HIV InfectionsPhase 1HVTN111NCT02997969

Safety and Immune Response to a Clade C DNA HIV Vaccine

A Phase 1 study testing DNA-HIV-PT123 vaccine and Protein/MF59 vaccine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The purpose of this study is to evaluate the safety and immune response to an HIV clade C DNA vaccine and to an MF59-adjuvanted clade C Env protein in healthy, HIV-uninfected adults. Read more about this study

Who is it for?: Ages 18 to 40 yearsHealthy volunteers can take part
Conditions the study is for: HIV Infections
What is being tested?: DNA-HIV-PT123 vaccine and Protein/MF59 vaccine
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 132 participants
Where: 5 sitesin 3 countries
Study dates: 21 Jun 2016to 11 Jul 2018
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 40 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

General and Demographic Criteria
Age of 18 to 40 years
Access to a participating HVTN 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; provides answers to a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
Agrees not to enroll in another study of an investigational research agent

Show all 41Show fewer

Good general health as shown by medical history, physical exam, and screening laboratory tests
HIV-Related Criteria:
Willingness to receive HIV test results
Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling.
Assessed by the clinic staff as being at "low risk" for HIV infection and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit.
Laboratory Inclusion Values:
Hemogram/Complete blood count (CBC)
Hemoglobin ≥ 11.0 g/dL for volunteers who were born female, ≥ 13.0 g/dL for volunteers who were born male
White blood cell count = 3,300 to 12,000 cells/mm^3
Total lymphocyte count ≥ 800 cells/mm^3
Remaining differential either within institutional normal range or with site physician approval
Platelets = 125,000 to 550,000/mm^3 Chemistry
Chemistry panel: ALT, AST, and ALP < 1.25 times the institutional upper limit of normal; creatinine ≤ institutional upper limit of normal.
Virology
Negative HIV-1 and -2 blood test: Sites may use locally available assays that have been approved by HVTN Laboratory Operations.
Negative Hepatitis B surface antigen (HBsAg)
Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase chain reaction (PCR) if the anti-HCV is positive Urine
Normal urine:
Negative urine glucose, and
Negative or trace urine protein, and
Negative or trace urine hemoglobin (if trace hemoglobin is present on dipstick, a microscopic urinalysis with red blood cells levels within institutional normal range).
Reproductive Status
Volunteers who were born female: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test performed prior to vaccination on the day of initial vaccination. Persons who are NOT of reproductive potential due to having undergone total hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing.
Reproductive status: A volunteer who was born female must:
Agree to consistently use effective contraception (Appendix B) for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment through the last required protocol clinic visit.
Effective contraception is defined as using 1 of the following methods:
Condoms (male or female), or
Diaphragm or cervical cap,
PLUS 1 of the following methods:
Intrauterine device (IUD),
Hormonal contraception (in accordance with applicable national contraception guidelines),
Successful vasectomy in the male partner (considered successful if a volunteer reports that a male partner has [1] documentation of azoospermia by microscopy, or [2] a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity after vasectomy); or
Any other contraceptive method approved by the HVTN 111 PSRT
Or not be of reproductive potential, such as having reached menopause (no menses for 1 year) or having undergone hysterectomy, bilateral oophorectomy, or tubal ligation;
Or be sexually abstinent. Volunteers who were born female must also agree not to seek pregnancy through alternative methods, such as artificial insemination or in vitro fertilization until after the last required protocol clinic visit Other Volunteers 21 years of age and older who were born female consenting to provide cervical samples: pap smear within the 3 years prior to enrollment, with the latest result reported as normal or ASCUS (atypical squamous cells of undetermined significance); for those 21 years and older that have not had a pap smear within the last 3 years prior to enrollment, must be willing to undergo a pap smear with the result reported as normal or ASCUS prior to sample collection.

Who cannot join

General
Blood products received within 120 days before first vaccination
Investigational research agents received within 30 days before first vaccination
Body mass index (BMI) ≥ 40; or BMI ≥ 35 with 2 or more of the following: systolic blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg, current smoker, known hyperlipidemia
Intent to participate in another study of an investigational research agent during the planned duration of the HVTN 111 study
Pregnant or breastfeeding Vaccines and other Injections

