Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Xpert Ultra and Xpert HIV-VL in People Living With HIV (UltraHIV)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03187964
Recruitment Status : Recruiting
First Posted : June 15, 2017
Last Update Posted : February 7, 2018
Sponsor:
Information provided by (Responsible Party):
Grant Theron, University of Stellenbosch

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 in a central lab. If a patient has virologic failure, these patients are 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 to a central laboratory. 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) monitoring results in faster patient viral load quantification compared to sending patient specimens to a centralised laboratory. 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 how long it takes to start treatment will be recorded. 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 laboratory VL testing. The time taken for patients to receive viral load results will be recorded. The time taken for patients to have ART regimen adjusted, receive adherence counselling or received HIV drug susceptibility testing 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.

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. 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).


Condition or disease Intervention/treatment Phase
HIV/AIDS TB - Tuberculosis Antiretroviral Therapy, Highly Active Diagnostic Test: PLHIV Point of Care Xpert Ultra Diagnostic Test: PLHIV Point of Care Xpert VL Not Applicable

Detailed Description:

Sensitive and rapid point-of-care diagnostics should reduce improve TB treatment outcomes however, tests meeting these criteria have, until recently, been unavailable, especially in PLHIV. PLHIV often have early stage TB disease at the time of ART initiation and paucibacillary sputum. The current frontline test for TB is the Xpert MTB/RIF, which uses the GeneXpert platform, and is deployed primarily at centralised reference laboratories (Clouse et al., 2012; Hanrahan et al., 2015). This approach has two major limitations: 1) the instruments' far-patient placement likely undermines its potential clinical impact; 2) Xpert MTB/RIF has suboptimal sensitivity in PLHIV 3) the GeneXpert platform is primarily used only for TB testing and no other assays such as Xpert HIV-1 Viral Load (VL).

Xpert MTB/RIF will shortly be succeeded by Xpert MTB/RIF Ultra (Xpert Ultra), which promises to increase the speed and sensitivity of TB diagnosis. Although Xpert Ultra will doubtlessly improve the detection of symptomatic patients, its greatest incremental benefit will likely arise in patients with low bacillary load (e.g., unselected HIV-positive patients initiating ART). Thus, Xpert Ultra has the potential to alter how TB is diagnosed in PLHIV by detecting TB before the disease has a chance to progress and before substantial transmission has occurred. The investigators will, in addition to Xpert Ultra on sputum, also perform TB testing using the urinary lateral flow (LF) LAM test, which may detect mycobacteria in asymptomatic PLHIV patients (Lawn et al., 2011). The use of Ultra on urine from PLHIV as part of preliminary investigation will also be explored.

The polyvalent utility of the GeneXpert hardware platform is, however, hitherto largely unexplored despite the widespread deployment of machines. HIV VL testing is currently done in South Africa according to the National HIV Treatment guidelines, which advise measuring HIV VL every six months for the first year of treatment and annually thereafter. HIV VL testing involves collection of a blood sample, transporting it to a centralised laboratory for VL quantification, reporting the result back to the clinic, and calling the patient back. If HIV VL is found to be over 1000 genomes per ml, the patient may not be adherent to the prescribed ART or may have drug-resistant HIV and, now that a failure of virologic suppression has been confirmed, the patient may be asked to give a second blood sample for drug susceptibility testing and may have a counselling visit scheduled, in order to improve the patient's adherence. There is, however, a large amount of discretion at local clinics as to what constitutes virologic failure and patients with increased VL may still receive these interventions, even if below the 1000 genomes per ml threshold. The investigators also intend to perform Xpert HIV-1 VL testing and, compared to patients who receive the standard-of-care of centralised VL testing, evaluate the proportion of patients without virologic suppression who are referred to a follow-up intervention (DST and/or adherence counselling).

