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

NCT ID: NCT06044792

Last Updated: 2023-09-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Total Enrollment

50 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-09-30

Study Completion Date

2028-01-01

Brief Summary

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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

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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

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Hiv AIDS CD4 Deficiency ART Treatment Resistant Disorders Treatment-Sensitive HIV Infection

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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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).

differences in CD4 reconstruction

Intervention Type OTHER

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).

differences in CD4 reconstruction

Intervention Type OTHER

Differences in the increase in CD4 lymphocyte count and CD4:CD8 ratio between patients with primary drug resistance mutations and those without these mutations.

Interventions

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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.

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medical University of Warsaw

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Central Contacts

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Andrzej Załęski, PhD

Role: CONTACT

+48600982185

References

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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.

Reference Type BACKGROUND
PMID: 28050923 (View on PubMed)

Gaines 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.

Reference Type BACKGROUND
PMID: 2261128 (View on PubMed)

Sobrino-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.

Reference Type BACKGROUND
PMID: 26920789 (View on PubMed)

Gazzola 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.

Reference Type BACKGROUND
PMID: 19123868 (View on PubMed)

Yang 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.

Reference Type BACKGROUND
PMID: 31965635 (View on PubMed)

Rhee 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.

Reference Type BACKGROUND
PMID: 32936523 (View on PubMed)

Bokharaei-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.

Reference Type BACKGROUND
PMID: 32119691 (View on PubMed)

Grant 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.

Reference Type BACKGROUND
PMID: 12095382 (View on PubMed)

Wensing 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.

Reference Type BACKGROUND
PMID: 31634862 (View on PubMed)

Other Identifiers

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HIV DRM - CD4 reconstruction

Identifier Type: -

Identifier Source: org_study_id

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