The dawn of precision medicine in HIV: state of the art of pharmacotherapy

References

• WHO, United Nations report on the global AIDS epidemic 2013. http://files.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2013/gr2013/UNAIDS_Global_Report_2013_en.pdf. 2015.
   Google Scholar
• CDC, HIV/AIDs statistics and surveillance CDC Available from: https://www.cdc.gov/hiv/statistics/overview/ataglance.html. 2015. Accessed on 25 Jun 2018
   Google Scholar
• NIH, Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available from http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed on 25 Jun 2018
   Google Scholar
• NIH, NCI and the precision medicine initiative. Available from: https://www.cancer.gov/research/areas/treatment/pmi-oncology. Accessed on 25 Jun 2018
   Google Scholar
• Yuen GJ, Morris DM, Mydlow PK, et al. Pharmacokinetics, absolute bioavailability, and absorption characteristics of lamivudine. J Clin Pharmacol. 1995;35(12):1174–1180.
   PubMed Web of Science ®Google Scholar
• Minuesa G, Huber-Ruano I, Pastor-Anglada M, et al. Drug uptake transporters in antiretroviral therapy. Pharmacol Ther. 2011;132(3):268–279.
   PubMed Web of Science ®Google Scholar
• FDA, Antiretroviral drugs used in the treatment of HIV infection. Available from: https://www.fda.gov/forpatients/illness/hivaids/treatment/ucm118915.htm. 2018. Accessed on 25 Jun 2018
   Google Scholar
• Anderson PL, Lamba J, Aquilante CL, et al. Pharmacogenetic characteristics of indinavir, zidovudine, and lamivudine therapy in HIV-infected adults: a pilot study. J Acquir Immune Defic Syndr. 2006;42(4):441–449.
   PubMed Web of Science ®Google Scholar
• Yuen GJ, Weller S, Pakes GE. A review of the pharmacokinetics of abacavir. Clin Pharmacokinet. 2008;47(6):351–371.
   PubMed Web of Science ®Google Scholar
• Moyle G, Boffito M, Fletcher C, et al. Steady-state pharmacokinetics of abacavir in plasma and intracellular carbovir triphosphate following administration of abacavir at 600 milligrams once daily and 300 milligrams twice daily in human immunodeficiency virus-infected subjects. Antimicrob Agents Chemother. 2009;53(4):1532–1538.
   PubMed Web of Science ®Google Scholar
• Mallal S, Nolan D, Witt C, et al. Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet. 2002;359(9308):727–732.
   PubMed Web of Science ®Google Scholar
• Norcross MA, Luo S, Lu L, et al. Abacavir induces loading of novel self-peptides into HLA-B*57: 01: an autoimmune model for HLA-associated drug hypersensitivity. Aids. 2012;26(11):F21–9.
   PubMed Web of Science ®Google Scholar
• Mallal S, Phillips E, Carosi G, et al. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med. 2008;358(6):568–579.
   PubMed Web of Science ®Google Scholar
• Hughes DA, Vilar FJ, Ward CC, et al. Cost-effectiveness analysis of HLA B*5701 genotyping in preventing abacavir hypersensitivity. Pharmacogenetics. 2004;14(6):335–342.
   PubMedGoogle Scholar
• Small CB, Margolis DA, Shaefer MS, et al. HLA-B*57:01 allele prevalence in HIV-infected North American subjects and the impact of allele testing on the incidence of abacavir-associated hypersensitivity reaction in HLA-B*57:01-negative subjects. BMC Infect Dis. 2017;17(1):256.
   PubMedGoogle Scholar
• Wang H, Lu X, Yang X, et al. The efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate in antiretroviral regimens for HIV-1 therapy: meta-analysis. Medicine (Baltimore). 2016;95(41):e5146.
   PubMed Web of Science ®Google Scholar
• 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. 2008;83(2):265–272.
   PubMed Web of Science ®Google Scholar
• Likanonsakul S, Suntisuklappon B, Nitiyanontakij R, et al. A single-nucleotide polymorphism in ABCC4 Is associated with tenofovir-related beta2-microglobulinuria in Thai patients with HIV-1 infection. PLoS One. 2016;11(1):e0147724.
   PubMed Web of Science ®Google Scholar
• Pushpakom SP, Liptrott NJ, Rodriguez-Novoa S, et al. Genetic variants of ABCC10, a novel tenofovir transporter, are associated with kidney tubular dysfunction. J Infect Dis. 2011;204(1):145–153.
   PubMed Web of Science ®Google Scholar
• Kiser JJ, Aquilante CL, Anderson PL, et al. Clinical and genetic determinants of intracellular tenofovir diphosphate concentrations in HIV-infected patients. J Acquir Immune Defic Syndr. 2008;47(3):298–303.
   PubMed Web of Science ®Google Scholar
• EMTRIVA®. (emtricitabine): highlights of prescribing information. 2008; Available from: http://wwwgileadcom/pdf/emtriva_pipdf. Accessed on 25 Jun 2018
   Google Scholar
• Back DJ, Burger DM, Flexner CW, et al. The pharmacology of antiretroviral nucleoside and nucleotide reverse transcriptase inhibitors: implications for once-daily dosing. J Acquir Immune Defic Syndr.2005;39(Suppl 1):S1–23. quiz S24-25.
   PubMed Web of Science ®Google Scholar
• Piliero PJ. Pharmacokinetic properties of nucleoside/nucleotide reverse transcriptase inhibitors. J Acquir Immune Defic Syndr. 2004;37(Suppl 1):S2–S12.
