What are the Antiretroviral Therapy (ART) regimens?

From the Guidelines

The most effective antiretroviral therapy (ART) regimens for treating HIV infection in adults typically consist of a combination of three drugs from at least two different drug classes, with a preference for integrase strand transfer inhibitor (INSTI)-based regimens such as dolutegravir/abacavir/lamivudine or bictegravir/tenofovir alafenamide/emtricitabine due to their high efficacy, minimal toxicity, and low risk of drug interactions, as recommended by the International Antiviral Society-USA panel in 2020 1.

Key Considerations for ART Regimens

• The choice of ART regimen should be individualized based on factors such as comorbidities, potential drug interactions, pregnancy status, and resistance testing results.
• INSTI-based regimens, such as dolutegravir and bictegravir, are preferred due to their high rates of viral suppression, minimal toxicity, and low risk of drug interactions 1.
• Other recommended initial ART regimens include darunavir/cobicistat/tenofovir alafenamide/emtricitabine, efavirenz plus tenofovir disoproxil fumarate/lamivudine, and raltegravir plus tenofovir alafenamide/emtricitabine, each with specific potential uses and cautions 1.

Monitoring and Adherence

• Regular monitoring of viral load is essential, with the goal of achieving undetectable levels (<50 copies/mL) within 6 months.
• Adherence to ART is crucial to prevent drug resistance and ensure long-term efficacy.
• Side effects vary by drug class but may include gastrointestinal symptoms, neuropsychiatric effects, or metabolic changes, though newer regimens generally have improved tolerability profiles.

Regimen Selection

• The selection of an ART regimen should consider the potential for drug interactions, particularly with concomitant medications, as well as the patient's renal function and other comorbidities.
• The use of fixed-dose combination regimens, such as single-tablet regimens, can improve adherence and simplify treatment 1.

From the FDA Drug Label

Table 19 compares the demographic and baseline characteristics between subjects in the darunavir/ritonavir 800 mg/100 mg once daily arm and subjects in the lopinavir/ritonavir 800 mg/200 mg per day arm in trial TMC114-C211 Table 20: Virologic Outcome of Randomized Treatment of Trial TMC114-C211 at 192 Weeks Table 21 compares the demographic and baseline characteristics between subjects in the darunavir/ritonavir 800 mg/100 mg once daily arm and subjects in the darunavir/ritonavir 600 mg/100 mg twice daily arm in trial TMC114-C229 Week 48 outcomes for subjects on darunavir/ritonavir 800 mg/100 mg once daily from trial TMC114-C229 are shown in Table 22 TMC114-C214 is a randomized, controlled, open-label Phase 3 trial comparing darunavir/ritonavir 600 mg/100 mg twice daily versus lopinavir/ritonavir 400 mg/100 mg twice daily in antiretroviral treatment-experienced, lopinavir/ritonavir-naïve HIV-1-infected adult subjects

The anti-retroviral therapy regimens mentioned in the drug label are:

• Darunavir/ritonavir 800 mg/100 mg once daily
• Lopinavir/ritonavir 800 mg/200 mg per day
• Darunavir/ritonavir 600 mg/100 mg twice daily
• Lopinavir/ritonavir 400 mg/100 mg twice daily These regimens were used in combination with other antiretroviral agents, such as TDF/FTC (tenofovir disoproxil fumarate/emtricitabine) and an optimized background regimen (OBR). The choice of regimen depends on the specific patient population and the clinical trial in which it was studied, as seen in trials TMC114-C211, TMC114-C229, and TMC114-C214 2.

From the Research

Antiretroviral Therapy Regimens

• The decision to start antiretroviral therapy (ART) should be based on factors such as CD4+ cell count, viral load, stage and tempo of the disease, and patient commitment 3.
• Recommended starting ART regimens include ictegravir plus tenofovir alafenamide (TAF)/emtricitabine (FTC), dolutegravir (DTG) plus abacavir/lamivudine, DTG plus TAF (or TDF)/FTC, or DTG plus 3TC 4.
• Initial laboratory evaluation should include CD4+ cell count, plasma HIV-1 RNA, and testing for HIV reverse transcriptase and protease resistance mutations 4.

First-Line and Second-Line Regimens

• A first-line, triple-nucleoside regimen may not be the best option, especially for people with more advanced disease 3.
• Recycling tenofovir and lamivudine/emtricitabine (XTC) with dolutegravir could provide a more tolerable, affordable, and scalable second-line regimen than dolutegravir with an optimized nucleoside reverse transcriptase inhibitor (NRTI) backbone 5.
• A high proportion of adults switching to second-line tenofovir/lamivudine/dolutegravir (TLD) achieved virologic suppression despite substantial baseline NRTI resistance 5.

Clinical Trials and Studies

• A randomized controlled trial is being conducted to determine the virologic efficacy of TLD with and without a lead-in supplementary dose of dolutegravir in patients failing a first-line regimen of tenofovir-emtricitabine-efavirenz (TEE) 6.
• The trial aims to compare TLD fixed dose combination daily with a lead-in supplementary 50 mg dolutegravir dose versus matching placebo taken 12 hours later for the first 14 days, in patients failing a first-line TEE regimen 6.
• The primary endpoint is proportion achieving viral load <50 copies/mL at week 24 using a modified intention-to-treat analysis and the U.S. Food and Drug Administration snapshot algorithm 6.