Two-drug dolutegravir-based antiretroviral therapy supported for HIV management

Real-world data indicates that dolutegravir (DTG)-based 2-drug antiretroviral therapy (ART) regimens are effective for HIV management. Moreover, the selection of DTG-based ART by treating clinicians is primarily driven by a desire to avoid long-term toxicities. These study results were published in Infectious Diseases and Therapy.

The first 2-drug ART regimen for HIV management was approved by the United States Food and Drug Administration (FDA) in 2017. Two-drug regimens have the potential to reduce drug-drug interactions, toxicity events, and treatment costs. Given the relatively short time these therapy options have been available, there are limited real-world data regarding their effectiveness in patients with HIV infection.

To bridge this knowledge gap, researchers conducted a retrospective chart review to characterize the real-world use of DTG-based 2-drug ART regimens among patients with HIV infection. Data for this analysis were sourced from adult patients (N=469) across 24 US sites who initiated DTG plus lamivudine (3TC) or switched to DTG/3TC or DTG plus rilpivirine (RPV). The primary study objectives were to describe the demographics, clinical characteristics, and clinical rationales for DTG/3TC and DTG/RPV switches/initiations among ART-naive (n=126) and ART-experienced patients (n=343).  Patients who were naive to ART initiated DTG/3TC and those who virologically suppressed either switched to DTG/3TC (n=192) or DTG/RPV (n=151).

Among patients who initiated DTG/3TC and those who switched to DTG/3TC or DTG/RPV, the mean (SD) ages were 37.4 (12.7), 49.1 (12.4), and 55.2 (12.3) years; 82%, 77%, and 74% were cisgender men; 61%, 65%, and 64% were White; and the mean (SD) CD4⁺ counts at baseline were 433.7 (279.5), 731.4 (332.0), and 705.7 (357.5) cells/mm³, respectively.

Patients in the ART-experienced group reported a median treatment duration of more than 8 years prior to baseline. In patients who initiated DTG/3TC and those who switched to DTG/3TC or DTG/RPV, the median duration of treatment over the study period was 65.3 (IQR, 43.4-92.6), 81.1 (IQR, 60.1-94.6) and 144.3 (IQR, 103.7-165.2) weeks, respectively.

The researchers identified drug resistance in 16% of patients who initiated DTG/3TC, 2% of those who switched to DTG/3TC, and 11% of those who switched to DTG/RPV.  Patients in the ART-naive group most commonly exhibited resistance to non-nucleoside reverse transcriptase inhibitors (13%) and those in the ART-experienced groups most commonly exhibited resistance to nucleoside reverse transcriptase inhibitors (2% and 10%, respectively).

A total of 94% of ART-naive patients who switched to DTG/3TC achieved virologic suppression, with suppression maintained among most of these patients (83%) at the final follow-up visit. For the ART-experienced patients, 96% of those who switched to DTG/3TC and 93% of those who switched to DTG/RPV maintained virologic suppression.

The researchers observed low rates of DTG/3TC discontinuation in both ART-naive (<1%) and ART-experienced (2%) patients. Discontinuations were attributed to persistent low-level viremia or viral blips (n=1), toxicity or intolerance (n=1), concerns related to weight gain (n=1), and patient preference (n=1). Among patients who switched to DTG/RPV, discontinuations occurred among 3% and were attributed to food requirements (n=2), virologic failure (n=1), and patient preference (n=1).

According to treating clinicians, the most common reason for initiating DTG-based 2-drug ART regimens was to avoid long-term toxicities. Other reported reasons included a desire to streamline treatment, a desire to manage existing toxicity or intolerance, patient preference, and convenience.

Study limitations include potential recall bias, insufficient data on drug resistance from ART-experienced patients, the predominance of male patients, and potential low generalizability to other HIV-positive populations.

According to the researchers, “DTG/3TC and DTG/RPV are effective in real-world settings, with few treatment discontinuations, supporting their continued use in people with HIV-1 in the USA.”

Disclosures: This study was supported by ViiV Healthcare, and multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

By Jessica Nye, PhD

References:

Schneider S, Blick G, Burke C, et al. Two‑drug regimens dolutegravir/lamivudine and dolutegravir/rilpivirine are effective with few discontinuations in US real‑world settings: results from the TANDEM Study. Infect Dis Ther. 2024;13(4):891-906. doi:10.1007/s40121-024-00961-y