Show all 43Show fewer

HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 111 PSRT will determine eligibility on a case-by-case basis.
Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine trial. Exceptions may be made for vaccines that have subsequently undergone licensure by the FDA. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 111 PSRT will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by the HVTN 111 PSRT on a case-by-case basis.
Live attenuated vaccines other than influenza vaccine received within 30 days before first vaccination or scheduled within 14 days after injection (eg, measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever)
Influenza vaccine or any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (eg, tetanus, pneumococcal, Hepatitis A or B)
Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination Immune System
Immunosuppressive medications received within 168 days before first vaccination. (Not excluded from participation: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3] topical corticosteroids for mild, uncomplicated dermatitis; or [4] a single course of oral/parenteral corticosteroids at doses < 2 mg/kg/day and length of therapy < 11 days with completion at least 30 days prior to enrollment.
Serious adverse reactions to vaccines or to vaccine components such as eggs, egg products, or neomycin, including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded: a volunteer who had a nonanaphylactic adverse reaction to pertussis vaccine as a child.)
Immunoglobulin received within 60 days before first vaccination
Autoimmune disease
Immunodeficiency Clinically significant medical conditions
Untreated or incompletely treated syphilis infection
Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to:
A process that would affect the immune response,
A process that would require medication that affects the immune response,
Any contraindication to repeated injections or blood draws,
A condition that requires active medical intervention or monitoring to avert grave danger to the volunteer's health or well-being during the study period,
A condition or process for which signs or symptoms could be confused with reactions to vaccine, or
Any condition specifically listed among the exclusion criteria below.
Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a volunteer's ability to give informed consent
Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.
Current anti-tuberculosis (TB) prophylaxis or therapy
Asthma other than mild, well-controlled asthma. (Symptoms of asthma severity as defined in the most recent National Asthma Education and Prevention Program (NAEPP) Expert Panel report). Exclude a volunteer who:
Uses a short-acting rescue inhaler (typically a beta 2 agonist) daily, or
Uses moderate/high dose inhaled corticosteroids, or
In the past year has either of the following:
Greater than 1 exacerbation of symptoms treated with oral/parenteral corticosteroids;
Needed emergency care, urgent care, hospitalization, or intubation for asthma.
Diabetes mellitus type 1 or type 2, including cases controlled with diet alone. (Not excluded: history of isolated gestational diabetes.)
Thyroidectomy, or thyroid disease requiring medication during the last 12 months
Hypertension:
If a person has been found to have elevated blood pressure or hypertension during screening or previously, exclude for blood pressure that is not well controlled. Well-controlled blood pressure is defined as consistently ≤ 140 mm Hg systolic and ≤ 90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be ≤ 150 mm Hg systolic and ≤ 100 mm Hg diastolic. For these volunteers, blood pressure must be ≤ 140 mm Hg systolic and ≤ 90 mm Hg diastolic at enrollment.
If a person has NOT been found to have elevated blood pressure or hypertension during screening or previously, exclude for systolic blood pressure ≥ 150 mm Hg at enrollment or diastolic blood pressure ≥ 100 mm Hg at enrollment.
Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions)
Malignancy (Not excluded: Volunteer who has had malignancy excised surgically and who, in the investigator's estimation, has a reasonable assurance of sustained cure. or who is unlikely to experience recurrence of malignancy during the period of the study)
Seizure disorder: History of seizure(s) within past three years. Also exclude if volunteer has used medications in order to prevent or treat seizure(s) at any time within the past 3 years.
Asplenia: any condition resulting in the absence of a functional spleen
History of hereditary angioedema, acquired angioedema, or idiopathic angioedema.

Trial locations and contacts

5 sites in 3 countries.

Country

City, postcode or hospital

5 sites in 3 countries

South Africa3 sites

Aurum Tembisa CRS
Johannesburg, Gauteng, 1632
Aurum Institute Klerksdorp CRS
Klerksdorp, North West, 2571
Isipingo CRS
Westville, KwaZulu-Natal, 3630

Other trials in South Africa

Tanzania1 site

National Institute for Medical Research (NIMR) - Mbeya Medical Research Center (MMRC) Network CRS
Mbeya

Other trials in Tanzania

Zambia1 site

Matero Reference Clinic CRS
Lusaka

Other trials in Zambia

About this study

Official title: A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of HIV Clade C DNA and of MF59-adjuvanted Clade C Env Protein, in Healthy, HIV-uninfected Adult Participants

The purpose of this study is to evaluate the safety and immune response to an HIV clade C DNA vaccine and to an MF59-adjuvanted clade C Env protein in healthy, HIV-uninfected adults.

Read the detailed description

This study will evaluate the safety, tolerability, and immunogenicity to DNA-HIV-PT123 (an HIV clade C DNA vaccine) and to Bivalent Subtype C gp120/MF59 in healthy, HIV-uninfected adults.

