Basis of selection of first and second line highly active antiretroviral therapy for HIV/AIDS on genetic barrier to resistance: A literature review

Long-term management of HIV/AIDS is at risk of increasing drug resistance1. Booster protease inhibitor (PI) and thymidine analogue-containing regimens have a high genetic barrier to resistance. Non-thymidine-analogue triple nucleoside/nucleotide reverse transcriptase inhibitor (NRTI/NtRTI) combination regimens and Non-nucleoside reverse transcriptase inhibitors on the contrary have a low genetic barrier to resistance. Unfortunately, several lowgenetic barrier agents select for mutations that confer broad class resistance. The selection of the K103N and Y181C mutations cause loss of activity to all currently available NNRTIs. Most NRTIs are rendered inactive by the selection of the K65R mutation. The M184V mutation in addition causes loss of activity to both lamivudine (3TC) and emicitrabine (FTC), but has been shown to confer viral resensitisation to zidovudine (ZDV), stavudine (d4T) and tenofovir (TDF)12 and delay in thymidine analogue mutations (TAMs) emergence. L74V mutation selection causes decreased antiviral activity of abacavir (ABC), didanosine (ddI), and zalcitabine (ddC), and when the mutated virus is selecting for both L74V and M184V, only the thymidine analogues (ZDV and
d4T) and TDF retain susceptibility. In this paper, we review literature focussing on the genetic barrier to resistance as the basis of selection of first and second line antiretroviral therapy.

• Population(s)
  • General HIV+ population
  • Other
• Engagement and Care Cascade
  • Treatment