Trial Outcomes & Findings for PD-1 Inhibition to Determine CNS Reservoir of HIV-Infection (NCT NCT03239899)
NCT ID: NCT03239899
Last Updated: 2025-10-02
Results Overview
The frequency of Grade 3 and higher Adverse Events (AEs) that are probably or definately causal to pembrolizumab was calculated for the duration of the study, i.e., up to 52 weeks following infusion of pembrolizumab.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
13 participants
Primary outcome timeframe
study duration (up to 52 weeks post infusion)
Results posted on
2025-10-02
Participant Flow
Participants with a diagnosis of HIV were recruited from the NIH Clinical Center and the local HIV community. Recruitment started on 4/1/2018 and ended on 11/22/2020.
68 individuals were pre-screened and 13 individuals met the eligibility criteria and expressed interest in participating in the study.
Participant milestones
| Measure |
HIV Participants
Participants who received 200mg Pembrolizumab administered as a one-time intravenous infusion.
|
|---|---|
|
Overall Study
STARTED
|
13
|
|
Overall Study
COMPLETED
|
6
|
|
Overall Study
NOT COMPLETED
|
7
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
PD-1 Inhibition to Determine CNS Reservoir of HIV-Infection
Baseline characteristics by cohort
| Measure |
HIV Participants
n=6 Participants
Participants who received 200mg Pembrolizumab administered as a one-time intravenous infusion.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
61 Years
STANDARD_DEVIATION 9.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: study duration (up to 52 weeks post infusion)The frequency of Grade 3 and higher Adverse Events (AEs) that are probably or definately causal to pembrolizumab was calculated for the duration of the study, i.e., up to 52 weeks following infusion of pembrolizumab.
Outcome measures
| Measure |
HIV Participants
n=6 Participants
Participants who received 200 mg Pembrolizumab administered as a one-time intravenous infusion
|
CSF Antibody Levels
Change in CSF antibody levels at 3 weeks post infusion compared to baseline
|
|---|---|---|
|
Frequency of Grade 3 or Higher Adverse Events
|
0 number of occurrences
|
—
|
SECONDARY outcome
Timeframe: 3 weeks after infusionAnalysis of the effects of pembrolizumab on various immunologic responses (antigens) was conducted at baseline and 3 weeks after infusion of pembrolizumab. Antibody responses have been correlated with cure responses in the "Berlin patient". Utilizing the "Berlin patient's" antibody levels as a benchmark for the post-treatment of the study participants, a change in the following antigens was analyzed at 3 weeks post-infusion of pembrolizumab, in CSF and serum: p24, Matrix, gp120, Reverse transcriptase, Integrate, Protease, and pg41. A positive value suggests exposure to the HIV protein; while a negative value suggests no exposure to the HIV protein.
Outcome measures
| Measure |
HIV Participants
n=6 Participants
Participants who received 200 mg Pembrolizumab administered as a one-time intravenous infusion
|
CSF Antibody Levels
n=6 Participants
Change in CSF antibody levels at 3 weeks post infusion compared to baseline
|
|---|---|---|
|
Change in HIV-specific Antibody Responses in the CSF and Serum Using LIPS Assay.
p24
|
0.99 Fold change
Standard Deviation 0.15
|
1.32 Fold change
Standard Deviation 0.76
|
|
Change in HIV-specific Antibody Responses in the CSF and Serum Using LIPS Assay.
Matrix
|
1.05 Fold change
Standard Deviation 0.20
|
0.87 Fold change
Standard Deviation 0.38
|
|
Change in HIV-specific Antibody Responses in the CSF and Serum Using LIPS Assay.
gp120
|
1.06 Fold change
Standard Deviation 0.31
|
1.13 Fold change
Standard Deviation 0.86
|
|
Change in HIV-specific Antibody Responses in the CSF and Serum Using LIPS Assay.
Reverse transcriptase
|
0.95 Fold change
Standard Deviation 0.11
|
1.35 Fold change
Standard Deviation 1.06
|
|
Change in HIV-specific Antibody Responses in the CSF and Serum Using LIPS Assay.
Integrase
|
0.99 Fold change
Standard Deviation 0.18
|
0.87 Fold change
Standard Deviation 0.50
|
|
Change in HIV-specific Antibody Responses in the CSF and Serum Using LIPS Assay.
Protease
|
0.99 Fold change
Standard Deviation 0.23
|
1.29 Fold change
Standard Deviation 0.96
|
|
Change in HIV-specific Antibody Responses in the CSF and Serum Using LIPS Assay.
gp41
|
1.07 Fold change
Standard Deviation 0.15
|
0.95 Fold change
Standard Deviation 0.29
|
SECONDARY outcome
Timeframe: 3 weeks after infusionA change in CSF cytokine profile was measured between baseline and 3 weeks after infusion of pembrolizumab. Cytokines are proteins that communicate with and trigger the immune system to attack invaders in the body. An increase in an individual cytokine level after 3 weeks suggests an immune reaction.
