Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents
Last Updated: January 28, 2016; Last Reviewed: January 28, 2016
Antiretroviral therapy (ART) for the treatment of HIV infection has improved steadily since the advent of potent combination therapy in 1996. ART has dramatically reduced HIV-associated morbidity and mortality and has transformed HIV infection into a manageable chronic condition. In addition, ART is highly effective at preventing HIV transmission.1 However, fewer than one-third of HIV-infected individuals in the United States have suppressed viral loads,2 mostly resulting from undiagnosed HIV infection and failure to link or retain diagnosed patients in care.
The Department of Health and Human Services (HHS) Panel on Antiretroviral Guidelines for Adults and Adolescents (the Panel) is a working group of the Office of AIDS Research Advisory Council (OARAC). The primary goal of the Panel is to provide HIV care practitioners with recommendations based on current knowledge of antiretroviral drugs (ARV) used to treat adults and adolescents with HIV infection in the United States. The Panel reviews new evidence and updates recommendations when needed. These guidelines include recommendations on baseline laboratory evaluations, treatment goals, benefits of ART and considerations when initiating therapy, choice of the initial regimen for ART-naive patients, ARV drugs or combinations to avoid, management of treatment failure, management of adverse effects and drug interactions, and special ART-related considerations in specific patient populations. This Panel works closely with the HHS Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children to provide recommendations for adolescents at different stages of growth and development. Recommendations for ART regimens in these guidelines are most appropriate for post-pubertal adolescents (i.e., sexual maturity rating [SMR] stages IV and V). Clinicians should follow recommendations in the Pediatric Guidelines when initiating ART in adolescents at SMR stage III or lower.3 For recommendations related to pre- (PrEP) and post- (PEP) HIV exposure prophylaxis for HIV uninfected persons, clinicians should consult recommendations from the Centers for Disease Control and Prevention (CDC).4
These guidelines represent current knowledge regarding the use of ARVs. Because the science of HIV evolves rapidly, the availability of new agents and new clinical data may change therapeutic options and preferences. Information included in these guidelines may not always be consistent with approved labeling for the particular drugs or indications, and the use of the terms “safe” and “effective” may not be synonymous with the Food and Drug Administration (FDA)-defined legal standards for drug approval. The Panel frequently updates the guidelines (current and archived versions of the guidelines are available on the AIDSinfo website at http://www.aidsinfo.nih.gov). However, the guidelines cannot always be updated apace with the rapid evolution of new data and cannot offer guidance on care for all patients. Patient management decisions should be based on clinical judgement and attention to unique patient circumstances.
The Panel recognizes the importance of clinical research in generating evidence to address unanswered questions related to the optimal safety and efficacy of ART, and encourages both the development of protocols and patient participation in well-designed, Institutional Review Board (IRB)-approved clinical trials.
Guidelines Development Process
|Goal of the guidelines||Provide guidance to HIV care practitioners on the optimal use of antiretroviral agents (ARVs) for the treatment of HIV infection in adults and adolescents in the United States.|
|Panel members||The Panel is composed of approximately 45 voting members who have expertise in HIV care and research, and includes at least one representative from each of the following U.S. Department of Health and Human Services (HHS) agencies: Centers for Disease Control and Prevention (CDC), Food and Drug Administration (FDA), Health Resource and Services Administration (HRSA), and National Institutes of Health (NIH). Approximately two-thirds of the Panel members are non-governmental scientific members. The Panel also includes four to five community members with knowledge in HIV treatment and care. The U.S. government representatives are appointed by their respective agencies; other Panel members are selected after an open announcement to call for nominations. Each member serves on the Panel for a 4 year term with an option for reappointment for an additional term. See the Panel Roster for a list of current Panel members.|
|Financial disclosure||All members of the Panel submit a written financial disclosure annually, reporting any association with manufacturers of ARV drugs or diagnostics used for management of HIV infections. A list of the latest disclosures is available on the AIDSinfo website (https://aidsinfo.nih.gov/contentfiles/AA_FinancialDisclosures.pdf).|
|Users of the guidelines||HIV treatment providers|
|Developer||Panel on Antiretroviral Guidelines for Adults and Adolescents—a working group of the Office of AIDS Research Advisory Council (OARAC)|
|Funding source||Office of AIDS Research, NIH|
|Evidence collection||The recommendations in the guidelines are based on studies published in peer reviewed journals. On some occasions, particularly when new information may affect patient safety, unpublished data presented at major conferences or prepared by the FDA and/or manufacturers as warnings to the public may be used as evidence to revise the guidelines.|
|Recommendation grading||As described in Table 2.|
|Method of synthesizing data||Each section of the guidelines is assigned to a working group of Panel members with expertise in the section’s area of interest. The working groups synthesize available data and propose recommendations to the Panel. The Panel discusses all proposals during monthly teleconferences. Recommendations endorsed by the Panel are included in the guidelines.|
|Other guidelines||These guidelines focus on ART use for HIV-infected adults and adolescents. For more detailed discussion on the use of antiretroviral therapy (ART) for children and pre-pubertal adolescents (SMR Stages I – III), clinicians should refer to the Pediatric Antiretroviral Guidelines.
