Efficacy and Safety Profiles of Dolutegravir Plus Lamivudine vs. Bictegravir/Emtricitabine/Tenofovir Alafenamide in Therapy-Naïve Adults with HIV-1
The treatment of human immunodeficiency virus (HIV) has seen significant advancements with the introduction of second-generation integrase strand transfer inhibitors (INSTIs). These drugs are characterized by a higher barrier to resistance, improved efficacy and safety profiles, and fewer drug-drug interactions. Among these, dolutegravir (DTG) and bictegravir (BIC) have emerged as preferred options for first-line treatment in most people with HIV (PWH). This article explores a retrospective multicenter study comparing the efficacy and safety of two regimens: DTG plus lamivudine (3TC) and bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in therapy-naïve adults with HIV-1 in China.
Background
The dual regimen of DTG plus 3TC has demonstrated non-inferior efficacy compared to DTG-based three-drug regimens (3DRs). However, direct comparative data on the efficacy and safety of DTG + 3TC and B/F/TAF in therapy-naïve PWH are limited. This study aimed to assess the antiviral potency and safety profiles of these two regimens in a real-world setting.
Methods
The study enrolled 280 participants initiating antiretroviral therapy (ART) with either DTG + 3TC or B/F/TAF between December 2020 and May 2022 in Guangdong and Guangxi, China. Participants were ART-naïve, aged 18 years or older, and had complete baseline data available. Exclusion criteria included pre-existing resistance mutations, hepatitis B virus co-infection, drug abuse, mental disorders, and pregnancy.
The primary outcome was the proportion of participants achieving target not detected (TND) status, defined as complete virological suppression (CVS), at weeks 4, 12, 24, and 48. Secondary outcomes included median time to TND, changes in CD4+ cell counts and CD4/CD8 ratio, and safety profiles. Subgroup analyses were conducted based on baseline viral load (VL) and CD4+ cell count.
Results
Baseline Characteristics
The study included 280 participants, with 137 (48.9%) on DTG + 3TC and 143 (51.1%) on B/F/TAF. The median age was 34 years, and 83.9% were male. The median baseline VL was 70,600 copies/mL, and the median baseline CD4+ cell count was 264 cells/µL. Baseline characteristics were similar between the two groups, except for a higher proportion of men who have sex with men (MSM) in the B/F/TAF group.
Virological Outcomes
At week 48, 96.4% of participants on DTG + 3TC and 100% on B/F/TAF achieved TND status (P = 0.064). At week 12, the TND response rate was significantly higher in the B/F/TAF group (78.3%) compared to the DTG + 3TC group (30.7%) (P < 0.001). This trend was consistent across subgroups stratified by baseline VL and CD4+ cell count. The median time to TND was 12 weeks for B/F/TAF and 24 weeks for DTG + 3TC (P < 0.001).
Immunological Outcomes
Both regimens showed significant increases in CD4+ cell counts and CD4/CD8 ratios from baseline to week 48. However, in the subgroup with baseline VL ≥100,000 copies/mL, the B/F/TAF group showed better CD4+ cell count recovery (182.0 cells/µL) compared to the DTG + 3TC group (127.0 cells/µL) (P = 0.009). No significant differences were observed in other subgroups.
Safety Profiles
The B/F/TAF group reported lower rates of drug-related adverse effects (DRAEs) (4.9%) compared to the DTG + 3TC group (13.1%) (P = 0.016). Common AEs in the DTG + 3TC group included fatigue, insomnia, and somnolence, while the B/F/TAF group reported gastrointestinal issues such as nausea and diarrhea. No serious AEs or deaths were reported.
Metabolic and Renal Outcomes
Both regimens led to increases in lipid parameters, body weight, and creatinine levels over 48 weeks. The DTG + 3TC group showed more favorable effects on triglycerides and high-density lipoprotein (HDL) cholesterol. Weight gain was more pronounced in the B/F/TAF group (+2.5 kg) compared to the DTG + 3TC group (+1.5 kg) (P = 0.033). No significant differences were observed in renal function parameters between the two groups.
Discussion
The study demonstrated that both DTG + 3TC and B/F/TAF are highly effective in achieving virological suppression in therapy-naïve PWH. However, B/F/TAF showed a faster decline in VL and higher TND rates at week 12 compared to DTG + 3TC. This difference may be attributed to the pharmacological properties of BIC, which has a lower in vitro IC50 and longer half-life compared to DTG. Additionally, the inclusion of TAF in the B/F/TAF regimen may enhance its overall potency.
The immunological outcomes were generally similar between the two regimens, with both showing significant increases in CD4+ cell counts and CD4/CD8 ratios. However, B/F/TAF demonstrated better CD4+ cell count recovery in participants with high baseline VL. This finding aligns with previous studies suggesting that B/F/TAF may offer advantages in immune recovery in advanced HIV cases.
In terms of safety, B/F/TAF was associated with fewer DRAEs compared to DTG + 3TC. The most common AEs in the DTG + 3TC group were neuropsychiatric events, while the B/F/TAF group reported gastrointestinal issues. The lower AE rates with B/F/TAF may contribute to better adherence and long-term treatment success.
Metabolic changes were observed in both groups, with DTG + 3TC showing a more favorable impact on triglycerides and HDL cholesterol. Weight gain was more pronounced in the B/F/TAF group, which raises concerns about long-term metabolic health. Further research is needed to understand the implications of these changes and their impact on the risk of metabolic syndrome.
Conclusion
This real-world study highlights the efficacy and safety of both DTG + 3TC and B/F/TAF in therapy-naïve adults with HIV-1. While both regimens achieved high rates of virological suppression at week 48, B/F/TAF demonstrated a faster decline in VL and higher TND rates at week 12. The B/F/TAF regimen also showed better CD4+ cell count recovery in participants with high baseline VL and was associated with fewer DRAEs. However, DTG + 3TC had a more favorable impact on metabolic changes, particularly in lipid profiles and weight gain.
These findings provide valuable insights for clinicians in selecting the most appropriate ART regimen based on individual patient characteristics and clinical scenarios. The rapid viral suppression achieved with B/F/TAF may be particularly beneficial in reducing secondary HIV transmission and improving adherence to lifelong ART. Further studies are needed to explore the long-term metabolic consequences of these regimens and their impact on overall health outcomes in PWH.
doi.org/10.1097/CM9.0000000000002907
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