Widespread use of antiretroviral agents and the epidemic of human immunodeficiency virus (HIV) strains resistant to these drugs have raised a lot of issues including the biology and clinical implications of HIV resistance, reliability of resistant assays and their role in clinical practice. In May 2000, the International AIDS panel endorsed and recommended the use of antiretroviral drug resistance testing in patients. Considerable data on HIV drug resistance testing that strongly suggest that utility of these assays may be of great value have been published and presented at major meetings. Although the genotypic and phenotypic assays are available for antiretroviral drug resistance testing, the testing has certain limitations. The role of these resistance assays is not clearly defined in clinical practice. Prospective studies are needed to define the long-term benefits of these assays. HIV drug resistance testing in the near future may become an important tool and standard of practice for patients infected with HIV. Clinicians caring for HIV-positive patients should be familiar with the antiretroviral drug resistant assays.
The Joint United Nations Program on HIV/AIDS Web site. Available at: http//www.unaids.org. Accessed July 26, 2000.
2.
Center for Disease Control and Prevention. HIV/AIDS Surveillance Report, 1999; 11(No.2):1-3.
3.
Center for Disease Control and Prevention. HIV/AIDS Surveillance Report, 1999; 11(No.1):1-3.
4.
Temesgen Z, Wright AJ. Antiretrovirals. Mayo Clinic Proceedings. 1999; 74:1284-1330.
5.
Bartlett JG, Chaisson R, Keruly J, et al. HAART: one of the most cost-effective therapies of the past decade. In: Programs & abstracts of the 12th World AIDS Conference; June 28-July 3, 1998; Geneva, Switzerland. Abstract 24380.
6.
Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining mortality and morbidity among patients with advanced HIV infection. N Engl J Med. 1998; 338:853-860.
7.
Moore RD, Chaisson RE. Natural history of HIV infection in the era of combination ART. AIDS.1999; 13:1993-2042.
8.
Carpenter C, Cooper D, Fischl M, et al. Antiretroviral therapy in adults. JAMA. 2000; 283:381-390.
9.
Panel on Clinical Practice for Treatment of HIV infection. Guidelines for the use of Antiretroviral Agents in HIV Infected Adults and Adolescents. Washington DC: U.S. Department of Health and Human Services and Henry J. Kaiser Family Foundation, 2000. Available from: http//www.hivatis.org.
10.
Henry, K.The case for more cautious, patient focused antiretroviral therapy. Ann Intern Med. 2000; 132:306-311.
11.
Mezzaroma I, Carlesimo M, Pinter E, et al. Clinical and immunologic response without decrease in virus load in patients with AIDS after 24 months of highly active antiretroviral therapy. Clinical Infectious Diseases. 1999; 29:1423-1430.
12.
Gallant J.Strategies for long-term success in the treatment of HIV infection. JAMA. 2000; 283:1329-1334.
13.
D’Souza M, Carins J, Plaeger S.Current evidence and future directions for targeting HIV entry. JAMA. 2000; 284:215-222.
14.
Arts EJ, Wainberg MA. Mechanisms of nucleoside analog antiviral activity and resistance during HIV reverse transcription. Antimicrob Agents Chemother. 1996; 40:527-540.
15.
Pantaleo G, Graziosi C, Fauci A.New concepts in the immunodeficiency virus infection. New Engl J Med. 1993; 328:327-335.
16.
Roos MT, Lange JM, De Goode RE, et al. Viral phenotype and immune response in primary HIV infection. J Infect Dis. 1992; 165:427-432.
17.
Halvir DV, Richman DD. Viral dynamics of HIV: implications for drug development and therapeutic strategies. Ann Intern Med. 1996; 124:984-994.
18.
Vella S.Clinical implications of resistance to antiretroviral drugs. AIDS Clinical Care. 1997; 9:45-49.
19.
Hirsch M, Conway B, D’Aquila R, et al. Antiretroviral drug resistance testing in adults with HIV infection. JAMA. 1998; 279:1984-1991.
20.
Hirsch M, Brun-Vezinet F, D’Aquila R, et al. Antiretroviral drug resistance testing in adult HIV-1 infection. JAMA. 2000; 283:2417-2426.
21.
Petropoulos CJ, Parkin NT, Limoli KLet al. A novel phenotypic drug susceptibility assay for HIV type 1. Antimicrob Agents Chemother. 2000; 44:920-928.
22.
Hellmann N, Johnson P, Petropoulos C, et al. Validation of the performance characteristics of a novel, rapid phenotypic drug susceptibility assay, PhenoSenseTM; HIV. Program and abstracts of the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 26-29, 1999; San Francisco, CA. Abstact 418.
23.
Vingerhoets J, Bloor S, Michiels L, et al. The accuracy and reproducibility of high throughput genotypic and phenotypic HIV-1 resistance testing under EN45001 and CLIA accreditation labels. Program and abstracts of the 7th Conference on Retroviruses and Opportunistic Infections. January 30-Feburary 2, 2000, San Francisco, CA. Abstract 793.
