Initial Regimens: ART-naïve Adults

Considerations

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

• If a woman wishes to conceive or is pregnant: Treatment of Pregnant Women Living with HIV or Women Considering Pregnancy
• If the person has an opportunistic infection: Initiation of ART regimen in persons with opportunistic infections
• If the person has TB: Antiretroviral regimens in TB/HIV co-infection
• If the person has HIV/HBV co-infection: The person should receive a TDF or TAF containing ART regimen unless history of tenofovir intolerance. In person non responding HBV vaccination consider TDF or TAF containing ART regimen
• If the person has potential treatment limiting co-morbidities: Co-morbidity section, dose adjustments for renal impairment and hepatic impairment
• If the person is treated with other medications: relevant Drug-drug interactions & other prescribing issues
• If the person has Swallowing Difficulties: Administration of ARVs in persons with swallowing difficulties
• If the person has acquired HIV while on regular oral PrEP intake: In this situation, change PrEP to a triple-drug ART regimen including a third drug with a high barrier to resistance (preferably, DTG, BIC or alternatively DRV/b) plus TXF/XTC without interrupting antiretrovirals. The danger of acute seroconversion syndrome and higher infectiousness would be arguments for immediate switch to triple therapy. ART should be adjusted with the results of genotypic resistance analysis 

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 some studies have shown similar virologic outcomes in ART-naïve persons 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

Additional Guidance

1. Treatment with INSTIs or TAF may be associated with weight increase
2. 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 very low 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: Screening and Diagnosis
   • history of fragility fracture, see Approach to Fracture Reduction
3. HIV infections occurring in the context of PrEP failure may be associated with resistance-associated mutations 
4. DOR is not active against HIV-2. DOR has not been compared to an INSTI and was shown to be non inferior to EFV and DRV. There is risk of resistance associated mutations in case of virological failure. Results of genotypic resistance test are necessary before starting DOR
5. ABC contraindicated if HLA-B*57:01 positive, not to be used for same day start. 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)
6. 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
7. EFV: not to be given if history of suicide attempts or mental illness; 400 or 600mg daily should be used; if rifampicin based regimen for tuberculosis is used, 600 mg dosing must be used; 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 other studies. DRV/r should be used with caution in persons with a high risk of cardiovascular risk
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