Contraindications: Abacavir is contraindicated in patients who test positive for HLA-B*5701 and should be avoided if HLA-B*5701 testing cannot be performed. |
Comorbid conditions: - Cardiovascular disease: Abacavir should generally be avoided in patients with (or at risk for) cardiovascular disease. In addition, if a patient requires a PI, we prefer to use atazanavir over other boosted PIs. Efavirenz and rilpivirine should be avoided, if possible, in patients at risk for torsades de pointes.
- HBV: Tenofovir (TAF or TDF)-emtricitabine is the preferred NRTI combination for patients with HIV/HBV coinfection. ART regimens that include emtricitabine and lamivudine without tenofovir should not be used.Δ
- Kidney disease:
- TDF should be avoided in patients with an eGFR <60 mL/min/1.73 m2. When TDF is administered with cobicistat, it should not be administered to patients with an eGFR <70 mL/min/1.73 m2.
- TAF can be used in patients with moderately reduced kidney function but should generally be avoided in patients with acute renal injury or an eGFR <30 mL/min/1.73 m2 unless they are on hemodialysis.
- The combination of dolutegravir plus lamivudine can be used for patients with severely reduced kidney function, but only if the HIV load is <500,000 copies/mL, there is no chronic HBV infection, and there is no transmitted resistance to NRTIs or INSTIs (if INSTI resistance testing was obtained as part of the initial evaluation). In addition, patients should not be taking concurrent medications that would significantly reduce the levels of either antiretroviral agent and should ideally have a CD4 count >200 cells/microL.
- Osteoporosis: TDF should be avoided.
- Mental health disorders: Efavirenz and rilpivirine should be used cautiously in patients with mental health disorders since both agents have been associated with depression and suicide.
- Tuberculosis: There may be significant interactions with rifamycins. Regimens containing dolutegravir or raltegravir may be used with dose adjustment of the integrase inhibitor. Dose adjustments are not needed if efavirenz-emtricitabine-TDF is used. For patients with latent tuberculosis, any of the preferred ART regimens can be used if isoniazid is employed for the treatment of latent tuberculosis.◊
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Persons of childbearing potential:§ Those who are planning to conceive should generally be started on a regimen that consists of a dual NRTI combination plus an integrase inhibitor. Preferred antiretroviral agents are those for which there are substantial experience and data documenting virologic efficacy, maternal and fetal safety, and tolerability during pregnancy. |
Adherence concerns: Regimens should include a dual-NRTI combination plus a third agent with a high barrier to resistance (eg, TAF-emtricitabine plus either dolutegravir or boosted darunavir). Bictegravir-emtricitabine-TAF also has a low risk of treatment-emergent resistance and a small tablet size, though there are fewer data than with dolutegravir. |
Drug interactions: Antiretroviral medications that require a boosting agent (eg, ritonavir or cobicistat) are associated with greater risk of drug interactions. Refer to the Lexicomp drug interaction program available within UpToDate for specific information on drug-drug interactions. |
Dosing considerations: Many regimens (eg, bictegravir-emtricitabine-TAF, dolutegravir-lamivudine, dolutegravir-abacavir-lamivudine, elvitegravir-cobicistat-emtricitabine-TAF, and darunavir-cobicistat-emtricitabine-TAF) are available as a single coformulated tablet administered once daily. By contrast, raltegravir is not coformulated with dual NRTIs, so the pill burden with regimens containing this drug is greater. In patients with severely reduced kidney function not on dialysis, some coformulated tablets cannot be used as dose adjustments are required. |
Baseline resistance testing: When initiating therapy pending the results of resistance testing, a regimen containing tenofovir-emtricitabine plus dolutegravir or bictegravir can be used. If one of these INSTIs is not available, a pharmacologically boosted PI is a reasonable alternative. |