HIV therapy challenge — What is a major reason antiretroviral drug treatment for HIV can fail over time without combination therapy and adherence?

Introduction:
HIV has a high mutation rate due to error-prone reverse transcriptase and large population sizes, enabling rapid selection of resistant variants. Understanding resistance explains why combination antiretroviral therapy and adherence are critical to long-term viral suppression.

Given Data / Assumptions:

• Reverse transcription lacks proofreading, generating diversity.
• Selective pressure from single-agent therapy favors resistant mutants.
• Protease, reverse transcriptase, and integrase inhibitors target essential viral enzymes.

Concept / Approach:
Connect viral mutability with target-based drugs: mutations in protease (or other targets) reduce inhibitor binding, conferring resistance. Combination therapy lowers the probability that a single variant is resistant to all drugs simultaneously.

Step-by-Step Solution:

Verification / Alternative check:
Genotypic resistance testing detects mutations in protease/RT/integrase correlating with reduced drug susceptibility; regimen changes based on these tests often restore suppression.

Why Other Options Are Wrong:

Common Pitfalls:
Underestimating adherence; assuming monotherapy suffices; overlooking the role of viral reservoirs but misattributing failure solely to drug instability.

Final Answer:
Resistance due to mutant viral enzymes, particularly protease, arising under drug pressure.