Clinical trials
IAVI T003
Identifier
NCT03721510
Link
https://clinicaltrials.gov/study/NCT03721510
Phase
Phase I/II
Status
Completed
Sponsor
International AIDS Vaccine Initiative
More details
This is a Phase 1/2a open label study to evaluate the safety, tolerability, pharmacokinetics and anti-viral activity of PGT121, VRC07-523LS and PGDM1400 for HIV prevention and therapy.
Purpose
A Phase 1/2a Study of PGT121, VRC07-523LS and PGDM1400 Monoclonal Antibodies in HIV-uninfected and HIV-infected Adults
Interventions
Intervention 1
PGT121 + VRC07-523LS
Intervention 2
PGT121 + VRC07-523LS + PGDM1400
Countries
United States of America
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2018-12-03
Anticipated Date of Last Follow-up
2022-05-06
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2021-10-25
Actual Completion Date
2022-05-02
Studied populations
Age Cohort
Genders
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
Yes
Comments about the studied
populations
1. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study.
2. In the opinion of the Principal Investigator or designee and based on Assessment of Informed Consent Understanding results, has understood the information provided and potential impact and/or risks linked to IV infusion and participation in the trial; written informed consent will be obtained from the volunteer before any study-related procedures are performed.
3. All volunteers born female engaging in sexual activity that could lead to pregnancy must commit to use an effective method of contraception from the day of the first IV infusion of investigational product until 6 months following the final investigational product administration
4. All sexually active vo
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
19
Allocation
Not provided
Intervention model
Parallel Assignment
Intervention
model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Other/Variable/Unknown
:
"once every 12 weeks
"
Studied LA-formulation(s)
Injectable
Studied route(s) of administration
Intravenous
Use case
Treatment
Key resources
Not provided
IPCAVD014/HTX1004
Identifier
NCT04983030
Link
https://clinicaltrials.gov/study/NCT04983030
Phase
Phase I/II
Status
Not provided
Sponsor
Boris Juelg, MD PhD
More details
A multicenter, randomized, parallel-group, placebo-controlled, double-blind, Phase 1/2a clinical study to investigate the safety, tolerability, immunogenicity and exploratory efficacy of a vaccine regimen consisting of an Ad26.Mos4.HIV prime and a boost with Modified Vaccinia Ankara (MVA)-BN-HIV in combination with broadly neutralizing antibodies (bNAb) PGT121, PGDM1400, and VRC07-523LS in human immunodeficiency virus type 1 (HIV-1)-infected study participants on suppressive anti-retroviral therapy (ART).
Purpose
Safety, Immunogenicity, Efficacy of Ad26.Mos4.HIV, MVA-BN-HIV and PGT121, PGDM1400, and VRC07-523LS in HIV-1-Infected Adults
Interventions
Intervention 1
Ad26.Mos4.HIV
Intervention 2
MVA-BN-HIV
Intervention 3
PGT121
Intervention 4
PGDM1400
Intervention 5
VRC07-523LS
Countries
United States of America
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2022-04-01
Anticipated Date of Last Follow-up
2025-02-03
Estimated Primary Completion Date
2026-02-28
Estimated Completion Date
2026-04-30
Actual Primary Completion Date
Not provided
Actual Completion Date
Not provided
Studied populations
Age Cohort
Genders
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied
populations
Inclusion Criteria:
1. Each potential study participant must pass the Test of Understanding (TOU), indicating that he or she understands the purpose of, and procedures required for the study, after reading the informed consent and after the investigator or designee has provided detailed information on the study and has answered the potential study participant's questions. Each study participant must subsequently sign the ICF, indicating that he or she is willing to participate in the study.
