HIV Vaccines Clinical Trials, Dosage, Indication, Side Effects
Human Immunodeficiency Virus (HIV) vaccine development accelerated in 2024, with candidates utilizing innovative technologies such as mRNA. Novotech's HIV Global, Clinical Trial Landscape report, revealed the biopharma industry has initiated over 1,000 HIV clinical trials worldwide since 2018. Developing HIV vaccines requires various clinical trials: phase 1, phase 2, phase 3, and phase 4; each development step is essential. The U.S. National Institutes of Health (NIH) published an article: Progress toward an HIV vaccine. The development of a preventive vaccine against HIV represents the best solution for controlling and eradicating the HIV pandemic, says the Vaccine Research Institute.
As of August 2024, the U.S. Food and Drug Administration (FDA), Brazil, Japan's National Institute of Infectious Diseases, the European Medicines Agency (EMA), and the United Kingdom had not approved an HIV prevention vaccine. On February 24, 2023, HIV.gov spoke with Dr. Dieffenbach, who noted that while there won't be an HIV vaccine in the near term, he encouraged anyone interested in learning about current HIV vaccine clinical trials to visit the HVTN website.
HIV Vaccine Candidates 2024
Following the discovery of HIV as a causative agent of AIDS, multiple HIV vaccine clinical trials have been conducted globally over the past 35 years. The use of nanotechnology in the design and improvement of HIV vaccines has recently advanced.
Moderna Inc. is advancing three Phase I clinical trials of HIV vaccines with partners (mRNA-1644/IAVI G002; mRNA-1644/IAVI G003; mRNA-1574/NIAID). mRNA-1574 is participating in the U.S. NIH's HVTN 302 study, there are three vaccine candidates: 1) BG505 MD39.3 mRNA, 2) BG505 MD39.3 gp151 mRNA, and 3) BG505 MD39.3 gp151 CD4KO mRNA.
ViiV Healthcare and GSK are advancing in the development of various HIV treatments (VH3810109, GSK3640254) that empower the suppression of the virus to undetectable levels.
eOD-GT8 60mer (mRNA-1644) - Developed by scientific teams at IAVI and Scripps Research and delivered via Moderna's mRNA platform. Recent findings from the Phase I clinical trial IAVI G001 showed that vaccination with the HIV immunogen eOD-GT8 60mer as a recombinant protein vaccine safely induced the targeted immune responses in 97% of recipients.
Vir Biotechnology, Inc. is developing VIR-1388, an investigational novel T-cell vaccine for the prevention of HIV based on the human cytomegalovirus vector (CMV) platform. A weakened version of CMV delivers the HIV vaccine material to the immune system without causing disease in the study participants.
HOOKIPA Pharma - Arenaviral therapeutic vaccines showed in a nonhuman, preclinical setting that 2-vector therapy induces a greater immune response than single-vector therapy and significantly reduces viral load.
AELIX Therapeutics S.L. - The therapeutic HIV vaccine, HIVACAT T-cell immunogen, is a novel HIV vaccine immunogen that leads to a prolonged period without Antiretroviral Treatment and supports the use of HTI vaccine for combination cure strategies for HIV—positive results from the phase 1 clinical study AELIX-002 published in the journal Nature Medicine.
CD40.HIVRI.Env is a vaccine candidate conducting a phase 1 clinical study and was developed by the Vaccine Research Institute (ANRS and Université Paris-Est Créteil, France) with a technology whose exclusive worldwide license is held by LinKinVax. On February 22, 2023, LinkinVax announced the observed counts of CD4+ T cells targeting specifically the HIV envelope protein produced after the vaccination remained stable until Week 48.
