What is eSACEP (efavirenz, stavudine, abacavir, lamivudine, and possibly a protease inhibitor) in HIV treatment?

Understanding eSACEP in HIV Treatment

eSACEP refers to a combination antiretroviral therapy regimen containing efavirenz, stavudine, abacavir, lamivudine, and possibly a protease inhibitor, which was used historically in HIV treatment but is no longer recommended due to the availability of more effective and less toxic regimens.

Components of eSACEP

• Efavirenz (EFV): A non-nucleoside reverse transcriptase inhibitor (NNRTI) that inhibits HIV-1 by noncompetitive inhibition of HIV-1 reverse transcriptase 1
• Stavudine (d4T): A nucleoside reverse transcriptase inhibitor (NRTI) that was commonly used in early HIV treatment regimens 2
• Abacavir (ABC): An NRTI that is converted by cellular enzymes to the active metabolite carbovir triphosphate, which inhibits HIV-1 reverse transcriptase 3
• Lamivudine (3TC): An NRTI that is phosphorylated intracellularly to its active form, which inhibits reverse transcriptase via DNA chain termination 3
• Protease Inhibitor (PI): Some variations of this regimen included a PI such as indinavir, nelfinavir, or ritonavir 2

Historical Context

• eSACEP emerged in the early era of combination antiretroviral therapy (ART), when treatment strategies were evolving from monotherapy to more effective multi-drug regimens 2
• In the early 2000s, various combinations of NRTIs, NNRTIs, and PIs were being explored to find optimal regimens for HIV treatment 2
• The combination aimed to target multiple stages of the HIV life cycle to effectively suppress viral replication 4

Limitations and Concerns

• Stavudine (d4T) is no longer recommended in current treatment guidelines due to significant toxicities including peripheral neuropathy, lipoatrophy, and mitochondrial toxicity 2
• Efavirenz is associated with neuropsychiatric side effects and is no longer a preferred agent in most current guidelines 2
• The regimen has a high pill burden compared to modern single-tablet regimens 2
• Drug interactions between components can be problematic, particularly when protease inhibitors are included 1

Evolution Beyond eSACEP

• Current guidelines have evolved to recommend integrase strand transfer inhibitor (InSTI)-based regimens as preferred first-line therapy due to superior efficacy, tolerability, and resistance profiles 2
• Modern recommended regimens include:
  • Bictegravir/tenofovir alafenamide/emtricitabine 2
  • Dolutegravir/abacavir/lamivudine 2
  • Dolutegravir plus tenofovir alafenamide/emtricitabine 2

Clinical Outcomes with eSACEP Components

• Studies comparing efavirenz-based regimens with triple-nucleoside regimens (like abacavir/lamivudine/zidovudine) found that efavirenz-containing regimens had superior virologic outcomes 5
• The combination of efavirenz, zidovudine, and lamivudine demonstrated greater antiviral activity and better tolerability than indinavir-based regimens in early studies 6
• Later research showed that abacavir/efavirenz/didanosine was an effective second-line regimen for patients who failed initial nucleoside/PI regimens 7

Key Takeaway

• eSACEP represents an historical approach to HIV treatment that has been superseded by more effective, less toxic, and more convenient regimens in current treatment guidelines 2
• Modern HIV treatment has moved toward simpler regimens with fewer side effects, typically based on integrase inhibitors rather than the NNRTI/NRTI/PI combinations used in regimens like eSACEP 2, 4