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.

Background: Opportunistic infections remain a leading cause of morbidity in people living with HIV (PLWH). Talaromyces marneffei ( T. marneffei ) accounts for up to 15% of HIV-related hospitalizations in endemic regions. Metagenomic next-generation sequencing (mNGS) offers rapid pathogen detection; however, its utility in diagnosing HIV-associated coinfections is uncertain. Methods: This retrospective study enrolled 56 hospitalized PLWH with coinfections at the Third Affiliated Hospital of Sun Yat-sen University from March 2022 to October 2024. All patients underwent pathogen detection using both mNGS and CTM, with their diagnostic performance compared. Clinical data, treatment adjustments, and outcomes were analyzed. Results: mNGS demonstrated significantly higher detection rate (84.4%, 54/64; 95% CI: 73.1–92.2%) than CTM (28.1%, 18/64; 95% CI: 17.6–40.8%; p < 0.0001), especially for T. marneffei detection (100% vs. 45.5%, p < 0.0001). mNGS identified T. marneffei in 39.3% ( n = 22/56) of patients, including two rare cases (urinary and intracranial infections) missed by CTM. mNGS revealed mixed infections in 82.1% (46/56) of patients, substantially higher than the 5.4% detected by CTM. Notably, mNGS-guided therapy adjustments occurred in 74.1% of cases, compared with 22.2% for CTM ( p < 0.001), correlating with clinical improvement in 90% (36/40) of adjusted regimens. Conclusion: Our data demonstrated that mNGS had a higher positive detection rate than CTM for detecting coinfections among PLWH, especially for T. marneffei and mixed infections. These results highlight the clinical value of mNGS as a complementary tool for pathogen identification in this vulnerable population.