Panel of prototypical recombinant infectious molecular clones resistant to nevirapine, efavirenz, etravirine, and rilpivirine

Abstract

We created a panel of 10 representative multi-nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant recombinant infectious molecular HIV-1 clones to assist researchers studying NNRTI resistance or developing novel NNRTIs. The cloned viruses contain most of the major NNRTI resistance mutations and most of the significantly associated mutation pairs that we identified in two network analyses. Each virus in the panel has intermediate- or high-level resistance to all or three of the four most commonly used NNRTIs.

Fig 1

Correlation network analysis of virus sequences with ≥1 major NNRTI resistance mutations in 8,035 viruses from 7,751 individuals in the Stanford HIV Drug Resistance Database (A) and in viruses from 80 individuals with intermediate- to high-level resistance to each NNRTI (B). Each node represents a major NNRTI resistance mutation. Each line represents a correlation between a pair of mutations, and the thickness of the line is proportional to the strength of the correlation (Spearman's rho). The gray ellipses are superimposed on pairs or triplets of major mutations present in the prototypical multi-NNRTI-resistant recombinant infectious molecular clones. None of the clones had the V106M, Y181I, Y188L, or G190E mutation.