. 2020 Sep 3;21(10):617–624. doi: 10.1111/hiv.12878

Table 1.

Combination antiretroviral therapy (ART) regimens for treatment‐naïve adult people living with HIV (PLWH)

Regimen	Main requirements	Additional guidance (footnotes)
Recommended regimens
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
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 bedtime or 2 h 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 bedtime or 2 h 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/r or PI/c
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 and 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
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: (I) ABC contraindicated if HLA‐B*57:01 positive. Even if HLA‐B*57:01 negative, counselling on hypersensitivity reaction risk still mandatory. ABC should be used with caution in persons with a high CVD risk (> 10%). (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‐glycoprotein (P‐gp), and at 25 mg when co‐administered 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 antiretroviral (ART) regimen does not include a booster, TAF and TDF have similar short‐term risks of renal adverse events leading to discontinuation and bone fractures.

TAF*** should be considered as a first choice**** over TDF in individuals with:

(1) established or high risk of chronic kidney disease (see Guideliness page 64); (2) co‐administration of medicines with nephrotoxic drugs or prior TDF toxicity (see Guidelines page 65); (3) osteoporosis/progressive osteopenia, high fracture risk asessement tool score or risk factors (see Guidelines page 61); (4) history of fragility fracture (see Guidelines pages 61 and 63).

***There are limited data on use of TAF with estimated glomerular filtration rate (eGFR) < 30 mL/min;

****Expert opinion pending clinical data.

(III) 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 (reference [12], [13] in the Guidelines). (IV) 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 the presence of an inducer (i.e. TB drugs or antiepileptics) or divalent cations (i.e. calcium, magnesium or iron), in which case RAL should be used bid. (V) DOR is not active against HIV‐2. (VI) RPV is not active against HIV‐2. (VII) A single study has shown an increase in CVD risk with cumulative use of DRV/r (reference [14] in the Guidelines). (VIII) 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. (IX) EFV: not to be given if history of suicide attempts or mental illness; not active against HIV‐2 and HIV‐1 group O strains. (X) Potential renal toxicity with ATV/b.

NRTI, nucleoside reverse transcriptase inhibitor; INSTI, integrase strand transfer inhibitor; HLA, human leucocyte antigen; ABC, abacavir; HBsAg, hepatitis B virus surface antigen; 3TC, lamivudine; DTG, dolutegravir; TAF, tenofovir alafenamide; FTC, emtricitabine; TDF, tenofovir disoproxil fumarate), BIC, bictegravir; DOR, doravirine; RAL, raltegravir; qd, once daily; bid, twice a day; VL, viral load; RPV, rilpivirine; PI/r, ritonavir‐boosted protease inhibitor; PI/c, cobicistat‐boosted protease inhibitor; EVG, elvitegravir; NNRTI, nonnucleoside reverse transcriptase inhibitor; ATV, atazanavir; CVD, cardiovascular disease.