Clinical Implications of HIV Low-level Viremia at Times of Highly Active Antiretroviral Treatment Regimens

Study Overview
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Brief Summary
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Retrospective analysis of HIV-1 positive patients treated with antiretroviral therapy in Essen (Germany) from 2004 on. Stored samples from selected patients (n=50) obtained for routine diagnostics will be used to analyze the gag gene, the V3-region of the env gene and immune cells.

Detailed Description
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The underlying study is a retrospective analysis of HIV-1 positive patients treated with antiretroviral therapy from Essen since 2004. Stored samples obtained for routine diagnostics will be used to analyze the gag gene, the V3-region and immune cells from selected patients. By comparing different groups of patients this study aims to identify clinical implications of low-level viremia (LLV) and persistent viremia (PV) at times of highly active antiretroviral treatment regimens (cART). The objectives of this study is to (1) determine how often LLV and PV occured during cART in Essen in the last 10 years and whether specific patterns can be correlated, (2) whether the evolution of PI drug resistance can be detected earlier in the gag than in the protease gene, (3) what kind of cellular tropism do HIV-1 isolates (RNA and proviral DNA) have at times of LLV, and (4) what kind of immune cells circulate in the blood during LLV and PV and what kind of functional properties do they have. The groups include patients starting cART as well as patients with cART. Furthermore, clinical data of patients are routinely documented and will be combined with results specifically obtained in this study in an anonymized data set. Since this is a retrospective study, there are no specific endpoints.

Official Title
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Clinical Implications of HIV Low-level Viremia at Times of Highly Active Antiretroviral Treatment Regimens

Conditions
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HIV-infection

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic HIV-1 infection Age > 18 years Patients treated in Essen in the last 10 years Exclusion Criteria: - no antiretroviral therapy / treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients starting cART<br>Patients starting cART. Grouping according to the time needed to reach viral loads below 1000, 500, 400, 200, 50 copies/ml, respectively. | |
| Patients with cART<br>Patients with cART. Grouping in patients without and with low-level-viremia (LLV) defined as two consecutive viral loads between 40 copies/ml and 200 copies/ml, 400 copies/ml, 500 copies/ml and 1000 copies/ml, respectively. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequencies of low-level viremia (LLV) during ART | Viral loads between 40 and 1000 copies/ml at two consecutive time points preceded by undetectable viral loads | In the last 10 years | 
| Frequencies of persistant viremia (PV) after start of ART | Viral loads above 50 copies/ml 26 weeks after start of antiretroviral treatment | In the last 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patterns associated with LLV or PV | CD4+ cell count, the CD4:CD8 ratio and the number of activated T cells (HLA-DR+), NK-cells (CD3-, CD16+, CD56+) and cytotoxic T-cells (CD3+, CD16+, CCD56+), HBV/HCV Co-Infection status. | In the last 10 years | 
| Detection of gag mutations |  | In the last 10 years | 
| HIV tropism during LLV or PV | Determination of the HIV tropism during LLV or PV in a subset of patients | In the last 10 years | 
| Cellular inflammation markers | Number of Tregs in the peripheral blood. Number of central memory and effector cells. | In the last 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1, antiretroviral treatment, low viral load, low-level viremia