Nevirapine-induced hepatotoxicity and pharmacogenetics: a retrospective study in a population from Mozambique. Pharmacogenomics 11(1), 23–31 (2010).
  CASGoogle Scholar
• 125 Rodriguez-Novoa S, Barreiro P, Rendón A, Jiménez-Nacher I, González-Lahoz J, Soriano V. Influence of 516G>T polymorphisms at the gene encoding the CYP450-2B6 isoenzyme on efavirenz plasma concentrations in HIV-infected subjects. Clin. Infect. Dis. 40(9), 1358–1361 (2005).
  Medline CASGoogle Scholar
• 126 Vitezica ZG, Milpied B, Lonjou C et al. HLA–DRB1*01 associated with cutaneous hypersensitivity induced by nevirapine and efavirenz. AIDS 22(4), 540–541 (2008).
  Medline CASGoogle Scholar
• 127 Littera R, Carcassi C, Masala A et al. HLA-dependent hypersensitivity to nevirapine in Sardinian HIV patients. AIDS 20(12), 1621–1626 (2006).
  Medline CASGoogle Scholar
• 128 Gatanaga H, Yazaki H, Tanuma J et al. HLA-Cw8 primarily associated with hypersensitivity to nevirapine. AIDS 21(2), 264–265 (2007).
  MedlineGoogle Scholar
• 129 Chantarangsu S, Mushiroda T, Mahasirimongkol S et al. HLA-B*3505 allele is a strong predictor for nevirapine-induced skin adverse drug reactions in HIV-infected Thai patients. Pharmacogenet. Genomics 19(2), 139–146 (2009).
  Medline CASGoogle Scholar
• 130 Wenning LA, Petry AS, Kost JT et al. Pharmacokinetics of raltegravir in individuals with UGT1A1 polymorphisms. Clin. Pharmacol. Ther. 85(6), 623–627 (2009).
  Medline CASGoogle Scholar
• 131 Neely M, Decosterd L, Fayet A et al. Pharmacokinetics and pharmacogenomics of once-daily raltegravir and atazanavir in healthy volunteers. Antimicrob. Agents Chemother. 54(11), 4619–4625 (2010).
  Medline CASGoogle Scholar
• 132 Álvarez E, Cuenca L, Morello J et al. Polymorphisms in the ABCB1 gene (P-glycoprotein) influences raltegravir concentration. Presented at: 6th IAS Conference on HIV Pathogenesis and Treatment. Rome, Italy, 17–20 July 2011 (Abstract MOPE200).
  Google Scholar
• 133 Turatti L, Sprinz E, Lazzaretti RK et al. Short communication: UGT1A1*28 variant allele is a predictor of severe hyperbilirubinemia in HIV-infected patients on HAART in southern Brazil. AIDS Res. Hum. Retroviruses 28(9), 1015–1018 (2012).
  Medline CASGoogle Scholar
• 134 Martin AM, Nolan D, James I et al. Predisposition to nevirapine hypersensitivity associated with HLA-DRB1*0101 and abrogated by low CD4 T-cell counts. AIDS 19(1), 97–99 (2005).
  Medline CASGoogle Scholar
• 135 Izzedine H, Hulot J-S, Villard E et al. Association between ABCC2 gene haplotypes and tenofovir-induced proximal tubulopathy. J. Infect. Dis. 194(11), 1481–1491 (2006).
  Medline CASGoogle Scholar
• 136 Giacomet V, Cattaneo D, Viganò A et al. Tenofovir-induced renal tubular dysfunction in vertically HIV-infected patients associated with polymorphisms in ABCC2, ABCC4 and ABCC10 genes. Pediatr. Infect. Dis. J. 32(10), e403–405 (2013).
  MedlineGoogle Scholar
• 137 Von Wichmann MÁ, Locutura J, Blanco JR et al. GESIDA quality care indicators for the care of persons infected by HIV/AIDS. Enferm. Infecc. Microbiol. Clin. 28(Suppl. 5), 6–88 (2010).
  MedlineGoogle Scholar
• 138 ASHP statement on the pharmacist's role in the care of patients with HIV infection. Am. J. Health. Syst. Pharm. 60(19), 1998–2003 (2003).
  MedlineGoogle Scholar
• 139 American Society of Health-System Pharmacists. ASHP guidelines on a standardized method for pharmaceutical care. Am. J. Health Syst. Pharm. 53(14), 1713–1716 (1996).
  MedlineGoogle Scholar
• 140 American Society of Health-System Pharmacists. ASHP guideline: minimum standard for pharmaceutical services in ambulatory care. Am. J. Health Syst. Pharm. 56(17), 1744–1753 (1999).
