Same-day Antiretroviral Therapy With BIC/F/TAF

HIV Infections Clinical Trial

Official title:

A Multicenter Clinical Trial to Evaluate the Feasibility and Outcome of Same-day Antiretroviral Therapy With Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/F/TAF) Among Patients Testing Positive by HIV Confirmatory Tests

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04712058
• Other study ID #: 202003020MIPB
• Status: Recruiting
• Phase: N/A
• Start date: January 20, 2021
• Est. completion date: January 31, 2023

Study information

• Verified date: December 2020
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

WHO had recommened rapid ART initiation, defined as starting ART within 7 days or on the same day after HIV diagnosis, to improve HIV care continuum. Prior studies revealed that point-of-care diagnostic methods for the detection of HIV RNA can accelerate linkage to care and reduce anxiety. By shortening the interval between infectious disease physician referral, time-lag between screening and confirmatory tests, with the use of the newly developed point-of-care immunochromatographic confirmatory test, initiating a safe and potent antiretroviral therapy, BIC/F/TAF, on the same day of HIV confirmation will be feasible to improve linkage to care and to shorten the interval between HIV diagnosis and viral suppression.

Description:

Background In 2015, WHO recommended that all patients be treated with combination antiretroviral therapy (cART) once the diagnosis of HIV infection was made. On the population level, starting cART soon after HIV diagnosis can prevent onward HIV transmission. Although WHO has recommended "treat-all" policy since 2015, there were still 1.8 million people becoming newly infected with HIV in 20179. The substantial loss of patients during the HIV care continuum among the most vulnerable populations have been major concerns in the cART scale-up. Therefore, the concept of rapid ART initiation, defined as starting ART within 7 days or even on the same day after HIV diagnosis was confirmed, was introduced to improve HIV care continuum. In several clinical trials, loss to follow-up was observed despite the clinical trial settings. From our prior study18, among 786 individuals who were screened positive for HIV, 2.4% never returned to the clinic for the confirmatory tests. Despite ART scale-up and the policy of rapid initiation, 30% the of patients who were diagnosed with HIV infection during 2017-2018 did not initiate cART within 7 days after HIV diagnosis was made. Prior studies revealed that point-of-care diagnostic methods for detection of HIV RNA can accelerate linkage to care and reduce anxiety. However, the cost of and the barriers to accessing the point-of-care HIV RNA testing remain high. By shortening the interval between infectious disease physician referral, time-lag between screening and confirmatory tests, with the use of newly developed point-of-care immunochromatographic confirmatory test, initiating a safe and potent antiretroviral therapy on the same day of HIV confirmation will be feasible to improve linkage to care and to shorten the interval between HIV diagnosis and viral suppression.

Study aim This study objective is to investigate the feasibility and outcomes of same-day initiation with Biktarvy (Bic/F/TAF) among patients who receive a diagnosis of HIV infection by confirmatory test.

Study Interventions This is a multi-center, single-arm, prospective cohort study. All individuals who fulfill the inclusion/exclusion criteria will be enrolled in our study and followed for 48 weeks. During the first visit at ID clinic, baseline clinical data will be collected by history taking, physical examination, and blood testing. The confirmatory test and baseline evaluations will be performed at the Visit 1. The test results will also be reported on the same day. Patients, who are HIV(+) by confirmatory test ,will receive a 7-day Biktarvy treatment and the first dose will be administered from Visit 1 (Day 1). The results of other evaluation including viral load, CD4 count, and coinfection will be available at visit 2.

At Visit 2, the clinical symptoms and the tolerability will be recorded. If participants continue to receive Biktarvy® at the discretion of the HIV treating physicians, Biktarvy will be continued according to the national HIV treatment guidelines, which will be reimbursed by the National Health Insurance, and the patients will be followed in our study for 48 weeks. If the patients are switched to other cART regimens than Bictarvy according to physician's clinical judgements, the participants will continue their follow-up in the study.

During the follow-up period, clinical information on symptoms, tolerability, and adverse effects with the use of face-to-face questionnaire interviews, and follow-up laboratory test results will be collected. to evaluate the efficacy and adverse effect according to the national HIV treatment guidelines and routine clinical practices.