   PubMed Web of Science ®Google Scholar
• Kasim NA, Whitehouse M, Ramachandran C, et al. Molecular properties of WHO essential drugs and provisional biopharmaceutical classification. Mol Pharm. 2004;1(1):85–96.
   PubMed Web of Science ®Google Scholar
• SUSTIVA. Sustiva prescribing information. Available from: http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=10348#section-4.1. Accessed on 25 Jun 2018
   Google Scholar
• Stahle L, Moberg L, Svensson JO, et al. Efavirenz plasma concentrations in HIV-infected patients: inter- and intraindividual variability and clinical effects. Ther Drug Monit. 2004;26(3):267–270.
   PubMed Web of Science ®Google Scholar
• Ghosn J, Chaix ML, Delaugerre C. HIV-1 resistance to first- and second-generation non-nucleoside reverse transcriptase inhibitors. AIDS Rev. 2009;11(3):165–173.
   PubMed Web of Science ®Google Scholar
• Miksys S, Tyndale RF. The unique regulation of brain cytochrome P450 2 (CYP2) family enzymes by drugs and genetics. Drug Metab Rev. 2004;36(2):313–333.
   PubMed Web of Science ®Google Scholar
• Kwara A, Lartey M, Sagoe KW, et al. 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. 2009;67(4):427–436.
   PubMed Web of Science ®Google Scholar
• 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. 2007;45(9):1230–1237.
   PubMed Web of Science ®Google Scholar
• Lam TN, Hui KH, Chan DP, et al. Genotype-guided dose adjustment for the use of efavirenz in HIV treatment. J Infect. 2015;71(5):607–609.
   PubMed Web of Science ®Google Scholar
• Bienczak A, Cook A, Wiesner L, et al. The impact of genetic polymorphisms on the pharmacokinetics of efavirenz in African children. Br J Clin Pharmacol. 2016;82(1):185–198.
   PubMed Web of Science ®Google Scholar
• Atwine D, Bonnet M, Taburet AM. Pharmacokinetics of efavirenz in patients on antituberculosis treatment in high human immunodeficiency virus and tuberculosis burden countries: a systematic review. Br J Clin Pharmacol. 2018;84(8):1641–1658.
   PubMed Web of Science ®Google Scholar
• Sharma M, Saravolatz LD. Rilpivirine: a new non-nucleoside reverse transcriptase inhibitor. J Antimicrob Chemother. 2013;68(2):250–256.
   PubMed Web of Science ®Google Scholar
• Usach I, Melis V, Peris JE. Non-nucleoside reverse transcriptase inhibitors: a review on pharmacokinetics, pharmacodynamics, safety and tolerability. J Int AIDS Soc. 2013;16:1–14.
   PubMed Web of Science ®Google Scholar
• Azijn H, Tirry I, Vingerhoets J, et al. TMC278, a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1. Antimicrob Agents Chemother. 2010;54(2):718–727.
   PubMed Web of Science ®Google Scholar
• Aouri M, Barcelo C, Guidi M, et al. Population pharmacokinetics and pharmacogenetics analysis of rilpivirine in HIV-1-infected individuals. Antimicrob Agents Chemother. 2017;61(1).
   PubMed Web of Science ®Google Scholar
• Behm MO, Yee KL, Liu R, et al. The effect of food on doravirine bioavailability: results from two pharmacokinetic studies in healthy subjects. Clin Drug Investig. 2017;37(6):571–579.
   PubMed Web of Science ®Google Scholar
• Smith SJ, Pauly GT, Akram A, et al. Rilpivirine and doravirine have complementary efficacies against NNRTI-resistant HIV-1 mutants. J Acquir Immune Defic Syndr. 2016;72(5):485–491.
   PubMed Web of Science ®Google Scholar
• Meizhen Feng MS, Min X, Grobler J, et al., NNRTI-resistant mutants are suppressed by doravirine at clinically.Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI); Feb 22-25, 2016; Boston, MA. Poster 506. http://www.croiconference.org/sites/default/files/posters-2016/506.pdf
   Google Scholar
• Merck Sharp & Dohme Corp. A phase 3 multicenter, double-blind, randomized, active comparator-controlled clinical trial to evaluate the safety and efficacy of doravirine (MK-1439) 100 mg once daily versus darunavir 800 mg once daily plus ritonavir 100 mg once daily, each in combination with TRUVADA™ or EPZICOM™/KIVEXA™, in treatment-naive HIV-1 infected subjects. In:ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US); Updated 2014 Oct 23;cited 2014 Oct 23;cited 2017 Oct 23;cited 2017 Aug 23;cited 2017 Aug 28. Available from. https://www.clinicaltrials.gov/ct2/show/NCT02275780.
   Google Scholar
• Squires K. Doravirine is non-inferior to darunavir/r in Phase 3 treatment-naïve trial at Week 48. Webcast presented at: Conference on Retroviruses and Opportunistic Infections (CROI); Feb 13-16, 2017; Seattle, Washington. Available from: http://www.croiwebcasts.org/console/player/33382?mediaType=slideVideo&. Last accessed on August 28, 2017.
   Google Scholar
• Jean-Michel Molina KS, Sax PE, Doravirine is non-inferior to darunavir/r in Phase 3 treatment-naive trial at Week 48. Abstract presented at: Conference on Retroviruses and Opportunistic Infections (CROI); Feb 13-16, 2017; Seattle, Washington. Available from: http://www.croiconference.org/sessions/doravirine-non-inferior-darunavirr-phase-3-treatment-na%C3%AFve-trial-week-48. Last accessed on August 28, 2017.
