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Considerations when selecting an initial antiretroviral regimen for nonpregnant persons with HIV-1¶[1,2]

Considerations when selecting an initial antiretroviral regimen for nonpregnant persons with HIV-1¶[1,2]
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 unless there is evidence of atazanavir resistance. Certain NNRTIs (eg, 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.◊
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 bictegravir or 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 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.
This table is meant for use with UpToDate content on regimen selection in treatment-naïve patients. The approach to regimen selection listed in this table reflect our approach to choosing an ART for nonpregnant treatment-naïve patients with HIV-1 and are a synthesis of guideline recommendations. Refer to the topics that discuss HIV in pregnancy for regimens used to treat pregnant women. Antiretrovirals separated by "-" (eg, TAF-emtricitabine) are available in single-tablet coformulations. For additional information and specific dosing recommendations, refer to the individual drug monographs available in UpToDate, as well as the topic that provides an overview of the different antiretroviral agents.

ART: antiretroviral therapy; eGFR: estimated glomerular filtration rate; HBV: hepatitis B virus; INSTI: integrase strand transfer inhibitor; NNRTI: non-nucleoside reverse transcriptase inhibitor; NRTI: nucleoside reverse transcriptase inhibitor; PI: protease inhibitor; TAF: tenofovir alafenamide; TDF: tenofovir disoproxil fumarate.

¶ If more than one comorbid condition is present, the clinician should review the options for each relevant scenario and select the most appropriate combination.

Δ Refer to the topic in UpToDate that discusses the treatment of patients with HIV and HBV.

◊ For additional information on agent selection for tuberculosis, refer to the UpToDate topics that discuss the treatment of active or latent tuberculosis in persons with HIV.

§ For additional information on regimen selection in persons of childbearing potential, refer to the topic in UpToDate that discusses HIV in women.

¥ An HIV genotype should be performed in all patients before initiating ART. Some genotypes do not test for integrase resistance. If a person acquires HIV while receiving cabotegravir for pre-exposure prophylaxis or or the source is known to have INSTI treatment failure or resistance, this test should be requested in addition to the traditional genotype.
References:
  1. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIVs. National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/whats-new (Accessed on February 10, 2024).
  2. Gandhi RT, Bedimo R, Hoy JF, et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2022 recommendations of the International Antiviral Society-USA Panel. JAMA 2023; 329:63.
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