The human immunodeficiency virus (HIV) is a retrovirus that affects millions globally. HIV rapidly changes within an infected individual. These changes, known as mutations, can significantly impact how the virus responds to antiretroviral therapies. Understanding these mutations is important for effective treatment and long-term management.
What Are HIV Resistance Mutations?
HIV resistance mutations are specific alterations in the virus’s genetic code that allow it to evade the effects of antiretroviral drugs. These mutations arise during the virus’s replication cycle, a process that occurs frequently in an infected person. During replication, an enzyme called reverse transcriptase converts the viral RNA into DNA. This enzyme is prone to making errors, meaning it frequently introduces changes into the new viral DNA.
Most errors during HIV replication are missense mutations, which occur when reverse transcriptase fails to properly distinguish between nucleoside triphosphates. These genetic changes can alter the structure of viral proteins, such as reverse transcriptase itself, protease, or integrase, which are targets for antiretroviral drugs. For example, mutations can alter the binding sites of drugs on these proteins, preventing the drug from attaching and inhibiting enzyme activity. When drugs can no longer bind effectively or interfere with viral processes, the virus becomes less susceptible to the medication.
Why Resistance Mutations Matter
HIV resistance mutations impact both individual patient care and public health. For individuals, the development of resistant strains can lead to treatment failure, meaning the prescribed antiretroviral therapy no longer effectively suppresses the virus. This can result in increased viral load, a decline in immune function, and progression of the disease. When initial treatments fail, patients may require more complex, expensive, or less tolerable drug regimens, often with more side effects.
The spread of drug-resistant HIV strains challenges global HIV control efforts. Resistant viruses can be transmitted from one person to another, leading to new infections that are difficult to treat. This transmitted drug resistance can undermine standard treatment guidelines and limit future options for newly infected individuals. Increasing prevalence complicates efforts to achieve widespread viral suppression, a goal for reducing HIV transmission globally.
Identifying and Addressing Resistance
Healthcare providers detect HIV resistance mutations through genotypic resistance testing. This test analyzes a patient’s viral DNA or RNA to identify specific genetic mutations that confer drug resistance. It looks for changes in genes that code for key viral enzymes targeted by antiretroviral drugs, such as reverse transcriptase, protease, and integrase. Results provide a detailed profile of which drugs the patient’s HIV strain is likely resistant to.
Once resistance is identified, test results guide treatment decisions. Providers can adjust the patient’s drug regimen, selecting alternative antiretroviral drugs or combinations still effective against the resistant strain. This may involve switching drug classes or using newer, more potent drugs designed to overcome common resistance mutations. Tailoring treatment based on resistance profiles helps ensure patients receive therapy with the highest chance of suppressing the virus and improving health outcomes.
Strategies to Prevent Resistance
Preventing the development and spread of HIV resistance mutations relies on several strategies. A primary approach involves consistent adherence to prescribed antiretroviral therapy (ART). Consistent medication intake maintains high drug concentrations, effectively suppressing viral replication and reducing the chances of new mutations. Skipping doses or inconsistent adherence allows the virus to replicate more freely, increasing resistance likelihood.
Another strategy is combination therapy, where multiple antiretroviral drugs from different classes are administered simultaneously. This approach targets different stages of the HIV life cycle, making it harder for the virus to develop resistance to all drugs at once. If a mutation confers resistance to one drug, the other drugs in the regimen can still suppress the virus. Additionally, early diagnosis and prompt ART initiation can help prevent the virus from replicating extensively and accumulating resistance mutations before treatment begins.