   Google Scholar
• Merck Sharp & Dohme Corp. A phase II A phase III multicenter, double-blind, randomized, active comparator-controlled clinical trial to evaluate the safety and efficacy of MK-1439A once-daily versus ATRIPLA™ once-daily in treatment-naïve HIV-1 infected subjects. In:ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US); updated 2015 Mar 26; cited 2015 Mar 26; cited 2017 Mar 26; cited 2017 Aug 26; cited 2017 Aug 28. Available from. https://www.clinicaltrials.gov/ct2/show/NCT02403674.
   Google Scholar
• Squires KE, Molina J-M, Sax PE, et al., Fixed-dose combination of doravirine/lamivudine/TDF is non-inferior to efavirenz/emtricitabine/TDF in treatment-naive adults with HIV-1 infection: week 48 results of the phase 3 DRIVE-AHEAD study. Slides presented at: International AIDS Society (IAS) Conference on HIV Science; Jul 23-26, 2017; Paris, France. Available from: http://programme.ias2017.org/PAGMaterial/PPT/2906_4292/IAS%20oral%20presentation__1439A-021%20Primary%20Results_Final_25July2017_Squires.pptx. Last accessed on August 28, 2017.
   Google Scholar
• Markowitz M, Morales-Ramirez JO, Nguyen BY, et al. Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10 days in treatment-naive HIV-1-infected individuals. J Acquir Immune Defic Syndr. 2006;43(5):509–515.
   PubMed Web of Science ®Google Scholar
• Cahn P, Kaplan R, Sax PE, et al. Raltegravir 1200 mg once daily versus raltegravir 400 mg twice daily, with tenofovir disoproxil fumarate and emtricitabine, for previously untreated HIV-1 infection: a randomised, double-blind, parallel-group, phase 3, non-inferiority trial. Lancet HIV. 2017;4(11):E486–E494.
   PubMed Web of Science ®Google Scholar
• Arab-Alameddine M, Fayet-Mello A, Lubomirov R, et al. Population pharmacokinetic analysis and pharmacogenetics of raltegravir in HIV-positive and healthy individuals. Antimicrob Agents Chemother. 2012;56(6):2959–2966.
   PubMed Web of Science ®Google Scholar
• Siccardi M, D’Avolio A, Rodriguez-Novoa S, et al. Intrapatient and interpatient pharmacokinetic variability of raltegravir in the clinical setting. Ther Drug Monit. 2012;34(2):232–235.
   PubMed Web of Science ®Google Scholar
• Calcagno A, Cusato J, Simiele M, et al. High interpatient variability of raltegravir CSF concentrations in HIV-positive patients: a pharmacogenetic analysis. J Antimicrob Chemother. 2014;69(1):241–245.
   PubMed Web of Science ®Google Scholar
• Cahn P. Candidates for inclusion in a universal antiretroviral regimen: dolutegravir. Curr Opin HIV AIDS. 2017;12(4):318–323.
   PubMed Web of Science ®Google Scholar
• Chen S, St Jean P, Borland J, et al. Evaluation of the effect of UGT1A1 polymorphisms on dolutegravir pharmacokinetics. Pharmacogenomics. 2014;15(1):9–16.
   PubMed Web of Science ®Google Scholar
• Tsuchiya K, Hayashida T, Hamada A, et al. Brief report: high peak level of plasma raltegravir concentration in patients with ABCB1 and ABCG2 genetic variants. J Acquir Immune Defic Syndr. 2016;72(1):11–14.
   PubMed Web of Science ®Google Scholar
• Podany AT, Scarsi KK, Fletcher CV. Comparative clinical pharmacokinetics and pharmacodynamics of HIV-1 integrase strand transfer inhibitors. Clin Pharmacokinet. 2017;56(1):25–40.
   PubMed Web of Science ®Google Scholar
• Calcagno A, Simiele M, Motta I, et al. Elvitegravir/cobicistat/tenofovir/emtricitabine penetration in the cerebrospinal fluid of three HIV-positive patients. AIDS Res Hum Retroviruses. 2016;32(5):409–411.
   PubMed Web of Science ®Google Scholar
• Barcelo C, Gaspar F, Aouri M, et al. Population pharmacokinetic analysis of elvitegravir and cobicistat in HIV-1-infected individuals. J Antimicrob Chemother. 2016;71(7):1933–1942.
   PubMed Web of Science ®Google Scholar
• Brik A, Wong CH. HIV-1 protease: mechanism and drug discovery. Org Biomol Chem. 2003;1(1):5–14.
   PubMed Web of Science ®Google Scholar
• van Leth F, Phanuphak P, Ruxrungtham K, et al. Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study. Lancet. 2004;363(9417):1253–1263.
   PubMed Web of Science ®Google Scholar
• Best BM, Letendre SL, Brigid E, et al. Low atazanavir concentrations in cerebrospinal fluid. AIDS. 2009;23(1):83–87.
   PubMed Web of Science ®Google Scholar
• Cleijsen RM, van de Ende ME, Kroon FP, et al. Therapeutic drug monitoring of the HIV protease inhibitor atazanavir in clinical practice. J Antimicrob Chemother. 2007;60(4):897–900.
   PubMed Web of Science ®Google Scholar
• Le Tiec C, Barrail A, Goujard C, et al. Clinical pharmacokinetics and summary of efficacy and tolerability of atazanavir. Clin Pharmacokinet. 2005;44(10):1035–1050.
   PubMed Web of Science ®Google Scholar
• 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. 2014;24(4):195–203.
   PubMed Web of Science ®Google Scholar
• Gammal RS, Court MH, Haidar CE, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for UGT1A1 and atazanavir prescribing. Clin Pharmacol Ther. 2016;99(4):363–369.
