First-line ART regimen DTG/3TC efficacious in adults with high HIV viral load

Dolutegravir (DTG) plus lamivudine (3TC) has high efficacy as first-line antiretroviral therapy (ART) in treatment-naive patients with HIV infection, including for those with very high baseline viral load, according to findings of a brief report published in Open Forum Infectious Diseases.

In the phase 3 clinical trials GEMINI-1 and GEMINI-2 (ClinicalTrials.gov Identifiers: NCT02831673 and NCT02831764), the 2-drug ART regimen DTG/3TC was found to be noninferior to DTG combined with tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) in ART-naive adults through week 144. Results of the single-arm STAT study (ClinicalTrials.gov Identifier: NCT03945981) also demonstrated that the fixed-dose combination DTG/3TC had high efficacy and a favorable safety profile when administered as first-line ART in a similar population.

In this post hoc analysis, researchers evaluated the efficacy and safety of DTG/3TC among ART-naive adults with HIV infection grouped by baseline viral load. Study patients with HIV infection who initiated either DTG/3TC (n=847) or DTG+TDF/FTC (n=717) were assessed for virologic suppression (HIV RNA, <50 copies/mL) and stratified into the following groups by baseline viral load (copies/mL):

• Group 1: <100,000 (DTG/3TC: n=655 and DTG+TDF/FTC: n=564)
• Group 2: 100,000 to <500,000 (DTG/3TC: n=159 and DTG+TDF/FTC: n=138)
• Group 3: 500,000 <1 million (DTG/3TC: n=20 and DTG+TDF/FTC: n=14)
• Group 4: ≥1 million (DTG/3TC: n=12 and DTG+TDF/FTC: n=1)

Among patients in the DTG/3TC cohorts in GEMINI-1/-2 and STAT and those in the DTG+TDF/FTC cohort in GEMINI-1/-2, the median ages were 32, 31, and 33 years; 16%, 8%, and 14% were women; 68%, 50%, and 70% were White; and 55%, 40%, and 55% had Centers for Disease Control and Prevention (CDC)-defined stage 2 disease, respectively.

Analysis of DTG/3TC and DTG+TDF/FTC recipients at week 144 showed that virologic suppression was achieved by 81% and 84% of those in Group 1, 83% and 84% of those in Group 2, 82% and 79% of those in Group 3, and 50% and 100% of those in Group 4, respectively. Nearly all patients who received DTG/3TC in the single-arm STAT study achieved virologic suppression at week 48, with the exception of 3 patients who had baseline viral loads of 100,000 to less than 500,000 copies/mL.

The increase in CD4 T-cell count was similar across patients in all viral load groups (Groups 1-4) over the study period. In the GEMINI trials, the change from baseline to week 144 was between 289.7 and 346.3 cells/mm³ in DTG/3TC recipients and between 285.0 and 345.0 cells/mm³ in DTG+TDF/FTC recipients. In the STAT study, the change from baseline to week 48 was between 239.4 and 539.5 cells/mm³ in DTG/3TC recipients.

Overall, no patient across any of the trials who met criteria for virologic failure developed treatment-emergent resistance. However, in patients with baseline viral loads at or above 500,000 copies/mL, 3 DTG/3TC recipients and 2 DTG+TDF/FTC recipients in the GEMINI trials and 4 DTG/3TC recipients in the STAT study experienced drug-related adverse events by the conclusion of the trial. Moreover, 1 DTG/3TC recipient in the STAT study (baseline viral load, ≥500,000 copies/mL) withdrew from the analysis due to an adverse event.

Limitations of this analysis include the small sample of patients with HIV infection who had high viral loads at baseline.

According to the researchers, “A key goal of HIV-1 treatment is maximal and durable suppression of plasma viral load (VL), which also reduces the risk of HIV transmission to sexual partners to zero.”

Disclosure: This research 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:

Rolle C-P, Arribas JR, Ortiz R, et al. Efficacy and safety outcomes in adults initiating dolutegravir/lamivudine with high viral load in the GEMINI-1/-2 and STAT trials. Open Forum Infect Dis. Published online March 7, 2025. doi:10.1093/ofid/ofaf135