2. Each study participant must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
3. Study participants are ≥18 to ≤70 years old on the day of signing the ICF.
4. Each study participant must have documented HIV-1 infection.
5. Must be on suppressive ART for a
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
36
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention
model description
Not provided
Masking
Double-blind masking
Masking description
Not provided
Frequency of administration
Other/Variable/Unknown
:
"once every 12 weeks
"
Studied LA-formulation(s)
Injectable
Studied route(s) of administration
Intravenous
Use case
Treatment
Key resources
Not provided
A5388
Identifier
NCT05719441
Link
https://clinicaltrials.gov/study/NCT05719441
Phase
Phase II
Status
Suspended
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
More details
A5388 is a phase II, two-arm, randomized, double-blind, placebo-controlled study that will enroll 48 antiretroviral therapy (ART)-naïve adults with acute HIV infection (AHI) in order to determine whether:
* Administration of combination HIV-specific broadly neutralizing antibody (bNAb) therapy in addition to ART during acute HIV infection (AHI) will be safe.
* Participants who receive combination bNAb therapy in addition to ART during AHI will be more likely to demonstrate a delay in time to HIV-1 RNA ≥1,000 copies/mL for 4 consecutive weeks compared to participants who receive placebo plus ART.
* Participants who receive combination bNAb therapy in addition to ART during AHI will demonstrate lower viral reservoirs and enhanced HIV-specific immunity compared to participants who receive pl
Purpose
A Clinical Trial of Combination HIV-Specific Broadly Neutralizing Monoclonal Antibodies Combined With ART Initiation During Acute HIV Infection to Induce HIV Remission
Interventions
Intervention 1
VRC07-523LS
Intervention 2
PGT121.414.LS
Intervention 3
Placebo
Intervention 4
ART
Countries
United States of America
Brazil
Peru
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2024-08-19
Anticipated Date of Last Follow-up
2025-04-17
Estimated Primary Completion Date
2028-04-06
Estimated Completion Date
2028-09-06
Actual Primary Completion Date
Not provided
Actual Completion Date
Not provided
Studied populations
Age Cohort
Genders
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied
populations
Inclusion Criteria:
Step 1:
1. Appropriate documentation from medical records of diagnosis of AHI prior to enrollment that includes one of the following:
1. A detectable HIV-1 RNA within 28 days prior to study entry AND a non-reactive HIV-1 antibody within 7 days prior to entry; OR
2. A detectable HIV-1 RNA or a reactive HIV-1 antibody within 28 days prior to study entry AND a negative/indeterminate Western Blot (WB) or negative/indeterminate Geenius HIV-1/HIV-2 Supplemental Assay within 7 days prior to entry; OR
3. A documented non-reactive HIV-1 antibody or negative HIV-1 RNA within 90 days prior to study entry AND a documented reactive HIV-1 antibody or positive WB that is negative for p31 band or a positive Geenius HIV-1/HIV-2 Supplemental Assay that is negative for p31 ban
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
48
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention
model description
Not provided
Masking
Double-blind masking
Masking description
Not provided
Frequency of administration
Other/Variable/Unknown
:
"once every 12 weeks
"
Studied LA-formulation(s)
Injectable
Studied route(s) of administration
Intravenous
Use case
Treatment
Key resources
Not provided
IAVI T002
Identifier
NCT03205917
Link
https://clinicaltrials.gov/study/NCT03205917
Phase
Phase I
Status
Completed
Sponsor
International AIDS Vaccine Initiative
More details
This is a Phase 1 study to evaluate the safety, tolerability, pharmacokinetics and anti-viral efficacy of the PGDM1400 and PGT121 and VRC07-523LS mAbs for HIV prevention and therapy.
