HIV resistance assay results and their effect on therapeutic decisions

Mascolini, Marka; Wensing, Annemarie M. J.bc; Boucher, Charles A. B.b

Research Letter
Author Information

aHIV/AIDS Reporting/Consulting, Bushkill, USA; bDepartment of Virology, Eijkman Winkler Institute, and cDepartment of Internal Medicine, Division of Infectious Diseases and AIDS, University Medical Center, Utrecht, the Netherlands.

Received: 15 September 2000; accepted: 25 September 2000.

Article Outline

HIV resistance to antiretroviral agents continues to frustrate attempts to fashion durable treatment regimens for large proportions of infected individuals [1–5]. The circulation of drug-resistant virus in infected populations has led inevitably to the transmission of such virus to newly infected individuals [6–9]. For this reason, clinicians treating people with HIV infection have begun to explore the clinical use of assays that detect mutations associated with viral resistance (genotypic assays), or to characterize susceptibility of a viral isolate to specific agents (phenotypic assays).

Because retrospective and prospective [10–13] studies demonstrated that such assays can help select a more virologically potent regimen, at least in the short term, panels of HIV experts have recommended their use in clinical practice [14,15]. No study has yet assessed how experienced HIV/AIDS practitioners use resistance testing, and how the results influence therapeutic decisions.

To address this lack of knowledge, we polled clinicians electronically concerning their attitudes about HIV resistance testing at the 1999 Interscience Conference on Antimicrobial Agents and Chemotherapy. Respondents used hand-held keypads to answer multiple-choice questions about their use of such assays, and about how specific assay results would influence treatment planning.

The audience included more than 600 clinicians, although different numbers responded to each question. Most respondents (443/618, 72%) treat 51 or more patients with HIV infection. Among 175 clinicians who treat 50 or fewer HIV-positive individuals, 76 (43%) said they never use resistance assays when switching therapy, compared with 30 out of 116 (26%) treating 51–100 HIV-positive patients and 75 out of 327 (23%) treating more than 100 patients. Those responses suggest that clinicians who see few HIV-positive patients feel less comfortable using resistance assays than more experienced practitioners. This reluctance may detract from the quality of care such physicians can render patients with HIV infection.

Most respondents (342/598, 57%) use only genotypic assays when switching antiretroviral therapy. Only 22 (4%) rely solely on phenotypic assays, whereas 91 (15%) use both assays, and 143 (24%) do not use resistance assays when changing regimens. The lack of reimbursement is the reason cited most often (43%) for not using resistance assays more.

We asked clinicians to consider resistance testing for a hypothetical patient in whom a protease inhibitor plus two nucleosides failed to control viral replication after 24 weeks. Then we asked how they would respond to three different assay results: (i) completely wild-type virus; (ii) multidrug-resistant virus; and (iii) partly resistant virus.

In this hypothetical patient, virological failure after 24 weeks of a standard first-line regimen would encourage 282 out of 604 clinicians (47%) to use a genotypic assay, 50 (8%) to use a phenotypic assay, and 87 (14%) to use both to help plan continued treatment. Genotyping would change the choice of subsequent therapy most often when the assay detects multidrug resistance (505/594 respondents, 85%), less often when it detects partial resistance (459/582, 79%), and least if it finds only wild-type virus (288/586, 49%).

If the assay detected partly or multidrug-resistant virus, the large proportions of respondents saying these results would change their treatment choice apparently accept findings [10–13] indicating that knowing mutation patterns in patients taking a failing regimen will help plan the next regimen. Genotypic results can rule out antiretroviral agents unlikely to suppress replication in a subsequent regimen. The 51% who responded that wild-type results after 24 weeks of unsuccessful therapy would not change their prescribing plans clearly believed that the patient needed better adherence counselling or questioning about drug side-effects rather than an automatic switch in antiretroviral agents.

Genotyping would sway 416 out of 586 clinicians (71%) to order a phenotypic assay if genotyping detected multidrug resistance. However, only 249 out of 527 respondents (47%) would turn to phenotyping if genotyping detected partial resistance, and only 60 out of 588 (10%) would order phenotyping when genotyping detected no mutations.

In the case of multidrug resistance, the 71% of clinicians who wanted phenotypic results may be disappointed in the ability of phenotyping to select active drugs for a patient who already has multidrug-resistant virus. Our interactive survey took place before two randomized trials found that phenotyping has little impact on virological response after switching therapy in such patients [16,17]. A third randomized trial [18] indicated that phenotyping helped clinicians select an effective subsequent regimen more often in patients with less treatment experience.

