Patient monitoring during HIV antiretroviral therapy
- John G Bartlett, MD
John G Bartlett, MD
- Editor-in-Chief — Infectious Diseases
- Section Editor — HIV; Pulmonary Infections
- Professor Emeritus
- Johns Hopkins University School of Medicine
- Paul E Sax, MD
Paul E Sax, MD
- Clinical Director, Division of Infectious Diseases
- Brigham and Women's Hospital
- Professor of Medicine
- Harvard Medical School
Proper utilization of antiretroviral therapy (ART) requires ongoing patient monitoring to assess therapeutic response and to identify adverse events related to chronic administration of potentially toxic medications. Failure to respond to a recommended ART regimen is almost always a result of suboptimal adherence or viral resistance.
This topic will address laboratory monitoring during ART. Discussions related to the initiation and modification of ART are found elsewhere. (See "Considerations prior to initiating antiretroviral therapy" and "Modifying HIV antiretroviral therapy regimens" and "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient" and "When to initiate antiretroviral therapy in HIV-infected patients" and "Overview of antiretroviral agents used to treat HIV".)
At each visit, patients should be interviewed regarding medication adherence in a nonjudgmental manner. Optimal adherence (ie, taking all medication doses at the time intervals prescribed) to an antiretroviral therapy (ART) regimen is important to help patients achieve and maintain virologic suppression. Adherence can vary over time and can be impacted by factors such as depression and substance use . Strict adherence is most important when patients are initiating or changing an ART regimen.
To enhance adherence, patients should understand the link between adherence and drug resistance. In addition, it is useful to discuss medication schedules with patients to help them link pill-taking behaviors to other daily activities (eg, brushing teeth). If the patient admits to difficulties with adherence, potential barriers could involve the number and timing of doses, sizes of pills, food restrictions, and treatment-limiting side effects. The patient should also be advised to notify the provider if there is an anticipated problem with adherence, such as elective surgery, or a prolonged intercurrent illness. (See "Overview of antiretroviral agents used to treat HIV".)
Adherence can be difficult to assess. As an example, one study demonstrated that clinicians incorrectly predicted adherence in 41 percent of patients . In addition, patients often exaggerate adherence to their provider. Pharmacy records are useful to help track compliance when refills are obtained from a single pharmacy source. Clinical trials have tried to assess whether directly observed therapy may improve virologic suppression rates. One meta-analysis of 12 studies suggested that such therapy seemed to offer no benefit over self-administered treatment . However, directly observed therapy may be beneficial in patient subgroups that are at high risk for nonadherence, such as those who are homeless . Other adherence interventions (eg, assessing serum drug concentrations, monitoring pill counts, or use of electronic drug monitoring devices) are not routinely recommended .
- Lazo M, Gange SJ, Wilson TE, et al. Patterns and predictors of changes in adherence to highly active antiretroviral therapy: longitudinal study of men and women. Clin Infect Dis 2007; 45:1377.
- Paterson DL, Swindells S, Mohr J, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med 2000; 133:21.
- Ford N, Nachega JB, Engel ME, Mills EJ. Directly observed antiretroviral therapy: a systematic review and meta-analysis of randomised clinical trials. Lancet 2009; 374:2064.
- Myers JE, Tsiouris SJ. Is there a place for directly observed therapy in HAART? Lancet 2009; 374:2030.
- 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.
- Bae JW, Guyer W, Grimm K, Altice FL. Medication persistence in the treatment of HIV infection: a review of the literature and implications for future clinical care and research. AIDS 2011; 25:279.
- Strategies for Management of Antiretroviral Therapy (SMART) Study Group, El-Sadr WM, Lundgren J, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 2006; 355:2283.
- 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).
- Aberg JA, Gallant JE, Ghanem KG, et al. Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2014; 58:1.
- Szczech LA. Tenofovir nephrotoxicity: focusing research questions and putting them into clinical context. J Infect Dis 2008; 197:7.
- Lucas GM, Ross MJ, Stock PG, et al. Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2014; 59:e96.
- Hughes MD, Johnson VA, Hirsch MS, et al. Monitoring plasma HIV-1 RNA levels in addition to CD4+ lymphocyte count improves assessment of antiretroviral therapeutic response. ACTG 241 Protocol Virology Substudy Team. Ann Intern Med 1997; 126:929.
- Thiébaut R, Morlat P, Jacqmin-Gadda H, et al. Clinical progression of HIV-1 infection according to the viral response during the first year of antiretroviral treatment. Groupe d'Epidémiologie du SIDA en Aquitaine (GECSA). AIDS 2000; 14:971.
- 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.
- Ghani AC, Ferguson NM, Fraser C, et al. Viral replication under combination antiretroviral therapy: a comparison of four different regimens. J Acquir Immune Defic Syndr 2002; 30:167.
- Polis MA, Sidorov IA, Yoder C, et al. Correlation between reduction in plasma HIV-1 RNA concentration 1 week after start of antiretroviral treatment and longer-term efficacy. Lancet 2001; 358:1760.
- Demeter LM, Hughes MD, Coombs RW, et al. Predictors of virologic and clinical outcomes in HIV-1-infected patients receiving concurrent treatment with indinavir, zidovudine, and lamivudine. AIDS Clinical Trials Group Protocol 320. Ann Intern Med 2001; 135:954.
