What to Start: Recommended Regimens for Initiating ART

As discussed in the Key Considerations for people living with HIV, there is no longer an immunologic cutoff for starting ART; that is, no CD4 count threshold below which ART should be initiated. Instead, the worldwide consensus is that ART should be initiated in all HIV-infected patients upon HIV diagnosis, regardless of CD4 cell count or clinical stage.

Specific recommendations vary between the World Health Organization (WHO) and regional governmental and nongovernmental organizations including the European AIDS Clinical Society (EACS), and the United States (US) Department of Health and Human Services (DHHS).1-3

Most guidelines agree, however, that the preferred or alternative choices for constructing an ART regimen for treatment-naïve HIV-infected patients include:

Integrase strand transfer inhibitor (INSTI) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs)
Nonnucleoside reverse transcriptase inhibitor (NNRTI) plus 2 NRTIs
Ritonavir-boosted protease inhibitor (PI) plus 2 NRTIs

The following is a list of currently available regimens cited by major guidelines as recommended, preferred, or alternative. See the individual guidelines for specific recommendations as well as indications as to the strength of evidence supporting each recommendation.
 

INSTI-Based Regimens:

Regimen Guidelines in which regimen is recommended

DTG/ABC/3TCa —only  for patients who are HLA-B*5701 negative
DHHS, EACS
DTG plus TDF/FTCa DHHS, EACS
EVG/c/TAF/FTC—only for patients with pre-treatment estimated CrCl ≥30 mL/min DHHS
EVG/c/TDF/FTC—only for patients with pre-treatment estimated CrCl ≥70 mL/min DHHS, EACS
RAL plus TDF/FTCa DHHS
RAL plus ABC/3TCa —only for patients who are HLA-B*5701 negative DHHS, EACS

NNRTI-Based Regimens:

Regimen Guidelines in which regimen is recommended
EFV/TDF/FTCa,b Preferred in WHO, alternative in DHHS and EACS
EFV plus ABC/3TCa,b —only for patients who are HLA-B*5701 negative and with pre-treatment HIV RNA <100,000 copies/mL Alternative in WHO and EACS
RPV/TDF/FTCa  —only for patients with pre-treatment HIV RNA <100,000 copies/mL and CD4 cell count >200 cells/mm3 Recommended in EACS, alternative in DHHS


PI-Based Regimens:

Regimen Guidelines in which regimen is recommended
ATV/c or ATV/r plus ABC/3TCa —only for patients who are HLA-B*5701 negative and with pre-treatment HIV RNA <100,000 copies/mL Alternative in EACS
ATV/c plus TDF/FTCa —only for patients with pre-treatment estimated CrCl ≥70 mL/min Alternative in EACS and DHHS
ATV/r plus TDF/FTCa Alternative in EACS and DHHS
DRV/c or DRV/r plus ABC/3TCa—only for patients who are HLA-B*5701 negative Alternative in EACS and DHHS
DRV/c plus TDF/FTCa —only for patients with pre-treatment estimated CrCl ≥70 mL/min Alternative in EACS and DHHS
DRV/r plus TDF/FTCa Alternative in EACS and DHHS
LPV/r (oncec or twice daily) plus TDF/FTCa Alternative in EACS

NOTE: DHHS and EACS guidelines include additional options for other regimens that may have reduced virologic activity, limited supporting data, greater toxicities, higher pill burden, drug interaction potential, or limitations for use in certain patient populations, but may nevertheless be useful for specific patients in certain situations. See the guidelines for more information.

a 3TC may be substituted for FTC or vice versa.
400 mg EFV may be substituted for 600 mg EFV per WHO guidelines
c Once daily LPV/r is not recommended for pregnant patients.

Note:  The following are available in fixed-doses co-formulations: ABC/3TC, ATV/c, DRV/c, DTG/ABC/3TC, EFV/TDF/FTC, EVG/c/TDF/FTC, LPV/r, RPV/TDF/FTC, and TDF/FTC.

Key to Acronyms:
3TC = lamivudine
ABC = abacavir
ARV = antiretroviral
ATV/c = cobicistat-boosted atazanavir
ATV/r = ritonavir-boosted atazanavir
CrCl = creatinine clearance
DRV/c = cobicistat-boosted darunavir
DRV/r = ritonavir-boosted darunavir
DTG = dolutegravir
EFV =efavirenz
EVG/c/TAF/FTC = elvitegravir/cobicistat/tenofovir alafenamide/emtricitabine
EVG/c/TDF/FTC = elvitegravir/cobicistat/tenofovir DF/emtricitabine
FTC = emtricitabine
INSTI = integrase strand transfer inhibitor
LPV/r = ritonavir-boosted lopinavir
NNRTI = non-nucleoside reverse transcriptase inhibitor
NRTI = nucleoside reverse transcriptase inhibitor
PI = protease inhibitor
RAL = raltegravir
RPV = rilpivirine
RTV = ritonavir
TAF = tenofovir alafenamide
TDF = tenofovir disoproxil fumarate

References:

  1. World Health Organization. Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection: Recommendations for a Public Health Approach. Geneva: World Health Organization; 2013 Jun.
  2. European AIDS Clinical Society. Guidelines Version 8.0. October 2015.
  3. Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. January 2016.