The study will enroll healthy, HIV-uninfected participants aged 18 to 40 years. Participants will be randomly assigned to one of 6 groups. Each group will receive experimental vaccine and protein and/or placebo at 4 study visits. Participants in Groups 1-3 will receive all injections via needle and syringe. Participants in Groups 4-6 will receive the DNA vaccine via Biojector, and protein and/or placebo via needle and syringe.

Participants in Groups 1 and 4 will receive the DNA vaccine at months 0, 1, 3, and 6 and the protein at months 3 and 6. Participants in Groups 2 and 5 will receive the DNA vaccine and the protein at months 0, 1, and 6 and placebo at month 3. Participants in Groups 3 and 6 will receive placebo at months 0, 1, 3, and 6.

Study visits will include a physical examination, an interview and/or questionnaire, HIV testing and HIV risk-reduction counseling, and urine and blood collection. Participants may optionally choose to provide rectal fluid, cervical fluid, or semen samples.

Conditions: HIV Infections
Being tested: DNA-HIV-PT123 vaccine, Protein/MF59 vaccine, Placebo
Keywords: HIV
Medical subject headings: HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DNA-HIV-PT123 vaccineBiological
Contains a mixture of 3 DNA plasmids in a 1:1:1 ratio, each at 1.33 mg: 1) clade C ZM96 gag, 2) clade C ZM96 gp140, and 3) clade C CN54 pol-nef, delivered at a total dose 4 mg administered as 1 mL intramuscularly (IM)
Protein/MF59 vaccineBiological
Also called Bivalent Subtype C gp120/MF59
clade C TV1.C gp120 Env and clade C 1086.C gp120 Env, each at a dose of 100 mcg, mixed with MF59 adjuvant, administered as 0.5 mL IM
PlaceboBiological
Also called Sodium Chloride, 0.9%
Sodium Chloride, 0.9%, administered by IM injection at volumes to match the active products

Study groups in NCT02997969
Study group	Role	What they receive
Group 1: DNA + Placebo + Protein/MF59	Active comparator	Participants will receive the DNA-HIV-PT123 vaccine in the left deltoid at months 0, 1, 3, and 6. They will receive placebo in the right deltoid at months 0 and 1, and the Protein/MF59 vaccine at months 3 and 6. All injections are via needle and syringe. Receives: Biological: DNA-HIV-PT123 vaccine; Biological: Protein/MF59 vaccine; Biological: Placebo
Group 2: DNA + Placebo + Protein/MF59	Active comparator	Participants will receive the DNA-HIV-PT123 vaccine in the left deltoid at months 0, 1, and 6. They will receive placebo in both deltoids at month 3, and the Protein/MF59 vaccine at months 0, 1, and 6. All injections are via needle and syringe. Receives: Biological: DNA-HIV-PT123 vaccine; Biological: Protein/MF59 vaccine; Biological: Placebo
Group 3: Placebo	Placebo comparator	Participants will receive placebo in both deltoids at months 0, 1, 3, and 6. All injections are via needle and syringe. Receives: Biological: Placebo
Group 4: DNA + Placebo + Protein/MF59	Active comparator	Participants will receive the DNA-HIV-PT123 vaccine via Biojector in the left deltoid at months 0, 1, 3, and 6. They will receive placebo in the right deltoid at months 0 and 1, and the Protein/MF59 vaccine at months 3 and 6, via needle and syringe. Receives: Biological: DNA-HIV-PT123 vaccine; Biological: Protein/MF59 vaccine; Biological: Placebo
Group 5: DNA + Placebo + Protein/MF59	Active comparator	Participants will receive the DNA-HIV-PT123 vaccine at months 0, 1, and 6, and placebo at month 3, in the left deltoid via Biojector. They will receive placebo at month 3, and the Protein/MF59 vaccine at months 0, 1, and 6, in the right deltoid via needle and syringe. Receives: Biological: DNA-HIV-PT123 vaccine; Biological: Protein/MF59 vaccine; Biological: Placebo
Group 6: Placebo	Placebo comparator	Participants will receive placebo in the left deltoid via Biojector, and in the right deltoid via needle and syringe, at months 0, 1, 3, and 6. Receives: Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Frequency of severe local and systemic reactogenicity signs and symptoms (pain, tenderness, erythema, induration, fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia)
Measured: Measured through Month 12
Frequency of adverse events (AEs)
By body system, Medical Dictionary for Regulatory Activities (MedDRA) preferred term, severity, and assessed relationship to study products
Measured: Measured through Month 12
Frequency of serious adverse events (SAEs), adverse events of special interest (AESIs), and new chronic conditions (requiring medical intervention for 30 days or more)
Measured: Measured through Month 12
Composite of safety laboratory measures: white blood cells (WBC), neutrophils, lymphocytes, hemoglobin, platelets, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphate (ALP), and creatinine
Measured: Measured through Month 12
Frequency of AEs leading to early participant withdrawal or early discontinuation of study products administration
Measured: Measured through Month 12
HIV-specific total immunoglobulin G (IgG) binding antibody response breadth and magnitude as assessed by multiplex assay
Measured: Measured through Month 6.5
Anti-V1/V2 scaffold IgG binding antibody responses as assessed by multiplex assay
Measured: Measured through Month 6.5
Presence of neutralizing antibody responses against HIV-1 isolates
Measured: Measured through Month 6.5
HIV-specific CD4+ T-cell responses as assessed by flow cytometry
Measured: Measured through Month 6.5
HIV-specific CD8+ T-cell responses as assessed by flow cytometry
Measured: Measured through Month 6.5

