Current WHO-Recommended ARV Regimens for Adults |
Efavirenz + TDF + lamivudine or emtricitabine (Atripla is a comparable pill marketed in the US) | NA (generic available) | $122 | -
Preferred first-line regimen
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Highly effective and well tolerated
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Drawbacks include weak resistance barrier, potential for kidney and bone toxicity, neuropsychiatric side effects, possible interaction with contraceptive implants, and greater incidence of severe adverse birth outcomes in pregnancies receiving TDF-containing regimens compared with zidovudine-containing regimens
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Lopinavir/ritonavir or atazanavir/ritonavir + zidovudineb + lamivudine | NA (generic available) | $305–$318 | -
Preferred second-line regimen
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Not available as a fixed-dose combination
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Resistance barrier suboptimal due to lack of second highly potent and robust agent to couple with the protease inhibitor
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Drug-drug interactions increased by ritonavir
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Highly Effective Alternatives, Not Ideal for Resource-Limited Settings |
Elvitegravir + TDF + emtricitabine + cobicistat (Stribild, the “quad” pill) | Gilead | $184 | -
Elvitegravir's resistance barrier is less robust than dolutegravir's
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Cobicistat increases drug-drug interactions and cost
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Bone and kidney toxicity possible with TDF
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A second-generation “quad” with TAF is in development and should decrease side effects and cost to a degree
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Dolutegravir + abacavir + lamivudine (Triumeq, the “tri” pill) | ViiV | $179 | |
Illustrative Improved (Hypothetical) 3-Drug Regimens |
Dolutegravir + TAF + lamivudine or emtricitabine | ViiV + Gilead | $60 | -
Higher resistance barrier and durability
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Reduced risk of renal and bone toxicity and manufacturing cost with TAF compared with TDF
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Primarily for first-line treatment, although it might have good activity as second-line for some patients
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Dolutegravir + boosted protease inhibitor + TAF | ViiV + Gilead + Others | $266–$357 (or morec) | |
Dolutegravir + TAF + doravirine | ViiV + Gilead + Merck | $64 | |
Illustrative Improved (Hypothetical) 2-Drug Maintenance Combinations (for use after undetectable viral load achieved) |
Dolutegravir + rilpivirine | ViiV + Janssen | <$40 | -
Excellent tolerability with minimal side effects
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Both agents are already approved, allowing for expedited development
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Proof of concept for efficacy available from LATTE study
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Downsides include interactions with TB regimens, food requirement, and suboptimal efficacy for second-line treatment
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Currently in late stage clinical development that could lead to licensure
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Cabotegravir + rilpivirine (long-acting injectable) | ViiV + Janssen | $40 | -
Injection every 1–2 months may reduce risk of resistance due to non-adherence and increase confidentiality and quality of life
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If patients are lost to follow-up, risk of resistance could be much higher than an oral formulation
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Other advantages and disadvantages may be similar to dolutegravir/rilpivirine oral combination above
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Currently in phase II development
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Dolutegravir + doravirine | ViiV + Merck | $50 | -
Doravirine's different resistance profile, lack of food requirement, shorter half-life, and possibly lower potential for TB medication interactions might make it a better partner for dolutegravir than rilpivirine as part of 2-drug regimen
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Might have efficacy in first- and/or second-line treatment
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This is a hypothetical combination, not in development, and doravirine is now in early phase III development
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Dolutegravir + lamivudine | ViiV | $46 | -
Might be effective and well tolerated in first-line treatment, preserving many second-line options
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This is a hypothetical combination, not in development, but because one company makes both medicines, fewer obstacles might exist to develop it
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Dolutegravir + TAF | ViiV + Gilead | $39 | -
Hypothetical combination for first-line treatment, with some possible efficacy in second-line
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Currently not in development
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Dolutegravir + boosted protease inhibitor | ViiV + Others | $252–$343 (or morec) | -
Hypothetical combination, not currently in development
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Could provide a very robust resistance barrier for second-line treatment
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