Purpose
A Clinical Trial of PGDM1400 and PGT121 and VRC07-523LS Monoclonal Antibodies in HIV-infected and HIV-uninfected Adults
Interventions
Intervention 1
PGDM1400/Placebo (3mg/kg IV)
Intervention 2
PGDM1400/Placebo (10mg/kg IV)
Intervention 3
PGDM1400/Placebo (30mg/kg IV)
Intervention 4
PGDM1400 + PGT121/Placebo (3mg/kg + 3mg/kg IV)
Intervention 5
PGDM1400 + PGT121/Placebo (10mg/kg + 10mg/kg IV)
Countries
United States of America
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2017-10-23
Anticipated Date of Last Follow-up
2020-09-11
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2020-04-20
Actual Completion Date
2020-04-20
Studied populations
Age Cohort
Genders
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
Yes
Comments about the studied
populations
Groups 1 and 2 Inclusion Criteria:
* HIV-uninfected males or females age 18-50 years old
* Willing to maintain low risk behavior for HIV infection
Groups 1 and 2 Exclusion Criteria:
• Confirmed HIV-infection, pregnancy or lactation, significant acute or chronic disease and clinically significant laboratory abnormalities
Group 3 Inclusion Criteria:
* HIV-infected males or females age 18-65 years old
* Not on antiretroviral therapy with HIV-1 RNA plasma level between 1,000 and 100,000 copies/ml, CD4 cell count ≥ 300 cells/uL
Group 3 Exclusion Criteria:
• Significant acute or chronic medical condition other than HIV infection, and clinically significant laboratory abnormalities
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
29
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention
model description
Not provided
Masking
Double-blind masking
Masking description
Not provided
Frequency of administration
Once
Studied LA-formulation(s)
Injectable
Studied route(s) of administration
Intravenous
Use case
Treatment
Key resources
Not provided
IAVI T001
Identifier
NCT02960581
Link
https://clinicaltrials.gov/study/NCT02960581
Phase
Phase I
Status
Completed
Sponsor
International AIDS Vaccine Initiative
More details
This is a Phase 1 study to evaluate the safety, tolerability, pharmacokinetics and anti-viral efficacy of the PGT121 monoclonal antibody for HIV prevention and therapy.
Purpose
Safety, PK and Antiviral Activity of PGT121 Monoclonal Antibody in HIV-uninfected and HIV-infected Adults
Interventions
Intervention 1
PGT121 3mg/kg IV
Intervention 2
PGT121 10mg/kg IV
Intervention 3
PGT121 30mg/kg IV
Intervention 4
PGT121 3mg/kg SC
Intervention 5
Placebo (0.9% Sodium Chloride Injection USP (Saline))
Countries
United States of America
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2016-11-01
Anticipated Date of Last Follow-up
2019-09-13
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2019-07-08
Actual Completion Date
2019-07-08
Studied populations
Age Cohort
Genders
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
Yes
Comments about the studied
populations
Group 1 Inclusion Criteria:
* HIV-uninfected males or females age 18-50 years old
* Willing to maintain low risk behavior for HIV infection
Group 1 Exclusion Criteria:
* confirmed HIV-infection, pregnancy or lactation, significant acute or chronic disease and clinically significant laboratory abnormalities
Group 2 Inclusion Criteria:
* HIV-infected males or females age 18-65 years old
* On a stable antiretroviral regimen with HIV-1 RNA plasma level \<50 copies/ml, CD4 cell count greater than or equal to 300 cells/uL
Group 2 Exclusion Criteria:
* history of AIDS-defining illness within the previous 5 years, significant acute or chronic medical condition other than HIV infection, and clinically significant laboratory abnormalities
Group 3 Inclusion Criteria:
* HIV-infected males or
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
48
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention
model description
Not provided
Masking
Double-blind masking
Masking description
Not provided
Frequency of administration
Once
Studied LA-formulation(s)
Injectable
Studied route(s) of administration
Intravenous
Use case
Treatment
Key resources
Not provided
HVTN 130/HPTN 089
Identifier
NCT03928821
Link
https://clinicaltrials.gov/study/NCT03928821
Phase
Phase I
Status
Completed
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
More details
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of combinations of monoclonal antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS administered via intravenous infusion in healthy, HIV-uninfected adults.
