HivNCT06044792
The Influence of Primary HIV-1 Drug Resistance Mutations on Immune Reconstruction in PLWH
An observational study of Hiv and AIDS, run by Medical University of Warsaw.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Hiv, AIDS, CD4 Deficiency
- What is being tested?
- differences in CD4 reconstruction
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 30 Sep 2023to 1 Jan 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- hematologic neoplasms
- use of chemotherapy, immunosuppressive drugs and other myelotoxic agents
- lack of patient's consent to participate in the study
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: 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.
Read the 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.
- Conditions
- Hiv, AIDS, CD4 Deficiency, ART, Treatment Resistant Disorders, Treatment-Sensitive HIV Infection
- Being tested
- differences in CD4 reconstruction
- Keywords
- HIV, CD4, DRM, drug resistance, immune reconstruction
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
differences in CD4 reconstructionOther
Differences in the increase in CD4 lymphocyte count and CD4:CD8 ratio between patients with primary drug resistance mutations and those without these mutations.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Other: differences in CD4 reconstruction | |
| 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). Receives: Other: differences in CD4 reconstruction |
What is being measured
The primary outcome is the main question the study is designed to answer.
Differences in CD4 recovery regarding the presence of HIV DRM
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.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2023
- Study start30 Sep 2023 (estimated)
- Primary completion30 Sep 2027 (estimated)
- Study completion1 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for HivStudies of the same condition, open and under way.
- More trials run by Medical University of WarsawThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Warsaw
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06044792
- Sponsor's protocol ID
- HIV DRM - CD4 reconstruction
- Status last verified
- Sep 2023
- First submitted
- 3 Sep 2023
- Last updated
- 21 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Data will be available on demand to the editors.
Publications
Shenoy N, Ramapuram JT, Shenoy A, Ahmed J, Srikant N. Incidence of Opportunistic Infections among HIV-Positive Adults on Highly Active Antiretroviral Therapy in a Teaching Hospital, India: Prospective Study. J Int Assoc Provid AIDS Care. 2017 May/Jun;16(3):309-311. doi: 10.1177/2325957416686192. Epub 2017 Jan 4.
PubMed 28050923Gaines H, von Sydow MA, von Stedingk LV, Biberfeld G, Bottiger B, Hansson LO, Lundbergh P, Sonnerborg AB, Wasserman J, Strannegaard OO. Immunological changes in primary HIV-1 infection. AIDS. 1990 Oct;4(10):995-9. doi: 10.1097/00002030-199010000-00008.
PubMed 2261128Sobrino-Vegas P, Moreno S, Rubio R, Viciana P, Bernardino JI, Blanco JR, Bernal E, Asensi V, Pulido F, del Amo J, Hernando V; Cohorte de la Red de Investigacion en Sida, Spain. Impact of late presentation of HIV infection on short-, mid- and long-term mortality and causes of death in a multicenter national cohort: 2004-2013. J Infect. 2016 May;72(5):587-96. doi: 10.1016/j.jinf.2016.01.017. Epub 2016 Feb 24.
PubMed 26920789Gazzola L, Tincati C, Bellistri GM, Monforte Ad, Marchetti G. The absence of CD4+ T cell count recovery despite receipt of virologically suppressive highly active antiretroviral therapy: clinical risk, immunological gaps, and therapeutic options. Clin Infect Dis. 2009 Feb 1;48(3):328-37. doi: 10.1086/595851.
PubMed 19123868Yang X, Su B, Zhang X, Liu Y, Wu H, Zhang T. Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders. J Leukoc Biol. 2020 Apr;107(4):597-612. doi: 10.1002/JLB.4MR1019-189R. Epub 2020 Jan 22.
PubMed 31965635Rhee SY, Kassaye SG, Barrow G, Sundaramurthi JC, Jordan MR, Shafer RW. HIV-1 transmitted drug resistance surveillance: shifting trends in study design and prevalence estimates. J Int AIDS Soc. 2020 Sep;23(9):e25611. doi: 10.1002/jia2.25611.
PubMed 32936523Bokharaei-Salim F, Esghaei M, Khanaliha K, Kalantari S, Marjani A, Fakhim A, Keyvani H. HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. PLoS One. 2020 Mar 2;15(3):e0229275. doi: 10.1371/journal.pone.0229275. eCollection 2020.
PubMed 32119691Grant RM, Hecht FM, Warmerdam M, Liu L, Liegler T, Petropoulos CJ, Hellmann NS, Chesney M, Busch MP, Kahn JO. Time trends in primary HIV-1 drug resistance among recently infected persons. JAMA. 2002 Jul 10;288(2):181-8. doi: 10.1001/jama.288.2.181.
PubMed 12095382Wensing AM, Calvez V, Ceccherini-Silberstein F, Charpentier C, Gunthard HF, Paredes R, Shafer RW, Richman DD. 2019 update of the drug resistance mutations in HIV-1. Top Antivir Med. 2019 Sep;27(3):111-121.
