Xpert Ultra and Xpert HIV-VL in People Living With HIV

NCT03187964 | Completed

• 1 other identifier: N14/10/136
• Study Type: interventional
• Target: 1,053
• Locations: 1 country
• Sites: 1

Brief Summary

TB is increasingly diagnosed using the GeneXpert platform, which can be used for a variety of tests (not just TB). HIV viral load monitoring is required at least annually in patients on ART to detect failure of virologic suppression, however, most HIV VL testing is done centrally. A patient with virologic failure is more likely to get TB. The investigators wish to see if Xpert done at the clinic results in faster patient TB diagnosis and treatment initiation compared to sending specimens away for central testing. In a different patient group (PLHIV returning for HIV treatment monitoring), the investigators wish to see if POC Xpert HIV-1 viral load (Xpert VL) testing results in faster patient viral load quantification compared to centralised testing. Both POC tests will use the same testing hardware. This polyvalent utility of the GeneXpert system is hitherto uninvestigated in this local setting. Newly diagnosed pre-ART HIV positive patients will be approached and asked to be a part of this study. Patients will be randomly assigned to Ultra done at the clinic or the normal off-site laboratory TB testing. The time taken for patients to get diagnosed and time-to-treatment will be recorded. We will also do exploratory diagnostic accuracy evaluations including but not limited to, Ultra when done on mouth samples, the new SILVAMP FujiLAM on urine, and host RNA blood signatures for active TB. Additionally, a different group of HIV positive patients (on ART) returning to the clinic for annual follow-up visits will also be asked to join the study. These patients will be randomly selected for either Xpert VL testing done at the clinic or the normal off-site testing. The time taken for patients to receive viral load results will be recorded. Should the patient's viral loads be found to be higher than anticipated and considered by the clinical to indicate a lack of viral suppression, the time taken for patients to have ART regimen adjusted, receive adherence counselling or received HIV drug susceptibility testing will be recorded. This project will confirm if Ultra TB testing performs well in PLHIV irrespective of symptoms and may produce evidence that supports universal TB testing in this important and vulnerable patient group, including using novel diagnostics on non-traditional specimen types. The investigators will also assess whether POC placement of Ultra and Xpert VL has benefits (e.g., more patients diagnosed for TB or VL monitored during the same day visit).

Conditions

HIV/AIDS; TB - Tuberculosis; Antiretroviral Therapy, Highly Active

Keywords

People Living with HIV (PLHIV); Xpert HIV-1 Viral Load (Xpert VL); Xpert Ultra; Antiretroviral treatment (ART)

Outcome Measures

Primary Outcomes (1)

• Treatment time

  Time-specific proportion of patients starting TB treatment (all patients and confirmed cases) in centralised diagnosis and treatment arm compared to POC arm (Xpert Ultra).

  Up to 8 weeks

Secondary Outcomes (7)

• TB diagnosis time

  Up to 8 weeks

• Urine LF-LAM, urine FujiLAM and urine Xpert Ultra in people investigated for TB

  Up to one week

• Tongue swab and oral wash Xpert Ultra, tongue swab in-house PCR, and tongue swab culture in people investigated for TB

  Up to one week

• Candidate host RNA blood signatures for active TB specified in Turner LRM et al., 2020 in people investigated for TB

  Up to one week

• HIV DST or adherence counselling

  Up to one week

Study Arms (4)

PLHIV Centralised Xpert Ultra

NO INTERVENTION

Patient sputum specimen collected at Kraaifontein Community Health Centre (KCHC) and sent for centralised Xpert Ultra TB testing at the National Health Laboratory Services (NHLS) facility in Greenpoint, Cape Town, South Africa. Centralised testing uses the established NHLS transportation, testing and report-back to clinic infrastructure according to the national algorithm.

PLHIV Point of Care Xpert Ultra

ACTIVE COMPARATOR

Patient sputum specimen collected at KCHC and Xpert Ultra TB testing done on site at point of care (POC).

Diagnostic Test: PLHIV Point of Care Xpert Ultra

PLHIV Centralised Xpert VL

NO INTERVENTION

Patient blood specimen collected at Kraaifontein Community Health Centre (KCHC) and sent for centralised viral load testing at the NHLS facility in Tygerberg Hospital, Cape Town, South Africa. Centralised testing uses the established NHLS transportation, testing and report-back to clinic infrastructure according to the national algorithm.

PLHIV Point of Care Xpert VL

ACTIVE COMPARATOR

Patient blood specimen collected at KCHC and Xpert HIV-1 viral load testing done on site at point of care (POC).

Diagnostic Test: PLHIV Point of Care Xpert VL

Interventions

PLHIV Point of Care Xpert Ultra DIAGNOSTIC_TEST

Sputum-based TB diagnostic test that takes 80 min to run. Test performed on the same day as the patient visit.

Also known as: GeneXpert

PLHIV Point of Care Xpert Ultra

PLHIV Point of Care Xpert VL DIAGNOSTIC_TEST

Blood-based HIV-1 VL diagnostic and monitoring test that takes 60 min to run. Test performed on the same day as the patient visit.