24.
Qari SH, Respess R, Weinstock H, et al. A comparative analysis of Virco Antivirogram and Virologic PhenoSense phenotypic assays for drug susceptibility of HIV-1. Antiviral Ther. 2000;5(Suppl 3):49.
25.
Gunthard HF, Wong JK, Ignacio CC, et al. Comparative performance of high density oligonucleotide sequencing and dideoxynucleottide sequencing of HIV type 1 pol from clinical samples. AIDS Res Hum Retroviruses. 1998; 14:869-867.
26.
Wrin T, Gamarnik A, Paxinos E, et al. Measuring the replicative fitness if recombinant HIV-1 vectors expressing protease and reverse transcriptase derived from patient viruses. Program and abstracts of the 7th Conference on Retroviruses and Opportunistic Infections. January 30-Feburary 2, 2000, San Francisco, CA. Abstract 233.
27.
Larder BA, Kemp SD, Hetogs K.Quantitative prediction of HIV-1 phenotypic drug resistance from genotypes: The virtual phenotype (Virtual/Phenotype). Antiviral Ther. 2000;5(Suppl 3):49.
28.
Werbiest W, Peeters M, Hetogs K, et al. Virtual/Phenotype is concordant with actual phenotype: A retrospective analysis of data from VIRA3001. Antiviral Ther.2000;5(Suppl 3):62.
29.
Tisdale M, Kemp SD, Parry NR, Lader BA. Rapid in vitro selection of HIV type 1 resistant to 3-thiacytadine inhibitors due to a mutation in the YMDD region of reverse transcriptase. Proc Natl Acad Sci USA1993; 90:5653-5656.
30.
Schuurman R, Demeter L, Reichelderfer P, et al. Worldwide evaluation of DNA sequencing approaches for identification of drug resistance mutations in human immunodeficiency virus type 1 reverse transcriptase. J Clin Microbiol. 1999; 37:2291-2296.
31.
Collin G, Descamps D.Telles F, et al. Differences in protease and reverse transcriptase sequences between the TruGene HIV-1 genotyping kit (Visible Genetics) and the ViroSeq genotyping system (PE Applied Biosystems). Anitivral Ther. 2000;5(Suppl 3):53.
32.
Hoover ML, Wentworth DN, Neaton JD, et al. A blinded comparison of two sequencing assays for resistance mutations in HIV-1 protease and reverse transcriptase genes in the GART Study (CPCRA 046). Antiviral Ther. 2000;5(Suppl 3):60.
33.
Erice A, Mayers DL, Strike DG, et al. Primary infection with zidovudine-resistant HIV type 1. N Engl J Med. 1993; 328:1163-1165.
34.
DeRonde A, Schuurman R, Goudsmith J, et al. First case of new infection with zidovudine-resistant HIV-1 among prospectively studied intravenous drug users and homosexual men in Amsterdam, The Netherlands. AIDS. 1996; 10:231-232.
35.
Conlon CP, Klenerman P, Edwards A, et al. Heterosexual transmission of HIV type 1 variants associated with zidovudine resistance. J Infect Dis. 1994; 169:411-415.
36.
Quigg M, Rebus S, France AJ, McMenamin J, et al. Mutations associated with zidovudine resistance in HIV-1 among recent seroconverters. AIDS. 1997; 11:835-836.
37.
Conway B, Montessori V, Rouleau D, et al. Primary lamivudine resistance in acute HIV infection. In: program and abstracts of International workshop on HIV drug resistance, treatment strategies and eradication; St. Petersburg, FL; June 25-28, 1997. Abstract 103.
38.
Imrie A, Beveridge A, Genn W, et al. Transmission of HIV type 1 resistant to nevirapine and zidovudine. J Infect Dis. 1997; 175:1502-1506.
39.
Boden D, Hurley A, Zhang L, et al. HIV-1 drug resistance in newly infected individuals. JAMA. 1999; 282:1135-1141.
40.
Little SJ, Daar ES, D’Aquilla RT, et al. Reduced antiretroviral drug susceptibility among patients with primary HIV infection. JAMA. 1999; 282:1142-1149.
41.
Wegner S, Brodine S, Mascola J, et al. Prevalence of genotypic and phenotypic resistance to antiretroviral drugs in a cohort of therapynaïve HIV-1 infected US military personnel. AIDS. 2000; 14:1009-1015.
42.
Weinstock H, Zaidi I, Respess R, et al. Genotypic and phenotypic evidence of antiretroviral drug resistance among drugnaïve persons recently diagnosed with HIV-1, USA, 1997-2000. Antiviral Ther. 2000; 5(Suppl 3):141.
43.