Uvax Bio, LLC announced in December 2023 that the U.S. NIH agreed to sponsor its HIV-1 vaccine candidate in a Phase 1 clinical trial to launch in the first quarter of 2024. The two vaccines being tested are based on Uvax Bio's proprietary 1c-SApNP® technology, displaying 20 uncleaved, prefusion-optimized (UFO) HIV envelope (Env) trimers in wild-type and glycan-trimmed forms (UVAX-1197 and UVAX-1107, respectively). The first participant was dosed in a Phase 1 clinical trial in Australia evaluating UVAX-1107 and UVAX-1197 on January 30, 2024. Uvax Bio's HIV-1 vaccines are combined with CpG 1018® adjuvant and aluminum hydroxide. In addition, research (April 2023) reported a single-component, self-assembling protein nanoparticle (1c-SApNP) could display 8 or 20 native-like Env trimers as vaccine candidates.
Helocyte, Inc.'s Triplex is a universal (non-HLA-restricted) recombinant Modified Vaccinia Ankara viral vector vaccine engineered to induce a robust and durable virus-specific T cell response to three immuno-dominant proteins linked to CMV complications in the post-transplant setting. On October 16, 2023, the Company announced that it executed an exclusive option agreement with the City of Hope for patent rights to use Triplex, a cytomegalovirus vaccine, in combination with cytomegalovirus-specific, Anti-Human Immunodeficiency Virus Chimeric Antigen Receptor (CMV/HIV-CAR) T Cells for the treatment of adults living with HIV.
ReiThera Srl, the Ragon Institute of Mass General, MIT, Harvard, and IAVI are developing a novel HIV vaccine candidate that will be composed of ReiThera's Gorilla adenoviral vector (GRAd) vector, belonging to species C adenoviruses that are considered among the most potent vaccine carriers for the induction of CD8 T-cell responses to the encoded antigens and having a low seroprevalence in humans, and HIV T-cell epitope. IAVI is the sponsor and will execute a phase I clinical trial.
CytoDyn Inc. submitted a revised HIV clinical trial protocol to the FDA on February 1, 2024. The Company believes this submission removes the current clinical hold. On February 29, 2024, the FDA withdrew the clinical hold.
PrEPVacc HIV Prevention Study
On December 6, 2023, the PrEPVacc study team announced that they were discontinuing vaccinations following an independent data safety committee review that determined there was a minimal chance these HIV vaccines could stop HIV acquisition. However, the study's oral preexposure prophylaxis (PrEP) arms continue. The PrEPVacc clinical study combines the evaluation of experimental HIV vaccines and PrEP. As of March 2023, the study tested two different formulations of daily oral PrEP to see if a new F/TAF formulation (Descovy®) is effective. This clinical trial will provide data for F/TAF among cisgender women (87% of PrEPVacc trial participants). F/TAF is approved for use in the US and UK for selected people.
HVTN HIV Vaccine Candidate Clinical Trials
The HVTN datasets for phase 1a-2 trials can be found at this link.
HVTN 502 is a phase 2b trial evaluating the MRK Ad5 HIV-1 gag/pol/nef vaccine in 3,000 men and women at high risk of HIV in North America, the Caribbean, South America, and Australia.
HVTN 505 is a phase 2b trial evaluating the DNA/rAd5 HIV-1 vaccine in 2,504 men or transgender women who have sex with men in the U.S.
HVTN 702 (Uhambo) is a phase 2b/3 trial evaluating the ALVAC-HIV + subtype C gp120/MF59 vaccine in 5,404 men and women at high risk of HIV in South Africa.
HVTN 703/HPTN 081 and HVTN 704/HPTN 085 are two parallel phase 2b trials evaluating passive infusion of the broadly neutralizing antibody VRC01 in 2,699 at-risk cisgender men and transgender persons in the Americas and Europe and 1,924 at-risk women in sub-Saharan Africa.
HIV Monoclonal Antibody
Trogarzo® (ibalizumab) is a monoclonal antibody antiretroviral therapy associated with favorable virologic outcomes used in routine care in heavily treatment-experienced people with HIV in a study posted in May 2023. Trogarzo is a long-acting, CD4-directed, post-attachment HIV-1 inhibitor.
The peer-reviewed journal Nature published a study on June 1, 20,22 that concluded two HIV-specific broadly neutralizing monoclonal antibodies, 3BNC117 and 10-1074, completely suppressed HIV for about 40 weeks in patients who participated in a U.S. government-funded phase 1 clinical trial. The findings suggest that future antibody therapies may offer effective HIV treatment for extended periods without antiretroviral therapy.