- Raboud JM, Rae S, Montaner JS. Predicting HIV RNA virologic outcome at 52-weeks follow-up in antiretroviral clinical trials. The INCAS and AVANTI Study Groups. J Acquir Immune Defic Syndr 2000; 24:433.
- Smith CJ, Staszewski S, Sabin CA, et al. Use of viral load measured after 4 weeks of highly active antiretroviral therapy to predict virologic outcome at 24 weeks for HIV-1-positive individuals. J Acquir Immune Defic Syndr 2004; 37:1155.
- Maggiolo F, Migliorino M, Pirali A, et al. Duration of viral suppression in patients on stable therapy for HIV-1 infection is predicted by plasma HIV RNA level after 1 month of treatment. J Acquir Immune Defic Syndr 2000; 25:36.
- Rousseau MN, Vergne L, Montes B, et al. Patterns of resistance mutations to antiretroviral drugs in extensively treated HIV-1-infected patients with failure of highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2001; 26:36.
- Alexander CS, Dong W, Chan K, et al. HIV protease and reverse transcriptase variation and therapy outcome in antiretroviral-naive individuals from a large North American cohort. AIDS 2001; 15:601.
- Eron JJ, Haubrich R, Lang W, et al. A phase II trial of dual protease inhibitor therapy: amprenavir in combination with indinavir, nelfinavir, or saquinavir. J Acquir Immune Defic Syndr 2001; 26:458.
- Torre D, Tambini R. Antiretroviral drug resistance testing in patients with HIV-1 infection: a meta-analysis study. HIV Clin Trials 2002; 3:1.
- Sungkanuparph S, Overton ET, Seyfried W, et al. Intermittent episodes of detectable HIV viremia in patients receiving nonnucleoside reverse-transcriptase inhibitor-based or protease inhibitor-based highly active antiretroviral therapy regimens are equivalent in incidence and prognosis. Clin Infect Dis 2005; 41:1326.
- Podsadecki TJ, Vrijens BC, Tousset EP, et al. Decreased adherence to antiretroviral therapy observed prior to transient human immunodeficiency virus type 1 viremia. J Infect Dis 2007; 196:1773.
- Nettles RE, Kieffer TL, Kwon P, et al. Intermittent HIV-1 viremia (Blips) and drug resistance in patients receiving HAART. JAMA 2005; 293:817.
- Gallant JE. Making sense of blips. J Infect Dis 2007; 196:1729.
- Laprise C, de Pokomandy A, Baril JG, et al. Virologic failure following persistent low-level viremia in a cohort of HIV-positive patients: results from 12 years of observation. Clin Infect Dis 2013; 57:1489.
- Mocroft A, Phillips AN, Gatell J, et al. Normalisation of CD4 counts in patients with HIV-1 infection and maximum virological suppression who are taking combination antiretroviral therapy: an observational cohort study. Lancet 2007; 370:407.
- Le Moing V, Thiébaut R, Chêne G, et al. Predictors of long-term increase in CD4(+) cell counts in human immunodeficiency virus-infected patients receiving a protease inhibitor-containing antiretroviral regimen. J Infect Dis 2002; 185:471.
- Grabar S, Kousignian I, Sobel A, et al. Immunologic and clinical responses to highly active antiretroviral therapy over 50 years of age. Results from the French Hospital Database on HIV. AIDS 2004; 18:2029.
- Piketty C, Weiss L, Thomas F, et al. Long-term clinical outcome of human immunodeficiency virus-infected patients with discordant immunologic and virologic responses to a protease inhibitor-containing regimen. J Infect Dis 2001; 183:1328.
- Sufka SA, Ferrari G, Gryszowka VE, et al. Prolonged CD4+ cell/virus load discordance during treatment with protease inhibitor-based highly active antiretroviral therapy: immune response and viral control. J Infect Dis 2003; 187:1027.
- Deeks SG, Barbour JD, Grant RM, Martin JN. Duration and predictors of CD4 T-cell gains in patients who continue combination therapy despite detectable plasma viremia. AIDS 2002; 16:201.
- Reekie J, Mocroft A, Sambatakou H, et al. Does less frequent routine monitoring of patients on a stable, fully suppressed cART regimen lead to an increased risk of treatment failure? AIDS 2008; 22:2381.
- Gale HB, Gitterman SR, Hoffman HJ, et al. Is frequent CD4+ T-lymphocyte count monitoring necessary for persons with counts >=300 cells/μL and HIV-1 suppression? Clin Infect Dis 2013; 56:1340.
- Girard PM, Nelson M, Mohammed P, et al. Can we stop CD4+ testing in patients with HIV-1 RNA suppression on antiretroviral treatment? AIDS 2013; 27:2759.
- Hirsch MS, Günthard HF, Schapiro JM, et al. Antiretroviral drug resistance testing in adult HIV-1 infection: 2008 recommendations of an International AIDS Society-USA panel. Clin Infect Dis 2008; 47:266.
- Medication persistence
- VISIT FREQUENCY
- GENERAL LABORATORY MONITORING
- VIROLOGIC RESPONSE
- Virologic failure
- Viral blips
- CD4 CELL COUNTS
- FREQUENCY OF IMMUNOLOGIC AND VIROLOGIC MONITORING
- Viral load monitoring
- Recommendations of others
- CD4 cell count monitoring
- DRUG RESISTANCE TESTING
- THERAPEUTIC DRUG MONITORING
- INDICATIONS FOR CHANGING THERAPY
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS