HIV TREATING MODERN ARVs: The Next Generation ARVs GOING BOLDLY TO CHANGE THE COURSE OF HIV TREATMENT IN WORLD as New Frontiers of HIV Treatment choice with naive or resistance patient
PROF.DRRAM ,HIV/AIDS,SEX Diseases,Deaddiction & Hepatitis Expert
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HIV/ AIDS,CANCER MODERN MEDICINES AVAILABLE AT CHEAP RATE.
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. Currently Available and Improved Hypothetical Combination ARVs ;---
Current WHO-Recommended ARV Regimens for Adults
Efavirenz + TDF + lamivudine or emtricitabine (Atripla is a comparable pill marketed in the US),cost;$122,Preferred first-line regimen.Action;Highly effective and well tolerated,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.
Lopinavir/ritonavir or atazanavir/ritonavir + zidovudineb + lamivudine,cost; $305–$318,Preferred second-line regimen,Not available as a fixed-dose combination.Action:Resistance barrier suboptimal due to lack of second highly potent and robust agent to couple with the protease inhibitor/drug-drug interactions increased by ritonavir.
Highly Effective Alternatives available as NOW A DAYS:---
Elvitegravir + TDF + emtricitabine + cobicistat (Stribild, the “quad” pill) Gilead company,Cost:$184.Elvitegravir's resistance barrier is less robust than dolutegravir's,Cobicistat increases drug-drug interactions and cost,
Bone and kidney toxicity possible with TDF,A second-generation “quad” with TAF is in development and should decrease side effects and cost to a degree.
Dolutegravir + abacavir + lamivudine (Triumeq, the “tri” pill),Company: ViiV,Cost:$179,Action:Abacavir is expensive to manufacture and is associated with a rare but potentially life-threatening hypersensitivity syndrome,Has utility for pediatrics due to abacavir not affecting bone.
Illustrative Improved (Hypothetical) 3-Drug Regimens:----
Dolutegravir + TAF + lamivudine or emtricitabine,company:ViiV + Gilead cost;$60,Action:Higher resistance barrier and durability,Reduced risk of renal and bone toxicity and manufacturing cost with TAF compared with TDF,Primarily for first-line treatment, although it might have good activity as second-line for some patients.
Dolutegravir + boosted protease inhibitor + TAF,Company:ViiV + Gilead + Others,Cost:$266–$357,Action:Improved second-line regimen, with a very robust resistance barrier that could make the need for third-line regimens very rare.
Dolutegravir + TAF + doravirine,company ;ViiV + Gilead + Merck, Cost; $64, Action:Might be effective for first- or second-line treatment as doravirine has in vitro activity against non-nucleoside reverse transcriptase–resistant isolates common in sub-Saharan Africa,Illustrative Improved (Hypothetical) 2-Drug Maintenance Combinations (for use after undetectable viral load achieved)
Dolutegravir + rilpivirine,company: ViiV + Janssen, Cost;<$40, Action:Excellent tolerability with minimal side effects,Both agents are already approved, allowing for expedited development.
Currently in late stage clinical development that could lead to licensure ;--
Cabotegravir + rilpivirine (long-acting injectable),company:ViiV + Janssen Cost:$40,Action:Injection every 1–2 months may reduce risk of resistance due to non-adherence and increase confidentiality and quality of life.
If patients are lost to follow-up, risk of resistance could be much higher than an oral formulation,Other advantages and disadvantages may be similar to dolutegravir/rilpivirine oral combination above.
Currently in phase II development:
Dolutegravir + doravirine,company:ViiV + Merck,cost:$50, Action: 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.Might have efficacy in first- and/or second-line treatment.
This is a hypothetical combination, not in development, and doravirine is now in early phase III development:
Dolutegravir + lamivudine,Company:ViiV , Cost:$46,Action:Might be effective and well tolerated in first-line treatment, preserving many second-line options.This is a hypothetical combination, not in development, but because one company makes both medicines, fewer obstacles might exist to develop it,
Dolutegravir + TAF,Cmpany:ViiV + Gilead,Cost;$39,Action:Hypothetical combination for first-line treatment, with some possible efficacy in second-line,Currently not in development.
Dolutegravir + boosted protease inhibitor,company:ViiV + Others,Cost: $252–$343,Action:Hypothetical combination, not currently in development,
Could provide a very robust resistance barrier for second-line treatment
Abbreviations: ARV, antiretroviral; NA, not applicable; TAF, tenofovir alafenamide fumarate; TB, tuberculosis; TDF, tenofovir disoproxil fumarate; WHO, World Health Organization.