Background: Dual regimen dolutegravir (DTG) plus lamivudine (3TC) has demonstrated non-inferior efficacy compared to DTG-based three-drug regimens (3DRs), yet directly comparative data regarding the efficacy and safety of DTG + 3TC and bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for therapy-naïve people with human immunodeficiency virus (HIV)-1 (PWH) are still limited. We aimed to assess the antiviral potency and safety profiles of DTG + 3TC vs. B/F/TAF based on antiretroviral therapy (ART)-naïve PWH in China. Methods: This retrospective multicenter study enrolled PWH initiating ART with DTG + 3TC or B/F/TAF from 2020 to 2022 in Guangdong and Guangxi. We analyzed response rates based on target not detected (TND) status using intention-to-treat (ITT) analysis. Subgroups were formed based on baseline viral load (VL) (<100,000 vs. ≥100,000 copies/mL) and CD4⁺ cell count (<200 vs. ≥200 cell/µL). Median time to TND VL was assessed by Kaplan–Meier method. We also measured changes from baseline in CD4⁺ cell counts, CD4/CD8 ratio, lipid parameters, weight, creatinine (Cr), estimated glomerular filtration rate (eGFR), and drug-related adverse effects (DRAEs). Results: We enrolled 280 participants, including 137 (48.9%) on DTG + 3TC and 143 (51.1%) on B/F/TAF. At week 48, 96.4% (132/137) on DTG+3TC and 100% (143/143) on B/F/TAF achieved TND (P = 0.064). At week 12, TND responses were higher with B/F/TAF (78.3% [112/143]) than DTG+3TC (30.7% [42/137]) (P <0.001). This trend held across subgroups. B/F/TAF achieved TND faster (12 weeks) than DTG+3TC (24 weeks) (P <0.001). No differences were seen in CD4⁺ cell count and CD4/CD8 ratio, except in the high-VL subgroup, where B/F/TAF showed better recovery. DRAEs were significantly lower with B/F/TAF (4.9% [7/143]) than with DTG + 3TC (13.1% [18/137]) (P = 0.016). Lipid parameters, body weight, and Cr increased in both groups over 48 weeks, with DTG+3TC showing a more favorable effect on triglycerides, high-density lipoprotein (HDL) cholesterol, and weight gain. Conclusions: In this real-life study, B/F/TAF led to a faster viral decline and fewer DRAEs compared to DTG+3TC. No significant difference was observed in the TND rate at week 48, regardless of baseline VL and CD4⁺ cell count. CD4⁺ recovery was superior for B/F/TAF in participants with high VL. The DTG + 3TC regimen had less impact on metabolic changes than B/F/TAF.

Limited real-world data on dolutegravir (DTG) plus lamivudine (3TC) for HIV-1-infected individuals have been reported. This study aimed to evaluated the real-world efficacy and safety of DTG + 3TC in ART-naïve HIV-1-infected adults in China. This real-world prospective observational cohort study enrolled HIV-1-infected adults receiving ART initiation with DTG + 3TC (D3 group) or tenofovir plus lamivudine and efavirenz (TDF + 3TC + EFV, TLE group) with subgroups of low viral load (LVL, ≤500,000 copies/mL) and high viral load (HVL, >500,000 copies/mL) according to baseline HIV-1 RNA. Efficacy were assessed by proportion of virologic suppression, changes of CD4⁺ cell count and CD4/CD8 ratio, HIV-1 DNA decay, and safety by symptoms and changes of laboratory indicators at week 4, 12, 24, 36, and 48. Totally 45 participants in D3 group and 95 in TLE group were enrolled. The proportion of HIV RNA < 50 copies/mL were 48.7% (19/39), 84.6% (33/39), 100% (39/39), 100% (39/39) in D3-LVL subgroup at week 4, 12, 24, 48, compared with 1.3% (1/75), 14.7% (11/75), 86.7% (65/75), 96.0% (72/75) in TLE-LVL subgroup, with P < .05 at week 4, 12, and 36. The proportion were 0.0% (0/6), 66.7% (4/6), 83.3% (5/6), 100% (6/6) in D3-HVL subgroup compared with 0.0% (0/20), 5.0% (1/20), 85.0% (17/20), 100% (20/20) in TLE-HVL subgroup, with P < .05 at week 12. No virologic rebound was observed in D3 group. Mean change of CD4/CD8 ratio were higher in D3-LVL versus TLE-LVL subgroup at each scheduled visit (P < .05), while CD4⁺ cell counts increased significantly in D3-HVL versus TLE-HVL subgroup at week 4 and 12 (P < .05). Less complaint of dizziness, insomnia, dreaminess and amnesia, lower elevated level of triglyceride and higher elevated level of creatinine from baseline to week 48 were documented in D3 group (P < .05). Total HIV-1 DNA decayed along with HIV-1 RNA after DTG + 3TC initiation in both D3-LVL and D3-HVL subgroups. DTG + 3TC achieved virological suppression more rapidly and stably versus TDF + 3TC + EFV in ART-naïve HIV-1-infected adults, with better immunological response and less adverse drug effect, and reduced total HIV-1 DNA effectively. DTG + 3TC is a potent regimen for ART-naïve individuals with HIV-1 infection.

