First-Line HIV Therapy: Integrase Inhibitors, Exceptions, and HLA-B*5701 Testing

"First-Line HIV Therapy: Integrase Inhibitors, Exceptions, and HLA-B*5701 Testing" takes up the question of how closely real-world prescribing follows current recommendations for initial HIV therapy.

Dr. Madison notes that the IAS-USA panel continues to favor integrase strand transfer inhibitor–based regimens built on bictegravir or dolutegravir. Dr. Astle confirms that this carries directly into his clinical practice. He presents patients with the evidence-based options available, but bictegravir- and dolutegravir-based regimens tend to be the most potent and effective. He describes them as second-generation integrase inhibitors with better tolerability and a lower risk of resistance. As a result, straying from these agents for initial treatment is rare. Dr. Madison shares that she used to describe these drugs to patients as the "virus busters."

Asked about exceptions, Dr. Astle identifies the most important one. Patients who previously received long-acting injectable cabotegravir for pre-exposure prophylaxis carry an increased risk of integrase inhibitor resistance. For these patients, a boosted darunavir–based regimen may be the preferred initial option.

Dr. Durham then explains why dolutegravir/abacavir/lamivudine moved from a recommended initial regimen to one reserved for certain clinical scenarios in the DHHS guidelines. He emphasizes that efficacy was never the concern, since it served as a highly effective first-line therapy for many years. The change reflects the guidelines' push toward starting treatment as soon as possible, even on the day of diagnosis. Abacavir requires HLA-B*5701 testing before use, because patients who test positive face a potentially life-threatening hypersensitivity reaction. Those results usually cannot be returned the same day, which makes the regimen impractical at diagnosis.

Dr. Durham reassures that patients already stable on the regimen have presumably been tested and have not experienced hypersensitivity. They can continue it for as long as it remains effective. The change mainly affects new diagnoses, where the regimen should generally be avoided. Dr. Madison connects the shift to the broader goal of removing barriers so patients can begin therapy on the same day.

Our next episode, "Beyond Viral Suppression: Holistic HIV Care and Remaining Treatment Gaps," turns to the holistic lens now shaping first-line decisions and the gaps that persist despite highly effective therapy.