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First-line ART
Key Principles and Recommended Regimens for First-line Antiretroviral Therapy

Released: May 22, 2019

Expiration: May 20, 2020

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In the United States, HIV treatment guidelines are periodically issued by both the IAS-USA2 and the DHHS.1 The DHHS reissues recommendations in response to new data that are compelling; the IAS-USA issues new guidelines biennially at each International AIDS Conference. The current versions of these guidelines are similar in that INSTI-based regimens are the recommended options for first-line regimens. In addition, the DHHS panel gives the provider a choice between tenofovir disoproxil fumarate (DF) or tenofovir alafenamide (AF) for those regimens including tenofovir. However, the IAS-USA panel excludes tenofovir DF from the generally recommended initial regimens, albeit with a note stating that tenofovir DF is a generally well tolerated and effective option when tenofovir AF is unavailable, but tenofovir DF is not recommended for patients with or at high risk for osteopenia/osteoporosis or renal impairment. In addition, the IAS-USA panel includes only 2 of the 4 currently available INSTIs in the generally recommended regimen list, whereas 3 of the 4 INSTIs are included among regimens recommended for most patients with HIV in the DHHS guidelines. The regimens most recently recommended as initial ART for most people with HIV by the DHHS are as follows1:

  • Abacavir/dolutegravir/lamivudine (only if HLA-B*5701 negative)
  • Dolutegravir plus either emtricitabine/tenofovir DF or emtricitabine/tenofovir AF
  • Raltegravir plus either emtricitabine/tenofovir DF or emtricitabine/tenofovir AF
  • Bictegravir/emtricitabine/tenofovir AF

The initial regimens generally recommended by the IAS-USA panel are as follows:

  • Abacavir/dolutegravir/lamivudine (only if HLA-B*5701 negative)
  • Dolutegravir plus emtricitabine/tenofovir AF
  • Bictegravir/emtricitabine/tenofovir AF

Table 1. DHHS and IAS-USA: Recommended ART Regimens for Treatment-Naive Patients1; 2

 

Guideline Recommendations Regarding Dolutegravir Use in Adults and Adolescents With HIV Who Are Pregnant or of Childbearing Potential
Initial results from an ongoing National Institutes of Health–funded birth surveillance study in Botswana, Tsepamo, reported an increased risk of neural tube defects (NTD) in infants whose mothers became pregnant while receiving dolutegravir-based ART (0.94% of 426 births in women receiving dolutegravir-based ART vs 0.12% of 11,300 births in women in women receiving non-dolutegravir–based ART),3 prompting the DHHS, the IAS-USA, and the EACS to provide interim recommendations for dolutegravir use in women of childbearing age.1,2,4 It is currently recommended by the DHHS, IAS-USA, and EACS not to start dolutegravir during the first trimester of pregnancy,1,2,4 and use of dolutegravir in women should be accompanied by counseling about the potential risks of NTDs if dolutegravir is taken during/near the time of conception and during the first 12 weeks of pregnancy.1,2 It is also recommended by the DHHS and IAS-USA panels to have a documented negative pregnancy test result before initiating dolutegravir in women of childbearing potential. Additional aspects of the interim recommendations related to first-line dolutegravir use in women are as follows:

  • For women wanting to become pregnant or who are sexually active and not using effective contraception: Do not initiate dolutegravir
  • For women not wanting to become pregnant and using effective contraception: Dolutegravir-based ART can be considered
    • Pregnancy testing is recommended before dolutegravir initiation
    • Discuss potential impact of dolutegravir on fetus and importance of effective contraception use

It is important to note that in the Tsepamo study, there has been no evidence of increased NTDs among infants born to mothers who initiated dolutegravir-based ART during pregnancy. Results from approximately 600 additional births among pregnant women receiving dolutegravir-based ART from conception are expected during the next 9 months and should provide further insight into this potential risk. An updated analysis reported at AIDS 2018 showed that as of July 2018, there were no additional cases of NTDs after 170 additional births with dolutegravir exposure at conception, providing an updated interim NTD prevalence rate of 0.67% (4/596; 95% CI: 0.26% to 1.70%) (Capsule Summary).5  

In addition to recommended regimens, the DHHS guidelines list regimens “to be used in certain clinical situations” (Table 2). The IAS-USA guidelines provide a list of regimens that are recommended only for patients for whom “generally recommended regimens are not available or not an option” (Table 2). Of note, the guidelines stress that choices should be “individualized on the basis of virologic efficacy, toxicity, pill burden, dosing frequency, drug–drug interaction potential, resistance testing results, comorbid conditions, and cost” and that “on the basis of individual patient characteristics and needs,” these regimens may, in some instances, be the optimal regimen for a patient. The subsequent sections of this module will address the treatment decisions facing clinicians when selecting from among these choices.

Table 2. DHHS First-line Regimens to be Used in Certain Clinical Situations1 and IAS-USA Initial Therapy Regimens Recommended for Patients When Generally Recommended Regimens Not Available or Not an Option2

 

The European AIDS Clinical Society (EACS) also regularly updates their guidelines for the treatment of HIV-infected adults.4 In these guidelines, the EACS recommends a regimen consisting of 2 NRTIs plus an INSTI for persons starting ART. However, they acknowledge that an ART regimen must be tailored to the individual and therefore also include additional regimens in the recommended category, which consist of 2 NRTIs plus an NNRTI or boosted PI (Table 3). These guidelines note that generic drugs may be substituted if they replace the same drug and do not break recommended fixed-dose coformulations.

Table 3. EACS: Recommended Initial Regimens for Treatment-Naive Patients4

 

In addition to the recommended regimens, the EACS guidelines also list several alternative regimens (Table 4). The EACS panel states that the alternatives are “to be used when none of the preferred regimens are feasible or available, whatever the reason.”

Table 4. EACS Alternative Initial Regimens for Treatment-Naive Patients4


Of interest, both the DHHS and the EACS guidelines include NRTI-sparing regimens, that is, regimens containing no NRTIs or containing only lamivudine.1,4 These regimens are included as “other combinations” under the alternative regimens in the EACS guidelines (Table 4),4 and as regimens to be used “when abacavir, tenofovir DF, or tenofovir AF cannot be used” in the alternative regimens tables of the DHHS and IAS-USA guidelines (Table 2).1,2 These recommendations acknowledge the potency and potential cost savings of 2-drug regimens, as well as the potential toxicity of abacavir and/or tenofovir as components of 3-drug regimens.

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