This prospective cohort study compared the efficacy of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and tenofovir/lamivudine/efavirenz (TLE) regimens in 88 treatment-naïve persons living with HIV. The BIC regimen achieved faster HIV-1 RNA suppression at week 12, with comparable suppression thereafter. Regarding HIV-1 DNA, the TLE group exhibited a more rapid decline, largely attributable to its higher baseline levels, while both groups converged to comparable levels at week 48; this difference was no longer significant after adjusting for baseline HIV-1 DNA levels. Notably, the BIC group had significantly lower baseline CD4 ⁺ counts, reflecting the real-world inclusion of individuals with more advanced disease. Cluster analysis within the BIC group revealed three distinct DNA decay trajectories. A subset of individuals with the lowest baseline CD4 ⁺ counts (Cluster 1, n = 16) showed stable HIV-1 DNA through week 48 followed by significant decline only after 72 weeks, with CD4/CD8 ratio recovery preceding the decline. The early DNA plateau may reflect the interplay between immune reconstitution and viral reservoir dynamics. These findings suggest that baseline immune status influences early viral reservoir dynamics and that the timing of reservoir reduction may be linked to immune restoration, highlighting the heterogeneity of integrase inhibitor responses and the potential value of baseline immune assessment in guiding individualized management.

Introduction Dolutegravir (DTG) plus lamivudine (3TC) is one of the preferred treatment regimens for HIV, yet evidence remains limited for people living with HIV (PLWH) with high baseline viral load. This study aims to evaluate the effectiveness of DTG/3TC in treatment-naive PLWH with baseline viral load > 500,000 copies/mL in China. Methods In this real-world multicenter cohort study, PLWH with baseline viral load (VL) > 500,000 copies/mL who initiated DTG/3TC were recruited across 18 clinical sites in China. Matched participants from the same sites with lower baseline VL were also included as a control group. Participants were followed for 48 weeks. The primary endpoint was virological suppression (HIV-1 RNA < 50 copies/mL) at week 48 using the US Food and Drug Administration snapshot algorithm. Results Of the 375 PLWH enrolled, 150 were classified into the high VL group and 225 into the low VL group. Baseline median HIV-1 RNA was 5.99 and 5.07 log₁₀ copies/mL, respectively. At week 48, virologic suppression was achieved in 88.0% (95% CI 82.8–93.2%) of the high VL group and 92.0% (95% CI 87.9–96.2%) of the low VL group (P = 0.233); 7.5% and 4.0% of participants in the high and low VL groups had plasma HIV-1 RNA ≥ 50 copies/mL, respectively. Median CD4 increases from baseline to week 48 were 153.5 and 147.0 cells/μL in the high and low VL groups, respectively (P = 0.408). Safety profiles were comparable, with one grade 3 adverse event in each group. Conclusions DTG/3TC showed favorable virological and safety outcomes in treatment-naive PLWH with baseline HIV-1 RNA > 500,000 copies/mL, suggesting that it may be a viable option for PLWH with high baseline viral load. Trial Registration Chinese Clinical Trial Registry: ChiCTR2300074854.