   PubMed Web of Science ®Google Scholar
• Kile DA, MaWhinney S, Aquilante CL, et al. A population pharmacokinetic-pharmacogenetic analysis of atazanavir. AIDS Res Hum Retroviruses. 2012;28(10):1227–1234.
   PubMed Web of Science ®Google Scholar
• Anderson PL, Aquilante CL, Gardner EM, et al. Atazanavir pharmacokinetics in genetically determined CYP3A5 expressors versus non-expressors. J Antimicrob Chemother. 2009;64(5):1071–1079.
   PubMed Web of Science ®Google Scholar
• Tie Y, Wang YF, Boross PI, et al. Critical differences in HIV-1 and HIV-2 protease specificity for clinical inhibitors. Protein Sci. 2012;21(3):339–350.
   PubMed Web of Science ®Google Scholar
• Tie Y, Boross PI, Wang YF, et al. High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multi-drug-resistant clinical strains. J Mol Biol. 2004;338(2):341–352.
   PubMed Web of Science ®Google Scholar
• Molto J, Xinarianos G, Miranda C, et al. Simultaneous pharmacogenetics-based population pharmacokinetic analysis of darunavir and ritonavir in HIV-infected patients. Clin Pharmacokinet. 2013;52(7):543–553.
   PubMed Web of Science ®Google Scholar
• Belkhir L, Elens L, Zech F, et al. Interaction between darunavir and etravirine is partly mediated by CYP3A5 polymorphism. PLoS One. 2016;11(10):e0165631.
   Web of Science ®Google Scholar
• Moyle GJ, Back D. Principles and practice of HIV-protease inhibitor pharmacoenhancement. HIV Med. 2001;2(2):105–113.
   PubMedGoogle Scholar
• Elens L, van Gelder T, Hesselink DA, et al. CYP3A4*22: promising newly identified CYP3A4 variant allele for personalizing pharmacotherapy. Pharmacogenomics. 2013;14(1):47–62.
   PubMed Web of Science ®Google Scholar
• Carter J, Keating. GM. ARAVIROC. Drugs. 2007;67(15):2277–2288. Discussion 2289-2290.
   PubMedGoogle Scholar
• Siccardi M, D’Avolio A, Nozza S, et al. Maraviroc is a substrate for OATP1B1 in vitro and maraviroc plasma concentrations are influenced by SLCO1B1 521 T>C polymorphism. Pharmacogenet Genomics. 2010;20(12):759–765.
   PubMed Web of Science ®Google Scholar
• Lu Y, Fuchs EJ, Hendrix CW, et al. CYP3A5 genotype impacts maraviroc concentrations in healthy volunteers. Drug Metab Dispos. 2014;42(11):1796–1802.
   PubMed Web of Science ®Google Scholar
• Lu Y, Fuchs EJ, Hendrix CW, et al. Response to “clinical relevance of CYP3A5 genotype on maraviroc exposures”. Drug Metab Dispos. 2015;43(5):773.
   PubMed Web of Science ®Google Scholar
• Stellbrink HJ, Reynes J, Lazzarin A, et al. Dolutegravir in antiretroviral-naive adults with HIV-1: 96-week results from a randomized dose-ranging study. AIDS. 2013;27(11):1771–1778.
   PubMed Web of Science ®Google Scholar
• de Saint-Martin L, Bressollette L, Perfezou P, et al. Impact of atazanavir-based HAART regimen on the carotid intima-media thickness of HIV-infected persons: a comparative prospective cohort. AIDS. 2010;24(18):2797–2801.
   PubMed Web of Science ®Google Scholar
• Lennox JL, Landovitz RJ, Ribaudo HJ, et al. Efficacy and tolerability of 3 nonnucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens for treatment-naive volunteers infected with HIV-1: a randomized, controlled equivalence trial. Ann Intern Med. 2014;161(7):461–471.
   PubMed Web of Science ®Google Scholar
• Molina JM, Clotet B, van Lunzen J, et al. Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO): 96 week results from a randomised, open-label, phase 3b study. Lancet HIV. 2015;2(4):e127–36.
   PubMed Web of Science ®Google Scholar
• Squires K, Kityo C, Hodder S, et al. Integrase inhibitor versus protease inhibitor based regimen for HIV-1 infected women (WAVES): a randomised, controlled, double-blind, phase 3 study. Lancet HIV. 2016;3(9):e410–e420.
   PubMed Web of Science ®Google Scholar
• NIH, Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV Available from: https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/11/what-to-start. Accessed on 25 Jun 2018
   Google Scholar
• Saravanan S, Kausalya B, Gomathi S, et al. Etravirine and rilpivirine drug resistance among HIV-1 subtype C infected children failing non-nucleoside reverse transcriptase inhibitor-based regimens in South India. AIDS Res Hum Retroviruses. 2017;33(6):567–574.
   PubMed Web of Science ®Google Scholar
• Gallant J, Hsue PY, Shreay S, et al. Comorbidities among US patients with prevalent HIV infection – a trend analysis. J Infect Dis. 2017;216(12):1525–1533.
   PubMed Web of Science ®Google Scholar
• Mayer KH, Loo S, Crawford PM, et al. Excess clinical comorbidity among HIV-infected patients accessing primary care in US community health centers. Public Health Rep. 2018;133(1):109–118.
   PubMed Web of Science ®Google Scholar
• Kelly SG, Plankey M, Post WS, et al. Associations between tobacco, alcohol, and drug use with coronary artery plaque among HIV-infected and uninfected men in the multicenter AIDS cohort study. PLoS One. 2016;11(1):e0147822.
   PubMed Web of Science ®Google Scholar
• Smith AM, Smouse SL, Tau NP, et al. Laboratory-acquired infections of Salmonella enterica serotype Typhi in South Africa: phenotypic and genotypic analysis of isolates. BMC Infect Dis. 2017;17(1):551.
