The DHHS recommends the use of a potent and complete triple therapy based on a dual nucleoside reverse transcriptase inhibitor (NRTI) for treatment initiation.1 This current standard of care has evolved from the use of NRTI monotherapy to NRTI combination therapy, and then further to highly active antiretroviral therapy (HAART), which added a third agent from another drug class to two NRTIs.1 Once available in the mid-1990s, HAART reduced AIDS-related mortality.1 The earliest incarnations of HAART had rigorous dosing schedules, heavy pill burden, and toxicity potential that could pose treatment management challenges.1,2

Today, durable virologic efficacy, better tolerability and toxicity profiles, and relative ease of use characterize regimens recommended in the DHHS Guidelines.1 Currently recommended regimens for antiretroviral treatment‐naive patients include1:

  • A dual-NRTI backbone, plus
  • An integrase Inhibitor (INSTI)

Characteristics of the components of a complete regimen can affect adherence differently.1,3 Higher levels of adherence are associated with the following antiretroviral (ARV) attributes1,4,5:

  • Once-daily dosing
  • Lower pill burden
  • Fewer side effects
  • No food requirement


There are various factors to consider when choosing an appropriate initial ARV regimen for individuals with HIV.1 A regimen should be based on individual patient considerations as well as characteristics of the regimen.1 Both the regimen’s characteristics and the patient’s likelihood of being adherent are considerations when optimizing use of antiretroviral therapy.1,2


  • Baseline viral load and CD4 count
  • Prior side effects
  • Comorbidities and coinfections
  • Concomitant medications
  • Adherence potential today and over the course of the patient’s lifetime
  • Baseline resistance


  • Virologic efficacy
  • Potential short- or long-term side effects
  • Pill burden
  • Dosing frequency
  • Drug-drug interaction potential
  • Cost
  • Potential short- or long-term toxicities
  • Convenience
  • Food effects
  1. U.S. Department of Health and Human Services. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Available at Accessed November 16, 2017.
  2. U.S. Department of Health and Human Services. Health Resources and Services Administration. Guide for HIV/AIDS Clinical Care—2014 Edition. Rockville, MD: U.S. Department of Health and Human Services; 2014.
  3. Parienti JJ, Bangsberg DR, Verdon R, Gardner EM. Better adherence with once-daily antiretroviral regimens: a meta-analysis. Clin Infect Dis. 2009;48(4):484-488.
  4. Nachega JB, Parienti JJ, Uthman OA, et al. Lower pill burden and once-daily antiretroviral treatment regimens for HIV infection: a meta-analysis of randomized controlled trials. Clin Infect Dis. 2014;58(9):1297-1307.
  5. Raboud J, Li M, Walmsley S, et al. Once daily dosing improves adherence to antiretroviral therapy. AIDS Behav. 2011;15(7):1397-1409.