Monitor of Adverse event and management The subjective adverse events will be inquired during each visit and recorded with the use of questionnaire interviews. According to the national HIV treatment guidelines in Taiwan, the liver and renal functions and muscle enzymes will be followed during treatment as part of the standard of care. The study team will provide best clinical care if adverse events develop and the cost of medical care required will be covered by the insurance company. Severe adverse event and withdrawal from the study will be reported to the primary investigator on a monthly basis. When the number of drop-out is higher than 30%, the enrollment will be stopped temporarily until the investigation ensures the safety of the participants.

Study Endpoints

1. Primary endpoints 1) The rate of retention in care at Week 48 2) The proportion of viral suppression (<50 copies/ml) at Week 48

2. Secondary endpoints 1) The rate of same-day initiation of ART among patients who receive a confirmed diagnosis of HIV infection 2) The proportion of viral suppression (<200 copies/ml) at Weeks 1, 4, and 48 3) Any/severe adverse effect of B/F/TAF before Weeks 4 and 48 4) Patient's satisfaction at Weeks 1, 4, and 48

Statistical analysis

1. This is a feasibility study aiming to investigate the rate of engagement in same-day ART initiation and retention in care at Week 48. No sample size calculation is needed. The sample size of 200 participants is estimated by taking into account the case numbers of newly diagnosed HIV-positive patients seeking HIV care and cART at each participating hospitals during the past 1 year.

2. Timetable for study and enrollment:

1) Total subjects expected to be enrolled: 200 2) Total subjects expected to enter treatment:

195 3) Total subjects expected to complete treatment: 191 4) Duration of enrolled period: 20 months 5) Number of subjects entering treatment per month: 10 ( 2 subjects per site)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: January 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Patients who test positive by HIV screening tests (4th generation Ag/Ab) by clinical care providers or by VCT counselors within 3 days of Visit 1.

• Aged 20 years or older

• Patient is willing to participate in this study and sign the written informed consent form

Exclusion Criteria:

• Prior HIV diagnosis

• Prior ART for HIV infection

• Chronic kidney disease, stage =4 (CCr <30 ml/min/1.73m2) or receiving dialysis

• Severe hepatic impairment (Child-Pugh score C) or clinical apparent hepatic impairment including jaundice or ascites

• Active or latent tuberculosis infection or clinical apparent central nervous system infection

• Pregnancy or breastfeeding

• Allergy to FTC or TDF containing medication

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Bictegravir / Emtricitabine / Tenofovir Alafenamide Oral Tablet [Biktarvy]
Biktarvy will be administered on the same day of diagnosis. The daily dosing will be continued for 48 weeks.

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (9)

Lead Sponsor	Collaborator
National Taiwan University Hospital	Changhua Christian Hospital, Chi Mei Medical Hospital, Chung Shan Medical University, Far Eastern Memorial Hospital, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung Municipal Ta-Tung Hospital, Mackay Memorial Hospital, National Cheng-Kung University Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (27)

Amanyire G, Semitala FC, Namusobya J, Katuramu R, Kampiire L, Wallenta J, Charlebois E, Camlin C, Kahn J, Chang W, Glidden D, Kamya M, Havlir D, Geng E. Effects of a multicomponent intervention to streamline initiation of antiretroviral therapy in Africa: a stepped-wedge cluster-randomised trial. Lancet HIV. 2016 Nov;3(11):e539-e548. doi: 10.1016/S2352-3018(16)30090-X. Epub 2016 Aug 27. — View Citation

Borges ÁH, Neuhaus J, Babiker AG, Henry K, Jain MK, Palfreeman A, Mugyenyi P, Domingo P, Hoffmann C, Read TR, Pujari S, Meulbroek M, Johnson M, Wilkin T, Mitsuyasu R; INSIGHT START Study Group. Immediate Antiretroviral Therapy Reduces Risk of Infection-Re — View Citation

Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, Godbole SV, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Cottle L, Zhang XC, Makhema J, Mills LA, Panchia R, Faesen S, Eron J, Gallant J, Havlir D, Swindells S, Elharrar V, Burns D, Taha TE, Nielsen-Saines K, Celentano DD, Essex M, Hudelson SE, Redd AD, Fleming TR; HPTN 052 Study Team. Antiretroviral Therapy for the Prevention of HIV-1 Transmission. N Engl J Med. 2016 Sep 1;375(9):830-9. doi: 10.1056/NEJMoa1600693. Epub 2016 Jul 18. — View Citation

Gallant J, Lazzarin A, Mills A, Orkin C, Podzamczer D, Tebas P, Girard PM, Brar I, Daar ES, Wohl D, Rockstroh J, Wei X, Custodio J, White K, Martin H, Cheng A, Quirk E. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. Lancet. 2017 Nov 4;390(10107):2063-2072. doi: 10.1016/S0140-6736(17)32299-7. Epub 2017 Aug 31. — View Citation

Girometti N, Nwokolo N, McOwan A, Whitlock G. Outcomes of acutely HIV-1-infected individuals following rapid antiretroviral therapy initiation. Antivir Ther. 2017;22(1):77-80. doi: 10.3851/IMP3080. Epub 2016 Sep 2. — View Citation

Guideline on When to Start Antiretroviral Therapy and on Pre-Exposure Prophylaxis for HIV. Geneva: World Health Organization; 2015 Sep. — View Citation

Guidelines for Managing Advanced HIV Disease and Rapid Initiation of Antiretroviral Therapy. Geneva: World Health Organization; 2017. No abstract available. — View Citation

Halperin J, Butler I, Conner K, Myers L, Holm P, Bartram L, Van Sickels N. Linkage and Antiretroviral Therapy Within 72 Hours at a Federally Qualified Health Center in New Orleans. AIDS Patient Care STDS. 2018 Feb;32(2):39-41. doi: 10.1089/apc.2017.0309. — View Citation

Huang YC, Sun HY, Chuang YC, Huang YS, Lin KY, Huang SH, Chen GJ, Luo YZ, Wu PY, Liu WC, Hung CC, Chang SC. Short-term outcomes of rapid initiation of antiretroviral therapy among HIV-positive patients: real-world experience from a single-centre retrospec — View Citation

INSIGHT START Study Group, Lundgren JD, Babiker AG, Gordin F, Emery S, Grund B, Sharma S, Avihingsanon A, Cooper DA, Fätkenheuer G, Llibre JM, Molina JM, Munderi P, Schechter M, Wood R, Klingman KL, Collins S, Lane HC, Phillips AN, Neaton JD. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. N Engl J Med. 2015 Aug 27;373(9):795-807. doi: 10.1056/NEJMoa1506816. Epub 2015 Jul 20. — View Citation

Koenig SP, Dorvil N, Dévieux JG, Hedt-Gauthier BL, Riviere C, Faustin M, Lavoile K, Perodin C, Apollon A, Duverger L, McNairy ML, Hennessey KA, Souroutzidis A, Cremieux PY, Severe P, Pape JW. Same-day HIV testing with initiation of antiretroviral therapy — View Citation

Labhardt ND, Ringera I, Lejone TI, Klimkait T, Muhairwe J, Amstutz A, Glass TR. Effect of Offering Same-Day ART vs Usual Health Facility Referral During Home-Based HIV Testing on Linkage to Care and Viral Suppression Among Adults With HIV in Lesotho: The — View Citation

Langwenya N, Phillips TK, Brittain K, Zerbe A, Abrams EJ, Myer L. Same-day antiretroviral therapy (ART) initiation in pregnancy is not associated with viral suppression or engagement in care: A cohort study. J Int AIDS Soc. 2018 Jun;21(6):e25133. doi: 10. — View Citation

Malloch L, Kadivar K, Putz J, Levett PN, Tang J, Hatchette TF, Kadkhoda K, Ng D, Ho J, Kim J. Comparative evaluation of the Bio-Rad Geenius HIV-1/2 Confirmatory Assay and the Bio-Rad Multispot HIV-1/2 Rapid Test as an alternative differentiation assay for CLSI M53 algorithm-I. J Clin Virol. 2013 Dec;58 Suppl 1:e85-91. doi: 10.1016/j.jcv.2013.08.008. Epub 2013 Aug 28. — View Citation