   PubMedGoogle Scholar
• Hamblin MA, Wordsworth S, Fermont JM, et al. Clinical applicability and cost of a 46-gene panel for genomic analysis of solid tumours: retrospective validation and prospective audit in the UK national health service. PLoS Med. 2017;14(2):e1002424.
   PubMed Web of Science ®Google Scholar
• Conrado T, Miranda-Filho Dde B, Bandeira F. Vitamin D deficiency in HIV-infected individuals: one more risk factor for bone loss and cardiovascular disease? Arq Bras Endocrinol Metabol. 2010;54(2):118–122.
   PubMed Web of Science ®Google Scholar
• Friis-Møller N, Thiébaut R, Reiss P, et al. Predicting the risk of cardiovascular disease in HIV-infected patients: the data collection on adverse effects of anti-HIV drugs study. Eur J Cardiovasc Prev Rehabil. 2010;17(5):491–501.
   PubMedGoogle Scholar
• Ryom L, Lundgren JD, El-Sadr W, et al. Cardiovascular disease and use of contemporary protease inhibitors: the D:A:D international prospective multicohort study. The Lancet HIV. 2018;5(6):e291-e300. e291-e300.
   PubMed Web of Science ®Google Scholar
• LaFleur J, Bress AP, Rosenblatt L, et al. Cardiovascular outcomes among HIV-infected veterans receiving atazanavir. Aids. 2017;31(15):2095–2106.
   PubMed Web of Science ®Google Scholar
• Gatell JM, Assoumou L, Moyle G, et al. Switching from a ritonavir-boosted protease inhibitor to a dolutegravir-based regimen for maintenance of HIV viral suppression in patients with high cardiovascular risk. Aids. 2017;31(18):2503–2514.
   PubMed Web of Science ®Google Scholar
• Santos JR, Saumoy M, Curran A, et al. The lipid-lowering effect of tenofovir/emtricitabine: a randomized, crossover, double-blind, placebo-controlled trial. Clin Infect Dis. 2015;61(3):403–408.
   PubMed Web of Science ®Google Scholar
• Faltz M, Bergin H, Pilavachi E, et al. Effect of the anti-retroviral drugs efavirenz, tenofovir and emtricitabine on endothelial cell function: role of PARP. Cardiovasc Toxicol. 2017;17(4):393–404.
   PubMed Web of Science ®Google Scholar
• Maggi P, Bellacosa C, Carito V, et al. Cardiovascular risk factors in patients on long-term treatment with nevirapine- or efavirenz-based regimens. J Antimicrob Chemother. 2011;66(4):896–900.
   PubMed Web of Science ®Google Scholar
• Gupta SK, Shen C, Moe SM, et al. Worsening endothelial function with efavirenz compared to protease inhibitors: a 12-month prospective study. PLoS One. 2012;7(9):e45716.
   PubMed Web of Science ®Google Scholar
• Durand M, Sheehy O, Baril JG, et al. Association between HIV infection, antiretroviral therapy, and risk of acute myocardial infarction: a cohort and nested case-control study using Quebec’s public health insurance database. J Acquir Immune Defic Syndr. 2011;57(3):245–253.
   PubMed Web of Science ®Google Scholar
• Abdelhady AM, Shugg T, Thong N, et al. Efavirenz inhibits the human ether-a-go-go related current (hERG) and induces QT interval prolongation in CYP2B6*6*6 allele carriers. J Cardiovasc Electrophysiol. 2016;27(10):1206–1213.
   PubMed Web of Science ®Google Scholar
• Tibotec P, Edurant Prescribing Information https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202022s000lbl.pdf. 2011. Accessed on 25 Jun 2018
   Google Scholar
• Natinal HIV curriculum Drug Interactions with Antiretroviral Medications. Available from https://www.hiv.uw.edu/go/antiretroviral-therapy/drug-drug-interactions/core-concept/all. Accessed on 25 Jun 2018
   Google Scholar
• Ichai P, Samuel D. Epidemiology of liver failure. Clin Res Hepatol Gastroenterol. 2011;35(10):610–617.
   PubMed Web of Science ®Google Scholar
• Soriano V, Barreiro P, Sherman KE. The changing epidemiology of liver disease in HIV patients. AIDS Rev. 2013;15(1):25–31.
   PubMed Web of Science ®Google Scholar
• Prosperi MC, Rosen-Zvi M, Altmann A, et al. Antiretroviral therapy optimisation without genotype resistance testing: a perspective on treatment history based models. PLoS One. 2010;5(10):e13753.
   PubMed Web of Science ®Google Scholar
• Chan-Tack KM, Struble KA, Birnkrant DB. Intracranial hemorrhage and liver-associated deaths associated with tipranavir/ritonavir: review of cases from the FDA’s adverse event reporting system. AIDS Patient Care STDS. 2008;22(11):843–850.
   PubMed Web of Science ®Google Scholar
• Parvez MK. HBV and HIV co-infection: impact on liver pathobiology and therapeutic approaches. World J Hepatol. 2015;7(1):121–126.
   PubMed Web of Science ®Google Scholar
• Huhn GD, Tebas P, Gallant J, et al. A randomized, open-label trial to evaluate switching to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide plus darunavir in treatment-experienced HIV-1-infected adults. J Acquir Immune Defic Syndr. 2017;74(2):193–200.
   PubMed Web of Science ®Google Scholar
• Soriano V, Vispo E, Labarga P, et al. Viral hepatitis and HIV co-infection. Antiviral Res. 2010;85(1):303–315.