PubMed 31634862
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Influence of Primary HIV-1 Drug Resistance Mutations on Immune Reconstruction in Patients Treated With Antiretroviral Drugs - an Observational Cohort Study.
- ClinicalTrials.gov ID
- NCT06044792
- Acronym / sponsor ID
- HIV DRM - CD4 reconstruction
- Conditions
- Hiv, AIDS, CD4 Deficiency, ART, Treatment Resistant Disorders, Treatment-Sensitive HIV Infection
- Keywords
- HIV, CD4, DRM, drug resistance, immune reconstruction
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Medical University of WarsawUniversity, hospital or other
- Study start
- 30 Sep 2023 (estimated)
- Primary completion
- 30 Sep 2027 (estimated)
- Study completion
- 1 Jan 2028 (estimated)
- First posted
- 21 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DRM negative | – | Other: differences in CD4 reconstructionThe 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). |
| DRM positive | – | Other: differences in CD4 reconstructionThe 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). |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (3 listed)
- hematologic neoplasms
- use of chemotherapy, immunosuppressive drugs and other myelotoxic agents
- lack of patient's consent to participate in the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| differences in CD4 reconstructionDifferences in the increase in CD4 lymphocyte count and CD4:CD8 ratio between patients with primary drug resistance mutations and those without these mutations. | Other | DRM negative, DRM positive |
Primary outcome
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2023.
- Background: PubMed 28050923Shenoy N, Ramapuram JT, Shenoy A, Ahmed J, Srikant N. Incidence of Opportunistic Infections among HIV-Positive Adults on Highly Active Antiretroviral Therapy in a Teaching Hospital, India: Prospective Study. J Int Assoc Provid AIDS Care. 2017 May/Jun;16(3):309-311. doi: 10.1177/2325957416686192. Epub 2017 Jan 4.
- Background: PubMed 2261128Gaines H, von Sydow MA, von Stedingk LV, Biberfeld G, Bottiger B, Hansson LO, Lundbergh P, Sonnerborg AB, Wasserman J, Strannegaard OO. Immunological changes in primary HIV-1 infection. AIDS. 1990 Oct;4(10):995-9. doi: 10.1097/00002030-199010000-00008.
- Background: PubMed 26920789Sobrino-Vegas P, Moreno S, Rubio R, Viciana P, Bernardino JI, Blanco JR, Bernal E, Asensi V, Pulido F, del Amo J, Hernando V; Cohorte de la Red de Investigacion en Sida, Spain. Impact of late presentation of HIV infection on short-, mid- and long-term mortality and causes of death in a multicenter national cohort: 2004-2013. J Infect. 2016 May;72(5):587-96. doi: 10.1016/j.jinf.2016.01.017. Epub 2016 Feb 24.
- Background: PubMed 19123868Gazzola L, Tincati C, Bellistri GM, Monforte Ad, Marchetti G. The absence of CD4+ T cell count recovery despite receipt of virologically suppressive highly active antiretroviral therapy: clinical risk, immunological gaps, and therapeutic options. Clin Infect Dis. 2009 Feb 1;48(3):328-37. doi: 10.1086/595851.
- Background: PubMed 31965635Yang X, Su B, Zhang X, Liu Y, Wu H, Zhang T. Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders. J Leukoc Biol. 2020 Apr;107(4):597-612. doi: 10.1002/JLB.4MR1019-189R. Epub 2020 Jan 22.
- Background: PubMed 32936523Rhee SY, Kassaye SG, Barrow G, Sundaramurthi JC, Jordan MR, Shafer RW. HIV-1 transmitted drug resistance surveillance: shifting trends in study design and prevalence estimates. J Int AIDS Soc. 2020 Sep;23(9):e25611. doi: 10.1002/jia2.25611.
- Background: PubMed 32119691Bokharaei-Salim F, Esghaei M, Khanaliha K, Kalantari S, Marjani A, Fakhim A, Keyvani H. HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. PLoS One. 2020 Mar 2;15(3):e0229275. doi: 10.1371/journal.pone.0229275. eCollection 2020.
- Background: PubMed 12095382Grant RM, Hecht FM, Warmerdam M, Liu L, Liegler T, Petropoulos CJ, Hellmann NS, Chesney M, Busch MP, Kahn JO. Time trends in primary HIV-1 drug resistance among recently infected persons. JAMA. 2002 Jul 10;288(2):181-8. doi: 10.1001/jama.288.2.181.
- Background: PubMed 31634862Wensing AM, Calvez V, Ceccherini-Silberstein F, Charpentier C, Gunthard HF, Paredes R, Shafer RW, Richman DD. 2019 update of the drug resistance mutations in HIV-1. Top Antivir Med. 2019 Sep;27(3):111-121.
- Individual participant dataSharing planned: No. Data will be available on demand to the editors.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
An observational study of Hiv and AIDS, run by Medical University of Warsaw.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 21 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Andrzej Załęski, PhD (+48600982185, andrzejzaleski84@wp.pl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differences in CD4 recovery regarding the presence of HIV DRM (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06044792, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2023.