Also known as: GeneXpert

PLHIV Point of Care Xpert VL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent obtained from patient
• Patient is more than 18 years old
• Patient is HIV positive
• Patient is receiving follow-up ART
• Patient is willing to provide blood specimens for study

You may not qualify if:

• Informed consent not obtained from patient
• Patient is less than 18 years old
• Patient is HIV negative or has unknown HIV status
• Patient is coming into clinic for first time ART
• Patient is not willing to provide blood specimens for study
• TB patients
• Informed consent obtained from patient
• Patient is more than 18 years old
• Patient is HIV positive
• Patient is coming into clinic for first ART visit
• Patient is willing to provide sputum and urine (blood is desirable, but not mandatory) specimens for study
• Informed consent not obtained from patient
• Patient is less than 18 years old
• Patient is HIV negative or has unknown HIV status
• Patient is not coming into clinic for first time ART

Sponsors & Collaborators

• University of Stellenbosch: lead

Study Sites (1)

Kraaifontein Community Health Centre

Cape Town, Western Cape, 7570, South Africa

Location

Related Publications (7)

• Hanrahan CF, Clouse K, Bassett J, Mutunga L, Selibas K, Stevens W, Scott L, Sanne I, Van Rie A. The patient impact of point-of-care vs. laboratory placement of Xpert((R)) MTB/RIF. Int J Tuberc Lung Dis. 2015 Jul;19(7):811-6. doi: 10.5588/ijtld.15.0013.

  PMID: 26056107 BACKGROUND

• Lawn SD, Brooks SV, Kranzer K, Nicol MP, Whitelaw A, Vogt M, Bekker LG, Wood R. Screening for HIV-associated tuberculosis and rifampicin resistance before antiretroviral therapy using the Xpert MTB/RIF assay: a prospective study. PLoS Med. 2011 Jul;8(7):e1001067. doi: 10.1371/journal.pmed.1001067. Epub 2011 Jul 26.

  PMID: 21818180 BACKGROUND

• Clouse K, Page-Shipp L, Dansey H, Moatlhodi B, Scott L, Bassett J, Stevens W, Sanne I, Van Rie A. Implementation of Xpert MTB/RIF for routine point-of-care diagnosis of tuberculosis at the primary care level. S Afr Med J. 2012 Sep 7;102(10):805-7. doi: 10.7196/samj.5851.

  PMID: 23034211 BACKGROUND

• Luabeya AK, Wood RC, Shenje J, Filander E, Ontong C, Mabwe S, Africa H, Nguyen FK, Olson A, Weigel KM, Jones-Engel L, Hatherill M, Cangelosi GA. Noninvasive Detection of Tuberculosis by Oral Swab Analysis. J Clin Microbiol. 2019 Feb 27;57(3):e01847-18. doi: 10.1128/JCM.01847-18. Print 2019 Mar.

  PMID: 30541931 BACKGROUND

• Broger T, Sossen B, du Toit E, Kerkhoff AD, Schutz C, Ivanova Reipold E, Ward A, Barr DA, Mace A, Trollip A, Burton R, Ongarello S, Pinter A, Lowary TL, Boehme C, Nicol MP, Meintjes G, Denkinger CM. Novel lipoarabinomannan point-of-care tuberculosis test for people with HIV: a diagnostic accuracy study. Lancet Infect Dis. 2019 Aug;19(8):852-861. doi: 10.1016/S1473-3099(19)30001-5. Epub 2019 May 30.

  PMID: 31155318 BACKGROUND

• Turner CT, Gupta RK, Tsaliki E, Roe JK, Mondal P, Nyawo GR, Palmer Z, Miller RF, Reeve BW, Theron G, Noursadeghi M. Blood transcriptional biomarkers for active pulmonary tuberculosis in a high-burden setting: a prospective, observational, diagnostic accuracy study. Lancet Respir Med. 2020 Apr;8(4):407-419. doi: 10.1016/S2213-2600(19)30469-2. Epub 2020 Mar 13.

  PMID: 32178775 BACKGROUND

• Zifodya JS, Kreniske JS, Schiller I, Kohli M, Dendukuri N, Schumacher SG, Ochodo EA, Haraka F, Zwerling AA, Pai M, Steingart KR, Horne DJ. Xpert Ultra versus Xpert MTB/RIF for pulmonary tuberculosis and rifampicin resistance in adults with presumptive pulmonary tuberculosis. Cochrane Database Syst Rev. 2021 Feb 22;2(2):CD009593. doi: 10.1002/14651858.CD009593.pub5.

  PMID: 33616229 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Latent Tuberculosis

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Latent Infection

Study Officials

• Grant Theron, PhD

  University of Stellenbosch

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 12, 2017
• First Posted: June 15, 2017
• Study Start: February 5, 2018
• Primary Completion: January 16, 2022
• Study Completion: April 4, 2022
• Last Updated: April 5, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: The data will be available once the findings are published.
• Access Criteria: Data access will be granted to interested collaborators and parties through sharing of data files or login information for the study's secure RedCap electronic database during the course of patient recruitment.

Locations

ZA (1)