Prospective HIV Chemotherapy Cohort Study

Study Overview
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Brief Summary
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Human Immunodeficiency Virus (HIV) infection is very successfully treated with a type of therapy called Highly Active AntiRetroviral Therapy (HAART). Although HAART has made a great improvement to the health and lives of all people living with HIV, HAART cannot be stopped because it is not able to 'cure' or eliminate the HIV virus from all cells in the body - the remaining viruses are referred to as 'latent' or sleeping virus. As soon as the HAART treatment is stopped the virus comes back (wakes up). It is for this reason that stopping HAART treatment is not recommended. However, it may be that other drugs if given with HAART could have a stronger effect on the latent virus. There is some evidence from laboratory research that suggests that some of the drugs we use to treat certain types of cancer may have an effect on the latent virus. The purpose of this research study is to use new laboratory research technology to measure the amount of 'latent' virus in people who are treated with HAART who then need to use chemotherapy treatments for cancer. We will look at whether the levels of HIV virus are reduced in patients having chemotherapy by looking at the virus levels before, during and after chemotherapy treatment. We do not know very much about how HIV persists in the body despite therapy and unless new approaches are developed, removal of the HIV virus from all cells in the body will not be possible.

Detailed Description
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STUDY DESIGN This study will be performed at one investigational site in the UK. This is a single centre, prospective observational cohort study of HIV positive individuals on suppressive HAART with malignancy undergoing chemotherapy. ELIGIBILITY Individuals receiving HAART and diagnosed with either lymphoma or Kaposi's sarcoma receiving combination chemotherapy agents, which include the vinca alkaloids and taxanes, will be eligible for this study.

Official Title
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Prospective Observational Study of HIV Positive Individuals on Suppressive HAART With Malignancy Undergoing Chemotherapy

Conditions
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HIV, Cancer

Intervention / Treatment
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* Other: No intervention for this study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 18 years and able to give written informed consent Be aware of their HIV status and the diagnosis of malignancy Have a plasma viral load of < 50 HIV-1 RNA copies/ml (on suppressive HAART) at enrolment Be designated to receive cytotoxic chemotherapy including one or more of the following agents: R-CHOP, ABVD, Liposomal doxorubicin (Caelyx) or liposomal daunorubicin (Daunoxome) or Paclitaxel Exclusion Criteria: Patients not receiving HAART A detectable (>50 HIV-1 RNA copies/ml) HIV plasma viral load at screening Opportunistic infections Unable or unwilling to give informed consent

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 |
| --- | --- |
| HIV & chemotherapy<br>Participants will be aged ≥ 18 years, aware of their HIV status and the diagnosis of malignancy, have a plasma viral load of < 50 HIV-1 RNA copies/ml (on suppressive HAART) at enrolment and be designated to receive cytotoxic chemotherapy including one or more of the following agents: R-CHOP, ABVD, Liposomal doxorubicin (Caelyx) or liposomal daunorubicin (Daunoxome) or Paclitaxel. There is no intervention for this study. Blood samples will be taken and if available from routine care surplus cerebrospinal fluid. | Other: No intervention for this study<br>* No intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proviral DNA | Comparison of proviral DNA quantification between baseline and at 12 weeks postcompletion of chemotherapy | 12 weeks postcompletion of chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proviral DNA | Quantification of proviral DNA (intracellular DNA/MRNA) | Baseline, prior to mid cycle of chemotherapy, prior to the final cycle of chemotherapy, 4 weeks post chemotherapy and 12 weeks post chemotherapy | 
| Viral RNA | Quantification of HIV-1 viral RNA transcripts | Baseline, prior to mid cycle of chemotherapy, prior to the final cycle of chemotherapy, 4 weeks post chemotherapy and 12 weeks post chemotherapy | 
| Ultra-low viral load | Quantification of HIV-1 ultra-low viral load (UL-VL) | Baseline, prior to mid cycle of chemotherapy, prior to the final cycle of chemotherapy, 4 weeks post chemotherapy and 12 weeks post chemotherapy | 
| Immune activation levels | Quantification of immune activation levels | Baseline, prior to mid cycle of chemotherapy, prior to the final cycle of chemotherapy, 4 weeks post chemotherapy and 12 weeks post chemotherapy | 
| Histone deacetylase inhibition | Degree of histone deacetylase inhibition | Baseline, prior to mid cycle of chemotherapy, prior to the final cycle of chemotherapy, 4 weeks post chemotherapy and 12 weeks post chemotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Chemotherapy, Cohort, Cancer, HAART, Malignancy