The Impact of HIV Genetic Polymorphisms and Subtype Differences on the Occurrence of Resistance to Antiretroviral Drugs
Figure 1
Subtype-specific poly-A nucleotide motifs lead to template pausing under pressure with thymidine analogues that favor K65R selection in subtype C and D67N selection in subtype B. Depiction of the template-based propensity of subtype C versus B viruses to develop the K65R mutation that is associated with broad cross-resistance among multiple members of the NRTI family of drugs. The codons located at positions 63, 64, and 65 in subtype C RT seem to be critically involved in the preferential development of K65R in subtype C. d4T: stavudine, ddI: didanosine, ABC: abacavir, TDF: tenofovir. It should be noted that the use of stavudine in particular has been shown to yeild K65R in subtype C infections with high frequency. Regimens that are based on the use of TDF and ABC, among other drugs, can help mitigate the development of the K65R mutation.