Outcome measures
| Measure |
HIV Participants
n=6 Participants
Participants who received 200 mg Pembrolizumab administered as a one-time intravenous infusion
|
CSF Antibody Levels
Change in CSF antibody levels at 3 weeks post infusion compared to baseline
|
|---|---|---|
|
Change in CSF Cytokine Profile Post-study Drug
EGF
|
1 Fold change
Standard Deviation 0
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
Eotaxin
|
1.68 Fold change
Standard Deviation 1.34
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
G-CSF
|
1 Fold change
Standard Deviation 0
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
GM-CSF
|
1 Fold change
Standard Deviation 0
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
IFNa2
|
1 Fold change
Standard Deviation 0
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
IFNg
|
1 Fold change
Standard Deviation 0
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
IL-10
|
1.42 Fold change
Standard Deviation 1.02
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
IL-12P40
|
1.49 Fold change
Standard Deviation 1.25
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
IL-12P70
|
1 Fold change
Standard Deviation 0
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
IL-13
|
1 Fold change
Standard Deviation 0
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
IL-15
|
0.92 Fold change
Standard Deviation 0.38
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
IL-17A
|
1 Fold change
Standard Deviation 0
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
IL-1RA
|
1.27 Fold change
Standard Deviation 0.67
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
IL-1a
|
1.45 Fold change
Standard Deviation 1.31
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
IL-1b
|
1 Fold change
Standard Deviation 0
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
IL-2
|
1 Fold change
Standard Deviation 0
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
IL-3
|
1 Fold change
Standard Deviation 0
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
IL-4
|
1 Fold change
Standard Deviation 0
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
IL-5
|
1 Fold change
Standard Deviation 0
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
IL-6
|
1 Fold change
Standard Deviation 0
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
IL-7
|
1 Fold change
Standard Deviation 0
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
IL-8
|
0.97 Fold change
Standard Deviation 0.26
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
IP-10
|
1.47 Fold change
Standard Deviation 1.11
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
MCP-1
|
2.05 Fold change
Standard Deviation 2.36
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
MIP-1a
|
0.93 Fold change
Standard Deviation 0.26
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
MIP-1b
|
1.16 Fold change
Standard Deviation 0.54
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
RANTES
|
1 Fold change
Standard Deviation 0
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
TNFa
|
1 Fold change
Standard Deviation 0
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
TNFb
|
1 Fold change
Standard Deviation 0
|
—
|
|
Change in CSF Cytokine Profile Post-study Drug
VEGF
|
1 Fold change
Standard Deviation 0
|
—
|
SECONDARY outcome
Timeframe: 3 weeks after infusionA change in peripheral CD4 counts was measured from baseline to 3 weeks post-infusion of pembrolizumab. CD4 T cells help coordinate the immune response by stimulating other immune cells, such as macrophages, B lymphocytes (B cells), and CD8 T lymphocytes (CD8 cells), to fight infection. HIV weakens the immune system by destroying CD4 cells. CD4 counts in the blood were measured at baseline and 3 weeks after infusion of pembrolizumab. A positive value suggests an increase in the CD4 count while a negative value suggests a decrease in the CD4 count.
Outcome measures
| Measure |
HIV Participants
n=6 Participants
Participants who received 200 mg Pembrolizumab administered as a one-time intravenous infusion
|
CSF Antibody Levels
Change in CSF antibody levels at 3 weeks post infusion compared to baseline
|
|---|---|---|
|
Peripheral CD4 Counts
|
-66.33 percent change
Standard Deviation 241.87
|
—
|
SECONDARY outcome
Timeframe: 3 weeks after infusionPopulation: Unable to verify the data from one participant, potentially skewing the results measuring the HIV RNA in CSF.
Change in HIV RNA levels was measured in plasma and CSF from baseline to 3 weeks after pembrolizumab infusion. A positive change value suggests an increase in viral load, while a negative change value suggests a decrease in viral load.
Outcome measures
| Measure |
HIV Participants
n=6 Participants
Participants who received 200 mg Pembrolizumab administered as a one-time intravenous infusion
|
CSF Antibody Levels
n=5 Participants
Change in CSF antibody levels at 3 weeks post infusion compared to baseline
|
|---|---|---|
|
HIV RNA in Plasma and CSF
|
8.66 percent change
Standard Deviation 9.3
|
16276.6 percent change
Standard Deviation 36382.17
|
SECONDARY outcome
Timeframe: 3 weeks after infusionChange in FDG-PET/CT metabolic uptake in the CNS from baseline to 3 weeks after infusion of pembrolizumab was measured. A change reflecting an increase in update might suggest higher metabolic activity in that brain region, while a change reflecting a decrease in uptake might suggest lower metabolic activity in that brain region.
