Skip to main content

Advertisement

Log in

Approach to the Treatment-experienced patient

  • Published:
Current HIV/AIDS Reports Aims and scope Submit manuscript

Abstract

Failure of antiretroviral therapy can occur for a variety of reasons, but is often caused by or accompanied by drug resistance, which increases with continued time on nonsuppressive, failing regimens. Response to early virologic failure on an initial regimen may be associated with minimal or no resistance and can sometimes be managed simply by reinforcing adherence or by intensifying therapy. Resistance testing is an important tool for managing patients who are failing therapy; it should be used in most cases to guide selection of the next regimen. For patients with extensive treatment experience and drug resistance, there are a variety of approaches that have been suggested when fully suppressive options are not available. Clinicians caring for such patients must balance the benefit of slower progression associated with continued therapy against the risk of increasing drug resistance and loss of future treatment options.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Deeks SG, Hecht FM, Swanson M, et al.: HIV RNA and CD4 cell count response to protease inhibitor therapy in an urban AIDS clinic: response to both initial and salvage therapy. AIDS 1999, 13:F35-F43.

    Article  PubMed  CAS  Google Scholar 

  2. Ledergerber B, Egger M, Opravil M, et al.: Clinical progression and virological failure on highly active antiretroviral therapy in HIV-1 patients: a prospective cohort study. Swiss HIV Cohort Study. Lancet 1999, 353:863–868.

    Article  PubMed  CAS  Google Scholar 

  3. Mocroft A, Phillips AN, Miller V, et al.: The use of and response to second-line protease inhibitor regimens: results from the EuroSIDA study. AIDS 2001, 15:201–209.

    Article  PubMed  CAS  Google Scholar 

  4. Department of Health and Human Services: Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents, March 23, 2004. Accessible at http://www.aidsinfo.nih.gov/. Accessed January 23, 2005. Extremely useful document because of the treatment guidelines and the comprehensive review of relevant data, including data about the management of treatment-experienced patients and the use of resistance testing.

  5. Havlir DV, Bassett R, Levitan D, et al.: Prevalence and predictive value of intermittent viremia with combination HIV therapy. JAMA 2001, 286:171–179.

    Article  PubMed  CAS  Google Scholar 

  6. Nettles RE, Kieffer T, Kwon P, et al.: Intermittent HIV-1 viremia (blips) and drug resistance in patients receiving HAART. JAMA 2005, 293:817–829.

    Article  PubMed  CAS  Google Scholar 

  7. Hermankova M, Ray SC, Ruff C, et al.: HIV-1 drug resistance profiles in children and adults with viral load of less than 50 copies/ml receiving combination therapy. JAMA 2001, 286:196–207.

    Article  PubMed  CAS  Google Scholar 

  8. Cohen Stuart JW, Wensing AM, Kovacs C, et al.: Transient relapses ("blips") of plasma HIV RNA levels during HAART are associated with drug resistance. J Acquir Immune Defic Syndr 2001. 28:105–113.

    Article  PubMed  CAS  Google Scholar 

  9. Martinez-Picado J, DePasquale MP, Kartsonis N, et al.: Antiretroviral resistance during successful therapy of HIV type 1 infection. Proc Natl Acad Sci USA 2000, 97:10948–10953.

    Article  PubMed  CAS  Google Scholar 

  10. Kempf DJ, Rode RA, Xu Y, et al.: The duration of viral suppression during protease inhibitor therapy for HIV-1 infection is predicted by plasma HIV-1 RNA at the nadir. AIDS 1998, 12:F9–14.

    Article  PubMed  CAS  Google Scholar 

  11. Pilcher CD, Miller WC, Beatty ZA, Eron JJ: Detectable HIV-1 RNA at levels below quantifiable limits by Amplicor HIV-1 monitor is associated with virologic relapse on antiretroviral therapy. AIDS 1999, 13:1337–1342.

