Real-World Evidence Supports DTG+3TC for ART in Diverse HIV Populations

Outcomes of the 2-drug antiretroviral therapy (ART) regimen dolutegravir (DTG) plus lamivudine (3TC) in real-world settings are consistent with those observed in phase 3 clinical trials, confirming its efficacy, tolerability, and high barrier to resistance among diverse populations with HIV infection. These study findings were published in Infectious Diseases and Therapy.

Both regional and international guidelines indicate the use of DTG+3TC as either first-line treatment for ART-naive patients or as a suppressed-switch option for ART-experienced patients.

Researchers at ViiV Healthcare conducted a systematic review and meta-analysis to determine the effectiveness and tolerability of DTG+3TC among patients with HIV infection in clinical practice. They searched publication databases for real-world studies on the use of DTG+3TC that were published between 2013 and 2024 or presented at medical conferences between 2016 and 2024. Eligible study patients included those who either initiated or switched to ART with DTG+3TC for HIV treatment. The primary outcomes were virologic suppression, virologic failure, and discontinuation for any reason at 48 or 96 weeks.

A total of 191 studies and 84 discrete cohorts were identified for the review. The pooled study population comprised 44,436 patients, of whom 20,060 had prior exposure to ART, 2346 were naive to ART, and 22,030 had an unknown history of ART use.

Among ART-naive patients, 32.6% and 24.1% had baseline viral loads at or above 100,000 and at or above 500,000 copies/mL, respectively. Among ART-experienced patients who switched to DTG+3TC, 2.6% to 3.4% had detectable viral loads at baseline, and 8.6% had a history of virologic failure. Data captured from 916 unique patients showed 12 (1.3%) with resistance-associated mutations (RAMs) prior to DTG+3TC initiation.

Pooled study data captured from ART-naive patients following DTG+3TC initiation showed estimated virologic suppression rates of 0.964 (95% CI, 0.945-0.979; I², 18%) at week 48 and 0.902 (95% CI, 0.816-0.966; I², 78%) at week 96. Estimates rates of virologic suppression for ART-experienced patients who switched regimens were 0.966 (95% CI, 0.950-0.980; I², 89%) and 0.971 (95% CI, 0.946-0.990; I², 91%) at weeks 48 and 96, respectively.

In regard to virologic failure after DTG+3TC initiation, ART-naive and ART-experienced patients showed respective rates of 0.001 (95% CI, 0.000-0.013; I², 51%) and 0.009 (95% CI, 0.005-0.015; I², 75%) at week 48 and 0.001 (95% CI, 0.000-0.008; I², 0%) and 0.015 (95% CI, 0.007-0.024; I², 74%) at week 96.

The estimated rates of treatment discontinuation for any reason among ART-naive patients were 0.052 (95% CI, 0.019-0.097; I², 81%) at week 48 and 0.130 (95% CI, 0.084-0.183; I², 0%) at week 96. Estimated rates of discontinuation among ART-experienced patients were higher at week 48 (0.067; 95% CI, 0.042-0.098; I², 94%) but lower at week 96 (0.084; 95% CI, 0.047-0.130; I², 90%). Overall, 2.5% of discontinuations were attributed to adverse events or toxicity, and 1.0% to drug-related adverse events.

Results of sensitivity analyses restricted to studies with the same definitions for both virologic suppression and virologic failure were consistent with those observed in the main analysis.

The researchers observed RAM-attributable virologic failure or viral blip among 4 (0.02%) ART-experienced patients and among no patients who were naive to ART.

Limitations of this analysis include the high number of single-arm noncomparative studies, the inability to fully assess treatment-emergent resistance, and insufficient data to distinguish between discontinuations related to treatment vs loss to follow-up.

According to the researchers, “These results continue to reinforce DTG+3TC as an effective and tolerable treatment across diverse populations…”

Disclosure: 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.