This survey showed that clinicians interested in resistance to antiretroviral agents already use resistance testing, unless the lack of reimbursement prevents some from doing so. Their answers to questions about hypothetical resistance test results generally indicated a good understanding of HIV resistance and its management. However, their faith in phenotyping for patients with multidrug-resistant virus may be misplaced.

Mark Mascolinia

Annemarie M. J. Wensingbc

Charles A. B. Boucherb

Back to Top | Article Outline


1. Kavlick MF, Wyvill K, Yarchoan R, Mitsuya H. Emergence of multi-dideoxynucleoside-resistant human immunodeficiency virus type 1 variants, viral sequence variation, and disease progression in patients receiving antiretroviral chemotherapy. J Infect Dis 1998, 177: 1506 –1513.
2. Casado JL, Hertogs K, Ruiz L. et al. Non-nucleoside reverse transcriptase inhibitor resistance among patients failing a nevirapine plus protease inhibitor-containing regimen. AIDS 2000, 14: F1 –F7.
3. Bacheler LT, Anton ED, Kudish P. et al. Human immunodeficiency virus type 1 mutations selected in patients failing efavirenz combination therapy. Antimicrob Agents Chemother 2000, 44: 2475 –2484.
4. DeGruttola V, Dix L, D'Aquila R. et al. The relation between baseline HIV drug resistance and response to antiretroviral therapy: re-analysis of retrospective and prospective studies using standardized data analysis plan. Antiviral Ther 2000, 5: 41 –48.
5. Winters MA, Baxter JD, Mayers DL. et al. Frequency of antiretroviral drug resistance mutations in HIV-1 strains from patients failing triple drug regimens. Antiviral Ther 2000, 5: 57 –63.
6. Boden D, Hurley A, Zhang L. et al. HIV-1 drug resistance in newly infected individuals. JAMA 1999, 282: 1135 –1141.
7. Little SJ, Daar ES, D'Aquila RT. et al. Reduced antiretroviral drug susceptibility among patients with primary HIV infection. JAMA 1999, 282: 1142 –1149.
8. Yerly S, Kaiser L, Race E, Bru JP, Clavel F, Perrin L. Transmission of antiretroviral-drug-resistant HIV-1 variants. Lancet 1999, 354: 729 –733.
9. Little SJ. Transmission and prevalence of HIV resistance among treatment-naive subjects. Antiviral Ther 2000, 5: 33 –40.
10. Zolopa AR, Shafer RW, Warford A. et al. HIV-1 genotypic resistance patterns predict response to saquinavir-ritonavir therapy in patients in whom previous protease inhibitor therapy had failed. Ann Intern Med 1999, 131: 813 –821.
11. Deeks SG, Hellmann HS, Grant RM. et al. Novel four-drug salvage treatment regimens after failure of a human immunodeficiency virus type 1 protease inhibitor-containing regimen: antiviral activity and correlation of baseline phenotypic drug susceptibility with virologic outcome. J Infect Dis 1999, 179: 1375 –1381.
12. Durant J, Clevenbergh P, Halfon S. et al. Drug-resistance genotyping in HIV-1 therapy: the VIRADAPT randomised controlled trial. Lancet 1999, 353: 2195 –2199.
13. Baxter JL, Mayers DL, Wentworth DN. et al. A randomized study of antiretroviral management based on plasma genotypic antiretroviral resistance testing in patients failing therapy. AIDS 2000, 14: F83 –F93.
14. Department of Health and Human Services (DHHS) and the Henry J. Kaiser Family Foundation Panel on Clinical Practices for Treatment of HIV Infection. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. 28 January 2000. Available at:
15. Carpenter CCJ, Cooper DA, Fischl MA. et al. Antiretroviral therapy in adults: updated recommendations of the International AIDS Society – USA panel. JAMA 2000, 283: 381 –390.
16. 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. 7th Conference on Retroviruses and Opportunistic Infections. January–February 2000 [Abstract 786].
17. 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.
18. Cohen C, Hunt S, Sension M, et al. Phenotypic resistance testing significantly improves response to therapy: a randomized trial (VIRA3001). 7th Conference on Retroviruses and Opportunistic Infections. January–February 2000 [Abstract 237].
© 2001 Lippincott Williams & Wilkins, Inc.