Outcome measures
| Measure |
HIV Participants
n=6 Participants
Participants who received 200 mg Pembrolizumab administered as a one-time intravenous infusion
|
CSF Antibody Levels
Change in CSF antibody levels at 3 weeks post infusion compared to baseline
|
|---|---|---|
|
Change in FDG-PET/CT Metabolic Uptake in CNS
Whole Brain
|
-0.85 percent change
Standard Deviation 0.88
|
—
|
|
Change in FDG-PET/CT Metabolic Uptake in CNS
Caudate
|
-1.48 percent change
Standard Deviation 1.88
|
—
|
|
Change in FDG-PET/CT Metabolic Uptake in CNS
Putamen
|
-1.28 percent change
Standard Deviation 1.57
|
—
|
|
Change in FDG-PET/CT Metabolic Uptake in CNS
Thalamus
|
-1.14 percent change
Standard Deviation 1.88
|
—
|
|
Change in FDG-PET/CT Metabolic Uptake in CNS
Frontal Lobe
|
-2.14 percent change
Standard Deviation 1.98
|
—
|
SECONDARY outcome
Timeframe: 3 weeks after infusionA change in PD-1 expression on CD4 and CD8 T cells in the CSF and blood cells, was measured from baseline to 3 weeks after infusion of Pembrolizumab. A decline in PD-1 expression on CD4 and CD8 T cells suggests more potential T cell targeting response.
Outcome measures
| Measure |
HIV Participants
n=6 Participants
Participants who received 200 mg Pembrolizumab administered as a one-time intravenous infusion
|
CSF Antibody Levels
Change in CSF antibody levels at 3 weeks post infusion compared to baseline
|
|---|---|---|
|
Change in PD-1 Expression in the CSF and Blood Cells
CD4+ in blood
|
-12.94 percent change
Standard Deviation 5.42
|
—
|
|
Change in PD-1 Expression in the CSF and Blood Cells
CD8+ in blood
|
-4.06 percent change
Standard Deviation 1.79
|
—
|
|
Change in PD-1 Expression in the CSF and Blood Cells
CD4+ in CSF
|
-14.05 percent change
Standard Deviation 10.63
|
—
|
|
Change in PD-1 Expression in the CSF and Blood Cells
CD8+ in CSF
|
-9.99 percent change
Standard Deviation 7.40
|
—
|
Adverse Events
HIV Participants
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
HIV Participants
n=6 participants at risk
Participants received 200mg Pembrolizumab administered as a one-time intravenous infusion.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
50.0%
3/6 • Number of events 3 • Adverse events were collected for the study duration beginning on day of infusion of Pembrolizumab up to week 52 post-infusion.
Adverse events were collected during each study visit utilizing a study questionnaire, ensuring each participant was solicited in the same manner.
|
|
Blood and lymphatic system disorders
Leukopenia
|
16.7%
1/6 • Number of events 1 • Adverse events were collected for the study duration beginning on day of infusion of Pembrolizumab up to week 52 post-infusion.
Adverse events were collected during each study visit utilizing a study questionnaire, ensuring each participant was solicited in the same manner.
|
|
Endocrine disorders
Adrenal Insufficiency
|
16.7%
1/6 • Number of events 1 • Adverse events were collected for the study duration beginning on day of infusion of Pembrolizumab up to week 52 post-infusion.
Adverse events were collected during each study visit utilizing a study questionnaire, ensuring each participant was solicited in the same manner.
|
|
General disorders
Fever
|
16.7%
1/6 • Number of events 1 • Adverse events were collected for the study duration beginning on day of infusion of Pembrolizumab up to week 52 post-infusion.
Adverse events were collected during each study visit utilizing a study questionnaire, ensuring each participant was solicited in the same manner.
|
|
Hepatobiliary disorders
Transaminitis
|
50.0%
3/6 • Number of events 4 • Adverse events were collected for the study duration beginning on day of infusion of Pembrolizumab up to week 52 post-infusion.
Adverse events were collected during each study visit utilizing a study questionnaire, ensuring each participant was solicited in the same manner.
|
|
Investigations
Blood Bicarbonate Decreased
|
33.3%
2/6 • Number of events 2 • Adverse events were collected for the study duration beginning on day of infusion of Pembrolizumab up to week 52 post-infusion.
