Combination Vaccination and Broadly Neutralising Antibody Therapy in HIV

Inclusion Criteria: * PWH aged ≥18 to ≤64 years old at screening * Able to give informed written consent including consent to long-term follow-up * Willing and able to comply with visit schedule and provide blood sampling * Willing to consent to their HIV care team being informed of their participation and sharing relevant clinical information * Stable on oral ART with suppressed undetectable HIV pVL 'target not detected' (TND) using local assays for ≥ 1 years (a single viral load measurement \>50 but \<500 copies/ml during this time period is allowable) * No evidence of viral insensitivity to GS-2872 based on proviral sequencing * No significant co-morbidities according to the investigator's opinion * Nadir CD4 \>200 cells/µl unless treatment commenced during documented acute seroconversion * Current CD4 count \>500 cells/µl or CD4:CD8 ratio \>1.0 * On integrase inhibitor (INSTI) or boosted protease inhibitor (bPI) based regimen at time of randomisation. If previously on non-nucleoside reverse transcriptase inhibitor (NNRTI) must have switched at least 4 weeks prior to randomisation * Adequate haemoglobin (Hb ≥12 g/dL for males, ≥11 g/dL for females) * Weight ≥ 50kg * Has received at least 3 doses of vaccination against coronavirus (COVID-19), at least 4 weeks prior to randomisation * Has received current seasonal vaccination against Influenza\* * People of childbearing potential\*\* must agree to use hormonal contraception, intrauterine device, intrauterine hormone-releasing system, or otherwise practice complete abstinence\*\*\* from at least two weeks before the first Investigational Medicinal Product (IMP) administration, for at least 20 months after the last IMP administration, and until undetectable viral load on ART * All participants must agree to take precautions to prevent onward transmission of HIV (such as condoms or PrEP) whilst they are off ART and/or have a detectable viral load \* Applicable during Influenza season (September-April inclusive). \*\*Individuals capable of becoming pregnant are defined as those who are fertile, with childbearing reproductive organs, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Permanent sterilisation of the participant's sole partner (e.g. vasectomy) is also accepted. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in those not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. \*\*\*Complete abstinence (defined as refraining from heterosexual intercourse) must be in line with the preferred and usual lifestyle of the participant. Barrier contraception, periodic abstinence (e.g. calendar, ovulation, symptothermal, post ovulation methods), withdrawal and progestogen-only oral hormonal contraception where inhibition of ovulation is not the primary mode of action are not acceptable methods of contraception. Exclusion Criteria: * • Previous ischaemic heart disease (ST or non-ST myocardial infarction, Q3-risk \>20, stable angina, unstable angina, stroke) * Any current or past history of malignancy, excluding squamous cell skin cancers * Concurrent opportunistic infection or other co-morbidity likely to occur during the trial e.g. malabsorption syndromes, autoimmune disease * Any contraindication to receipt of BHIVA recommended combination antiretrovirals * Current treatment with injectable ART * HTLV-1 co-infection * Any evidence of major antiretroviral resistance mutations * Evidence of HBV infection requiring treatment (HBsAg+, or HBcAb+ without HBsAb+) * Evidence of HCV infection (HCVAg+ and/or HCV RNA detected) * Individuals at high risk from severe Covid-19 disease who may be defined in accordance with NHSE guidance as vulnerable and shielded (as per the view of participant's physician) * Current or planned systemic immunosuppressive therapy (inhaled and topical corticosteroids are allowed) * Participation in another research study involving receipt of an investigational medicinal product (IMP) in the 3 months preceding enrolment or 5 half-lives of the investigational medicinal product, whichever is longer, or planned participation during the study period (concurrent observational studies are allowed) * History of anaphylaxis or severe adverse reaction to antibody infusions, or hypersensitivity to GS-2872 or GS-5423 or to any constituent products or excipients thereof * History of anaphylaxis or severe adverse reaction to any previous vaccine * A history of thrombosis with thrombocytopaenia syndrome (TTS) following vaccination with any adenoviral vector vaccines * A history of anti-phospholipid syndrome * A history of heparin-induced thrombocytopenia * A history of cerebral venous sinus thrombosis * Any history of other bleeding or clotting disorders of clinical significance according to the investigator's discretion * Known anti-PF4 antibody positivity * Treatment with IV immunoglobulin or other monoclonal antibody treatments planned during the duration of the trial * Clinically significant abnormal blood test results at screening including 1. Moderate to severe hepatic impairment as defined by significant liver impairment with evidence of advanced fibrosis or cirrhosis with decompensation 2. ALT \>5 x ULN 3. eGFR \<601 4. uPCR \>30 mg/mmol 5. INR \>1.5 * Evidence of organ dysfunction or any clinically significant deviation from normal in medical history, physical examination and/or vital signs that the investigator believes is a preclusion from enrolment into the study * Active alcohol or substance use that, in the investigator's opinion, will prevent adequate adherence with study requirements * Insufficient venous access that will allow scheduled blood draws as per protocol * Concern regarding likelihood of participant not taking precautions to prevent HIV transmission during treatment interruption period * Pregnancy, lactation or intending to become pregnant * Participants unable to be followed closely for geographic, social or psychological reasons * Participants unable to adequately understand written or verbal English to appropriately consent to the study