Human Immunodeficiency Virus
Conditions
Keywords
HIV, immunologic failure, proof of concept, CD4+ T cell recovery, immunological non-responders, Nicotinamide Mononucleotide
Brief summary
This proof-of-concept study aims to investigate the potential impact of supplementing with Nicotinamide Mononucleotide (NMN), a direct precursor of NAD+ on CD4+ T cell recovery in virologically suppressed HIV patients experiencing immunological failure on ART. We hypothesize that NMN supplementation will increase intracellular NAD+ levels, thereby improving CD4+ T cell function and potentially reversing immunological failure. A small cohort of patients will be recruited to evaluate the primary outcome of change in CD4+ T cell count from baseline to the end of the study period after receiving NMN daily for 12 weeks. Secondary outcomes including safety and tolerability, impact on pro-inflammatory markers, increase in NAD+ levels, immune activation markers and change in quality of life questionnaire scores. Patients will participate in two in person visits including a baseline and end of study with two telephone encounters. Patients will take 1,000mg NMN daily for a total of 12 weeks during which they will keep a daily log of doses taken and any side effects experienced. At all visits labs and quality of life questionnaire will be completed with complete physical exam to be done at baseline and end of study visit.
Interventions
DIETARY_SUPPLEMENTNicotinamide Mononucleotide
The dietary supplement NMN \[1,000mg\] will be taken orally by participants daily for a total of 12 weeks
Sponsors
DoNotAge.org
TriHealth Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
proof of concept
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HIV-infected adults aged 18 years or older * Virologically suppressed on ART documented with two negative viral loads separated by at least 6 months * Confirmed diagnosis of immunological failure (CD4+ T cell count \<350 cells/µL 2 years after effective ART initiation) * Willing to provide informed consent
Exclusion criteria
* Active opportunistic infections * Known allergies or sensitivities to NMN or any components of the NMN supplement * Current or recent use of other supplements or medications known to affect NAD+ metabolism (Niacin, NR, NMNH, etc.) * Pregnancy or breastfeeding * Significant liver or kidney disease * Active malignancy * History of uncontrolled substance abuse * Severe medical conditions that might interfere with study participation * Unable to consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Outcome | 12 weeks | The primary outcome of this study will be the change in CD4+ T cell count from baseline to the end of the study period. \[normal range: 500-1500 cells/mm\^3; improved outcomes with increase to normal range\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HLA-DR expression | collected at baseline visit followed by monthly collections for total of 3 months | HLA-DR expression \[healthy individuals \<5-10% HLA DR CD 4+ T cell expression and \<5% |
| TNF-alpha | collected at baseline visit followed by monthly collections for total of 3 months | (Ref Interval: \<=7.2) Cytokines- Results are used to understand the pathophysiology of immune, infectious, or inflammatory disorders |
| NAD(+) levels | collected at baseline visit followed by monthly collections for total of 3 months | Ranges from 10-500 µM during normal physiological state; however, it's levels can vary by age as well as metabolic and disease states |
| CD38 | collected at baseline visit followed by monthly collections for total of 3 months | Changes in immune activation markers - CD38 expression \[healthy individuals expression on T cell \<10-20%, untreated HIV elevated \>60-90%, HIV on ART \ 20-30%; low percentage correlates with improved immune function\] |
| HS-CRP | collected at baseline visit followed by monthly collections for total of 3 months | Ref Interval: \<=3.0 mg/L |
| Changes on Quality-of-life Questionnaire (QOL): WHO QOL HIV BREF | collected at baseline visit followed by monthly collections for total of 3 months | Domain scores between 4-20 with higher score correlating with improved QOL |
| IL-6 | collected at baseline visit followed by monthly collections for total of 3 months | (Ref Interval: \<=2.0 pg/mL ) Cytokines- Results are used to understand the pathophysiology of immune, infectious, or inflammatory disorders |
Contacts
Primary ContactMartin L. Gnoni, MD
Backup ContactMadelyn Mirande, DO
Outcome results
None listed