    Article  PubMed  CAS  Google Scholar 

  12. Raboud JM, Rae S, Hogg RS, et al.: Suppression of plasma virus load below the detection limit of a human immunodeficiency virus kit is associated with longer virologic response than suppression below the limit of quantitation. J Infect Dis 1999, 180:1347–1350.

    Article  PubMed  CAS  Google Scholar 

  13. Nettles RE, Kieffer TL, Simmons RP, et al.: Genotypic resistance in HIV-1-infected patients with persistently detectable lowlevel viremia while receiving highly active antiretroviral therapy. Clin Infect Dis 2004, 39:1030–1037.

    Article  PubMed  CAS  Google Scholar 

  14. Lanier R, Scott J, Steel H, et al.: Multivariate analysis of predictors of response to abacavir: comparison of prior antiretroviral therapy, baseline HIV RNA, CD4 count, and viral resistance [abstract]. Antivir Ther 1999, 4(Suppl 1):56.

    Google Scholar 

  15. Schooley RT, Ruane P, Myers RA, et al.: Tenofovir DF in antiretroviral-experienced patients: results from a 48-week, randomized, double-blind study. AIDS 2002, 16:1257–1263.

    Article  PubMed  CAS  Google Scholar 

  16. Shulman N, Zolopa A, Havlir D, et al.: Virtual inhibitory quotient predicts response to ritonavir boosting of indinavirbased therapy in human immunodeficiency virus-infected patients with ongoing viremia. Antimicrob Agents Chemother 2002, 46:3907–3916.

    Article  PubMed  CAS  Google Scholar 

  17. 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 a standardized data analysis plan. Antivir Ther 2000, 5:41–48.

    PubMed  CAS  Google Scholar 

  18. Hanna GJ, D’Aquila RT: Clinical use of genotypic and phenotypic drug resistance testing to monitor antiretroviral chemotherapy. Clin Infect Dis 2001, 32:774–82.

    Article  PubMed  CAS  Google Scholar 

  19. Haubrich R, Demeter L: Clinical utility of resistance testing: retrospective and prospective data supporting use and current recommendations. J Acquir Immune Defic Syndr 2001, 26:S51-S59.

    Article  PubMed  CAS  Google Scholar 

  20. Shafer RW: Genotypic testing for human immunodeficiency virus type-1 drug resistance. Clin Microbiol Rev 2002, 15:247–277.

    Article  PubMed  CAS  Google Scholar 

  21. Baxter JD, Mayers DL, Wentworth DN, et al.: A randomized study of antiretroviral management based on plasma genotypic antiretroviral resistance testing in patients failing therapy. Community Programs for Clinical Research on AIDS (CPCRA 046) Study Team for the Terry Beirn Community Programs for Clinical Research on AIDS. AIDS 2000, 14:F83-F93.

    Article  PubMed  CAS  Google Scholar 

  22. Cingolani A, Antinori A, Rizzo MG, et al.: Usefulness of monitoring HIV drug resistance and adherence in individuals failing highly active antiretroviral therapy: a randomized study. AIDS 2002, 16:369–379.

    Article  PubMed  CAS  Google Scholar 

  23. Cohen CJ, Hunt S, Sension M, et al.: A randomized trial assessing the impact of phenotypic resistance testing on antiretroviral therapy. AIDS 2002, 16:579–588.

    Article  PubMed  CAS  Google Scholar 

  24. Durant J, Clevenbergh P, Halfon P, et al.: Drug-resistance genotyping in HIV-1 therapy: the VIRADAPT randomised controlled trial. Lancet 1999, 353:2195–2199.

    Article  PubMed  CAS  Google Scholar 

  25. Haubrich R, Keiser P, Kemper C, et al.: CCTG 575: a randomized, prospective study of phenotype testing versus standard of care for patients failing antiretroviral therapy. Antivir Ther 2001, 6:63.

    Google Scholar 

  26. Meynard JL, Vray M, Morand-Joubert L, et al.: Phenotypic or genotypic resistance testing for choosing antiretroviral therapy after treatment failure: a randomized trial. AIDS 2002, 16:727–736.

