The trajectory of HIV therapy over the past four decades is a testament to medical innovation and resilience. From the first antiretroviral medications to the advent of long-acting therapies, treatment strategies have continuously evolved, transforming HIV from a terminal illness to a chronic, manageable condition.1 Understanding this evolution is critical for medical providers to navigate current and future therapeutic landscapes.
The introduction of azidothymidine (AZT) in March 1987 marked a watershed moment in HIV treatment.2 As the first FDA-approved antiretroviral drug, AZT significantly reduced viral replication but was associated with high toxicity and limited efficacy when used alone.2 The subsequent development of combination antiretroviral therapy (ART) in the mid-1990s revolutionized care, using multiple agents to suppress viral load effectively and prevent resistance.2
Highly active antiretroviral therapy (HAART) became the standard of care, dramatically reducing morbidity and mortality. Fixed-dose combinations, such as bictegravir/emtricitabine/tenofovir alafenamide, simplified regimens, improving adherence and accessibility.3 Moreover, the integration of integrase strand transfer inhibitors (INSTIs) like dolutegravir into ART regimens has set new benchmarks for efficacy, tolerability, and resistance profiles.4
In recent years, long-acting injectable therapies have emerged, offering an alternative approach to treatment. The combination of cabotegravir and rilpivirine enables bi-monthly administration, providing another option for those seeking to address adherence challenges.5 The FDA’s approval of these injectables reflects a broader shift toward patient-centered care models, accommodating diverse treatment preferences and needs.
Emerging therapies aim to advance beyond ART by targeting the latent HIV reservoir, which remains a significant obstacle to a cure.6 Gene-editing technologies, such as CRISPR-Cas9, show promise in excising proviral DNA, while therapeutic vaccines aim to enhance the immune system’s ability to control the virus autonomously. Broadly neutralizing antibodies (bNAbs) are also under investigation for their potential to target diverse HIV strains and serve as adjunctive or standalone therapies.7
As therapies advance, providers must remain informed about their implications for practice. By integrating historical insights with emerging innovations, we can optimize treatment strategies, enhance patient outcomes, and bring the prospect of an HIV cure closer to reality, despite the challenges with developing an effective vaccine.8
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