These guidelines also include a brief discussion on the management of women of reproductive age and pregnant women.
|Update plan||The Panel meets monthly by teleconference to review data that may warrant modification of the guidelines. Updates may be prompted by new drug approvals (or new indications, dosing formulations, or frequency of dosing), new safety or efficacy data, or other information that may have an impact on the clinical care of patients. In the event of new data of clinical importance, the Panel may post an interim announcement with recommendations on the AIDSinfo website until the guidelines can be updated with the appropriate changes. Updated guidelines are available on the AIDSinfo website (http://www.aidsinfo.nih.gov).|
|Public comments||A 2-week public comment period follows release of the updated guidelines on the AIDSinfo website. The Panel reviews comments received to determine whether additional revisions to the guidelines are indicated. The public may also submit comments to the Panel at any time at email@example.com.|
Basis for Recommendations
Recommendations in these guidelines are based upon scientific evidence and expert opinion. Each recommended statement includes a letter (A, B, or C) that represents the strength of the recommendation and a Roman numeral (I, II, or III) that represents the quality of the evidence that supports the recommendation (see Table 2).
Strength of Recommendation
Quality of Evidence for Recommendation
|A: Strong recommendation for the statement
B: Moderate recommendation for the statement
C: Optional recommendation for the statement
|I: One or more randomized trials with clinical outcomes and/or validated laboratory endpoints
II: One or more well-designed, non-randomized trials or observational cohort studies with long-term clinical outcomes
III: Expert opinion
HIV Expertise in Clinical Care
Several studies have demonstrated that overall outcomes in HIV-infected patients are better when care is delivered by clinicians with HIV expertise (e.g., care for a larger panel of patients),5-9 reflecting the complexity of HIV infection and its treatment. Appropriate training, continuing education, and clinical experience are all components of optimal care. Providers who do not have this requisite training and experience should consult HIV experts when needed.
- Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. Aug 11 2011;365(6):493-505. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21767103.
- Centers for Disease Control and Prevention. HIV in the United States: the stages of care—CDC Fact Sheet. 2014. Available at http://www.cdc.gov/nchhstp/newsroom/docs/HIV-Stages-of-Care-Factsheet-508.pdf. Accessed December 21, 2015.
- Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the use of antiretroviral agents in pediatric HIV infection. 2014. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/pediatricguidelines.pdf. Accessed January 12, 2016.
- Centers for Disease Control and Prevention, U.S. Public Health Service. Pre-exposure prophylaxis for the prevention of HIV infection in the United States—2014: a clinical practice guideline. 2014. Available at http://www.cdc.gov/hiv/pdf/PrEPguidelines2014.pdf. Accessed November 2, 2015.
- Kitahata MM, Van Rompaey SE, Shields AW. Physician experience in the care of HIV-infected persons is associated with earlier adoption of new antiretroviral therapy. J Acquir Immune Defic Syndr. Jun 1 2000;24(2):106-114. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10935685.
- Landon BE, Wilson IB, McInnes K, et al. Physician specialization and the quality of care for human immunodeficiency virus infection. Arch Intern Med. May 23 2005;165(10):1133-1139. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15911726.
- Kitahata MM, Van Rompaey SE, Dillingham PW, et al. Primary care delivery is associated with greater physician experience and improved survival among persons with AIDS. J Gen Intern Med. Feb 2003;18(2):95-103. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12542583.
- Delgado J, Heath KV, Yip B, et al. Highly active antiretroviral therapy: physician experience and enhanced adherence to prescription refill. Antivir Ther. Oct 2003;8(5):471-478. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14640395.
- O'Neill M, Karelas GD, Feller DJ, et al. The HIV Workforce in New York State: Does Patient Volume Correlate with Quality? Clin Infect Dis. Dec 15 2015;61(12):1871-1877. Available at http://www.ncbi.nlm.nih.gov/pubmed/26423383.