    Article  PubMed  Google Scholar 

  27. Tural C, Ruiz L, Holtzer C, et al.: Clinical utility of HIV-1 genotyping and expert advice: the Havana trial. AIDS 2002, 16:209–218.

    Article  PubMed  Google Scholar 

  28. British HIV Association: British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy, July 2003. Accessible at http:// www.bhiva.org/guidelines/2003/hiv/index.html. Accessed January 23, 2005.

  29. Yeni PG, Hammer SM, Hirsch MS, et al.: Treatment for adult HIV infection: 2004 recommendations of the International AIDS Society—USA panel. JAMA 2004, 292:251–265. Though less detailed than the DHHS document (ref 4), this paper provides both guidelines and an excellent review of the relevant data on antiretroviral therapy, including management of treatmentexperienced patients.

    Article  PubMed  CAS  Google Scholar 

  30. Aleman S, Soderbarg K, Visco-Comandini U, et al.: Drug resistance at low viraemia in HIV-1-infected patients with antiretroviral combination therapy. AIDS 2002, 16:1039–1044.

    Article  PubMed  Google Scholar 

  31. Condra JH, Holder DJ, Schleif WA, et al.: Genetic correlates of in vivo viral resistance to indinavir, a HIV type-1 protease inhibitor. J Virol 1996, 70:8270–8276.

    PubMed  CAS  Google Scholar 

  32. Descamps D, Flandre P, Calvez V, et al.: Mechanisms of virologic failure in previously untreated HIV-infected patients from a trial of induction-maintenance therapy. Trilege Study Team. JAMA 2000, 283:205–211.

    Article  PubMed  CAS  Google Scholar 

  33. Gallego O, de Mendoza C, Perez-Elias MJ, et al.: Drug resistance in patients experiencing early virological failure under a triple combination including indinavir. AIDS 2001, 15:1701–1706.

    Article  PubMed  CAS  Google Scholar 

  34. Havlir DV, Hellmann NS, Petropoulos CJ, et al.: Drug susceptibility in HIV infection after viral rebound in patients receiving indinavir-containing regimens. JAMA 2000, 283:229–234.

    Article  PubMed  CAS  Google Scholar 

  35. Maguire M, Gartland M, Moore S, et al.: Absence of zidovudine resistance in antiretroviral-naive patients following zidovudine/ lamivudine/protease inhibitor combination therapy: virological evaluation of the AVANTI 2 and AVANTI 3 studies. AIDS 2000, 14:1195–1201.

    Article  PubMed  CAS  Google Scholar 

  36. Mouroux M, Yvon-Groussin A, Peytavin G, et al.: Early virological failure in naive HIV patients receiving saquinavir (softgel capsule)-stavudine-zalcitabine (MIKADO trial) is not associated with mutations conferring viral resistance. J Clin Microbiol 2000, 38:2726–2730.

    PubMed  CAS  Google Scholar 

  37. Colonno R, Rose R, McLaren C, et al.: Identification of I50L as the signature atazanavir (ATV)-resistance mutation in treatment-naive HIV-1-infected patients receiving ATV-containing regimens. J Infect Dis 2004, 189:1802–1810.

    Article  PubMed  CAS  Google Scholar 

  38. Hertogs K, Bloor S, Kemp SD, et al.: Phenotypic and genotypic analysis of clinical HIV-1 isolates reveals extensive protease inhibitor cross-resistance: a survey of over 6000 samples. AIDS 2000, 14:1203–1210.

    Article  PubMed  CAS  Google Scholar 

  39. Kempf DJ, King MS, Bernstein B, et al.: Incidence of resistance in a double-blind study comparing lopinavir/ritonavir plus stavudine and lamivudine to nelfinavir plus stavudine and lamivudine. J Infect Dis 2004, 189:51–60.