  MedlineGoogle Scholar
• 141 Baldominos G, Castillo I. Recomendaciones para el desarrollo de Atención Farmacéutica a pacientes externos. Comisión de normas y procedimientos de la Sociedad Española de Farmacia Hospitalaria. España (2002). www.sefh.es/normas/Pacientes_externos.pdf.
  Google Scholar
• 142 Codina C, Delgado O. Recomendaciones para desarrollar un programa de atención farmacéutica al paciente VIH. Comisión de normas y procedimientos de la Sociedad Española de Farmacia Hospitalaria. España (2001). www.sefh.es/normas/Paciente_VIH.pdf
  Google Scholar
• 143 Tseng A, Seet J, Phillips EJ. The evolution of three decades of antiretroviral therapy: challenges, triumphs and the promise of the future. Br. J. Clin. Pharmacol. 79(2), 182–194 (2015).
  Medline CASGoogle Scholar
• 144 Morillo Verdugo R, Sáez De La Fuente J, Calleja Hernandez MÁ. MAPEX: look deeper, looking away. Farm. Hosp. 39(4), 189–191 (2015).
  MedlineGoogle Scholar
• 145 Saberi P, Dong BJ, Johnson MO, Greenblatt RM, Cocohoba JM. The impact of HIV clinical pharmacists on HIV treatment outcomes: a systematic review. Patient Prefer. Adherence 6, 297–322 (2012).• Systematic review that provides evidence of the benefits of pharmaceutical care in patients with HIV.
  MedlineGoogle Scholar
• 146 Ma A, Chen DM, Chau FM, Saberi P. Improving adherence and clinical outcomes through an HIV pharmacist's interventions. AIDS Care 22(10), 1189–1194 (2010).
  MedlineGoogle Scholar
• 147 March K, Mak M, Louie SG. Effects of pharmacists' interventions on patient outcomes in an HIV primary care clinic. Am. J. Health Syst. Pharm. 64(24), 2574–2578 (2007).
  MedlineGoogle Scholar
• 148 Hernández Arroyo MJ, Cabrera Figueroa SE, Sepúlveda Correa R et al. Impact of a pharmaceutical care program on clinical evolution and antiretroviral treatment adherence: a 5-year study. Patient Prefer. Adherence 7, 729–739 (2013).• 5-year study that suggests that the establishment and maintenance of a pharmaceutical care program may increase adherence to antiretroviral treatment, increase duration of undetectable plasma viral loads and improve patient lymphocyte counts.
  MedlineGoogle Scholar
• 149 Heelon M, Skiest D, Tereso G et al. Effect of a clinical pharmacist's interventions on duration of antiretroviral-related errors in hospitalized patients. Am. J. Health Syst. Pharm. 64(19), 2064–2068 (2007).
  MedlineGoogle Scholar
• 150 Merchen BA, Gerzenshtein L, Scarsi KK et al. HIV-specialized pharmacists’ impact on prescribing errors in hospitalized patients on antiretroviral therapy. Presented at: 51st Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, IL, USA, 17–20 September 2011 (Abstract H2-794).
  Google Scholar
• 151 Panel de Expertos de Secretaría del Plan Nacional sobre el Sida, Sociedad Española de Farmacia Hospitalaria, GDEDS. Improving adhesion to antiretroviral treatment. Farm. Hosp. 32(6), 349–357 (2008).
  MedlineGoogle Scholar
• 152 Lima VD, Harrigan R, Bangsberg DR et al. The combined effect of modern highly active antiretroviral therapy regimens and adherence on mortality over time. J. Acquir. Immune Defic. Syndr. 50(5), 529–536 (2009).
  Medline CASGoogle Scholar
• 153 Wood E, Hogg RS, Yip B, Harrigan PR, O'Shaughnessy MV, Montaner JSG. Effect of medication adherence on survival of HIV-infected adults who start highly active antiretroviral therapy when the CD4⁺ cell count is 0.200 to 0.350 × 10(9) cells/L. Ann. Intern. Med. 139(10), 810–816 (2003).
  MedlineGoogle Scholar
• 154 Paterson DL, Swindells S, Mohr J et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann. Intern. Med. 133(1), 21–30 (2000).•• Suggests that in order to suppress the replication of HIV replication, a rate of adherence to antiretroviral treatment greater than or equal to 95% is required.
  Medline CASGoogle Scholar
• 155 Bangsberg DR. Less than 95% adherence to nonnucleoside reverse-transcriptase inhibitor therapy can lead to viral suppression. Clin. Infect. Dis. 43(7), 939–941 (2006).
