Developing adaptive HIV treatment guidelines incorporating drug resistance surveillance and genotype-tailored therapies

The persistent global burden of HIV demands treatment frameworks that are both responsive and personalized, particularly in the face of rising drug resistance. Current antiretroviral therapy (ART) guidelines, while effective in many contexts, often lag behind the rapid emergence of HIV drug-resistant mutations and fail to account for inter-individual genetic variability that influences therapeutic response. This article examines the imperative to develop adaptive HIV treatment guidelines that integrate real-time drug resistance surveillance and genotype-tailored therapeutic strategies. Beginning from a global overview of ART evolution, the discussion narrows to highlight the challenges posed by acquired and transmitted resistance patterns, especially in resource-limited settings with high viral diversity and limited genomic monitoring infrastructure. We evaluate the benefits of incorporating routine resistance testing into national treatment protocols, including improved regimen durability, reduced treatment failure, and better alignment with WHO 95-95-95 targets. In parallel, we explore the potential of pharmacogenomic data such as host CYP450 polymorphisms and HLA profiles to optimize drug selection and dosing, minimizing toxicity and enhancing adherence. Using case studies from sub-Saharan Africa, Asia, and the U.S., we demonstrate the feasibility and clinical utility of integrating drug resistance data and host genomics into national HIV guidelines. The article concludes with a framework for adaptive policy design, leveraging artificial intelligence, electronic health records, and regional surveillance networks to support dynamic, patient-centric HIV treatment pathways. Such an approach represents a paradigm shift towards precision public health, where real-world data directly inform equitable, effective HIV care across diverse populations.