Clinical trial NCT06044792: The Influence of Primary HIV-1 Drug Resistance Mutations on Immune Reconstruction in PLWH
Official title: The Influence of Primary HIV-1 Drug Resistance Mutations on Immune Reconstruction in Patients Treated With Antiretroviral Drugs - an Observational Cohort Study.
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Hiv
AIDS
CD4 Deficiency
ART
Treatment Resistant Disorders
Treatment-Sensitive HIV Infection
Keywords: HIV
CD4
DRM
drug resistance
immune reconstruction
Lead sponsor: Medical University of Warsaw
Sponsor class: OTHER
First posted: 2023-09-21
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Differences in CD4 recovery regarding the presence of HIV DRM
timeFrame: 4 years
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
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