Easterbrook PJ, Hertogs K, Waters A, et al. Very low prevalence of antiretroviral drug resistance among HIV-1 seroconverters, London, 1984-91. Antiviral Ther. 2000; 5(Suppl 3):141.
44.
Schinazi RF, Larder BA, Mellors JW. Mutations in retroviral genes associated with drug resistance. Int Antivir News. 1997; 5:129-142.
45.
Wilson J, Bean P.A physician’s primer to Antiretroviral Drug Resistance Testing. The AIDS Reader. 2000; 10:469-478.
46.
Lanier R, Danehower S, Daluge S, et al. Genotypic and phenotypic correlates of response to abacavir (ABC, 1592) Abstract 52. Antiviral Ther. 1998; 3 (Suupl 1):36.
47.
Katlama C, Valantin Ma, Matheron S, et al. Efficacy and tolerability of stavudine plus lamivudine in treatment-naïve and treatment-experienced patients with HIV-1 infection. Ann Intern Med. 1998; 129:525-531.
48.
Calvez V, Costagliola D, Descamps D, et al. Resistance and viral response to stavudine/lamivudine combination in zidovudine, diadanosine and zalcitabine experienced patients in ALTIS 2 ANRS trial. Antiviral Ther. 2000; 5(Suppl 3):83-84.
49.
Whitcomb J.Reduced susceptibility to NRTI is associated with NNRTI hypersensitivity in Virus from HIV-1 infected patients. Program and abstracts of the 7th Conference on Retroviruses and Opportunistic Infections. January 30- Feburary 2, 2000, San Francisco, CA. Abstract234.
50.
Tebas P, Patick AK, Kane EM, et al. Virologic responses to a ritonavir-saquinavir containing regimen in patients who had previously failed nelfinavir. AIDS.1999; 13:F23-F28.
51.
Deeks SG, Grant RM, Beatty GW, et al. Activity of a ritonavir plus saquinavir containing regimen in patients with virologic evidence of indinavir or ritonavir failure. AIDS. 1998; 12:F97-F102.
52.
D’Aquila RT, Johnson VA, Welles SLet al. Zidovudine resistance and HIV-1 disease progression during antiretroviral therapy. Ann Intern Med. 1995; 122:401-408.
53.
Japour AJ, Welles S, D’Aquilla RTet al. Zidovudine resistance mutations in HIV isolated from patients after long-term zidovudine treatment. J Infect Dis. 1995; 171:1172-1179.
54.
Zolopa AR, Schafer RW, Warford A, et al. HIV-1 genotypic resistance patterns predict response to saquinavir-ritonavir therapy in patients in whom previous protease therapy had failed. Ann Intern Med. 1999; 131:813-821.
55.
Durant J, Clevenbergh P, Halfon P, et al. Drug-resistance genotyping in HIV-1 therapy: the VIRADAPT randomized controlled trial. Lancet. 1993; 353:2195-2199.
56.
Baxter J, Mayers D, Wentworth D, et al. A randomized study of antiretroviral management based on plasma genotypic antiretroviral resistance testing in patients failing therapy. AIDS. 2000; 14:F83-F93.
57.
De Luca A, Cingolani A, Murri R, et al. Usefulness of antiretroviral resistance genotyping and of patient-reported adherence assessment in unselected HIV viremia patients on HAART: a prospective randomized study. Program and abstracts of the XIII International AIDS Conference; July 9-14, 2000; Durban, South Africa. Abstract TuPpA1222.
58.
Cohen C, Hunt S, Sension M, et al. Phenotypic resistance testing significantly improves response to therapy: a randomized trial (VIRA 3001). Program and abstracts of the 7th Conference on Retroviruses and Opportunistic Infections, January 30-February 2, 2000; San Francisco, CA. Abstract 237.
59.
Melnick D, Rosenthal J, Cameron M, et al. Impact of phenotypic antiretroviral drug resistance testing on the response to salvage antiretroviral therapy (ART) in heavily experienced patients. Program and abstracts of the 7th Conference on Retroviruses and Opportunistic Infections. January 30-February 2, 2000, San Francisco, CA. Abstract 786.
60.
Meynard JL, Vray M, Morand-Joubert L, et al. Impact of treatment guided by phenotypic or genotypic resistance tests on the response to antiretroviral therapy: A randomized trial (NARVAL, ANRS 088). Antiviral Ther. 2000; 5(Suppl 3):67-68.
61.
Haubrich R, Kemper C, Witt P, et al. Reproducibility of an HIV phenotype resistance assay in clinical practice. Program and abstracts of the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 26-29, 1999; San Francisco, CA. Abstract 417.
62.
Simpson KN. Budget impacts of the integration of genotypic antiretroviral resistance testing into HIV treatment guidelines. Program and abstracts of 7th Conference on Retro-viruses and Opportunistic Infections. January 30-February 2, 2000, San Francisco, CA. Abstract 789.
