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Medical Pharmacology Chapter 36: Antiviral Drugs
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Protease Inhibitors
Antiretroviral Drugs Used in Treating HIV Infection
→Protease Inhibitors
There are a number of protease inhibitor-based regimens.5
FDA-approved protease inhibitors include:
ATV (atazanavir)
ATV/c (cobicistat-boosted atazanavir)
FPV (fosamprenavir)
IDV (indinavir)
LPV/r (ritonavir-boosted lopinavir)
NFV (nelfinavir)
RTV (ritonavir)
TPV (tipranavir) and
SQV (saquinavir).5
Antiretroviral
virologic potency has been demonstrated with protease inhibitor-based
protocols, especially with cobicistat (PK) enhancement.5
For protocols utilizing ritonavir boosting both durability of pharmacological efficacy in treatment-naïve individuals along with a "high genetic barrier" to resistance have been shown.5
In antiretroviral treatment-naïve individuals, recommended protease inhibitors should exhibit four primary characteristics: 5
Anti-retroviral virologic efficacy
Low pill count
Once daily dosing, and
Good tolerability
Using these factors, once-daily darunavir with ritonavir boosting (DRV/r) is classified as a recommended protease inhibitor based protocol. (2015).5
This
recommendation is characterized as AI (i.e. "strong
recommendation for the statement" based on "one or more
randomized trials with clinical outcomes and/or validated
laboratory endpoints."
Alternative protease-inhibitor-based regimen options include: ATV/c + TDF/FTC [cobicistat-boosted atazanavir + tenofovir disoproxil fumarate/emtricitabine].
This
combination is appropriate only for individuals
exhibiting pre-treatment estimated creatinine clearance (CrCl) ≥
70 mL/min.
This recommendation is characterized as BI ("moderate recommendation for the statement" and "one or more randomized trials with clinical outcomes and/or validated laboratory endpoints").
ATV/r + TDF/FTC [ritonavir-boosted atazanavir + tenofovir disoproxil fumarate/emtricitabine] is another alternative regimen protease inhibitor protocol..
This recommendation is characterized as BI ("moderate recommendation for the statement" with "one or more randomized trials with clinical outcomes and/or validated laboratory endpoints").
(DRV/c or DRV/r, i.e. cobicistat or ritonavir-boosted darunavir) plus abacavir (ABC)/lamivudine (3TC) is another protease-inhibitor alternative regimen option.
This
option is only appropriate for patients who are HLA-B*5701
negative.
This recommendation is characterized as BIII for DRV/c ["moderate recommendation for the statement" based on "expert opinion") and BII for DRV/r ["moderate recommendation for the statement" based on one or more well-design, non-randomized trials or observational cohort studies with long-term clinical outcomes."
DRV/c + TDF/FTC [cobicistat-boosted darunavir plus tenofovir disoproxil fumarate with emtricitabine] combination represents another protease inhibitor alternative regimen option.
This
combination is only appropriate for individuals with
pre-treatment estimated creatinine clearance (CrCl) ≥ 70 mL/min.
The statement is characterized as BII ["moderate recommendation for the statement" with "one or more well-design, nonrandomized trials or observational cohort studies with long-term clinical outcomes".]5
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Strength of Recommendation |
Quality of Evidence for Recommentation |
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A: Strong recommendation for the statement |
I: One or more randomized trials with clinical outcomes and/or validated laboratory endpoints |
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B: Moderate recommendation for the statement |
II: One or more well-designed, non-randomized trials or observational cohort studies with long-term clinical outcomes |
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C: Optional recommendation fro the statement |
III. Expert opinion |
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3TC = lamivudine |
ABC = abacavir |
ARV = antiretroviral |
ATV/c = cobicistat-boosted atazanavir |
ATV/r = ritonavir-boosted atazanavir ear |
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DRV/r= ritonavir-boosted darunavir |
DTG = dolutegravir |
EFV = efavirenz |
EVG/c/TDF/FTC = elvitegravir/cobicistat/tenofovir DF/emtricitabine |
FTC = emtricitabine |
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LPV/r = ritonavir-boosted lopinavir |
RAL = raltegravir |
RPV =rilpivirine |
RTV = ritonavir |
TDF = tenofovir disoproxil fumarate |
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INSTI = integrase strand transfer inhibitor |
NNRTI = nonnucleoside reverse transcriptase inhibitor |
NRTI = nucleoside reverse transcriptase inhibitor |
PI = protease inhibitor |
CrCl = creatinine clearance |
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