Leronlimab, a CCR5 antagonist IgG4 monoclonal antibody, is designed to bind to C-C chemokine receptor type 5 (CCR5), a protein on the surface of specific immune system cells believed to play a role in numerous disease processes, including HIV.
A small phase I clinical trial led by Massachusetts General Hospital has tested an anti-HIV strategy involving an adeno-associated viral vector-based gene delivery system that instructs cells to pump out antibodies that block HIV. The treatment was safe and well-tolerated in the trial of eight adults with HIV. In addition, all participants produced measurable amounts of anti-HIV antibodies in their blood as of April 11, 2022.
ViiV Healthcare N6LS is a broadly neutralizing antibody that works by binding to a specific site (gp120) on the surface of HIV, preventing its entry into immune system cells (CD4+ T-cells). By blocking HHIV'sentry into human CD4+ cells, the virus cannot replicate, and the HIV transmission process may be prevented.
HIV Prevention
In August 2023, the U.S. Preventive Services Task Force recommended that clinicians prescribe preexposure prophylaxis using effective antiretroviral therapy to persons at increased risk of HIV acquisition to decrease the risk of acquiring HIV.
The U.S. FDA-approved Apretude (cabotegravir extended-release injectable suspension) for use in at-risk adults and adolescents weighing at least 35 kilograms for preexposure prevention to reduce the risk of sexually acquired HIV on December 20, 2021.
According to an editorial published in JAMA Internal Medicine, cabotegravir can be taken once every two months.
EDURANT® is a human immunodeficiency virus type 1 (HIV-1) specific, nonnucleoside reverse transcriptase inhibitor (NNRTI) indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-naïve patients 12 years of age and older and weighing at least 35 kg with HIV-1 RNA less than or equal to 100,000 copies/mL.
Gilead Sciences, Inc. announced on December 22, 2022, that Sunlenca® (lenacapavir), in combination with other antiretroviral, was Approved by the U.S. FDA for the treatment of HIV-1 infection in heavily treatment-experienced adults with multi-drug resistant HIV-1 infection. Sunlenca offers a twice-yearly treatment option for adults with HIV that their current treatment regimen does not adequately control. In May 2022, the NEJM published an ORIGINAL ARTICLE: Capsid Inhibition with Lenacapavir in Multidrug-Resistant HIV-1 Infection.
Gilead Sciences, Inc. announced on February 22, 2023, data evaluating lenacapavir in combination with broadly neutralizing antibodies (bNAbs) teropavimab and zinlirvimab as a potential long-acting treatment regimen with twice-yearly dosing. Results from the Phase 1b clinical trial demonstrated the investigational combination was generally well tolerated with high efficacy in select virologically suppressed participants living with HIV. The combination of lenacapavir with teropavimab and zinlirvimab will advance to a Phase 2 study in 2023 in virologically suppressed people with HIV.
Gilead Sciences, Inc.'s open-label phase 1 clinical study evaluated the efficacy and safety profile of Biktarvy® (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) in 33 virologically suppressed pregnant women with HIV. On December 12, 2023, the study's conclusion stated pharmacokinetic and safety data, combined with maintenance of robust virologic suppression, suggest that once-daily B/F/TAF without dose adjustment is appropriate during pregnancy.
The UB-421 SC formulation Semzuvolimab is in Phase 2 clinical trial development for HIV treatment, Last Update was Posted on February 23, 2023, with an Estimated Study Completion Date of December 31, 2025. The study protocol is entitled: Single arm Open-Label Phase 2 Trial of anti-CD4 Antibody UB-421 in Combination with Optimized Background Antiretroviral Therapy in Patients with Multi-Drug Resistant HIV-1 InfectThe NIAID/NIH sponsors this trialD/NIH. It was developed to provide a convenient delivery method compared to the IV route so patients can self-administer the medication.
Sexually Transmitted Disease Vaccines
The sexually transmitted disease vaccine summary was updated in 2024.
