The Influence of Primary HIV-1 Drug Resistance Mutations on Immune Reconstruction in PLWH

September 17, 2023 updated by: Medical University of Warsaw

The Influence of Primary HIV-1 Drug Resistance Mutations on Immune Reconstruction in Patients Treated With Antiretroviral Drugs - an Observational Cohort Study.

Since the reasons for differential immune reconstitution in HIV-infected patients are still not fully understood, we considered it reasonable to investigate whether the presence of primary HIV drug resistance mutations could be one of the factors of inadequate immune reconstitution.

Evaluation of unfavorable factors of immune reconstitution can help identify patients at risk of persistently low CD4 cell counts and CD4:CD8 ratios and requiring careful monitoring for progression to AIDS.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Untreated HIV infection leads to progressive and permanent impairment of the immune system, and the successive loss of peripheral blood CD4+ T lymphocytes results in progression to AIDS. Effective antiretroviral therapy (ART) can prevent the decline and even cause the restore of the normal level of CD4+ cells.

CD4+ count ≥ 500 cells/µl and CD4:CD8 ratio ≥ 1 are considered normal, while patients with persistently lower CD4+ and CD4:CD8 ratios despite ART treatment are defined as having an inadequate immune response, which may result in an increased risk progression to AIDS, and thus higher mortality rates. Clinical risk factors for impaired CD4+ regeneration have not been fully established, however, older age, male gender, low CD4+ cell count and low CD4:CD8 ratio at diagnosis are associated with a poorer immune response to ART.

As well, HIV drug resistance also plays an important role in the process of immune reconstruction. Despite the very good results of ART, the emergence of drug-resistant mutations in the HIV virus, which may lead to treatment failure, is a cause for concern. The prevalence of HIV-1 drug resistance mutations reported worldwide ranges from 5% to 25%. Primary drug resistance of HIV occurs in people who have not previously been treated with ART. These people start ART treatment with a lower genetic barrier, a higher risk of virological failure and a higher risk of developing resistance to other drugs, which may lead to insufficient immune reconstruction and progression to AIDS.

Study Type

Observational

Enrollment (Estimated)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

Sampling Method

Non-Probability Sample

Study Population

Patients who will meet the inclusion and not the exclusion criteria will be divided into the 2 groups: with and without DRMs, depending on the results of HIV genotyping. In cohorts subsequent CD4 count and CD4/CD8 ratio will be assessed every 6-12 months in the 4 -year period. Differences in the increase in CD4+ lymphocyte count and CD4:CD8 ratio between patients with primary drug resistance mutations and those without these mutations were taken as the endpoint.

Description

Inclusion Criteria:

  • HIV-1 confirmed infection
  • ART naive patients > 18 years
  • virological suppression after 6 months of ART
  • available results of HIV genotyping before the start of ART

Exclusion Criteria:

  • hematologic neoplasms
  • use of chemotherapy, immunosuppressive drugs and other myelotoxic agents
  • lack of patient's consent to participate in the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
DRM negative

The cohort of patients, who will meet inclusion criteria, with HIV infections and no drug resistance mutations detected.

Epidemiological (age, sex, origin, sexual preferences) and clinical data (HIV viral load, CD4+ cell count, presence of AIDS-defining diseases, co-infection with HBV and HCV) will be collected at the time of diagnosis.

Subsequent controls of HIV viral load, level of CD4 and CD4/CD8 ratio will be carried out in accordance with the standard of care for an HIV-infected patient (usually every 6-12 months).
Other: differences in CD4 reconstruction
Differences in the increase in CD4 lymphocyte count and CD4:CD8 ratio between patients with primary drug resistance mutations and those without these mutations.
DRM positive

The cohort of patients, who will meet inclusion criteria, with HIV infections and detected primary drug resistance mutations.

Epidemiological (age, sex, origin, sexual preferences) and clinical data (HIV viral load, CD4+ cell count, presence of AIDS-defining diseases, co-infection with HBV and HCV) will be collected at the time of diagnosis.

Subsequent controls of HIV viral load, level of CD4 and CD4/CD8 ratio will be carried out in accordance with the standard of care for an HIV-infected patient (usually every 6-12 months).
Other: differences in CD4 reconstruction
Differences in the increase in CD4 lymphocyte count and CD4:CD8 ratio between patients with primary drug resistance mutations and those without these mutations.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Differences in CD4 recovery regarding the presence of HIV DRM
Time Frame: 4 years
Differences in the increase in CD4+ lymphocyte (cells/µL) count and CD4:CD8 ratio between patients with primary drug resistance mutations and those without these mutations were taken as the endpoint.
4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of Warsaw

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 30, 2023

Primary Completion (Estimated)

September 30, 2027

Study Completion (Estimated)

January 1, 2028

Study Registration Dates

First Submitted

September 3, 2023

First Submitted That Met QC Criteria

September 17, 2023

First Posted (Actual)

September 21, 2023

Study Record Updates

Last Update Posted (Actual)

September 21, 2023

Last Update Submitted That Met QC Criteria

September 17, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • HIV DRM - CD4 reconstruction

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Data will be available on demand to the editors.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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