Purpose
Evaluating the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Combinations of Monoclonal Antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS Administered Via Intravenous Infusion
Interventions
Intervention 1
PGT121
Intervention 2
PGDM1400
Intervention 3
10-1074
Intervention 4
VRC07-523LS
Countries
United States of America
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2019-07-17
Anticipated Date of Last Follow-up
2022-06-15
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2021-03-25
Actual Completion Date
2021-03-25
Studied populations
Age Cohort
Genders
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
Yes
Comments about the studied
populations
Inclusion Criteria:
General and Demographic Criteria
* Age of 18 to 50 years
* Access to a participating clinical research site (CRS) and willingness to be followed for the planned duration of the study
* Ability and willingness to provide informed consent
* Assessment of understanding: volunteer demonstrates understanding of this study and completes a questionnaire prior to first study product administration with verbal demonstration of understanding of all questionnaire items answered incorrectly
* Agrees not to enroll in another study of an investigational research agent until completion of the last required protocol clinic visit
* Good general health as shown by medical history, physical exam, and screening laboratory tests
HIV-Related Criteria:
* Willingness to receive HIV test re
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
27
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention
model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Once
Studied LA-formulation(s)
Injectable
Studied route(s) of administration
Intravenous
Use case
Treatment
Key resources
Not provided
IPCAVD014/HTX1004
Identifier
NCT04983030
Link
https://clinicaltrials.gov/study/NCT04983030
Phase
Phase I/II
Status
Not provided
Sponsor
Boris Juelg, MD PhD
More details
A multicenter, randomized, parallel-group, placebo-controlled, double-blind, Phase 1/2a clinical study to investigate the safety, tolerability, immunogenicity and exploratory efficacy of a vaccine regimen consisting of an Ad26.Mos4.HIV prime and a boost with Modified Vaccinia Ankara (MVA)-BN-HIV in combination with broadly neutralizing antibodies (bNAb) PGT121, PGDM1400, and VRC07-523LS in human immunodeficiency virus type 1 (HIV-1)-infected study participants on suppressive anti-retroviral therapy (ART).
Purpose
Safety, Immunogenicity, Efficacy of Ad26.Mos4.HIV, MVA-BN-HIV and PGT121, PGDM1400, and VRC07-523LS in HIV-1-Infected Adults
Interventions
Intervention 1
Ad26.Mos4.HIV
Intervention 2
MVA-BN-HIV
Intervention 3
PGT121
Intervention 4
PGDM1400
Intervention 5
VRC07-523LS
Countries
United States of America
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2022-04-01
Anticipated Date of Last Follow-up
2025-02-03
Estimated Primary Completion Date
2026-02-28
Estimated Completion Date
2026-04-30
Actual Primary Completion Date
Not provided
Actual Completion Date
Not provided
Studied populations
Age Cohort
Genders
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied
populations
Inclusion Criteria:
1. Each potential study participant must pass the Test of Understanding (TOU), indicating that he or she understands the purpose of, and procedures required for the study, after reading the informed consent and after the investigator or designee has provided detailed information on the study and has answered the potential study participant's questions. Each study participant must subsequently sign the ICF, indicating that he or she is willing to participate in the study.
2. Each study participant must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
3. Study participants are ≥18 to ≤70 years old on the day of signing the ICF.
4. Each study participant must have documented HIV-1 infection.
5. Must be on suppressive ART for a
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
36
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention
model description
Not provided
Masking
Double-blind masking
Masking description
Not provided
Frequency of administration
Other/Variable/Unknown
:
"once every 12 weeks
"
Studied LA-formulation(s)
Injectable
Studied route(s) of administration
Intravenous
Use case
Treatment
Key resources
Not provided
STUDY00007810
Identifier
NCT04144335
Link
https://clinicaltrials.gov/study/NCT04144335
Phase
Phase I/II
Status
Withdrawn
Sponsor
University of Minnesota
More details
To assess the safety of combination immune therapy in HIV-infected participants whose HIV is controlled with ART, by determining the incidence and severity of adverse events.