   PubMed Web of Science ®Google Scholar
• Osinusi A, Townsend K, Kohli A, et al. Virologic response following combined ledipasvir and sofosbuvir administration in patients with HCV genotype 1 and HIV co-infection. JAMA. 2015;313(12):1232–1239.
   PubMed Web of Science ®Google Scholar
• Gupta SK, Mamlin BW, Johnson CS, et al. Prevalence of proteinuria and the development of chronic kidney disease in HIV-infected patients. Clin Nephrol. 2004;61(1):1–6.
   PubMed Web of Science ®Google Scholar
• Swanepoel CR, Atta MG, D’Agati VD, et al. Kidney disease in the setting of HIV infection: conclusions from a kidney disease: improving global outcomes (KDIGO) Controversies Conference. Kidney Int. 2018;93(3):545–559.
   PubMed Web of Science ®Google Scholar
• Rosenberg AZ, Naicker S, Winkler CA, et al. HIV-associated nephropathies: epidemiology, pathology, mechanisms and treatment. Nat Rev Nephrol. 2015;11(3):150–160.
   PubMed Web of Science ®Google Scholar
• Mocroft A, Kirk O, Reiss P, et al. Estimated glomerular filtration rate, chronic kidney disease and antiretroviral drug use in HIV-positive patients. AIDS. 2010;24(11):1667–1678.
   PubMed Web of Science ®Google Scholar
• Zaidan M, Lescure FX, Brocheriou I, et al. Tubulointerstitial nephropathies in HIV-infected patients over the past 15 years: a clinico-pathological study. Clin J Am Soc Nephrol. 2013;8(6):930–938.
   PubMed Web of Science ®Google Scholar
• Calza L. Renal toxicity associated with antiretroviral therapy. HIV Clin Trials. 2012;13(4):189–211.
   PubMed Web of Science ®Google Scholar
• Grinspoon S, Carr A. Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med. 2005;352(1):48–62.
   PubMed Web of Science ®Google Scholar
• Grunfeld C, Pang M, Doerrler W, et al. Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. J Clin Endocrinol Metab. 1992;74(5):1045–1052.
   PubMed Web of Science ®Google Scholar
• Christeff N, Melchior JC, de Truchis P, et al. Increased serum interferon alpha in HIV-1 associated lipodystrophy syndrome. Eur J Clin Invest. 2002;32(1):43–50.
   PubMed Web of Science ®Google Scholar
• Hruz PW, Murata H, Mueckler M. Adverse metabolic consequences of HIV protease inhibitor therapy: the search for a central mechanism. Am J Physiol Endocrinol Metab. 2001;280(4):E549–53.
   PubMed Web of Science ®Google Scholar
• Lenhard JM, Croom DK, Weiel JE, et al. HIV protease inhibitors stimulate hepatic triglyceride synthesis. Arterioscler Thromb Vasc Biol. 2000;20(12):2625–2629.
   PubMed Web of Science ®Google Scholar
• Vigano A, Aldrovandi GM, Giacomet V, et al. Improvement in dyslipidaemia after switching stavudine to tenofovir and replacing protease inhibitors with efavirenz in HIV-infected children. Antivir Ther. 2005;10(8):917–924.
   PubMed Web of Science ®Google Scholar
• Fabiano V, Giacomet V, Vigano A, et al. Long-term body composition and metabolic changes in HIV-infected children switched from stavudine to tenofovir and from protease inhibitors to efavirenz. Eur J Pediatr. 2013;172(8):1089–1096.
   PubMed Web of Science ®Google Scholar
• Papagianni M, Metallidis S, Tziomalos K. Novel insights in the management of dyslipidemia in patients with HIV infection. Curr Pharmacol Rep. 2018;4(2):112–119.
   Google Scholar
• Group ISS, Lundgren JD, Babiker AG, et al. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015;373(9):795–807.
   PubMed Web of Science ®Google Scholar
• Group TAS, Danel C, Moh R, et al. A trial of early antiretrovirals and isoniazid preventive therapy in Africa. N Engl J Med. 2015;373(9):808–822.
   PubMed Web of Science ®Google Scholar
• Havlir DV, Kendall MA, Ive P, et al. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N Engl J Med. 2011;365(16):1482–1491.
   PubMed Web of Science ®Google Scholar
• Abdool Karim SS, Naidoo K, Grobler A, et al. Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med. 2010;362(8):697–706.
   PubMed Web of Science ®Google Scholar
• Fletcher CV, Anderson PL, Kakuda TN, et al. Concentration-controlled compared with conventional antiretroviral therapy for HIV infection. AIDS. 2002;16(4):551–560.
   PubMed Web of Science ®Google Scholar
• Ford J, Khoo SH, Back DJ. The intracellular pharmacology of antiretroviral protease inhibitors. J Antimicrob Chemother. 2004;54(6):982–990.
   PubMed Web of Science ®Google Scholar
• Eichelbaum M, Fromm MF, Schwab M. Clinical aspects of the MDR1 (ABCB1) gene polymorphism. Ther Drug Monit. 2004;26(2):180–185.
   PubMed Web of Science ®Google Scholar
• Kim RB, Leake BF, Choo EF, et al. Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clin Pharmacol Ther. 2001;70(2):189–199.
   PubMed Web of Science ®Google Scholar
• Pal D, Kwatra D, Minocha M, et al. Efflux transporters- and cytochrome P-450-mediated interactions between drugs of abuse and antiretrovirals. Life Sci. 2011;88(21–22):959–971.
   PubMed Web of Science ®Google Scholar
• Zamber CP, Lamba JK, Yasuda K, et al. Natural allelic variants of breast cancer resistance protein (BCRP) and their relationship to BCRP expression in human intestine. Pharmacogenetics. 2003;13(1):19–28.
