Evaluation of the treatment-experienced patient failing HIV therapy
- Eric S Daar, MD
Eric S Daar, MD
- Professor of Medicine
- David Geffen School of Medicine at UCLA
The goal of antiretroviral therapy is to suppress the plasma HIV RNA below the limits of assay detection (<20 to 75 copies/mL depending upon the assay used). Suppressing the viral load prevents the emergence of drug-resistant virus and disease progression [1,2]. However, certain HIV-infected patients will experience virologic failure on their antiretroviral regimen. Such individuals require a detailed evaluation to determine the reason for failure and the best approach to achieve viral suppression.
The evaluation of the patient failing their antiretroviral regimen will be reviewed here. Selecting a new regimen is discussed elsewhere. (See "Selecting an antiretroviral regimen for treatment-experienced HIV-infected patients who are failing therapy".)
For individuals starting a new regimen, virologic failure is defined as the inability to achieve a viral load <200 copies/mL within 24 weeks of initiating antiretroviral therapy. For individuals who were initially able to suppress their viral load, virologic failure is defined as a recurrence of viremia to >200 copies/mL on two consecutive measurements taken approximately one month apart [3,4].
In contrast, intermittent "blips" of low level viremia (20 to 200 copies/mL) are generally not associated with the emergence of drug-resistant virus; thus, intermittent viral blips should not prompt a change in therapy . The clinical significance and management of persistent viremia in the range of 50 to 200 copies/mL is less clear. We generally continue the current regimen with counseling to enhance adherence and to avoid drug-drug and drug-food interactions. However, in some cases (eg, patients who have continued difficulty adhering to a daily regimen), we change to a pharmacologically-boosted protease inhibitor (PI) if they are not already on this class of drugs, to minimize the risk of emerging resistance. (See 'Assess medication adherence' below.)
REASONS FOR VIROLOGIC FAILURE
Virologic failure typically results from poor adherence to an antiretroviral therapy (ART) regimen, or from drug-drug or drug-food interactions that impair absorption. Patients with virologic failure may or may not have drug-resistant virus. The risk of developing drug resistance depends, in part, upon the type of regimen (eg, one that contains an agent with a high versus low barrier to resistance), as well as the level of adherence. (See 'Nonadherence' below and 'Poor absorption or altered metabolism' below and 'Resistance' below.)
- Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf (Accessed on January 28, 2016).
- Günthard HF, Aberg JA, Eron JJ, et al. Antiretroviral treatment of adult HIV infection: 2014 recommendations of the International Antiviral Society-USA Panel. JAMA 2014; 312:410.
- Ribaudo, H. Virologic failure endpoint definition in clinical trials. Presented at the 16th Conference on Retroviruses and Opportunistic Infections 2009 Abstract #580 (Accessed on January 25, 2011).
- Antiretroviral Therapy Cohort Collaboration (ART-CC), Vandenhende MA, Ingle S, et al. Impact of low-level viremia on clinical and virological outcomes in treated HIV-1-infected patients. AIDS 2015; 29:373.
- Nettles RE, Kieffer TL, Kwon P, et al. Intermittent HIV-1 viremia (Blips) and drug resistance in patients receiving HAART. JAMA 2005; 293:817.
- Deeks SG, Gange SJ, Kitahata MM, et al. Trends in multidrug treatment failure and subsequent mortality among antiretroviral therapy-experienced patients with HIV infection in North America. Clin Infect Dis 2009; 49:1582.
- 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 2012; 156:817.
- Nettles RE, Kieffer TL, Parsons T, et al. Marked intraindividual variability in antiretroviral concentrations may limit the utility of therapeutic drug monitoring. Clin Infect Dis 2006; 42:1189.
- 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.
- Haubrich RH, Kemper CA, Hellmann NS, et al. A randomized, prospective study of phenotype susceptibility testing versus standard of care to manage antiretroviral therapy: CCTG 575. AIDS 2005; 19:295.
- Cooper DA, Steigbigel RT, Gatell JM, et al. Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med 2008; 359:355.
- VIROLOGIC FAILURE
- REASONS FOR VIROLOGIC FAILURE
- Poor absorption or altered metabolism
- INITIAL ASSESSMENT
- Patients who present on treatment
- - Assess medication adherence
- - Assess for poor absorption or altered metabolism
- - Assess for drug resistance
- Patients who present off treatment
- Patients who become HIV-infected while taking pre-exposure prophylaxis
- PATIENTS WITH DRUG-RESISTANT VIRUS
- Additional resistance testing
- Antiretroviral medication history
- Patient related factors
- SUMMARY AND RECOMMENDATIONS