Initial Regimens: ART-naïve Adult

Initial Combination Regimen for ART-naïve Adult PLWH

Considerations

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

Recommended regimens

  • One of the following to be selected *,**
Out of the recommended regimens in PLWH starting ART, we favour the use of an unboosted INSTI with a high genetic barrier (DTG or BIC) as preferred third agent. Tailoring antiretroviral regimens for each individual is essential as other classes of third agents (e.g. PI/b) might be indicated in the presence of resistance

* Only drugs currently licensed for initiation of therapy by the EMA are taken into consideration (in alphabetical order)
** 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

Regimen Main requirements Footnotes (additional guidance)
2 NRTIs + INSTI (PREFERRED)
ABC/3TC + DTG
ABC/3TC/DTG
HLA-B*57:01 negative
HBsAg negative
I (ABC: HLA-B*57:01, cardiovascular risk)
TAF/FTC or TDF/FTC or TDF/3TC + DTG  

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

III Weight increase

TAF/FTC/BIC    
TAF/FTC or TDF/FTC or TDF/3TC + RAL qd or bid  

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

IV (RAL: dosing)

1 NRTI + INSTI
DTG + 3TC

HBsAg negative
HIV-VL < 500,000 copies/mL
CD4 count > 200 cells/μL

 
2 NRTIs + NNRTI

TAF/FTC or TDF/FTC or TDF/3TC + DOR

TDF/3TC/DOR

 

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

V (DOR: HIV-2)

TAF/FTC or TDF/FTC or TDF/3TC + RPV

TAF/FTC/RPV

TDF/FTC/RPV

CD4 count > 200 cells/μL
HIV-VL < 100,000 copies/mL
Not on proton pump inhibitor
With food

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

VI (RPV: HIV-2)

2 NRTIs + PI/r or PI/c

TAF/FTC or TDF/FTC or TDF/3TC + DRV/c or DRV/r

TAF/FTC/DRV/c

With food

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

VII (DRV/r: cardiovascular risk)

Alternative regimens

Regimen Main requirements Footnotes (additional guidance)
2 NRTIs + INSTI
ABC/3TC + RAL qd or bid

HBsAg negative
HLA-B*57:01 negative

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

IV (RAL: dosing)

TDF/FTC/EVG/c

TAF/FTC/EVG/c

With food

II    (TDF: prodrug types. Renal and bone toxicity)

VIII (EVG/c: use in renal impairment)

2 NRTIs + NNRTI
ABC/3TC +EFV HLA-B*57:01 negative
HBsAg negative
HIV-VL < 100,000 copies/mL
At bed time or 2 hours before dinner

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

IX  (EFV: suicidality. HIV-2 or HIV-1 group 0)

TAF/FTC or TDF/FTC or TDF/3TC + EFV

TDF/FTC/EFV

At bed time or 2 hours before dinner

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

IX (EFV: suicidality. HIV-2 or HIV-1 group 0)

2 NRTIs + PI/b

ABC/3TC + ATV/c or ATV/r

HLA-B*57:01 negative
HBsAg negative
HIV-VL < 100,000 copies/mL
Not on proton pump inhibitor
With food

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

X  (ATV/b & renal toxicity)

ABC/3TC + DRV/c or DRV/r

HLA-B*57:01 negative
HBsAg negative
With food

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

VII (DRV/r and cardiovascular risk)

TAF/FTC or TDF/FTC or TDF/3TC + ATV/c or ATV/r

Not on proton pump inhibitor
With food

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

X (ATV/b: renal toxicity)

Other combinations

Regimen Main requirements Footnotes (additional guidance)
RAL 400 mg bid + DRV/c or DRV/r

HBsAg negative
HIV-VL < 100,000 copies/mL
CD4 > 200 cells/μL
With food

VII (DRV/r: cardiovascular risk)

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 (> 20%)
  2. II 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. So far, there are only limited long-term data on TAF. If the ART regimen does not include a booster, TAF and TDF have a similar shortterm 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

*** There are limited data on use of TAF with eGFR < 30 mL/min
**** Expert opinion pending clinical data

  1. Two randomized controlled trials (performed in South Africa and Cameroon) showed that, in comparison with EFV, treatment with DTG in naïve persons was associated with increased weight gain when combined with TAF/FTC, TDF/FTC or TDF/3TC. The effect on increased weight was more important for women under treatment containing both DTG and TAF [12], [13]
  2. 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
  3. DOR is not active against HIV-2
  4. RPV is not active against HIV-2
  5. A single study has shown increase in CVD risk with cumulative use of DRV/r [14]
  6. TDF/FTC/EVG/c to be used only if eGFR ≥ 70 mL/min. It is recommended that TDF/FTC/EVG/c is not initiated in persons with eGFR < 90 mL/min unless this is the preferred treatment
  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. Potential renal toxicity with ATV/b