Adverse events were collected during each study visit utilizing a study questionnaire, ensuring each participant was solicited in the same manner.
|
|
Investigations
Lipase Increased
|
16.7%
1/6 • Number of events 1 • Adverse events were collected for the study duration beginning on day of infusion of Pembrolizumab up to week 52 post-infusion.
Adverse events were collected during each study visit utilizing a study questionnaire, ensuring each participant was solicited in the same manner.
|
|
Investigations
Cholesterol High
|
16.7%
1/6 • Number of events 1 • Adverse events were collected for the study duration beginning on day of infusion of Pembrolizumab up to week 52 post-infusion.
Adverse events were collected during each study visit utilizing a study questionnaire, ensuring each participant was solicited in the same manner.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
33.3%
2/6 • Number of events 3 • Adverse events were collected for the study duration beginning on day of infusion of Pembrolizumab up to week 52 post-infusion.
Adverse events were collected during each study visit utilizing a study questionnaire, ensuring each participant was solicited in the same manner.
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
16.7%
1/6 • Number of events 1 • Adverse events were collected for the study duration beginning on day of infusion of Pembrolizumab up to week 52 post-infusion.
Adverse events were collected during each study visit utilizing a study questionnaire, ensuring each participant was solicited in the same manner.
|
|
Metabolism and nutrition disorders
Hypernatremia
|
16.7%
1/6 • Number of events 1 • Adverse events were collected for the study duration beginning on day of infusion of Pembrolizumab up to week 52 post-infusion.
Adverse events were collected during each study visit utilizing a study questionnaire, ensuring each participant was solicited in the same manner.
|
|
Metabolism and nutrition disorders
Dehydration
|
16.7%
1/6 • Number of events 1 • Adverse events were collected for the study duration beginning on day of infusion of Pembrolizumab up to week 52 post-infusion.
Adverse events were collected during each study visit utilizing a study questionnaire, ensuring each participant was solicited in the same manner.
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
33.3%
2/6 • Number of events 2 • Adverse events were collected for the study duration beginning on day of infusion of Pembrolizumab up to week 52 post-infusion.
Adverse events were collected during each study visit utilizing a study questionnaire, ensuring each participant was solicited in the same manner.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
16.7%
1/6 • Number of events 1 • Adverse events were collected for the study duration beginning on day of infusion of Pembrolizumab up to week 52 post-infusion.
Adverse events were collected during each study visit utilizing a study questionnaire, ensuring each participant was solicited in the same manner.
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
16.7%
1/6 • Number of events 1 • Adverse events were collected for the study duration beginning on day of infusion of Pembrolizumab up to week 52 post-infusion.
Adverse events were collected during each study visit utilizing a study questionnaire, ensuring each participant was solicited in the same manner.
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
16.7%
1/6 • Number of events 1 • Adverse events were collected for the study duration beginning on day of infusion of Pembrolizumab up to week 52 post-infusion.
Adverse events were collected during each study visit utilizing a study questionnaire, ensuring each participant was solicited in the same manner.
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
16.7%
1/6 • Number of events 1 • Adverse events were collected for the study duration beginning on day of infusion of Pembrolizumab up to week 52 post-infusion.
Adverse events were collected during each study visit utilizing a study questionnaire, ensuring each participant was solicited in the same manner.
|
|
Nervous system disorders
Leukoencephalopathy
|
16.7%
1/6 • Number of events 1 • Adverse events were collected for the study duration beginning on day of infusion of Pembrolizumab up to week 52 post-infusion.
Adverse events were collected during each study visit utilizing a study questionnaire, ensuring each participant was solicited in the same manner.
|
|
Nervous system disorders
Paresthesia
|
16.7%
1/6 • Number of events 1 • Adverse events were collected for the study duration beginning on day of infusion of Pembrolizumab up to week 52 post-infusion.
Adverse events were collected during each study visit utilizing a study questionnaire, ensuring each participant was solicited in the same manner.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
1/6 • Number of events 1 • Adverse events were collected for the study duration beginning on day of infusion of Pembrolizumab up to week 52 post-infusion.
Adverse events were collected during each study visit utilizing a study questionnaire, ensuring each participant was solicited in the same manner.
|
|
Skin and subcutaneous tissue disorders
Rash
|
33.3%
2/6 • Number of events 3 • Adverse events were collected for the study duration beginning on day of infusion of Pembrolizumab up to week 52 post-infusion.
Adverse events were collected during each study visit utilizing a study questionnaire, ensuring each participant was solicited in the same manner.
|
|
Gastrointestinal disorders
Diarrhea
|
16.7%
1/6 • Number of events 1 • Adverse events were collected for the study duration beginning on day of infusion of Pembrolizumab up to week 52 post-infusion.
Adverse events were collected during each study visit utilizing a study questionnaire, ensuring each participant was solicited in the same manner.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place