Meulbroek M, Pujol F, Pérez F, Dalmau-Bueno A, Taboada H, Marazzi G, Carrillo A, Cabas A, Gata A, Aldabó E, Roldán B, Coll P, Añez F, Pantaleón J, Mochales M, Gómez V, Marín O, Mir JF, Decoca J, Saz J. BCN Checkpoint: same-day confirmation of reactive HIV — View Citation

Minn AC, Kyaw NTT, Aung TK, Mon OM, Htun T, Oo MM, Moe J, Mon AA, Satyanarayana S, Oo HN. Attrition among HIV positive children enrolled under integrated HIV care programme in Myanmar: 12 years cohort analysis. Glob Health Action. 2018;11(1):1510593. doi: 10.1080/16549716.2018.1510593. — View Citation

Misumi J, Gardes J, Gonzalez MF, Corvol P, Menard J. Angiotensinogen's role in ANG formation, renin release, and renal hemodynamics in isolated perfused kidney. Am J Physiol. 1989 Apr;256(4 Pt 2):F719-27. — View Citation

Moon HW, Huh HJ, Oh GY, Lee SG, Lee A, Yun YM, Hur M. Evaluation of the Bio-Rad Geenius HIV 1/2 Confirmation Assay as an Alternative to Western Blot in the Korean Population: A Multi-Center Study. PLoS One. 2015 Sep 30;10(9):e0139169. doi: 10.1371/journal.pone.0139169. eCollection 2015. — View Citation

O'Connor J, Vjecha MJ, Phillips AN, Angus B, Cooper D, Grinsztejn B, Lopardo G, Das S, Wood R, Wilkin A, Klinker H, Kantipong P, Klingman KL, Jilich D, Herieka E, Denning E, Abubakar I, Gordin F, Lundgren JD; INSIGHT START study group. Effect of immediate initiation of antiretroviral therapy on risk of severe bacterial infections in HIV-positive people with CD4 cell counts of more than 500 cells per µL: secondary outcome results from a randomised controlled trial. Lancet HIV. 2017 Mar;4(3):e105-e112. doi: 10.1016/S2352-3018(16)30216-8. Epub 2017 Jan 5. — View Citation

Pilcher CD, Ospina-Norvell C, Dasgupta A, Jones D, Hartogensis W, Torres S, Calderon F, Demicco E, Geng E, Gandhi M, Havlir DV, Hatano H. The Effect of Same-Day Observed Initiation of Antiretroviral Therapy on HIV Viral Load and Treatment Outcomes in a US Public Health Setting. J Acquir Immune Defic Syndr. 2017 Jan 1;74(1):44-51. — View Citation

Rodger AJ, Cambiano V, Bruun T, Vernazza P, Collins S, Degen O, Corbelli GM, Estrada V, Geretti AM, Beloukas A, Raben D, Coll P, Antinori A, Nwokolo N, Rieger A, Prins JM, Blaxhult A, Weber R, Van Eeden A, Brockmeyer NH, Clarke A, Del Romero Guerrero J, Raffi F, Bogner JR, Wandeler G, Gerstoft J, Gutiérrez F, Brinkman K, Kitchen M, Ostergaard L, Leon A, Ristola M, Jessen H, Stellbrink HJ, Phillips AN, Lundgren J; PARTNER Study Group. Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study. Lancet. 2019 Jun 15;393(10189):2428-2438. doi: 10.1016/S0140-6736(19)30418-0. Epub 2019 May 2. — View Citation

Rosen S, Fox MP. Retention in HIV care between testing and treatment in sub-Saharan Africa: a systematic review. PLoS Med. 2011 Jul;8(7):e1001056. doi: 10.1371/journal.pmed.1001056. Epub 2011 Jul 19. Review. — View Citation

Rosen S, Maskew M, Fox MP, Nyoni C, Mongwenyana C, Malete G, Sanne I, Bokaba D, Sauls C, Rohr J, Long L. Initiating Antiretroviral Therapy for HIV at a Patient's First Clinic Visit: The RapIT Randomized Controlled Trial. PLoS Med. 2016 May 10;13(5):e1002015. doi: 10.1371/journal.pmed.1002015. eCollection 2016 May. Erratum in: PLoS Med. 2016 Jun;13(6):e1002050. — View Citation

