NNRTI Resistance Notes
Last updated on Jun 10, 2008
| Resistance Matrix | Resistance Mutation Comments | Resistance Mutation Scores | Drug Summaries |
| Non-Nucleoside RT Inhibitor (NNRTI) Resistance Mutations | |||||||||||||||
| 98 | 100 | 101 | 103 | 106 | 108 | 179 | 181 | 188 | 190 | 225 | 227 | 230 | 236 | 238 | |
| Cons | A | L | K | K | V | V | V | Y | Y | G | P | F | M | P | K |
| NVP | G | I | EP | NS | AM | I | DEF | CIV | LHC | ASE | LC | L | T | ||
| DLV | G | I | EP | NS | AM | I | DEF | CIV | LHC | E | C | L | L | T | |
| EFV | G | I | EP | NS | AM | I | DEF | CIV | LHC | ASE | H | C | L | T | |
| ETR† | G | I | EP | DEF | CIV | LHC | ASE | C | L | T | |||||
LEGEND Mutations in bold red are associated with higher levels of phenotypic resistance or clinical evidence for reduced virological response.
ADDITIONAL MUTATIONS Several additional uncommon mutations at these positions are also associated with NNRTI therapy or reduced NNRTI susceptibility including: K101NH, K103TH, G190QCTV (PR Harrigan AIDS 2005, S Rhee JID 2005).
POLYMORPHIC MUTATIONS A98S, K101RQ, K103R, V106I, E138A, V179I, and K238R are polymorphic substitutions with little if any effect on drug resistance with one notable exception - K103R, which occurs in 1% to 2% of untreated persons, reduces NVP, DLV, and EFV susceptibility ~15-fold in combination with V179D (N Parkin AAC 2006).
MUTATIONS AT ADDITIONAL POSITIONS E138K has been selected in vitro by ETR and causes low-level reduced susceptibility to each of the NNRTIs (J Vingerhoets JV 2001, G Su AT 2000). L234I has been selected in vitro by ETR and acts synergistically with Y181C to reduce ETR susceptibility (J Vingerhoets JV 2001). L318F is a nonpolymorphic NNRTI-selected mutation that reduces DLV, NVP, and possibly ETR susceptibility (PR Harrigan AIDS 2002, J Vingerhoets JV 2005). Several polymorphic mutations such as K101Q, I135TM, V179I, and L283I and several NRTI-selected mutations such as L74V, H221Y and N348I may cause subtle reductions in NNRTI susceptibility (F Ceccherini-Silberstein JV 2007, SH Yap PLOS Med 2007).
† A univariate analysis of genotype-virological outcome data found that persons with viruses with ≥ 3 of the following mutations responded similarly to placebo and ETR in the DUET trials: V90I, A98G, L100I, K101EP, V106I, V179DF, Y181CIV, and G190AS. (J Vingerhoets HIVDRW 2007). V90I and V106I are polymorphisms that occur at similar frequency in NNRTI-treated and untreated persons (Marvel or RTPosMutSummary).
ADDITIONAL MUTATIONS Several additional uncommon mutations at these positions are also associated with NNRTI therapy or reduced NNRTI susceptibility including: K101NH, K103TH, G190QCTV (PR Harrigan AIDS 2005, S Rhee JID 2005).
POLYMORPHIC MUTATIONS A98S, K101RQ, K103R, V106I, E138A, V179I, and K238R are polymorphic substitutions with little if any effect on drug resistance with one notable exception - K103R, which occurs in 1% to 2% of untreated persons, reduces NVP, DLV, and EFV susceptibility ~15-fold in combination with V179D (N Parkin AAC 2006).
MUTATIONS AT ADDITIONAL POSITIONS E138K has been selected in vitro by ETR and causes low-level reduced susceptibility to each of the NNRTIs (J Vingerhoets JV 2001, G Su AT 2000). L234I has been selected in vitro by ETR and acts synergistically with Y181C to reduce ETR susceptibility (J Vingerhoets JV 2001). L318F is a nonpolymorphic NNRTI-selected mutation that reduces DLV, NVP, and possibly ETR susceptibility (PR Harrigan AIDS 2002, J Vingerhoets JV 2005). Several polymorphic mutations such as K101Q, I135TM, V179I, and L283I and several NRTI-selected mutations such as L74V, H221Y and N348I may cause subtle reductions in NNRTI susceptibility (F Ceccherini-Silberstein JV 2007, SH Yap PLOS Med 2007).
† A univariate analysis of genotype-virological outcome data found that persons with viruses with ≥ 3 of the following mutations responded similarly to placebo and ETR in the DUET trials: V90I, A98G, L100I, K101EP, V106I, V179DF, Y181CIV, and G190AS. (J Vingerhoets HIVDRW 2007). V90I and V106I are polymorphisms that occur at similar frequency in NNRTI-treated and untreated persons (Marvel or RTPosMutSummary).