The frequency of each mutation at position 98 according to subtype and drug-class experience. Data are shown for the 8 most common subtypes. The number of persons in each subtype/treatment category is shown beneath the subtype. Mutations occurring at a frequency >0.5% are shown. Each mutation is also a hyper-link to a separate web page with information on each isolate, including literature references with PubMed abstracts, the GenBank accession number, and complete sequence and treatment records.
- A98G is a nonpolymorphic accessory mutation that reduces NVP susceptibility by ~5-fold and EFV susceptibility by about 3-fold. It has a weight of 1.0 in the Tibotec ETR genotypic susceptibility score.
The first row shows the frequency of the mutation in persons who are RTI-naive (indicated in green). The second row shows the frequency of the mutation in persons who have received one or more NRTIs (No NNRTIs). The third row shows the frequency of the mutation in persons who have received one or more NNRTIs (+/- NRTIs). The following rows show the frequency of the mutation in persons who have received only a single NNRTI. Mutation rates that differ significantly between treated and untreated isolates are indicated in yellow.
|Pos||WT||NRTI (but no NNRTI) Treated Persons|| ||NNRTI Treated Persons|
||G 1.8 ||S 6.2|
|G 1.3 ||S 76 ||G 2.5|
|S 1.3 || ||G 2.6 ||S 7.5|
|G 0.7 ||G 8.0|
Mutation pattern data is not available for A98.
|A98G||>=0||ETR||0||0|| || |
|A98P||>=0||ETR||0||0|| || |
|A98S||>=0||ETR||0||0|| || |
A complete summary of additional in vitro susceptibility data for viruses with A98 obtained using other assays including the Antivirogram can be found here.
||Least Square Regression (LSR) was used to learn the relative contribution of each mutation to the fold decrease in susceptibility for an ARV. The figure on the left (click to enlarge the figure) shows the regression coefficients (which correlate with the contribution to resistance) for the 24 nonpolymorphic NNRTI-resistance mutations shown to contribute decreased susceptibility to at least one NNRTI. A complete description of the method that generates this figure can be found at Rhee et al PNAS 2006.|
|Reference||Previous NNRTI||Follow-up NNRTI||Other Rx||No.Pts||Weeks||Effect of baseline mutations on response|
Katlama (2007), Lazzarin (2007), DUET
|93% had received >= 1 NNRTI. All had >=1 NNRTI resistance mutation at screening or from a historical genotype||ETR vs placebo||DRV/RTV + OB||406||24||13 baseline mutations were associated with a decreased response to ETR: V90I, A98G, L100I, K101EP, V106I, V179DF, Y181CIV, G190AS. When 3 or more of these mutations were present, the response to ETR was no different from placebo.|
DUET follow-up study
|93% had received >= 1 NNRTI. All had >=1 NNRTI resistance mutation at screening or from a historical genotype||ETR vs placebo||DRV/RTV + OB||406||24||3 baseline mutations were identified as associated with a decreased VR (defined by RNA <50 copies/ml) at W24: K101H, E138A and V179T in addition to the 13 (V90I, A98G, L100I, K101EP, V106I, V179DF, Y181CIV, G190AS) in Madruga 2007 study. 77% of patients with none of these 16, 61% patients with one of these 16, 56% with two and 38% with >=3 were associated with a decreased VR.|