HIV
Conditions
Brief summary
The goal of this clinical trial is to see if Efavirenz (EFV) intensification to a baseline combination antiretroviral regimen (cART) can help reduce the size of the latent reservoir in people living with HIV (PLWH). The main questions this study aims to address are: 1. is the addition of EFV to a cART regimen safe and well tolerated? 2. Is there a reduction in the blood and tissue HIV reservoir after intensification? Researchers will compare each participants reservoir size prior to and post EFV intensification.
Detailed description
To evaluate the safety and tolerability of efavirenz (EFV) intensification on the HIV-1 reservoir. Participants with well controlled HIV, specifically with a HIV viral load (VL) \<500 for at least 48 weeks will be eligible. Prior to enrollment, we will prescreen individuals to ensure they do not have a polymorphism in cytochrome P450 (CYP450) which results in rapid metabolism of the study drug efavirenz. Leukapheresis and lymph node (LN) fine needle aspirates will be collected at baseline. Participants eligible to participate will begin taking Efavirenz in addition to their baseline combination antiretroviral therapy. Blood samples (120ml) will be collected twice at day 30 and day 90 for cell associated HIV RNA and HIV DNA assessments. Follow-up LN aspirates and follow-up Leukapheresis will be collected at completion of study, between day 150-180, based on scheduling. At day 90 pharmacokinetic (PK) evaluation of EFV will take place to ensure therapeutic levels of Efavirenz. At the completion of the 180 day course of efavirenz, participants will stop efavirenz but continue their baseline HIV regimen. Cluster of Differentiation 4 (CD4), HIV viral load (VL) and monitoring chemistries will be performed at visits on day 30, day 90 and day 150-180.
Interventions
DRUGEfavirenz 600mg
Take One pill daily for 6 months in addition to baseline combination antiretroviral therapy regimen
Sponsors
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Each participant will be their own control for size of latent reservoir. We will compare each person's reservoir before and after addition of Efavirenz.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. At least 18 years of age 2. Diagnosis of HIV 3. Documentation of at least two historical HIV-1 RNA viral load measurements \<500 copies/mL while on ART obtained by standard assay. 4. No known non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations. 5. Currently on a stable regimen including an integrase strand transfer inhibitor (INSTI) and two nucleoside reverse transcriptase inhibitors (NRTI). Receiving the current regimen for at least 90 days prior to study entry with no intention to change for the duration of the study.
Exclusion criteria
1. Untreated depression, defined as a Patient health questionnaire 9 (PHQ-9) score \> 15 at time of enrollment 2. Known prior NNRTI resistance, or INSTI resistance. 3. Cytochrome 450 polymorphism resulting in rapid or delayed metabolism of Efavirenz 4. Not currently on a PI based regimen. 5. Does not have an immunocompromising medical condition. (ie malignancies particularly leukemia, lymphoma, use of immunosuppressive or antineoplastic drugs or X-ray treatment). 6. Chronic, acute, or recurrent infections that are current and serious, in the opinion of the site investigator. 7. Breastfeeding patients as well as those whom are pregnant or plan to become pregnant during period of the study. 8. Those with active Hepatitis C or Hepatitis B.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety as Measured by Adverse Events | From time of enrollment until completion of study on average 5 months | Safety as measured by number of serious adverse events, adverse events leading to study discontinuation or adverse events considered clinically significant |
| Size of the Latent Reservoir (Cluster of Differentiation 4 (CD4) Cells With Intact Provirus/Million CD4 T Cells) | (1) at study enrolment and (2) 4 months post EFV intensification | Size of intact provirus pre and post Efavirenz intensification as measured by IPDA. (CD4 cells with intact provirus/million CD4T cells) Time frame: IPDA (CD4 T cells carrying intact HIV provirus per million total CD4 T cells) at least of two time points (1) at study enrolment and (2) 4 months post EFV intensification |
Countries
United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Age, Continuous | 47.8 years STANDARD_DEVIATION 12.2 |
| intact proviral DNA reservoir (IPDA )-PRE | 236.9 CD4 cells w/ intact provirus/mil CD4 T |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 7 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 0 / 7 |
| serious Total, serious adverse events | 1 / 7 |
Outcome results
None listed