Initial Regimens: ART-naïve Adult

Initial Combination Regimen for ART-naïve Adult PLWH

Considerations

Before selecting an ART regimen, it is critical to review:

- Only drugs currently licensed for initiation of therapy by the EMA are included (in alphabetical order)
- Recommended regimens should be considered first and are preferable for most persons. Antiretroviral drugs in the Recommended category provide a combination of essential characteristics for an optimal treatment such as long-term efficacy, barrier to resistance, safety, tolerability and few drug-drug interactions. Alternative regimens should be considered if recommended regimens are not feasible
- An increasing number of generic HIV drugs are now available, and their use can lead to large cost savings. The use of generic forms of drugs included in recommended regimens should therefore be encouraged, even if single tablet regimens are not used, as recent studies have shown similar virologic outcomes  in ART-naïve PLWH receiving either a single pill or two pills qd
- Tailoring antiretroviral regimens for each individual is essential in the presence of resistance
- For a wider review of possible drug-related adverse events, please see: Adverse Effects of ARVs and Drug Classes

 

Regimen Main requirements Additional Guidance (see footnotes)
Recommended regimens
2 NRTIs + INSTI
ABC/3TC + DTG
ABC/3TC/DTG
HLA-B*57:01 negative
HBsAg negative

I (ABC: HLA-B*57:01, cardiovascular risk)

II (Weight increase (DTG))

TAF/FTC/BIC   II (Weight increase (BIC, TAF))

TAF/FTC or TDF/XTC + DTG

 

II (Weight increase (DTG, TAF))

III (TDF: prodrug types. Renal and bone toxicity. TAF dosing)

TAF/FTC or TDF/XTC + RAL qd or bid

 

II (Weight increase (RAL, TAF))

III (TDF: prodrug types. Renal and bone toxicity. TAF dosing)

IV (RAL: dosing)

1 NRTI + INSTI
XTC + DTG or 3TC/DTG

HBsAg negative
HIV-VL < 500,000 copies/mL 
Not recommended after PrEP failure

II (Weight increase (DTG))

V (3TC/DTG not after PrEP failure)

2 NRTIs + NNRTI
TAF/FTC or TDF/XTC + DOR or TDF/3TC/DOR  

II (Weight increase (TAF))

III (TDF: prodrug types. Renal and bone toxicity. TAF dosing)

VI (DOR: caveats, HIV-2)

Alternative regimens
2 NRTIs + NNRTI

TAF/FTC or TDF/XTC + EFV or TDF/FTC/EFV

At bedtime or 2 hours before dinner

II (Weight increase (TAF)

III (TDF: prodrug types. Renal and bone toxicity. TAF dosing)

VII (EFV: neuro-psychiatric adverse events. HIV-2 or HIV-1 group 0)

TAF/FTC or TDF/XTC + RPV or TAF/FTC/RPV or TDF/FTC/RPV

CD4 count > 200 cells/μL

HIV-VL < 100,000 copies/mL

Not on gastric pH increasing agents

With food

II (Weight increase (TAF))

III (TDF: prodrug types. Renal and bone toxicity. TAF dosing)

VIII (RPV: HIV-2)

2 NRTIs + PI/r or PI/c

TAF/FTC or TDF/XTC + DRV/c or DRV/r or TAF/FTC/DRV/c

With food

II (Weight increase (TAF))

III (TDF: prodrug types. Renal and bone toxicity. TAF dosing)

IX (DRV/r: cardiovascular risk)

X (Boosted regimens and drug-drug interactions)

 

Additional Guidance

  1. ABC contraindicated if HLA-B*57:01 positive. Even if HLA-B*57:01 negative, counselling on HSR risk still mandatory. ABC should be used with caution in persons with a high CVD risk (> 10%), see: Prevention of Cardiovascular Disease (CVD)
  2. Treatment with INSTIs or TAF may be associated with weight increase
  3. In certain countries, TDF is labelled as 245 mg rather than 300 mg to reflect the amount of the prodrug (tenofovir disoproxil) rather than the fumarate salt (tenofovir disoproxil fumarate). There are available generic forms of TDF, which instead of fumarate use phosphate, maleate, and succinate salts. They can be used interchangeably
    When available, combinations containing TDF can be replaced by the same combinations containing TAF. TAF is used at 10 mg when coadministered with drugs that inhibit P-gp, and at 25 mg when coadministered with drugs that do not inhibit P-gp
    The decision whether to use TDF or TAF depends on individual characteristics as well as availability
    If the ART regimen does not include a booster, TAF and TDF have a similar short-term risk of renal adverse events leading to discontinuation and bone fractures
    TAF*** should be considered as a first choice**** over TDF in individuals with:
    • established or high risk of CKD, see Kidney disease;
    • co-administration of medicines with nephrotoxic drugs or prior TDF toxicity, see Nephrotoxicity;
    • osteoporosis / progressive osteopenia, high FRAX score or risk factors, see Bone disease;
    • history of fragility fracture, see Bone disease
  4. RAL can be given as RAL 400 mg bid or RAL 1200 mg (two, 600 mg tablets) qd. Note: RAL qd should not be given in presence of an inducer (i.e. TB drugs, antiepileptics) or divalent cations (i.e. calcium, magnesium, iron), in which case RAL should be used bid
  5. HIV infections occurring in the context of PrEP failure may be associated with resistance-associated mutations. 3TC/DTG may be used in in this context only if there is no documented resistance in genotypic test
  6. DOR is not active against HIV-2. DOR has not demonstrated non-inferiority to INSTI. There is risk of resistance associated mutations in case of virological failure. Results of genotypic resistance test are necessary before starting DOR
  7. EFV: not to be given if history of suicide attempts or mental illness; not active against HIV-2 and HIV-1 group O strains
  8. RPV is not active against HIV-2
  9. A single large study has shown increase in CVD risk with cumulative use of DRV/r, not confirmed in smaller studies
  10. Boosted regimens with RTV or COBI are at higher risk of drug-drug interactions, see Drug-drug interactions

*** There are limited data on use of TAF with eGFR < 10 mL/min
**** Expert opinion pending clinical data