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Jun 201611 Jul 2018

First posted20 Dec 2016 (estimated)
Study start21 Jun 2016
Primary completion11 Jul 2018
Study completion11 Jul 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (3)Papers the sponsor has linked to this study.
Other trials for HIV InfectionsStudies of the same condition, open and under way.
More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 132 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02997969
Sponsor's protocol ID: HVTN 111
Acronym: HVTN111
Status last verified: Jun 2019
First submitted: 16 Dec 2016
Last updated: 21 Jun 2019
Results posted: No
Data monitoring committee: Yes
Individual data sharing: No

Publications

Moodie Z, Li SS, Giorgi EE, Williams LD, Dintwe O, Carpp LN, Chen S, Seaton KE, Sawant SS, Zhang L, Heptinstall J, Liu S, Grunenberg N, Tomaka F, Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Ake JA, Vasan S, Pantaleo G, Frank I, Baden LR, Goepfert PA, Keefer M, Chirenje M, Hosseinipour MC, Mngadi K, Laher F, Garrett N, Bekker LG, De Rosa S, Andersen-Nissen E, Kublin JG, Lu S, Gilbert PB, Gray GE, Corey L, McElrath MJ, Tomaras GD. A polyvalent DNA prime with matched polyvalent protein/GLA-SE boost regimen elicited the most robust and broad IgG and IgG3 V1V2 binding antibody and CD4+ T cell responses among 13 HIV vaccine trials. Emerg Microbes Infect. 2025 Dec;14(1):2485317. doi: 10.1080/22221751.2025.2485317. Epub 2025 Apr 7.
PubMed 40190112
Hanass-Hancock J, Carpenter B, Reddy T, Nzuza A, Gaffoor Z, Goga A, Andrasik M. Participants' characteristics and motivations to screen for HIV vaccine and monoclonal antibody trials in KwaZulu-Natal, South Africa. Trials. 2021 Dec 11;22(1):897. doi: 10.1186/s13063-021-05792-7.
PubMed 34895272
Hosseinipour MC, Innes C, Naidoo S, Mann P, Hutter J, Ramjee G, Sebe M, Maganga L, Herce ME, deCamp AC, Marshall K, Dintwe O, Andersen-Nissen E, Tomaras GD, Mkhize N, Morris L, Jensen R, Miner MD, Pantaleo G, Ding S, Van Der Meeren O, Barnett SW, McElrath MJ, Corey L, Kublin JG; HVTN 111 Protocol Team. Phase 1 Human Immunodeficiency Virus (HIV) Vaccine Trial to Evaluate the Safety and Immunogenicity of HIV Subtype C DNA and MF59-Adjuvanted Subtype C Envelope Protein. Clin Infect Dis. 2021 Jan 23;72(1):50-60. doi: 10.1093/cid/ciz1239.
PubMed 31900486

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder

All HIV Infections trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of HIV Clade C DNA and of MF59-adjuvanted Clade C Env Protein, in Healthy, HIV-uninfected Adult Participants
ClinicalTrials.gov ID: NCT02997969
Acronym / sponsor ID: HVTN111 / HVTN 111
Conditions: HIV Infections
Keywords: HIV
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 132 participants (actual)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
Collaborators: HIV Vaccine Trials Network, IPPOX Foundation, Novartis Vaccines
Study start: 21 Jun 2016 (actual)
Primary completion: 11 Jul 2018 (actual)
Study completion: 11 Jul 2018 (actual)
First posted: 20 Dec 2016 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to evaluate the safety and immune response to an HIV clade C DNA vaccine and to an MF59-adjuvanted clade C Env protein in healthy, HIV-uninfected adults.

