HIV: resistance mutations

Thanks to Dan Kuritzkes+Suzanne McCluskey for talk on drug resistance today in the HIV core lecture series! @MGHBWHIDFellows #IDFellows @ID_fellows #IDTwitter

To review high yield mutations, check these prior 🧵

NRTI: https://twitter.com/BIDMC_IDFellows/status/1270812037321502720
NNRTI:

Additional NNRTI mutations:
🧬E138K🧬
▪️Key rilpivirine resistance mutation
▪️Cross-resistance to ETR

🧬V106I, F227C🧬
▪️Key doravirine resistance mutations

Notes on PI resistance:
🔹RTV-boosted PIs have high barrier to resistance
🔹Prolonged use in setting of virologic failure can select for resistance
🔹More mutations = broader cross-resistance
🔹Certain mutations confer resistance to some drugs, sensitize to others: I50L, L76V

Notes on INSTI resistance:
🔹Resistance common at time of virologic failure for RAL, EVG
🔹To date, de novo emergence of resistance to DOL and BIC is rare
🔹Extensive cross-R bt RAL, EVG
🔹Many RAL and EVG-R isolates remain susceptible to DOL and BIC

When to consider resistance testing:
🔷ART naive: initiating ART

🔷ART experienced:
🔹Re-initiating ART
🔹Virologic failure (most successful if HIV RNA >1000 cp/mL but can consider if 500-1000 cp/mL)
🔹Sometimes: low level viremia, suppressed and contemplating regimen switch


Resistance test timing for ART-experienced
🔸Most ideal: on therapy
🔸Next best: within 4 wks of being off ART
🔸Least useful: off ART >4wks


Assemble the cumulative genotype as some mutations may not be detected:
🔸 if mutant <20% viral popul
🔸if archived in reservoir
🔸some mutations persist w/o drug pressure, but many do not

Originally tweeted by BIDMC Infectious Diseases Fellowship (@BIDMC_IDFellows) on 14 August, 2020.

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