Stevens WS, Gous NM, MacLeod WB, Long LC, Variava E, Martinson NA, Sanne I, Osih R, Scott LE. Multidisciplinary Point-of-Care Testing in South African Primary Health Care Clinics Accelerates HIV ART Initiation but Does Not Alter Retention in Care. J Acqui — View Citation

TEMPRANO ANRS 12136 Study Group, Danel C, Moh R, Gabillard D, Badje A, Le Carrou J, Ouassa T, Ouattara E, Anzian A, Ntakpé JB, Minga A, Kouame GM, Bouhoussou F, Emieme A, Kouamé A, Inwoley A, Toni TD, Ahiboh H, Kabran M, Rabe C, Sidibé B, Nzunetu G, Konan R, Gnokoro J, Gouesse P, Messou E, Dohoun L, Kamagate S, Yao A, Amon S, Kouame AB, Koua A, Kouamé E, Ndri Y, Ba-Gomis O, Daligou M, Ackoundzé S, Hawerlander D, Ani A, Dembélé F, Koné F, Guéhi C, Kanga C, Koule S, Séri J, Oyebi M, Mbakop N, Makaila O, Babatunde C, Babatounde N, Bleoué G, Tchoutedjem M, Kouadio AC, Sena G, Yededji SY, Assi R, Bakayoko A, Mahassadi A, Attia A, Oussou A, Mobio M, Bamba D, Koman M, Horo A, Deschamps N, Chenal H, Sassan-Morokro M, Konate S, Aka K, Aoussi E, Journot V, Nchot C, Karcher S, Chaix ML, Rouzioux C, Sow PS, Perronne C, Girard PM, Menan H, Bissagnene E, Kadio A, Ettiegne-Traore V, Moh-Semdé C, Kouame A, Massumbuko JM, Chêne G, Dosso M, Domoua SK, N'Dri-Yoman T, Salamon R, Eholié SP, Anglaret X. A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa. N Engl J Med. 2015 Aug 27;373(9):808-22. doi: 10.1056/NEJMoa1507198. Epub 2015 Jul 20. — View Citation

Tinguely C, Schild-Spycher T, Bahador Z, Gowland P, Stolz M, Niederhauser C. Comparison of a conventional HIV 1/2 line immunoassay with a rapid confirmatory HIV 1/2 assay. J Virol Methods. 2014 Sep;206:1-4. doi: 10.1016/j.jviromet.2014.05.010. Epub 2014 May 27. — View Citation

Wohl D, Clarke A, Maggiolo F, Garner W, Laouri M, Martin H, Quirk E. Patient-Reported Symptoms Over 48 Weeks Among Participants in Randomized, Double-Blind, Phase III Non-inferiority Trials of Adults with HIV on Co-formulated Bictegravir, Emtricitabine, a — View Citation

* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Retention in care at Week 48	The proportion of patients who returned for the scheduled clinic visit at week 48	week 48 ± 4wk
Primary	Viral suppression at Week 48	The proportion of viral suppression (<50 copies/ml) at week 48	week 48 ± 4wk
Secondary	Acceptability of same-day initiation	The rate of same-day initiation of ART among patients who receive a confirmed diagnosis of HIV infection	Day 1
Secondary	Viral suppression at Week 1, 4, 48	The proportion of viral suppression (<200 copies/ml) at Week 1, 4, 48	Week 1 ± 3 days, Week 4± 1 week, Week 48± 4 week
Secondary	Adverse effect at Week 4 and 48	Any/severe adverse effect of B/F/TAF before Weeks 4 and 48	Week 4± 1 week, Week 48± 4 week
Secondary	Patient's satisfaction at Weeks 1, 4, and 48	Patient's satisfaction with HIV Treatment Satisfaction Questionnaire at Weeks 1, 4, and 48	Week 1 ± 3 days, Week 4± 1 week, Week 48± 4 week