Detailed description

This study will evaluate the safety, tolerability, and immunogenicity to DNA-HIV-PT123 (an HIV clade C DNA vaccine) and to Bivalent Subtype C gp120/MF59 in healthy, HIV-uninfected adults.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 6

Arm	Type	Receives
Group 1: DNA + Placebo + Protein/MF59	Active comparator	Biological: DNA-HIV-PT123 vaccine, Biological: Protein/MF59 vaccine, Biological: PlaceboParticipants will receive the DNA-HIV-PT123 vaccine in the left deltoid at months 0, 1, 3, and 6. They will receive placebo in the right deltoid at months 0 and 1, and the Protein/MF59 vaccine at months 3 and 6. All injections are via needle and syringe.
Group 2: DNA + Placebo + Protein/MF59	Active comparator	Biological: DNA-HIV-PT123 vaccine, Biological: Protein/MF59 vaccine, Biological: PlaceboParticipants will receive the DNA-HIV-PT123 vaccine in the left deltoid at months 0, 1, and 6. They will receive placebo in both deltoids at month 3, and the Protein/MF59 vaccine at months 0, 1, and 6. All injections are via needle and syringe.
Group 3: Placebo	Placebo comparator	Biological: PlaceboParticipants will receive placebo in both deltoids at months 0, 1, 3, and 6. All injections are via needle and syringe.
Group 4: DNA + Placebo + Protein/MF59	Active comparator	Biological: DNA-HIV-PT123 vaccine, Biological: Protein/MF59 vaccine, Biological: PlaceboParticipants will receive the DNA-HIV-PT123 vaccine via Biojector in the left deltoid at months 0, 1, 3, and 6. They will receive placebo in the right deltoid at months 0 and 1, and the Protein/MF59 vaccine at months 3 and 6, via needle and syringe.
Group 5: DNA + Placebo + Protein/MF59	Active comparator	Biological: DNA-HIV-PT123 vaccine, Biological: Protein/MF59 vaccine, Biological: PlaceboParticipants will receive the DNA-HIV-PT123 vaccine at months 0, 1, and 6, and placebo at month 3, in the left deltoid via Biojector. They will receive placebo at month 3, and the Protein/MF59 vaccine at months 0, 1, and 6, in the right deltoid via needle and syringe.
Group 6: Placebo	Placebo comparator	Biological: PlaceboParticipants will receive placebo in the left deltoid via Biojector, and in the right deltoid via needle and syringe, at months 0, 1, 3, and 6.

Who may qualify

Ages: 18 to 40 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (41 listed)

General and Demographic Criteria
Age of 18 to 40 years
Access to a participating HVTN 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; provides answers to a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly

Key exclusion criteria (43 listed)

General
Blood products received within 120 days before first vaccination
Investigational research agents received within 30 days before first vaccination
Body mass index (BMI) ≥ 40; or BMI ≥ 35 with 2 or more of the following: systolic blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg, current smoker, known hyperlipidemia
Intent to participate in another study of an investigational research agent during the planned duration of the HVTN 111 study

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
DNA-HIV-PT123 vaccineContains a mixture of 3 DNA plasmids in a 1:1:1 ratio, each at 1.33 mg: 1) clade C ZM96 gag, 2) clade C ZM96 gp140, and 3) clade C CN54 pol-nef, delivered at a total dose 4 mg administered as 1 mL intramuscularly (IM)	Biological	Group 1: DNA + Placebo + Protein/MF59, Group 2: DNA + Placebo + Protein/MF59, Group 4: DNA + Placebo + Protein/MF59, Group 5: DNA + Placebo + Protein/MF59
Protein/MF59 vaccineAlso: Bivalent Subtype C gp120/MF59clade C TV1.C gp120 Env and clade C 1086.C gp120 Env, each at a dose of 100 mcg, mixed with MF59 adjuvant, administered as 0.5 mL IM	Biological	Group 1: DNA + Placebo + Protein/MF59, Group 2: DNA + Placebo + Protein/MF59, Group 4: DNA + Placebo + Protein/MF59, Group 5: DNA + Placebo + Protein/MF59
PlaceboAlso: Sodium Chloride, 0.9%Sodium Chloride, 0.9%, administered by IM injection at volumes to match the active products	Biological	Group 1: DNA + Placebo + Protein/MF59, Group 2: DNA + Placebo + Protein/MF59, Group 3: Placebo, Group 4: DNA + Placebo + Protein/MF59, Group 5: DNA + Placebo + Protein/MF59, Group 6: Placebo

