What mutation likely explains the resistance to zidovudine in an HIV patient?

Zidovudine (AZT) is a nucleoside reverse transcriptase inhibitor (NRTI) used in the treatment of HIV. The effectiveness of zidovudine can be compromised by mutations in the reverse transcriptase enzyme, which is responsible for converting viral RNA into DNA—a critical step in the viral life cycle. When the viral reverse transcriptase undergoes specific mutations, its ability to incorporate zidovudine into the viral DNA is diminished, leading to drug resistance.

The term "RNA-dependent DNA polymerase" refers to the same reverse transcriptase enzyme in this context. Mutations in this enzyme can result in reduced binding affinity for zidovudine, allowing the virus to replicate despite the presence of the drug. This mechanism of resistance is directly tied to the structure and function of the reverse transcriptase, making it the mutation that most likely explains the resistance observed in patients receiving zidovudine.

In contrast, integrase, neuraminidase, and protease are associated with different functions within the HIV lifecycle and do not directly relate to zidovudine resistance mechanisms. Thus, the mutation in RNA-dependent DNA polymerase is the most relevant factor in explaining the resistance to zidovudine in this scenario.