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

NCT06044792 | Not Yet Recruiting

• 1 other identifier: HIV DRM - CD4 reconstruction
• Study Type: observational
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

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

Keywords

HIV; CD4; DRM; drug resistance; immune reconstruction

Outcome Measures

Primary Outcomes (1)

• 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.

  4 years

Study Arms (2)

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

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

Interventions

differences in CD4 reconstruction 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 negative; DRM positive

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Medical University of Warsaw: lead

Related Publications (9)

• 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.

  PMID: 28050923 BACKGROUND

• 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.

  PMID: 2261128 BACKGROUND

• 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.

  PMID: 26920789 BACKGROUND

• 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.

  PMID: 19123868 BACKGROUND

• 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.

  PMID: 31965635 BACKGROUND

• 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.

  PMID: 32936523 BACKGROUND

• 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.

  PMID: 32119691 BACKGROUND

• 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.

  PMID: 12095382 BACKGROUND

• 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.

  PMID: 31634862 BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

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

Central Study Contacts

Andrzej Załęski, PhD

CONTACT

+48600982185; andrzejzaleski84@wp.pl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2023
• First Posted: September 21, 2023
• Study Start: September 30, 2023
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: September 21, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share