The investigators propose a study which implements Xpert Ultra (in unselected PLHIV) and Xpert HIV-1 VL (in PLHIV on ART) in Cape Town, South Africa. Furthermore, the GeneXpert platform's polyvalent feasibility, time-to-result and -treatment (Xpert Ultra and LF LAM), and effect on interventions to improve VL (Xpert HIV-1 VL) will be examined.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Diagnostic
Official Title: Feasibility, Accuracy, and Effect of Polyvalent Point-of-care Xpert MTB/RIF Ultra and Xpert HIV-1 Viral Load Testing in HIV-positive Patients Initiating ART: a Randomised Controlled Trial
Actual Study Start Date : February 5, 2018
Estimated Primary Completion Date : October 31, 2019
Estimated Study Completion Date : March 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
No Intervention: PLHIV Centralised Xpert Ultra
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.
Active Comparator: PLHIV Point of Care Xpert Ultra
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
Sputum-based TB diagnostic test that takes 80 min to run. Test performed on the same day as the patient visit.
Other Name: GeneXpert

No Intervention: PLHIV Centralised Xpert VL
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.
Active Comparator: PLHIV Point of Care Xpert VL
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
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.
Other Name: GeneXpert




Primary Outcome Measures :
  1. Treatment time [ Time Frame: Up to 8 weeks ]
    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).


Secondary Outcome Measures :
  1. TB diagnosis time [ Time Frame: Up to 8 weeks ]
    Time-specific proportion of patients diagnosed in centralised diagnosis and treatment arm compared to POC arm (Xpert Ultra for TB and XpertVL for VL)

  2. LAM and Xpert Ultra Urine [ Time Frame: Up to one week ]
    Proportion of patients who are LF-LAM and Xpert Ultra urine positive

  3. HIV DST or adherence counselling [ Time Frame: Up to one week ]
    Time-specific proportion of patients without virologic suppression identified to require adherence counselling and/or HIV drug susceptibility testing

  4. Time to referral for HIV regimen adjustment or adherence counselling in patients without virologic suppression [ Time Frame: Up to 8 weeks ]
    Time-specific proportion of patients without virologic suppression referred for adherence counselling and/or switching to a second-line ART regimen

  5. Initial lost to follow-up [ Time Frame: Up to 12 weeks ]
    Time-specific proportion of patients with a known TB diagnosis or increase in HIV VL that do not successfully start treatment (TB) or HIV adherence counselling, DST or regimen change (VL)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

HIV-positive viral load monitoring patients

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Patient has been on TB treatment within the last 60 days
  • Patient is not willing to provide sputum and urine specimens for study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03187964


Contacts
Layout table for location contacts
Contact: Grant Theron, PhD (+27) 021 938 9693 ext 9693 gtheron@sun.ac.za

Locations
Layout table for location information
South Africa
Kraaifontein Community Health Centre Recruiting
Cape Town, Western Cape, South Africa, 7570
Contact: Grant Theron, PhD    (+27) 21 938 9693 ext 9693    gtheron@sun.ac.za   
Contact: Byron WP Reeve, PhD    (+27) 21 938 9954 ext 9954    byronreeve@sun.ac.za   
Sponsors and Collaborators
University of Stellenbosch
Investigators
Layout table for investigator information
Principal Investigator: Grant Theron, PhD University of Stellenbosch

Publications:
Layout table for additonal information
Responsible Party: Grant Theron, Associate Professor, University of Stellenbosch
ClinicalTrials.gov Identifier: NCT03187964     History of Changes
Other Study ID Numbers: N14/10/136
First Posted: June 15, 2017    Key Record Dates
Last Update Posted: February 7, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Collaborators will have access to de-identified IPD data. Other researchers wishing to access the data will be required to sign a data sharing agreement as per institutional policies.
Supporting Materials: Study Protocol
Informed Consent Form (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.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Grant Theron, University of Stellenbosch:
People Living with HIV (PLHIV)
Xpert HIV-1 Viral Load (Xpert VL)
Xpert Ultra
Antiretroviral treatment (ART)
Additional relevant MeSH terms:
Layout table for MeSH terms
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections