HIV Infections
Conditions
Brief summary
This study will evaluate the safety and virologic effect of an experimental human monoclonal antibody (mAb), VRC-HIVMAB060-00-AB (VRC01), alone or in combination with antiretroviral therapy (ART), in adults during early acute HIV infection.
Detailed description
Human monoclonal antibodies (mAbs) may have the potential to treat HIV infection by preventing the spread of the virus. This study will evaluate an experimental mAB known as VRC-HIVMAB060-00-AB (VRC01). The purpose of this study is to evaluate the safety and virologic effect of VRC01, alone or in combination with ART, in adults with early acute HIV infection. Researchers will also evaluate the effect of VRC01 on the establishment of an HIV reservoir during early acute HIV infection. This study will enroll participants who are diagnosed with early acute HIV infection. Participants will be randomly assigned to one of three groups: Group 1 will begin ART and receive a single infusion of placebo at Day 0. Group 2 will begin ART and receive a single infusion of VRC01 at Day 0. Group 3 will receive a single infusion of VRC01 on Day 0 and begin ART on Day 7. ART will vary by country and will consist of country guideline-recommended, available first line combination therapy: currently either efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg or efavirenz 600 mg/lamivudine 300 mg/tenofovir disoproxil fumarate 300 mg. This initial ART regimen may be adjusted or switched to an alternate regimen as clinically indicated for regimen intolerance or failure. Study visits will occur at Days 0, 1, 3, 7, 10, 14, 18, 21, 25, 28, 42, 56, 84, 112, 168, and 175. Visits will include a physical examination, medical history review, and blood collection. Neurocognitive testing will take place on Day 168. Some participants may take part in optional study procedures at various time points during the study including mucosal secretion collection, rectosigmoid biopsy, lymph node biopsy, leukapheresis, and lumbar puncture.
Interventions
BIOLOGICALVRC01
40 mg/kg of VRC01 will be administered as an intravenous infusion over 30 to 60 minutes using a volumetric pump
BIOLOGICALPlacebo for VRC01
Administered as an intravenous infusion over 30 to 60 minutes using a volumetric pump
DRUGAntiretroviral therapy (ART) (regimen will vary within countries and by patient)
ART is provided by the study sites and consists of country guideline-recommended, available first line once-daily oral combination therapy: currently either efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg or efavirenz 600 mg/lamivudine 300 mg/tenofovir disoproxil fumarate 300 mg. This initial ART regimen may be adjusted or switched to an alternate regimen as clinically indicated for regimen intolerance or failure.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Able and willing to complete the informed consent process * Passes Test of Understanding * 18 to 50 years of age * Experiencing early acute HIV-1 infection as defined by blood samples on at least two separate days positive by nucleic acid testing within 21 days of a negative nucleic acid HIV-1 test OR by a positive nucleic acid test or a positive 4th generation enzyme immunoassay (EIA) in the context of a negative 2nd or negative 3rd generation HIV EIA test * No history of antiretroviral therapy for any indication in the last 30 days. * In general good health * Willing to have blood samples collected and stored * Able to participate for 25 weeks for study visits * Willing to have photo or fingerprint taken for identification purposes Female-Specific Criteria: * Agrees not to become pregnant from the time of study enrollment until the last study visit. If a woman has no history of hysterectomy, tubal ligation or menopause, she must agree to use an effective birth control method: abstinence; male or female condoms; diaphragm or cervical cap with spermicide; intrauterine device; contraceptive hormones delivered by pills, patch, injections, or vaginally; and hormonal implants under the skin; or a male partner who has previously undergone a vasectomy. * Negative beta-human chorionic gonadotropin (HCG) pregnancy test (urine or serum) on day of enrollment for any woman unless she is post-menopause for 24 consecutive months or has undergone a surgical procedure that precludes pregnancy
Exclusion criteria
* Weight less than 46 kg or greater than 115 kg * Previous receipt of humanized or human monoclonal antibody whether licensed or investigational * Ongoing AIDS-related opportunistic infection (including oral thrush or active tuberculosis) * Severe acute retroviral syndrome (as defined in Appendix I of the protocol) or clinical condition (other than HIV infection) constituting an indication for immediate antiretroviral therapy per local country guidelines * Active injection drug use within previous 12 months * History of a severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis in the 2 years prior to enrollment * History of chronic urticaria * Physical finding on examination considered indicative of significant disease such as murmur (other than functional), hepatosplenomegaly, focal neurological deficit * Hypertension that is not well controlled by medication * Positive hepatitis B surface antigen at any time in the past * History of hepatitis C infection * Untreated syphilis infection * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2 times the upper limit of normal (ULN). * Absolute neutrophil count (ANC) less than 740 cells/mm\^3 * Estimated glomerular filtration rate (GFR) less than 50 ml/min within the past 90 days * Breastfeeding * Pregnancy * Receipt of licensed vaccine or other investigational study agent within 28 days prior to enrollment or past participation in an investigational HIV vaccine study with receipt of active product * Current or planned participation in another interventional clinical trial during the study period * Chronic or recurrent use of medications that modify host immune response, e.g., oral or parenteral steroids, cancer chemotherapy * Any other chronic or clinically significant medical condition that in the opinion of investigator would jeopardize the safety or rights of the volunteer. Including, but not limited to: diabetes mellitus type I, chronic hepatitis, renal failure; OR clinically significant forms of: drug or alcohol abuse, mental illness, severe asthma, autoimmune disease, psychiatric disorders, heart disease, or cancer. * Study site employee
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Grade 3 or Greater mAb-related Reactogenicity and mAb-related Adverse Events (AEs) | Measured through Week 24 | This outcome is the combined total number of grade 3 or higher mAb-related reactogenicity events and mAb-related adverse events for each group. Only grade 3 reactogenicity events/AEs that are determined by the study physicians to be related to mAb are included. Adverse events, including reactogenicity events, are graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events v2.0 dated November 2014. This outcome is the total number of solicited adverse events (reactogenicity events) that had a severity of grade 3 or higher and were related to the mAb. Note that higher grades indicate worse severity. |
| Plasma Viral Load Change From Day 0 to Day 7 | Measured through Day 7 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measurement of Plasma Viremia Including Single Copy HIV RNA Quantification | Measured through Week 24 | In samples with HIV RNA less than 50 copies/ml at Day 7, Day 14, and Week 24 |
| Measurement of Cell-associated HIV RNA and DNA in the Peripheral Compartment | Measured through Week 24 (Day 168) | — |
| Percentage of Participants Experiencing Acute Retroviral Syndrome | Measured through Week 24 | — |
| Percentage of Participants Experiencing a Hospitalization | Measured through Week 24 | — |
| Time to Virologic Suppression (Less Than 50 Copies/ml) in Plasma | Measured through Week 24 | — |
| Percentage of Participants Experiencing Non-AIDS-related Conditions | Measured through Week 24 | — |
| Measurement of CD4 + T Cells | Measured through Week 24 | Decrease from baseline to nadir, increase from nadir to Week 24, and overall change from baseline to Week 24 |
| Measurement of VRC01 Levels in Peripheral Blood | Measured through Week 24 | — |
| Percentage of Participants Experiencing Opportunistic Infections | Measured through Week 24 | — |
| Number of Total Viremic Copy Days (Area Under Viral Load Curve) From Day 0 to Week 24 | Measured through Week 24 | — |
Countries
Kenya, Tanzania, Thailand, Uganda
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1: Immediate ART and Placebo Infusion Participants will start ART and will receive a single infusion of placebo at Day 0.
Placebo for VRC01: Administered as an intravenous infusion over 30 to 60 minutes using a volumetric pump
Antiretroviral therapy (ART) (regimen will vary within countries and by patient): ART is provided by the study sites and consists of country guideline-recommended, available first line once-daily oral combination therapy: currently either efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg or efavirenz 600 mg/lamivudine 300 mg/tenofovir disoproxil fumarate 300 mg. This initial ART regimen may be adjusted or switched to an alternate regimen as clinically indicated for regimen intolerance or failure. | 8 |
| Group 2: Immediate ART and VRC01 Infusion Participants will start ART and receive a single infusion of VRC01 at Day 0.
VRC01: 40 mg/kg of VRC01 will be administered as an intravenous infusion over 30 to 60 minutes using a volumetric pump
Antiretroviral therapy (ART) (regimen will vary within countries and by patient): ART is provided by the study sites and consists of country guideline-recommended, available first line once-daily oral combination therapy: currently either efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg or efavirenz 600 mg/lamivudine 300 mg/tenofovir disoproxil fumarate 300 mg. This initial ART regimen may be adjusted or switched to an alternate regimen as clinically indicated for regimen intolerance or failure. | 8 |
| Group 3: Immediate VRC01 Infusion and Subsequent ART Participants will receive a single infusion of VRC01 on Day 0 followed by ART initiation on Day 7.
VRC01: 40 mg/kg of VRC01 will be administered as an intravenous infusion over 30 to 60 minutes using a volumetric pump
Antiretroviral therapy (ART) (regimen will vary within countries and by patient): ART is provided by the study sites and consists of country guideline-recommended, available first line once-daily oral combination therapy: currently either efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg or efavirenz 600 mg/lamivudine 300 mg/tenofovir disoproxil fumarate 300 mg. This initial ART regimen may be adjusted or switched to an alternate regimen as clinically indicated for regimen intolerance or failure. | 8 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Group 1: Immediate ART and Placebo Infusion | Group 2: Immediate ART and VRC01 Infusion | Group 3: Immediate VRC01 Infusion and Subsequent ART | Total |
|---|---|---|---|---|
| Age, Continuous | 21.9 years STANDARD_DEVIATION 4.6 | 23.5 years STANDARD_DEVIATION 3.2 | 24.9 years STANDARD_DEVIATION 2.5 | 23.4 years STANDARD_DEVIATION 3.6 |
| Baseline CD4+ Count | 595.724 cells/microLiter STANDARD_DEVIATION 252.35 | 500.839 cells/microLiter STANDARD_DEVIATION 99.899 | 410.991 cells/microLiter STANDARD_DEVIATION 158.902 | 502.518 cells/microLiter STANDARD_DEVIATION 188.803 |
| Baseline Viral Load | 5.8115 log10(copies/mL) STANDARD_DEVIATION 1.2286 | 5.6740 log10(copies/mL) STANDARD_DEVIATION 0.8927 | 5.5753 log10(copies/mL) STANDARD_DEVIATION 0.712 | 5.6869 log10(copies/mL) STANDARD_DEVIATION 0.9306 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 8 Participants | 8 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Fiebig Stage Fiebig Stage 1 | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Fiebig Stage Fiebig Stage 2 | 3 Participants | 3 Participants | 3 Participants | 9 Participants |
| Fiebig Stage Fiebig Stage 3 | 2 Participants | 3 Participants | 1 Participants | 6 Participants |
| Fiebig Stage Fiebig Stage 4 | 1 Participants | 0 Participants | 3 Participants | 4 Participants |
| Fiebig Stage Fiebig Stage 5 | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 5 Participants | 5 Participants | 15 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Kenya | 2 participants | 2 participants | 2 participants | 6 participants |
| Region of Enrollment Tanzania | 0 participants | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Thailand | 5 participants | 5 participants | 5 participants | 15 participants |
| Region of Enrollment Uganda | 1 participants | 0 participants | 1 participants | 2 participants |
| Sex/Gender, Customized Gender Female | 2 Participants | 3 Participants | 2 Participants | 7 Participants |
| Sex/Gender, Customized Gender Male | 6 Participants | 4 Participants | 4 Participants | 14 Participants |
| Sex/Gender, Customized Gender Transgender | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 8 / 8 | 7 / 8 | 7 / 8 |
| serious Total, serious adverse events | 2 / 8 | 0 / 8 | 1 / 8 |
Outcome results
Primary
Number of Participants With Grade 3 or Greater mAb-related Reactogenicity and mAb-related Adverse Events (AEs)
This outcome is the combined total number of grade 3 or higher mAb-related reactogenicity events and mAb-related adverse events for each group. Only grade 3 reactogenicity events/AEs that are determined by the study physicians to be related to mAb are included. Adverse events, including reactogenicity events, are graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events v2.0 dated November 2014. This outcome is the total number of solicited adverse events (reactogenicity events) that had a severity of grade 3 or higher and were related to the mAb. Note that higher grades indicate worse severity.
Time frame: Measured through Week 24
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1: Immediate ART and Placebo Infusion | Number of Participants With Grade 3 or Greater mAb-related Reactogenicity and mAb-related Adverse Events (AEs) | 0 Participants |
| Group 2: Immediate ART and VRC01 Infusion | Number of Participants With Grade 3 or Greater mAb-related Reactogenicity and mAb-related Adverse Events (AEs) | 0 Participants |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Number of Participants With Grade 3 or Greater mAb-related Reactogenicity and mAb-related Adverse Events (AEs) | 1 Participants |
Primary
Plasma Viral Load Change From Day 0 to Day 7
Time frame: Measured through Day 7
Population: All randomized participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Immediate ART and Placebo Infusion | Plasma Viral Load Change From Day 0 to Day 7 | -1.5238 log(copies/mL) | Standard Deviation 0.8018 |
| Group 2: Immediate ART and VRC01 Infusion | Plasma Viral Load Change From Day 0 to Day 7 | -1.6108 log(copies/mL) | Standard Deviation 0.8174 |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Plasma Viral Load Change From Day 0 to Day 7 | -0.2336 log(copies/mL) | Standard Deviation 0.9635 |
Comparison: Pairwise Wilcoxon rank-sum test using 10,000 bootstrapped samples.p-value: 0.645Wilcoxon (Mann-Whitney)
p-value: 0.007Wilcoxon (Mann-Whitney)
p-value: 0.003Wilcoxon (Mann-Whitney)
Secondary
Measurement of CD4 + T Cells
Decrease from baseline to nadir, increase from nadir to Week 24, and overall change from baseline to Week 24
Time frame: Measured through Week 24
Population: Change is analyzed using participants with data at both time points.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Group 1: Immediate ART and Placebo Infusion | Measurement of CD4 + T Cells | Change from Nadir to Day 168 | 381.398 cells/microLiter |
| Group 1: Immediate ART and Placebo Infusion | Measurement of CD4 + T Cells | Change from Baseline to Nadir | -84.034 cells/microLiter |
| Group 1: Immediate ART and Placebo Infusion | Measurement of CD4 + T Cells | Change from Baseline to Day 168 | 336.134 cells/microLiter |
| Group 2: Immediate ART and VRC01 Infusion | Measurement of CD4 + T Cells | Change from Nadir to Day 168 | 343.764 cells/microLiter |
| Group 2: Immediate ART and VRC01 Infusion | Measurement of CD4 + T Cells | Change from Baseline to Nadir | -47.206 cells/microLiter |
| Group 2: Immediate ART and VRC01 Infusion | Measurement of CD4 + T Cells | Change from Baseline to Day 168 | 333.485 cells/microLiter |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Measurement of CD4 + T Cells | Change from Baseline to Nadir | -42.209 cells/microLiter |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Measurement of CD4 + T Cells | Change from Baseline to Day 168 | 254.594 cells/microLiter |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Measurement of CD4 + T Cells | Change from Nadir to Day 168 | 226.995 cells/microLiter |
Comparison: Comparison of change in CD4+ T cells in Groups 1 and 2 from baseline to Nadirp-value: 0.694Wilcoxon (Mann-Whitney)
Comparison: Comparison of change in CD4+ T cells in Groups 1 and 3 from baseline to Nadirp-value: 0.729Wilcoxon (Mann-Whitney)
Comparison: Comparison of change in CD4+ T cells in Groups 1 and 2 from Nadir to Day 168p-value: 0.694Wilcoxon (Mann-Whitney)
Comparison: Comparison of change in CD4+ T cells in Groups 1 and 3 from Nadir to Day 168p-value: 0.393Wilcoxon (Mann-Whitney)
Comparison: Comparison of change in CD4+ T cells in Groups 1 and 2 from Baseline to Day 168p-value: >0.999Wilcoxon (Mann-Whitney)
Comparison: Comparison of change in CD4+ T cells in Groups 1 and 3 from Baseline to Day 168 p-value calculated using 10,000 bootstrapped samplesp-value: >0.999Wilcoxon (Mann-Whitney)
Secondary
Measurement of Cell-associated HIV RNA and DNA in the Peripheral Compartment
Time frame: Measured through Week 24 (Day 168)
Population: Virologic population consists of all randomized participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Immediate ART and Placebo Infusion | Measurement of Cell-associated HIV RNA and DNA in the Peripheral Compartment | Day 28 | 2.821 log10 copies/mL | Standard Deviation 1.357 |
| Group 1: Immediate ART and Placebo Infusion | Measurement of Cell-associated HIV RNA and DNA in the Peripheral Compartment | Day 7 | 3.690 log10 copies/mL | Standard Deviation 0.708 |
| Group 1: Immediate ART and Placebo Infusion | Measurement of Cell-associated HIV RNA and DNA in the Peripheral Compartment | Day 0 | 4.036 log10 copies/mL | Standard Deviation 0.95 |
| Group 1: Immediate ART and Placebo Infusion | Measurement of Cell-associated HIV RNA and DNA in the Peripheral Compartment | Day 3 | 3.427 log10 copies/mL | Standard Deviation 1.268 |
| Group 1: Immediate ART and Placebo Infusion | Measurement of Cell-associated HIV RNA and DNA in the Peripheral Compartment | Day 168 | 2.169 log10 copies/mL | Standard Deviation 1.516 |
| Group 2: Immediate ART and VRC01 Infusion | Measurement of Cell-associated HIV RNA and DNA in the Peripheral Compartment | Day 7 | 2.780 log10 copies/mL | Standard Deviation 0.979 |
| Group 2: Immediate ART and VRC01 Infusion | Measurement of Cell-associated HIV RNA and DNA in the Peripheral Compartment | Day 0 | 3.214 log10 copies/mL | Standard Deviation 1.571 |
| Group 2: Immediate ART and VRC01 Infusion | Measurement of Cell-associated HIV RNA and DNA in the Peripheral Compartment | Day 3 | 3.553 log10 copies/mL | Standard Deviation 0.561 |
| Group 2: Immediate ART and VRC01 Infusion | Measurement of Cell-associated HIV RNA and DNA in the Peripheral Compartment | Day 28 | 2.095 log10 copies/mL | Standard Deviation 1.296 |
| Group 2: Immediate ART and VRC01 Infusion | Measurement of Cell-associated HIV RNA and DNA in the Peripheral Compartment | Day 168 | 1.283 log10 copies/mL | Standard Deviation 1.616 |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Measurement of Cell-associated HIV RNA and DNA in the Peripheral Compartment | Day 168 | 2.656 log10 copies/mL | Standard Deviation 0.768 |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Measurement of Cell-associated HIV RNA and DNA in the Peripheral Compartment | Day 28 | 2.823 log10 copies/mL | Standard Deviation 1.309 |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Measurement of Cell-associated HIV RNA and DNA in the Peripheral Compartment | Day 0 | 3.940 log10 copies/mL | Standard Deviation 1.298 |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Measurement of Cell-associated HIV RNA and DNA in the Peripheral Compartment | Day 7 | 3.924 log10 copies/mL | Standard Deviation 0.482 |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Measurement of Cell-associated HIV RNA and DNA in the Peripheral Compartment | Day 3 | 4.090 log10 copies/mL | Standard Deviation 0.432 |
Secondary
Measurement of Plasma Viremia Including Single Copy HIV RNA Quantification
In samples with HIV RNA less than 50 copies/ml at Day 7, Day 14, and Week 24
Time frame: Measured through Week 24
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Group 1: Immediate ART and Placebo Infusion | Measurement of Plasma Viremia Including Single Copy HIV RNA Quantification | Day 7 | 4.2877 log-10(copies/mL) |
| Group 1: Immediate ART and Placebo Infusion | Measurement of Plasma Viremia Including Single Copy HIV RNA Quantification | Week 24 (Day 168) | 0.9223 log-10(copies/mL) |
| Group 1: Immediate ART and Placebo Infusion | Measurement of Plasma Viremia Including Single Copy HIV RNA Quantification | Day 14 | 3.2345 log-10(copies/mL) |
| Group 2: Immediate ART and VRC01 Infusion | Measurement of Plasma Viremia Including Single Copy HIV RNA Quantification | Day 7 | 4.0632 log-10(copies/mL) |
| Group 2: Immediate ART and VRC01 Infusion | Measurement of Plasma Viremia Including Single Copy HIV RNA Quantification | Week 24 (Day 168) | 0.9035 log-10(copies/mL) |
| Group 2: Immediate ART and VRC01 Infusion | Measurement of Plasma Viremia Including Single Copy HIV RNA Quantification | Day 14 | 3.0389 log-10(copies/mL) |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Measurement of Plasma Viremia Including Single Copy HIV RNA Quantification | Week 24 (Day 168) | 0.7993 log-10(copies/mL) |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Measurement of Plasma Viremia Including Single Copy HIV RNA Quantification | Day 14 | 3.6189 log-10(copies/mL) |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Measurement of Plasma Viremia Including Single Copy HIV RNA Quantification | Day 7 | 5.3417 log-10(copies/mL) |
Comparison: Comparison of groups 1 and 2 for data from day 7p-value: 0.645Wilcoxon (Mann-Whitney)
Comparison: Comparison between groups 1 and 3 for data from day 7p-value: 0.028Wilcoxon (Mann-Whitney)
Comparison: Comparison of groups 1 and 2 for data from day 14p-value: 0.798Wilcoxon (Mann-Whitney)
Comparison: Comparison of groups 1 and 3 for data from day 14p-value: 0.505Wilcoxon (Mann-Whitney)
Comparison: Comparison of groups 1 and 2 at study day 168 (week 24)p-value: >0.999Wilcoxon (Mann-Whitney)
Comparison: Comparison of groups 1 and 3 at study day 168p-value: 0.497Wilcoxon (Mann-Whitney)
Secondary
Measurement of VRC01 Levels in Peripheral Blood
Time frame: Measured through Week 24
Population: The analysis population for this outcome is defined as those in the virologic population who have available samples for measuring the amount of VRC01 in the peripheral compartment. Some participants did not have samples available for the PK analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Immediate ART and Placebo Infusion | Measurement of VRC01 Levels in Peripheral Blood | Day 14 | 0 ng/mL | Standard Deviation 0 |
| Group 1: Immediate ART and Placebo Infusion | Measurement of VRC01 Levels in Peripheral Blood | Day 1 (Pre) | 0 ng/mL | Standard Deviation 0 |
| Group 1: Immediate ART and Placebo Infusion | Measurement of VRC01 Levels in Peripheral Blood | Day 56 | 0 ng/mL | Standard Deviation 0 |
| Group 1: Immediate ART and Placebo Infusion | Measurement of VRC01 Levels in Peripheral Blood | Day 168 | 0 ng/mL | Standard Deviation 0 |
| Group 1: Immediate ART and Placebo Infusion | Measurement of VRC01 Levels in Peripheral Blood | Day 1 (Post) | 0 ng/mL | Standard Deviation 0 |
| Group 1: Immediate ART and Placebo Infusion | Measurement of VRC01 Levels in Peripheral Blood | Day 21 | 0 ng/mL | Standard Deviation 0 |
| Group 1: Immediate ART and Placebo Infusion | Measurement of VRC01 Levels in Peripheral Blood | Day 3 | 0 ng/mL | Standard Deviation 0 |
| Group 1: Immediate ART and Placebo Infusion | Measurement of VRC01 Levels in Peripheral Blood | Day 28 | 0 ng/mL | Standard Deviation 0 |
| Group 1: Immediate ART and Placebo Infusion | Measurement of VRC01 Levels in Peripheral Blood | Day 7 | 0 ng/mL | Standard Deviation 0 |
| Group 2: Immediate ART and VRC01 Infusion | Measurement of VRC01 Levels in Peripheral Blood | Day 3 | 276.813 ng/mL | Standard Deviation 81.678 |
| Group 2: Immediate ART and VRC01 Infusion | Measurement of VRC01 Levels in Peripheral Blood | Day 14 | 91.275 ng/mL | Standard Deviation 27.295 |
| Group 2: Immediate ART and VRC01 Infusion | Measurement of VRC01 Levels in Peripheral Blood | Day 1 (Post) | 1136.667 ng/mL | Standard Deviation 303.078 |
| Group 2: Immediate ART and VRC01 Infusion | Measurement of VRC01 Levels in Peripheral Blood | Day 7 | 169.288 ng/mL | Standard Deviation 46.161 |
| Group 2: Immediate ART and VRC01 Infusion | Measurement of VRC01 Levels in Peripheral Blood | Day 56 | 13.800 ng/mL | Standard Deviation 16.716 |
| Group 2: Immediate ART and VRC01 Infusion | Measurement of VRC01 Levels in Peripheral Blood | Day 1 (Pre) | 0 ng/mL | Standard Deviation 0 |
| Group 2: Immediate ART and VRC01 Infusion | Measurement of VRC01 Levels in Peripheral Blood | Day 28 | 37.438 ng/mL | Standard Deviation 19.377 |
| Group 2: Immediate ART and VRC01 Infusion | Measurement of VRC01 Levels in Peripheral Blood | Day 168 | 0 ng/mL | Standard Deviation 0 |
| Group 2: Immediate ART and VRC01 Infusion | Measurement of VRC01 Levels in Peripheral Blood | Day 21 | 58.583 ng/mL | Standard Deviation 17.117 |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Measurement of VRC01 Levels in Peripheral Blood | Day 168 | 3.350 ng/mL | Standard Deviation 8.206 |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Measurement of VRC01 Levels in Peripheral Blood | Day 21 | 47.717 ng/mL | Standard Deviation 20.103 |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Measurement of VRC01 Levels in Peripheral Blood | Day 1 (Pre) | 0 ng/mL | Standard Deviation 0 |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Measurement of VRC01 Levels in Peripheral Blood | Day 1 (Post) | 741.250 ng/mL | Standard Deviation 458.083 |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Measurement of VRC01 Levels in