   PubMedGoogle Scholar
• Kohlrausch FB, de Cassia Estrela R, Barroso PF, et al. The impact of SLCO1B1 polymorphisms on the plasma concentration of lopinavir and ritonavir in HIV-infected men. Br J Clin Pharmacol. 2010;69(1):95–98.
   PubMed Web of Science ®Google Scholar
• Berno G, Zaccarelli M, Gori C, et al. Potential implications of CYP3A4, CYP3A5 and MDR‐1 genetic variants on the efficacy of Lopinavir/Ritonavir (LPV/r) monotherapy in HIV‐1 patients. J Int AIDS Soc. 2014;17(4S3):19589.
   PubMedGoogle Scholar
• Informa S EuResist prediction system. Available from: http://engine.euresist.org/. Accessed on 25 Jun 2018
   Google Scholar
• RDI, RDI’s HIV treatment response prediction system HIV-TRePS v9.6.4.0 https://www.hivrdi.org/treps/. Accessed on 25 Jun 2018
   Google Scholar
• Beerenwinkel N, Sing T, Lengauer T, et al. Computational methods for the design of effective therapies against drug resistant HIV strains. Bioinformatics. 2005;21(21):3943–3950.
   PubMed Web of Science ®Google Scholar
• Wensing AM, Calvez V, Gunthard HF, et al. 2017 update of the drug resistance mutations in HIV-1. Top Antivir Med. 2017;24(4):132–133.
   PubMedGoogle Scholar
• Rhee SY, Gonzales MJ, Kantor R, et al. Human immunodeficiency virus reverse transcriptase and protease sequence database. Nucleic Acids Res. 2003;31(1):298–303.
   PubMed Web of Science ®Google Scholar
• Van Laethem K, De Luca A, Antinori A, et al. A genotypic drug resistance interpretation algorithm that significantly predicts therapy response in HIV-1-infected patients. Antivir Ther. 2002;7(2):123–129.
   PubMed Web of Science ®Google Scholar
• Altmann A Keeping models that predict response to antiretroviral therapy up-to-date: fusion of pure data-driven approaches with rules-based methods Available from: http://www.altmann.eu/documents/posters/20090327_EUHIDRW_Altmann_fusion.pdf. Accessed on 25 Jun 2018
   Google Scholar
• Beerenwinkel N, Schmidt B, Walter H, et al. Diversity and complexity of HIV-1 drug resistance: a bioinformatics approach to predicting phenotype from genotype. Proc Natl Acad Sci U S A. 2002;99(12):8271–8276.
   PubMed Web of Science ®Google Scholar
• Stanford U. HIV-SEQ database Available from: https://hivdb.stanford.edu/. Accessed on 25 Jun 2018
   Google Scholar
• Abhyanker R VIRCONET Trademark Information. Available from: https://www.trademarkia.com/virconet-76013546.html. Accessed on 25 Jun 2018
   Google Scholar
• Jiamsakul A, Chaiwarith R, Durier N, et al. Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. J Med Virol. 2016;88(2):234–243.
   PubMed Web of Science ®Google Scholar
• Berger EA, Doms RW, Fenyo EM, et al. A new classification for HIV-1. Nature. 1998;391(6664):240.
   PubMed Web of Science ®Google Scholar
• Mullins Lab, u.o.W. Web PSSM Available from: https://indra.mullins.microbiol.washington.edu/webpssm/. Accessed on 25 Jun 2018
   Google Scholar
• Kaiser R Geno2pheno[resistance]. Available from: https://www.geno2pheno.org/. Accessed on 25 Jun 2018
   Google Scholar
• Cashin K PhenoSeq. Available from: http://tools.burnet.edu.au/phenoseq/. Accessed on 25 Jun 2018
   Google Scholar
• Volberding PA. HIV treatment and prevention: an overview of recommendations from the IAS-USA antiretroviral guidelines panel. Top Antivir Med. 2017;25(1):17–24.
   PubMedGoogle Scholar
• Woelk CH, Beliakova-Bethell N, Goicoechea M, et al. Gene expression before HAART initiation predicts HIV-infected individuals at risk of poor CD4+ T-cell recovery. AIDS. 2010;24(2):217–222.
   PubMed Web of Science ®Google Scholar
• 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. 2002;359(9300):30–36.
   PubMed Web of Science ®Google Scholar
• Mukonzo JK, Roshammar D, Waako P, et al. A novel polymorphism in ABCB1 gene, CYP2B6*6 and sex predict single-dose efavirenz population pharmacokinetics in Ugandans. Br J Clin Pharmacol. 2009;68(5):690–699.
   PubMed Web of Science ®Google Scholar
• 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. 2005;192(11):1931–1942.
   PubMed Web of Science ®Google Scholar
• de la Tribonniere X, Broly F, Deuffic-Burban S, et al. ABCB1 allele polymorphism is associated with virological efficacy in naive HIV-infected patients on HAART containing nonboosted PIs but not boosted PIs. HIV Clin Trials. 2008;9(3):192–201.
   PubMed Web of Science ®Google Scholar
• Ahuja SK, Kulkarni H, Catano G, et al. CCL3L1-CCR5 genotype influences durability of immune recovery during antiretroviral therapy of HIV-1-infected individuals. Nat Med. 2008;14(4):413–420.
   PubMed Web of Science ®Google Scholar
• Fernandez S, Rosenow AA, James IR, et al. Recovery of CD4+ T Cells in HIV patients with a stable virologic response to antiretroviral therapy is associated with polymorphisms of interleukin-6 and central major histocompatibility complex genes. J Acquir Immune Defic Syndr. 2006;41(1):1–5.