    Article  PubMed  CAS  Google Scholar 

  40. McManus S, Yates P, White S, et al.: GW 433908 in antiretroviral therapy (ART)-naïve subjects: absence of resistance at 48 weeks with boosted regimen and amprenavir (APV)-like resistance profile with unboosted regimen [abstract]. Paper presented at the 10th Conference on Retroviruses and Opportunistic Infections, Boston, February 10–14, 2004.

  41. Deeks SG, Wrin T, Liegler T, et al.: Virologic and immunologic consequences of discontinuing combination antiretroviraldrug therapy in HIV-infected patients with detectable viremia. N Engl J Med 2001, 344:472–480.

    Article  PubMed  CAS  Google Scholar 

  42. Grabar S, Le Moing V, Goujard C, et al.: Clinical outcome of patients with HIV-1 infection according to immunologic and virologic response after 6 months of highly active antiretroviral therapy. Ann Intern Med 2000, 133:401–410.

    PubMed  CAS  Google Scholar 

  43. Piketty C, Weiss L, Thomas F, et al.: Long-term clinical outcome of HIV-infected patients with discordant immunologic and virologic responses to a protease inhibitor-containing regimen. J Infect Dis 2001, 183:1328–1335.

    Article  PubMed  CAS  Google Scholar 

  44. Miller V, Cozzi-Lepri A, Hertogs K, et al.: HIV-drug susceptibility and treatment response to mega-HAART regimen in patients from the Frankfurt HIV cohort. Antivir Ther 2000, 5:49–55.

    PubMed  CAS  Google Scholar 

  45. Montaner JS, Harrigan PR, Jahnke N, et al.: Multiple drugrescue therapy for HIV-infected individuals with prior virologic failure to multiple regimens. AIDS 2001, 15:61–69.

    Article  PubMed  CAS  Google Scholar 

  46. Katlama C, Dominguez S, Gourlain K, et al.: Benefit of treatment interruption in HIV-infected patients with multiple therapeutic failures: a randomized controlled trial (ANRS 097). AIDS 2004, 18:217–226.

    Article  PubMed  CAS  Google Scholar 

  47. Miller V, Cozzi-Lepri A, Hertogs K, et al.: HIV drug susceptibility and treatment response to mega-HAART regimen in patients from the Frankfurt HIV cohort. Antivir Ther 2000, 5:49–55.

    PubMed  CAS  Google Scholar 

  48. Delaugerre C, Valantin MA, Mouroux M, et al.: Re-occurrence of HIV-1 drug mutations after treatment re-initiation following interruption in patients with multiple treatment failure. AIDS 2001, 15:2189–2191.

    Article  PubMed  CAS  Google Scholar 

  49. Deeks SG, Wrin T, Liegler T, et al.: Virologic and immunologic consequences of discontinuing combination antiretroviraldrug therapy in HIV-infected patients with detectable viremia. N Engl J Med 2001, 344:472–480.

    Article  PubMed  CAS  Google Scholar 

  50. Lawrence J, Mayers DL, Hullsiek KH, et al.: Structured treatment interruption in patients with multidrug resistant HIV. N Engl J Med 2003, 349:837–846.

    Article  PubMed  Google Scholar 

  51. Deeks SG, Martin JN, Hoh R, et al.: Continued reverse transcriptase inhibitor therapy is sufficient to maintain short-term partial suppression of multidrug resistant viremia [abstract]. Paper presented at the 10th Conference on Retroviruses and Opportunistic Infections, Boston, 10–14, 2003.

  52. Castagna A, Danise A, Carini E, et al.: Pilot study to evaluate immunologic response to lamivudine monotherapy versus treatment interruption in failing HIV-1-infected subjects harbouring the M184V mutation [abstract]. Paper presented at the XV International AIDS Conference, Bangkok, Thailand, July 11–16, 2004.

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gallant, J.E. Approach to the Treatment-experienced patient. Curr HIV/AIDS Rep 2, 83–89 (2005). https://doi.org/10.1007/s11904-005-0023-5

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11904-005-0023-5

Keywords

Navigation