How Antiretroviral Therapy Adherence Affects HIV Drug Resistance Development

Freddie Sophia

Introduction

Adherence to Antiretroviral Therapy (ART) is a cornerstone of successful HIV treatment, playing a critical role in suppressing the virus and preventing the development of drug resistance. HIV is a rapidly mutating virus, and when the virus is not sufficiently suppressed, the likelihood of the virus adapting to the medications increases. This adaptation, or resistance, occurs when the virus mutates in ways that enable it to survive despite the presence of antiretrovirals in the bloodstream. Therefore, poor adherence to ART is one of the most significant factors contributing to the emergence of HIV drug resistance. When an individual with HIV is prescribed antiretroviral drugs, the goal is to reduce the viral load to undetectable levels and keep it there for the long term. For this to happen, patients must consistently take their medications as prescribed this means not missing doses, taking the correct dose at the correct time, and following any dietary or other instructions associated with the therapy. ART is highly effective when followed properly, reducing the risk of HIV transmission and promoting immune system recovery. However, when adherence falters, the consequences are severe, as the virus can replicate and evolve, creating resistant strains. Drug resistance occurs when the virus develops mutations that enable it to escape the effects of one or more components of the ART regimen. This typically happens when the medication level in the body is not high enough to suppress the virus completely, which can occur in cases of missed doses or inconsistent adherence. In such cases, the virus is not eradicated, and instead, it continues to replicate, creating an environment where mutations are more likely to occur. If these mutations result in a strain of the virus that is resistant to the prescribed drugs, treatment options become limited, and the effectiveness of current therapy diminishes. This can lead to treatment failure, a rise in viral load, and, if not addressed, deterioration in immune function [1,2].

Description

The development of HIV drug resistance is often a gradual process. It typically starts with minor mutations that allow the virus to partially evade the effects of one drug, and over time, as more mutations accumulate, resistance to additional drugs may develop. When a patient is not adherent to ART, there is a higher likelihood that these mutations will occur because the virus is not exposed to therapeutic drug concentrations consistently. This is particularly problematic with regimens involving drugs that target specific viral enzymes, like reverse transcriptase or protease inhibitors. Since HIV replication is ongoing throughout the body, any lapse in treatment gives the virus the chance to mutate and become resistant to one or more of the drugs in the regimen. In addition to the risk of developing resistance to individual drugs, poor adherence can also result in cross-resistance, where the virus becomes resistant to multiple drugs that share similar mechanisms of action. This is especially concerning when a patientâ??s first-line regimen becomes ineffective due to resistance, as it may leave fewer treatment options available. In these cases, healthcare providers may have to resort to second- or third-line therapies, which often involve more complex regimens, are more expensive, and may have more side effects.

Conclusion

Adherence to antiretroviral therapy is critical in preventing HIV drug resistance and ensuring the long-term success of HIV treatment. Poor adherence can lead to the emergence of drug-resistant HIV strains, limiting future treatment options and complicating care. Therefore, addressing adherence challenges through patient education, support systems, and simpler treatment regimens is essential. Healthcare providers and patients must work together to ensure that ART is taken consistently and effectively, ultimately reducing the risk of resistance and improving the health and quality of life for people living with HIV. Through a combined effort to address the barriers to adherence, it is possible to sustain the fight against HIV and prevent the further spread of resistance.

References

1. Diks, Annieck M., Lisanne A. Overduin, Laurens D. Van Leenen and Lennert Slobbe, et al. "B-cell immunophenotyping to predict vaccination outcome in the immunocompromised-A systematic review." Front Immunol 12 (2021): 690328. Google Scholar Cross Ref Indexed at 2. Syeda, Madiha Zahra, Tu Hong, Chunming Huang and Wenhua Huang, et al. "B cell memory: From generation to reactivation: A multipronged defense wall against pathogens." Cell Death Discov 10 (2024): 117. Google Scholar Cross Ref Indexed at