Efficacy and Safety of the ACC017-Based Antiretroviral Regimen in Treatment-Experienced Adults With HIV-1 Harboring Non-Nucleoside Reverse Transcriptase Inhibitor Resistance Mutations

This trial is a randomized, double-blind, placebo-controlled clinical study conducted in treatment-experienced adults with NNRTI-resistant HIV-1, designed to preliminarily evaluate the efficacy, safety, and resistance profile of the core drug ACC017 in this population. The study consists of two treatment phases: a functional monotherapy period (double-blind phase) and an extended optimized treatment period (open-label phase). The first phase is the functional monotherapy period (W1-W2). After initial screening, eligible participants will return to the hospital on D1 for final eligibility review and baseline examinations. Those who pass the review will be randomized in a 2:1 ratio to either ACC017 tablets (N=8, 40 mg, once daily \[QD\]) or matching placebo (N=4), replacing the core NNRTI drug in the failing background regimen while maintaining the original backbone NRTIs unchanged. Treatment will continue for 2 weeks. The second phase is the extended optimized treatment period (W3-W16). All participants who complete the functional monotherapy period will receive ACC017 tablets (40 mg QD) in combination with an optimized backbone regimen (i.e., ACC017 replaces the core NNRTI drug in the failing background regimen, while the investigator adjusts the backbone drugs based on HIV genotypic resistance test results to ensure at least one backbone NRTI remains sensitive, if applicable). Treatment will continue for 14 weeks.

Inclusion Criteria: Participants must meet all of the following criteria to be eligible for this trial: 1. Voluntarily sign the informed consent form before screening and be able to comply with the protocol procedures or agreed requirements; 2. Age ≥18 years (inclusive) at the time of signing the informed consent, regardless of gender; 3. Diagnosed with HIV-1 infection before screening, having received the current first-line antiretroviral therapy (i.e., one NNRTI combined with two NRTIs) for at least 6 months (changes in treatment regimen due to tolerability issues or other adverse reactions are acceptable), with treatment interruption ≤4 weeks before screening (if applicable); 4. Before and at screening, no prior use of INSTI, PI, or other novel antiretroviral drugs (including but not limited to fusion inhibitors \[FI\] or capsid inhibitors \[CAI\]), including for pre-exposure prophylaxis (PrEP) and/or post-exposure prophylaxis (PEP); 5. At least one HIV-1 RNA test result ≥400 copies/mL within 8 weeks before screening, and confirmed HIV-1 RNA ≥400 copies/mL at screening (with ≥7 days between the two tests); or at least one HIV-1 RNA test result ≥50 copies/mL to \5× upper limit of normal (ULN), or ALT \>3×ULN with total bilirubin (TBIL) \>1.5×ULN or direct bilirubin (DBIL) \>ULN, or other laboratory abnormalities graded ≥3 per CTCAE v5.0; 7. At screening, creatinine clearance \