  Medline CASGoogle Scholar
• 156 Maggiolo F, Ravasio L, Ripamonti D et al. Similar adherence rates favor different virologic outcomes for patients treated with nonnucleoside analogues or protease inhibitors. Clin. Infect. Dis. 40(1), 158–163 (2005).
  Medline CASGoogle Scholar
• 157 Shuter J. Forgiveness of non-adherence to HIV-1 antiretroviral therapy. J. Antimicrob. Chemother. 61(4), 769–773 (2008).
  Medline CASGoogle Scholar
• 158 Ortego C, Huedo-Medina TB, Llorca J et al. Adherence to highly active antiretroviral therapy (HAART): a meta-analysis. AIDS Behav. 15(7), 1381–1396 (2011).
  MedlineGoogle Scholar
• 159 Thompson MA, Mugavero MJ, Amico KR et al. Guidelines for improving entry into and retention in care and antiretroviral adherence for persons with HIV: evidence-based recommendations from an International Association of Physicians in AIDS Care panel. Ann. Intern. Med. 156(11), 817–833 (2012).
  MedlineGoogle Scholar
• 160 Holtzman CW, Brady KA, Yehia BR. Retention in care and medication adherence: current challenges to antiretroviral therapy success. Drugs 75(5), 445–454 (2015).
  Medline CASGoogle Scholar
• 161 Rocha BS, Silveira MPT, Moraes CG, Kuchenbecker RS, Dal-Pizzol TS. Pharmaceutical interventions in antiretroviral therapy: systematic review and meta-analysis of randomized clinical trials. J. Clin. Pharm. Ther. 40(3), 251–258 (2015).
  Medline CASGoogle Scholar
• 162 Tseng A, Foisy M, Hughes CA et al. Role of the pharmacist in caring for patients with HIV/AIDS: clinical practice guidelines. Can. J. Hosp. Pharm. 65(2), 125–145 (2012).
  MedlineGoogle Scholar
• 163 Cuenca MRC, Cuenca MDC, Verdugo RM. Availability and medical professional involvement in mobile healthcare applications related to pathophysiology and pharmacotherapy of HIV/AIDS. Eur. J. Hosp. Pharm. doi:10.1136/ejhpharm-2013-000340 ejhpharm-2013-000340 (2013).
  Google Scholar
• 164 Entorno 2.0 en la Atención Farmacéutica al Paciente con Patologías Víricas (2014). http://es.slideshare.net/cpvfarvalme/entorno-20-en-la-atencin-farmacutica-al-paciente-con-patologas-vricas.• The best iOS and Android Apps of 2015 aimed at HIV patients.
  Google Scholar
• 165 iTunes App Store. AIDS info HIV/AIDS Glossary. https://itunes.apple.com/us/app/aidsinfo-hiv-aids-glossary/id397417517?mt=8.
  Google Scholar
• 166 Healthline. The Best HIV iPhone and Android Apps of the Year. www.healthline.com/health/hiv-aids/top-iphone-android-apps.
  Google Scholar
• 167 Vadlapatla RK, Patel M, Paturi DK, Pal D, Mitra AK. Clinically relevant drug–drug interactions between antiretrovirals and antifungals. Expert Opin. Drug Metab. Toxicol. 10(4), 561–580 (2014).
  Medline CASGoogle Scholar
• 168 Gunda DW, Kasang C, Kidenya BR et al. Plasma concentrations of efavirenz and nevirapine among HIV-infected patients with immunological failure attending a tertiary hospital in north-western Tanzania. PLoS ONE 8(9), e75118 (2013).
  Medline CASGoogle Scholar
• 169 Valverde MP, Cabrera S. Implantación de una actividad de seguimiento integral de pacientes con tratamiento antirretroviral. 7° Seminario de Atención Farmacéutica. Grupo VIH de la SEFH. Madrid, Spain, 105–126 (2007).
  Google Scholar
• 170 Wolf CR, Smith G, Smith RL. Science, medicine, and the future: pharmacogenetics. BMJ 320(7240), 987–990 (2000).
  Medline CASGoogle Scholar
• 171 Mckinnon R, Anderson C. Transforming pharmaceutical education to accelerate the acceptance and implementation of personalized medicine. Am. J. Pharm. Educ. 75(6), 107 (2011).
  MedlineGoogle Scholar
• 172 Tuteja S, Haynes K, Zayac C, Sprague JE, Bernhardt B, Pyeritz R. Community pharmacists' attitudes towards clinical utility and ethical implications of pharmacogenetic testing. Per. Med. 10(8), 793–800 (2013).
  CASGoogle Scholar