Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase.

Background: HIV-1 nucleoside reverse transcriptase inhibitors (NRTIs) have been used in the clinic for over twenty years. Interestingly, the complete resistance pattern to this class has not been fully elucidated. Novel mutations in RT appearing during treatment failure are still being identified.

Evolution of a novel 5-amino-acid insertion in the beta3-beta4 loop of HIV-1 reverse transcriptase.

HIV-1 isolates harbouring an insertion in the beta3-beta4 loop of reverse transcriptase (RT) confer high-level resistance to nucleoside analogues. We have identified a novel 5-amino-acid insertion (KGSNR amino acids 66-70) in a patient on prolonged nucleoside combination therapy (didanosine and stavudine) and investigated which factors were responsible for its outgrowth. Remarkably, only small fold increases in drug resistance to nucleoside analogues were observed compared to wild type.

Selection of zidovudine resistance mutations and escape of human immunodeficiency virus type 1 from antiretroviral pressure in stavudine-treated pediatric patients.

The relationship between clinical changes in stavudine activity and stavudine resistance was investigated in 16 human immunodeficiency virus (HIV)-infected children who received stavudine monotherapy for 18 months. Seven patients responded well to stavudine therapy, 3 experienced transient reductions in virus load, and all others had no detectable virologic response. In both the responders and nonresponders, no changes in stavudine susceptibility or specific baseline/emergent mutations in reverse transcriptase were observed.