Purpose
N-803 Combined With the Broadly Neutralizing Antibodies Plus or Minus haNK Cells for HIV
Interventions
Intervention 1
N-803 and bNAbs
Intervention 2
haNK™ Cells
Countries
United States of America
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
2020-01-01
Actual Start Date
Not provided
Anticipated Date of Last Follow-up
2020-10-21
Estimated Primary Completion Date
2020-12-31
Estimated Completion Date
2020-12-31
Actual Primary Completion Date
Not provided
Actual Completion Date
Not provided
Studied populations
Age Cohort
Genders
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied
populations
Inclusion Criteria:
* HIV-1 infection
* On continuous antiretroviral therapy for \> 12 months without any interruptions of greater than 14 consecutive days in the last 12 months
* Screening plasma HIV RNA levels \< 20 copies/mL on all available determinations in past 12 months (isolated single values ≥ 20 but \< 200 copies/mL will be allowed if they were preceded and followed by viral load determinations \< 20 copies/mL)
* Screening CD4+ T-cell count ≥ 400 cells/mm3
Exclusion Criteria:
* Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
* Active or recent malignancy requiring systemic chemotherapy or surgery in the preceding 36 months or for whom such therapies are expected in the subsequent 12 months; minor surgical removal of localized s
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
Not provided
Allocation
Randomized
Intervention model
Sequential assignment
Intervention
model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Other/Variable/Unknown
:
"Once every 3 weeks
"
Studied LA-formulation(s)
Injectable
Studied route(s) of administration
Intravenous
Use case
Treatment
Key resources
Not provided
HVTN 136/HPTN 092
Identifier
NCT04212091
Link
https://clinicaltrials.gov/study/NCT04212091
Phase
Phase I
Status
Completed
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
More details
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of the monoclonal antibody PGT121.414.LS administered alone and in combination with VRC07-523LS via intravenous or subcutaneous infusions in healthy, HIV-uninfected adult participants.
Purpose
Evaluating the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of the Monoclonal Antibody PGT121.414.LS Administered Alone and in Combination With VRC07-523LS Via Intravenous or Subcuta
Interventions
Intervention 1
PGT121.414.LS
Intervention 2
VRC07-523LS
Countries
United States of America
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2020-11-10
Anticipated Date of Last Follow-up
2024-12-10
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2023-01-18
Actual Completion Date
2023-01-18
Studied populations
Age Cohort
Genders
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
Yes
Comments about the studied
populations
Inclusion Criteria:
General and Demographic Criteria
* Age of 18 to 50 years
* Access to a participating Clinical Research Site (CRS) and willingness to be followed for the planned duration of the study
* Ability and willingness to provide informed consent
* Assessment of understanding: volunteer demonstrates understanding of this study and completes a questionnaire prior to first study product administration with verbal demonstration of understanding of all questionnaire items answered incorrectly
* Agrees not to enroll in another study of an investigational research agent until completion of the last required protocol clinic visit
* Good general health as shown by medical history, physical exam, and screening laboratory tests
HIV-Related Criteria:
* Willingness to receive HIV test re
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
33
Allocation
Randomized
Intervention model
Sequential assignment
Intervention
model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Other/Variable/Unknown
Studied LA-formulation(s)
Injectable
Studied route(s) of administration
Intravenous
Use case
Treatment
Key resources
Not provided
Supporting material
Publications
Stephenson, K. E., Julg, B., Tan, C. S., Zash, R., Walsh, S. R., Rolle, C. P., Monczor, A. N., Lupo, S., Gelderblom, H. C., Ansel, J. L., Kanjilal, D. G., Maxfield, L. F., Nkolola, J., Borducchi, E. N., Abbink, P., Liu, J., Peter, L., Chandrashekar, A., Nityanandam, R., Lin, Z., … Barouch, D. H. (2021). Safety, pharmacokinetics and antiviral activity of PGT121, a broadly neutralizing monoclonal antibody against HIV-1: a randomized, placebo-controlled, phase 1 clinical trial. Nature medicine, 27(10), 1718–1724. https://doi.org/10.1038/s41591-021-01509-0