Primary outcome

Frequency of severe local and systemic reactogenicity signs and symptoms (pain, tenderness, erythema, induration, fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia)
Time frame: Measured through Month 12
Frequency of adverse events (AEs)
Time frame: Measured through Month 12
By body system, Medical Dictionary for Regulatory Activities (MedDRA) preferred term, severity, and assessed relationship to study products
Frequency of serious adverse events (SAEs), adverse events of special interest (AESIs), and new chronic conditions (requiring medical intervention for 30 days or more)
Time frame: Measured through Month 12
Composite of safety laboratory measures: white blood cells (WBC), neutrophils, lymphocytes, hemoglobin, platelets, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphate (ALP), and creatinine
Time frame: Measured through Month 12
Frequency of AEs leading to early participant withdrawal or early discontinuation of study products administration
Time frame: Measured through Month 12
HIV-specific total immunoglobulin G (IgG) binding antibody response breadth and magnitude as assessed by multiplex assay
Time frame: Measured through Month 6.5
Anti-V1/V2 scaffold IgG binding antibody responses as assessed by multiplex assay
Time frame: Measured through Month 6.5
Presence of neutralizing antibody responses against HIV-1 isolates
Time frame: Measured through Month 6.5
HIV-specific CD4+ T-cell responses as assessed by flow cytometry
Time frame: Measured through Month 6.5
HIV-specific CD8+ T-cell responses as assessed by flow cytometry
Time frame: Measured through Month 6.5

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2019.
Derived from this study: PubMed 40190112Moodie Z, Li SS, Giorgi EE, Williams LD, Dintwe O, Carpp LN, Chen S, Seaton KE, Sawant SS, Zhang L, Heptinstall J, Liu S, Grunenberg N, Tomaka F, Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Ake JA, Vasan S, Pantaleo G, Frank I, Baden LR, Goepfert PA, Keefer M, Chirenje M, Hosseinipour MC, Mngadi K, Laher F, Garrett N, Bekker LG, De Rosa S, Andersen-Nissen E, Kublin JG, Lu S, Gilbert PB, Gray GE, Corey L, McElrath MJ, Tomaras GD. A polyvalent DNA prime with matched polyvalent protein/GLA-SE boost regimen elicited the most robust and broad IgG and IgG3 V1V2 binding antibody and CD4+ T cell responses among 13 HIV vaccine trials. Emerg Microbes Infect. 2025 Dec;14(1):2485317. doi: 10.1080/22221751.2025.2485317. Epub 2025 Apr 7.
Derived from this study: PubMed 34895272Hanass-Hancock J, Carpenter B, Reddy T, Nzuza A, Gaffoor Z, Goga A, Andrasik M. Participants' characteristics and motivations to screen for HIV vaccine and monoclonal antibody trials in KwaZulu-Natal, South Africa. Trials. 2021 Dec 11;22(1):897. doi: 10.1186/s13063-021-05792-7.
Derived from this study: PubMed 31900486Hosseinipour MC, Innes C, Naidoo S, Mann P, Hutter J, Ramjee G, Sebe M, Maganga L, Herce ME, deCamp AC, Marshall K, Dintwe O, Andersen-Nissen E, Tomaras GD, Mkhize N, Morris L, Jensen R, Miner MD, Pantaleo G, Ding S, Van Der Meeren O, Barnett SW, McElrath MJ, Corey L, Kublin JG; HVTN 111 Protocol Team. Phase 1 Human Immunodeficiency Virus (HIV) Vaccine Trial to Evaluate the Safety and Immunogenicity of HIV Subtype C DNA and MF59-Adjuvanted Subtype C Envelope Protein. Clin Infect Dis. 2021 Jan 23;72(1):50-60. doi: 10.1093/cid/ciz1239.
Individual participant dataSharing planned: No

Related trials for HIV Infections

Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mina Hosseinipour study chair

UNC Project- Lilongwe

5 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing DNA-HIV-PT123 vaccine and Protein/MF59 vaccine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 41 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in South Africa, Tanzania, Zambia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency of severe local and systemic reactogenicity signs and symptoms (pain, tenderness, erythema, induration, fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia) (time frame: Measured through Month 12). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02997969, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2019.