病毒抑制之第一型人類免疫缺乏病毒 (HIV-1) 患者

主要目標 第 2 期： •評估改用每週口服 GS 1720 併用 GS-4182 相較於繼續使用 bictegravir/emtricitabine/tenofovir alafenamide（BVY；複方配製，Biktarvy®），在第 24 週時對於病毒抑制之 HIV-1 患者 (PWH) 的療效 第 3 期： •評估改用每週口服 GS 1720/GS-4182 固定劑量組合 (FDC) 錠劑療程相較於繼續使用 BVY，在第 48 週時對於病毒抑制之 PWH 的療效 次要目標 第 2 期： •評估改用每週口服 GS 1720 併用 GS-4182 相較於繼續使用 BVY，在第 12、24 和 48 週時對於病毒抑制之 PWH 的療效 •評估每週口服 GS-1720 併用 GS-4182 在第 12、24 和 48 週時的安全性和耐受性 •評估每週口服 GS-1720 併用 GS-4182 的藥物動力學 (PK) 第 3 期： •評估改用每週口服 GS 1720/GS-4182 FDC 相較於繼續使用 BVY，在第 48 和 96 週時對於病毒抑制之 PWH 的療效 •評估每週口服 GS-1720/GS-4182 FDC 在第 48 和96 週時的安全性和耐受性

錠劑
錠劑

GS-1720
GS-4182

110
110

325 mg
300 mg

第 2 期：
•依據美國 (US) 食品藥物管理局 (FDA) 定義的快照演算法，判定第 24 週 HIV-1 RNA ≥50 copies/mL的受試者比例

第 3 期：
•依據美國 FDA 定義的快照演算法，判定第 48 週 HIV-1 RNA ≥50 copies/mL 的受試者比例

Participants must meet all of the following inclusion criteria to be eligible for participation in this study:
1. Participants 18 years of age or older and able to understand and give written informed consent.
2. Participants assigned male at birth and participants assigned female at birth and of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified methods of ontraception as described in Appendix 11.5.
3. Documented plasma HIV-1 RNA < 50 copies/mL for ≥ 24 weeks before and at screening.
4. Receiving BVY for ≥ 24 weeks prior to screening.

Participants who meet any of the following exclusion criteria are not eligible to be enrolled in this study:
1) Prior use of, or exposure to LEN, GS-1720, or GS-4182.
2) History of virologic failure while on an INSTI-based regimen.
3) Documented INSTI resistance, specifically, resistance-associated mutations (RAMs) E92G/Q, G118R, F121Y, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene.
4) Prior use of any LA parenteral ARVs such as monoclonal antibodies (mAbs) or broadly neutralizing antibodies (bNAbs) targeting HIV-1, injectable cabotegravir (including oral cabotegravir lead-in), or injectable rilpivirine.
5) Any of the following laboratory values at screening:
a) CD4 cell count < 200 cells/mm3 at screening
b) Glomerular filtration rate < 60 mL/min according to the Modification of Diet in Renal Disease formula {Lacombe 2008, Levey 2006}
c) Hepatic transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 1.5 × upper limit of normal (ULN)
d) Direct bilirubin > 1.5 × ULN
e) Platelets count < 50,000 cells/mm3
f) Hemoglobin < 8.0 g/dL
6) Active tuberculosis infection.
7) Active or occult hepatitis B virus (HBV) infection as defined below (regardless of other HBV
serologic results). Participants found to be susceptible to HBV infection should be recommended to receive an HBV vaccination.
a) Hepatitis B surface antigen positive (HBsAg+)
(or)
b) Hepatitis B core antibody positive (HBcAb+) and hepatitis B surface antibody negative
(HBsAb-).
8) Active hepatitis C virus (HCV) defined as detectable HCV RNA. Note: Participants with
prior/inactive HCV infection (defined as undetectable HCV RNA) may enroll.
9) Moderate/severe hepatic impairment or a history of or current clinical decompensated liver
cirrhosis (eg, ascites, encephalopathy, or variceal bleeding).
10) Current alcohol or substance use judged by the investigator to potentially interfere with participant study compliance.
11) Have been treated within 6 months of study screening or expected to receive during the study immunosuppressant therapies or chemotherapeutic agents (eg, chronic [at least 4 weeks] systemic steroids, immunoglobulins, and other immune- or cytokine-based therapies).
12) Participation in any other clinical study, including observational studies, without prior
approval from the Sponsor is prohibited while participating in this study.
13) Positive serum pregnancy test at screening or positive pregnancy test at Day 1
(Appendix 11.5).
14) Participants with plans to breastfeed during the study period and within 60 days following the
last dose of study drug.
15) Serious illness requiring hospitalizations within 30 days prior to screening and during the
screening period or active malignancy requiring acute systemic treatment.
16) Known hypersensitivity to the study drug, its metabolites, or formulation excipient.
17) Abnormal electrocardiogram (ECG) at the screening visit that is clinically significant as
determined by the investigator.
18) Requirement for ongoing therapy with or prior use of any prohibited medications listed in
Section 5.3.
19) Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the participant unsuitable for the study or unable to comply with the dosing requirements, including medical history of psychotic disorder and/or use of antipsychotic medications prescribed for psychosis.