Human immunodeficiency virus (HIV)-1-specific broadly neutralizing monoclonal antibodies are currently under development to treat and prevent HIV-1 infection. We performed a single-center, randomized, double-blind, dose-escalation, placebo-controlled trial of a single administration of the HIV-1 V3-glycan-specific antibody PGT121 at 3, 10 and 30 mg kg–1 in HIV-uninfected adults and HIV-infected adults on antiretroviral therapy (ART), as well as a multicenter, open-label trial of one infusion of PGT121 at 30 mg kg–1 in viremic HIV-infected adults not on ART (no. NCT02960581). The primary endpoints were safety and tolerability, pharmacokinetics (PK) and antiviral activity in viremic HIV-infected adults not on ART. The secondary endpoints were changes in anti-PGT121 antibody titers and CD4+ T-cell count, and development of HIV-1 sequence variations associated with PGT121 resistance. Among 48 participants enrolled, no treatment-related serious adverse events, potential immune-mediated diseases or Grade 3 or higher adverse events were reported. The most common reactions among PGT121 recipients were intravenous/injection site tenderness, pain and headache. Absolute and relative CD4+ T-cell counts did not change following PGT121 infusion in HIV-infected participants. Neutralizing anti-drug antibodies were not elicited. PGT121 reduced plasma HIV RNA levels by a median of 1.77 log in viremic participants, with a viral load nadir at a median of 8.5 days. Two individuals with low baseline viral loads experienced ART-free viral suppression for ≥168 days following antibody infusion, and rebound viruses in these individuals demonstrated full or partial PGT121 sensitivity. The trial met the prespecified endpoints. These data suggest that further investigation of the potential of antibody-based therapeutic strategies for long-term suppression of HIV is warranted, including in individuals off ART and with low viral load.
Badamchi-Zadeh A, Tartaglia LJ, Abbink P, Bricault CA, Liu P, Boyd M, Kirilova M, Mercado NB, Nanayakkara OS, Vrbanac VD, Tager AMLarocca RA, Seaman MS, Barouch DH2018.Therapeutic Efficacy of Vectored PGT121 Gene Delivery in HIV-1-Infected Humanized Mice. J Virol92:10.1128/jvi.01925-17.https://doi.org/10.1128/jvi.01925-17
Broadly neutralizing antibodies (bNAbs) are being explored for HIV-1 prevention and cure strategies. However, administration of purified bNAbs poses challenges in resource-poor settings, where the HIV-1 disease burden is greatest. In vivo vector-based production of bNAbs represents an alternative strategy. We investigated adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors to deliver the HIV-1-specific bNAb PGT121 in wild-type and immunocompromised C57BL/6 mice as well as in HIV-1-infected bone marrow-liver-thymus (BLT) humanized mice. Ad5.PGT121 and AAV1.PGT121 produced functional antibody in vivo. Ad5.PGT121 produced PGT121 rapidly within 6 h, whereas AAV1.PGT121 produced detectable PGT121 in serum by 72 h. Serum PGT121 levels were rapidly reduced by the generation of anti-PGT121 antibodies in immunocompetent mice but were durably maintained in immunocompromised mice. In HIV-1-infected BLT humanized mice, Ad5.PGT121 resulted in a greater reduction of viral loads than did AAV1.PGT121. Ad5.PGT121 also led to more-sustained virologic control than purified PGT121 IgG. Ad5.PGT121 afforded more rapid, robust, and durable antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected humanized mice. Further evaluation of vector delivery of HIV-1 bNAbs is warranted, although approaches to prevent the generation of antiantibody responses may also be required.
IMPORTANCE Broadly neutralizing antibodies (bNAbs) are being explored for HIV-1 prevention and cure strategies, but delivery of purified antibodies may prove challenging. We investigated adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors to deliver the HIV-1-specific bNAb PGT121. Ad5.PGT121 afforded more rapid, robust, and durable antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected humanized mice.
Additional documents
No documents were uploaded
Useful links
There are no additional links
