TAF + FTC + BIC

• Co-formulated in a single pill regimen:
  • Biktarvy

TAF + FTC + DTG

• Co-formulated in a 2 pill regimen:
  • Descovy (TAF+FTC) & Tivicay (DTG)

TDF + FTC + DTG

• Co-formulated in a 2 pill regimen:
  • Truvada (TDF+FTC) & Tivicay (DTG)

• Very similar in structure and are considered interchangeable. They are not used together.
• Choose ONE of them to combine with a separate NRTI. Typically:
  • [Emtricitabine with Tenofovir]
  • [Lamivudine with Abacavir]
• - Emtricitabine in rare circumstances can cause hyperpigmentation

• Typically combined with FTC. 
• TDF is a prodrug of TAF. 
• Overall TAF used more frequently as it is less likely to cause renal & bone toxicity compared to TDF. 
• Circumstances where TDF preferred: when also using rifampin (TAF interacts with rifamycins) & PreP as TDF is the only formulation that’s FDA approved for PrEP   
• + Active against HBV
• - Renal toxicity (Avoid TDF if GFR <50, TAF if GFR <30) 
• - Decreased bone density 
• - Possible weight gain with TAF

• Typically combined with 3TC
• + Not nephrotoxic
• - Contraindicated in patients with HLA-B*5701 allele due to hypersensitivity reaction (must have negative result before starting)
• - May increase risk of CVD events. Avoid in patients with CA

•  BIKTARVY (with TAF/FTC) 
• + Available in single tablet regimen 
• - Emerging data on weight gain 
• - Not much data/experience of its use in pregnancy

• TRIUMEQ (with ABC/3TC) 
• JULUCA (with RPV) 
• DOVATO (with 3TC) 
• +Higher barrier to resistance than EVG or RAL 
• +If using rifamycins, preferred over BIC
• - Emerging data on weight gain 
• - Interacts with metformin- can’t exceed 1g metformin per day 
• No co-formulations with TAF/TDF   

NOTE

Use at conception & in very early pregnancy has been associated with a slightly higher prevalence of neural tube defects. However, the overall prevalence was low & when compared to other ARTs, it was not meaningfully different (Zash et al., 2019). Dolutegravir based regimens are all considered first line in pregnancy

• GENVOYA (with TAF/FTC) 
• STRIBLID (with TDF/FTC) 
• +Available in single tablet regimen with TAF/FTC 
• - Low barrier to resistance (compared to BIC or DTG) 
• - Needs boosting with Cobicistat (c) which increases drug interactions

• + More data on its safety in pregnancy
• - Low barrier to resistance (compared to BIC or DTG)
• Virologic failure may lead to two-class resistance (INSTI plus NRTI)
• - No co-formulations. Need to use BID dosing in pregnancy
• - Some reports of rhabdomyolysis

+ Comes as a long acting injectable with rilpivirine

• SYMTUZA (with TAF/FTC/cobcistat) 
• + Best tolerated PI 
• - Needs boosting with Ritonavir(r) or Cobicistat (c) 
• - Avoid in severe liver disease 
• - Can increase risk of CVD

• + Less metabolic syndrome effects
• - Needs boosting with Ritonavir(r) or Cobicistat(c)
• - Needs gastric acid and food for optimal absorption. Can’t use PPI >20 mg omeprazole with it
• - Increased risk of kidney stones and AKI
• - Can cause indirect hyperbilirubinemia
• - Avoid in severe liver disease

• ATRIPLA (with TDF/FTC)
• + Single pill coformulation with TDF/FTC
• - Neuropsychiatric side effects (vivid dreams + may increase suicide risk + “hungover feeling”)
• - Increase LFTs with risk of fulminant hepatitis (Child Pugh B and C)
• - CYP450 inducer – > decreases methadone levels (may precipitate opioid withdrawal when initiated)
• - Prolongs QT

• ODEFSEY (with TAF/FTC) 
• COMPLERA (with TDF/FTC) 
• JULUCA (with DTG) 
• + Less metabolic syndrome effects
• - Needs food (400 calorie meal) for optimal absorption. 
• - Needs gastric acid for optimal absorption. Caution with H2 blockers, avoid PPIs. 
• - Not as good at a higher viral load. Use in PLWH with CD4 T-cell counts >200 cells/μL and HIV RNA <100,000 copies/mL 
• - Neuropsychiatric side effects (vivid dreams + may increase suicide risk) 
• - Prolongs QT

• DELSTRIGO (with TDF/FTC)
• + BEST IN CLASS 
• + Unique resistance pathway from other NNRTIs

• + One of the common meds used in the setting of drug resistance 
• - Rash (can be mild, but SJS also reported) 
• - Drug interactions

• Resistance pattern
• HLA-B*5701 allele status (for Abacavir)
• Concomitant HBV infection (if HbSag +, include TAF/TDF in regimen)
• Concomitant treatment for TB/LTBI (check drug-drug interactions especially when using rifampin)
• Cardiovascular risk factors
• Comorbid conditions (e.g. kidney disease, liver disease, osteoporosis, psychiatric illness, concern for weight gain, cancer/autoimmune disease)
• Interaction with other medications (see table in DHHS guideline or Liverpool drug interaction website included below)
• Pill burden (single tablet regimen vs. other regimens vs. long acting injectable)
• Woman of child bearing age/ pregnancy

• Tool to assist on deciding on a regimen https://www.hivassist.com/tool
• Liverpool HIV Drug-Drug interactions: https://www.hiv-druginteractions.org/checker
• Brochure with coformulations, brand names and pill pictures: https://aidsetc.org/sites/default/files/resourcesfiles/HIV%20Med%20ChartJune%202019.pdf
• DHHS 2021 guidelines on management of HIV: https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/whats-new-guidelines
• JAMA IAS USA guidelines: https://jamanetwork.com/journals/jama/ar:cle-abstract/2771873
• Stanford tool to look up genotype mutations and resistance: https://hivdb.stanford.edu/hivdb/by-mutations/

Paul Sax M.D. Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient. Post TW, ed.  UpToDate. Waltham, MA: UpToDate Inc. hmps://www.uptodate.com (Accessed on Aug, 2021) 

Courtney Fletcher, PharmD. Overview of antiretroviral agents used to treat HIV. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. hmps://www.uptodate.com (Accessed on Aug 2021) 

John E. Bennett, Raphael Dolin, Martin J. Blaser. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. Philadelphia, PA :Elsevier/Saunders, 2015. 

Spec, Andrej, et al. Comprehensive Review of Infectious Diseases. Elsevier, 2020

Created by Dr. Hawra Al Lawa 

Reviewed by Dr. Rajesh Gandhi and Dr. Robert Goldstein (MGH ID)