   PubMed Web of Science ®Google Scholar
• Zhu D, Taguchi-Nakamura H, Goto M, et al. Influence of single-nucleotide polymorphisms in the multidrug resistance-1 gene on the cellular export of nelfinavir and its clinical implication for highly active antiretroviral therapy. Antivir Ther. 2004;9(6):929–935.
   PubMed Web of Science ®Google Scholar
• Parathyras J, Gebhardt S, Hillermann-Rebello R, et al. A pharmacogenetic study of CD4 recovery in response to HIV antiretroviral therapy in two South African population groups. J Hum Genet. 2009;54(5):261–265.
   PubMed Web of Science ®Google Scholar
• Nasi M, Borghi V, Pinti M, et al. MDR1 C3435T genetic polymorphism does not influence the response to antiretroviral therapy in drug-naive HIV-positive patients. AIDS. 2003;17(11):1696–1698.
   PubMed Web of Science ®Google Scholar
• Brumme ZL, Dong WW, Chan KJ, et al. Influence of polymorphisms within the CX3CR1 and MDR-1 genes on initial antiretroviral therapy response. AIDS. 2003;17(2):201–208.
   PubMed Web of Science ®Google Scholar
• Hendrickson SL, Jacobson LP, Nelson GW, et al. Host genetic influences on highly active antiretroviral therapy efficacy and AIDS-free survival. J Acquir Immune Defic Syndr. 2008;48(3):263–271.
   PubMed Web of Science ®Google Scholar
• Saitoh A, Singh KK, Powell CA, et al. An MDR1-3435 variant is associated with higher plasma nelfinavir levels and more rapid virologic response in HIV-1 infected children. AIDS. 2005;19(4):371–380.
   PubMed Web of Science ®Google Scholar
• Saitoh A, Sarles E, Capparelli E, et al. CYP2B6 genetic variants are associated with nevirapine pharmacokinetics and clinical response in HIV-1-infected children. AIDS. 2007;21(16):2191–2199.
   PubMed Web of Science ®Google Scholar
• Yimer G, Ueda N, Habtewold A, et al. Pharmacogenetic & pharmacokinetic biomarker for efavirenz based ARV and rifampicin based anti-TB drug induced liver injury in TB-HIV infected patients. PLoS One. 2011;6(12):e27810.
   PubMed Web of Science ®Google Scholar
• Gibson RM, Schmotzer CL, Quinones-Mateu ME. Next-generation sequencing to help monitor patients infected with HIV: ready for clinical use? Curr Infect Dis Rep. 2014;16(4):401.
   PubMed Web of Science ®Google Scholar
• Wang C, Mitsuya Y, Gharizadeh B, et al. Characterization of mutation spectra with ultra-deep pyrosequencing: application to HIV-1 drug resistance. Genome Res. 2007;17(8):1195–1201.
   PubMed Web of Science ®Google Scholar
• Dudley DM, Chin EN, Bimber BN, et al. Low-cost ultra-wide genotyping using Roche/454 pyrosequencing for surveillance of HIV drug resistance. PLoS One. 2012;7(5):e36494.
   PubMed Web of Science ®Google Scholar
• Ram D, Leshkowitz D, Gonzalez D, et al. Evaluation of GS junior and MiSeq next-generation sequencing technologies as an alternative to Trugene population sequencing in the clinical HIV laboratory. J Virol Methods. 2015;212:12–16.
   PubMed Web of Science ®Google Scholar
• Gupta S, Taylor T, Patterson A, et al. A robust PCR protocol for HIV drug resistance testing on low-level viremia samples. Biomed Res Int. 2017;2017:4979252.
   PubMedGoogle Scholar
• Lengauer T, Pfeifer N, Kaiser R. Personalized HIV therapy to control drug resistance. Drug Discov Today Technol. 2014;11:57–64.
   PubMedGoogle Scholar
• Rosen-Zvi M, Altmann A, Prosperi M, et al. Selecting anti-HIV therapies based on a variety of genomic and clinical factors. Bioinformatics. 2008;24(13):i399–406.
   PubMed Web of Science ®Google Scholar
• Revell AD, Wang D, Boyd MA, et al. The development of an expert system to predict virological response to HIV therapy as part of an online treatment support tool. AIDS. 2011;25(15):1855–1863.
   PubMed Web of Science ®Google Scholar
• Rosenbloom DI, Hill AL, Rabi SA, et al. Antiretroviral dynamics determines HIV evolution and predicts therapy outcome. Nat Med. 2012;18(9):1378–1385.
   PubMed Web of Science ®Google Scholar
• Churchill MJ, Gorry PR, Cowley D, et al. Use of laser capture microdissection to detect integrated HIV-1 DNA in macrophages and astrocytes from autopsy brain tissues. J Neurovirol. 2006;12(2):146–152.
   PubMed Web of Science ®Google Scholar
• Honeycutt JB, Thayer WO, Baker CE, et al. HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy. Nat Med. 2017;23(5):638–643.
   PubMed Web of Science ®Google Scholar
• Cory TJ, He H, Winchester LC, et al. Alterations in P-Glycoprotein expression and function between macrophage subsets. Pharm Res. 2016;33(11):2713–2721.
   PubMed Web of Science ®Google Scholar
• Moreau A, Le Vee M, Jouan E, et al. Drug transporter expression in human macrophages. Fundam Clin Pharmacol. 2011;25(6):743–752.
   PubMed Web of Science ®Google Scholar
• Kim RB, Fromm MF, Wandel C, et al. The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Invest. 1998;101(2):289–294.
   PubMed Web of Science ®Google Scholar