Peripheral Blood | Day 3 | 259.600 ng/mL | Standard Deviation 90.044 |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Measurement of VRC01 Levels in Peripheral Blood | Day 7 | 156.043 ng/mL | Standard Deviation 51.723 |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Measurement of VRC01 Levels in Peripheral Blood | Day 28 | 32.850 ng/mL | Standard Deviation 16.682 |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Measurement of VRC01 Levels in Peripheral Blood | Day 56 | 7.933 ng/mL | Standard Deviation 8.5 |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Measurement of VRC01 Levels in Peripheral Blood | Day 14 | 87.750 ng/mL | Standard Deviation 32.66 |
p-value: 0.8629Wilcoxon (Mann-Whitney)
Secondary
Number of Total Viremic Copy Days (Area Under Viral Load Curve) From Day 0 to Week 24
Time frame: Measured through Week 24
Population: All randomized participants
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group 1: Immediate ART and Placebo Infusion | Number of Total Viremic Copy Days (Area Under Viral Load Curve) From Day 0 to Week 24 | 1.81 days |
| Group 2: Immediate ART and VRC01 Infusion | Number of Total Viremic Copy Days (Area Under Viral Load Curve) From Day 0 to Week 24 | 1.74 days |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Number of Total Viremic Copy Days (Area Under Viral Load Curve) From Day 0 to Week 24 | 2.34 days |
p-value: 0.369Kruskal-Wallis
Secondary
Percentage of Participants Experiencing Acute Retroviral Syndrome
Time frame: Measured through Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1: Immediate ART and Placebo Infusion | Percentage of Participants Experiencing Acute Retroviral Syndrome | 1 Participants |
| Group 2: Immediate ART and VRC01 Infusion | Percentage of Participants Experiencing Acute Retroviral Syndrome | 0 Participants |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Percentage of Participants Experiencing Acute Retroviral Syndrome | 0 Participants |
Secondary
Percentage of Participants Experiencing a Hospitalization
Time frame: Measured through Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1: Immediate ART and Placebo Infusion | Percentage of Participants Experiencing a Hospitalization | 2 Participants |
| Group 2: Immediate ART and VRC01 Infusion | Percentage of Participants Experiencing a Hospitalization | 0 Participants |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Percentage of Participants Experiencing a Hospitalization | 1 Participants |
Secondary
Percentage of Participants Experiencing Non-AIDS-related Conditions
Time frame: Measured through Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1: Immediate ART and Placebo Infusion | Percentage of Participants Experiencing Non-AIDS-related Conditions | 8 Participants |
| Group 2: Immediate ART and VRC01 Infusion | Percentage of Participants Experiencing Non-AIDS-related Conditions | 7 Participants |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Percentage of Participants Experiencing Non-AIDS-related Conditions | 7 Participants |
p-value: >0.999Fisher Exact
Comparison: This test compares group 1 to groups 2 and 3 combined (1 vs. 2 \& 3)p-value: 0.39Barnard's test
Secondary
Percentage of Participants Experiencing Opportunistic Infections
Time frame: Measured through Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1: Immediate ART and Placebo Infusion | Percentage of Participants Experiencing Opportunistic Infections | 0 Participants |
| Group 2: Immediate ART and VRC01 Infusion | Percentage of Participants Experiencing Opportunistic Infections | 0 Participants |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Percentage of Participants Experiencing Opportunistic Infections | 0 Participants |
Secondary
Time to Virologic Suppression (Less Than 50 Copies/ml) in Plasma
Time frame: Measured through Week 24
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1: Immediate ART and Placebo Infusion | Time to Virologic Suppression (Less Than 50 Copies/ml) in Plasma | 58.0 Days |
| Group 2: Immediate ART and VRC01 Infusion | Time to Virologic Suppression (Less Than 50 Copies/ml) in Plasma | 43.5 Days |
| Group 3: Immediate VRC01 Infusion and Subsequent ART | Time to Virologic Suppression (Less Than 50 Copies/ml) in Plasma | 87.0 Days |
p-value: 0.347Log Rank