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HIV-ASSIST: ART Simplification
Antiretroviral Therapy Simplification in Treatment-Experienced People With HIV: Using HIV-ASSIST

Released: June 01, 2023

Josep M. Llibre
Josep M. Llibre, MD, PhD
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Key Takeaways

•    The HIV-ASSIST tool can support HIV specialist healthcare professionals in simplifying ART regimens for medically complex, treatment-experienced PWH. 
•    The rules-based HIV-ASSIST algorithm incorporates HIV resistance mutation and prior virologic failure data into its recommended ART regimens.


People with HIV (PWH) and previous virologic failures usually can achieve complete virologic suppression with salvage antiretroviral therapy (ART) regimens. As new information emerges, however, these complex salvage regimens need a second look to check for possibilities of regimen simplification. In such instances, HIV-ASSIST, a free online decision support tool, can assist healthcare professionals with ART selection decisions and facilitate access to infectious disease consultation. 

This complex, rules-based algorithm is fed with data from the US Department of Health and Human Services (DHHS) and International Antiviral Society-USA (IAS-USA) guidelines, Stanford University HIV Drug Resistance Database, and University of Liverpool HIV Drug Interactions Checker, and is reviewed by a panel of scientific advisors. An ongoing process to test and refine the algorithm is key to ensuring that it stays up to date.

A Medically Complex Patient Case

Let’s consider a 61-year-old woman with hypertension who is receiving amlodipine and losartan/hydrochlorothiazide who smokes tobacco and who has a history of IV opioid use disorder. She was diagnosed with HIV in 1997; her initial CD4 count was 111 cells/mm3 and HIV-1 RNA was 615,000 copies/mL.

  • 1997: She received nucleos(t)ide reverse-transcriptase inhibitor (NRTI) monotherapy for 4 years with zidovudine, then didanosine, then zalcitabine.
  • 2001: She started her first highly active ART regimen with indinavir plus lamivudine/stavudine and maintained virologic suppression (HIV-1 RNA <80 copies/mL) for the next 3 years.
  • 2004: She self-discontinued her ART and was admitted to the hospital with disseminated tuberculosis. She then restarted ART and until 2009 received different regimens of boosted protease inhibitors plus 2 NRTIs. Because of medication intolerance and lack of motivation, she discontinued her ART regimen again. She was readmitted with esophageal candidiasis and trigeminal herpes zoster.
  • 2011: Her HIV-1 RNA was 1.8 million copies/mL, and her CD4 count was 18 cells/mm3. After treatment counseling and provision of psychological support, she restarted ART with darunavir (DRV)/ritonavir plus etravirine plus raltegravir plus tenofovir disoproxil fumarate/emtricitabine (FTC), on which she achieved viral suppression.
  • 2016: Her ART regimen was changed to coformulated elvitegravir (EVG)/cobicistat (COBI)/tenofovir alafenamide (TAF)/FTC plus once-daily DRV plus rilpivirine. Her HIV-1 RNA has been undetectable (<20 copies/mL) since 2020, and she maintained an immune discordance with a CD4 count of 293 cells/mm3 at last check.

A careful review of her HIV genotype results shows that she has an R5 HIV-1, V82A, L90M and Q58E (protease), M184V, T215C/S and K291Q (reverse transcriptase), and no integrase mutations. Of importance, she has never experienced virologic failure while receiving a regimen containing an integrase strand transfer inhibitor.

She is experiencing treatment fatigue and asks about the possibility of treatment simplification after maintaining an undetectable HIV-1 RNA for years.

HIV-ASSIST ART Selection

What is the HIV-ASSIST expert guidance? It ranks bictegravir (BIC)/TAF/FTC and dolutegravir (DTG) plus TAF/FTC as the first options for this patient, with a weighted score of 1.2 for each. A score ≤1.5 - the lower the better - means a strong evidence of efficacy based on current IAS-USA and DHHS guidelines, while factoring in treatment history, comorbidities, comedications, HIV resistance mutations, and other patient-specific factors (Figure 1).

Both of these top 2 choices represent an opportunity to simplify the patient’s ART regimen. The main difference between them is that BIC/TAF/FTC has a lower pill number (1 pill vs 2 pills).

Figure 1. HIV-ASSIST output shows options for simplifying ART for a treatment-experienced PWH.

In the tool, clicking on any regimen opens a new window with a complete education sheet containing data underpinning that regimen. There is a full additional information sheet with mutation penalties based on the Stanford database (Figure 2).

Figure 2. HIV-ASSIST output explanation of mutation penalties.

My Preferred Regimen

In this case, I agree with the recommendations from HIV-ASSIST. Switching to BIC/TAF/FTC in treatment-experienced PWH has demonstrated durable efficacy in maintaining viral suppression in PWH with preexisting M184V/I plus 2 low-impact thymidine analogue mutations (TAMs). In a pooled analysis of randomized trials that evaluated antiretroviral switches, 179 of 182 subjects with M184V/I and 32 of 33 with M184V/I and 1 or 2 TAMs maintained HIV-1 RNA <50 copies/mL at last visit. These data are quite reassuring and offer the highest level of evidence to date to address this specific scenario.

Either of the top 2 regimens from HIV-ASSIST—BIC/TAF/FTC or DTG plus TAF/FTC—would be a great way to streamline her regimen and decrease her pill burden.

Your Thoughts?

What are your strategies to streamline complex ART regimens in PWH with long-term virologic suppression, HIV resistance mutations, and previous virologic failures? Join the conversation by posting a comment below.