Christina M. Madison, PharmD, FCCP, AAHIVP

AIDS was first described in June 1981 when a report published in the CDC’s 

) documented 5 previously healthy individuals with pneumocystis pneumonia, a disease known to mostly affect severely immunocompromised people.

 In 1983, the virus that causes AIDS was identified; it was later named human immunodeficiency virus (HIV).

The medical community has now strived to eradicate HIV for almost 40 years. During that time, those who work closely with HIV have determined that developing and introducing vaccines is the only way to end the AIDS epidemic.

 However, at this moment, the FDA has not approved any prophylactic or therapeutic HIV vaccines, as candidate vaccines have failed or shown limited and questionable efficacy.

Despite this difficulty, promising new vaccines are being studied. The success of the COVID-19 messenger RNA (mRNA) vaccines from Pfizer/BioNTech and Moderna has given many HIV advocates hope that a preventive mRNA vaccine is on the horizon. Adding to this excitement is a phase 1 clinical trial (NCT05001373) that began in September 2021 studying a sequence of mRNA vaccines that may prevent HIV.

This article discusses NCT05001373 and places the trial in the context of research that paved the way for it, institutions supporting the trial, and other HIV research and vaccines in development.

NCT05001373: ASSESSING AN mRNA HIV VACCINE SEQUENCE

The mRNA vaccine trial (NCT05001373) investigates the hypothesis that vaccination by a germline-targeting prime and then by directional boost immunogens can both provoke B-cell specific class response and steer early maturation toward broadly neutralizing antibody (bnAb) growth through an mRNA platform.

This randomized, first-in-human, open label study examines HIV-1 uninfected adults in good general health. Adults 18 to 50 years of age who apply for the trial and meet all inclusion and no exclusion criteria will be enrolled and randomized. Then, depending upon their assigned group, trial participants will receive either or both of the experimental mRNA vaccines (mRNA- 1644 [eOD-GT8 60mer mRNA], mRNA- 1644v2-Core [Core-g28v2 60mer mRNA]) via intramuscular injection. Safety and tolerability, the primary outcome measure, will be assessed by the proportion of participants with mild, moderate, or severe adverse effects at different times throughout the study. Investigators will also study immunogenicity, the secondary outcome measure, by means of presence and magnitude of relevant immune biomarkers at 10 months.

Investigators estimate an enrollment of 56 participants and study completion by May 1, 2023.

RESEARCH BEHIND THE TRIAL: BNABS AND NCT03547245

The bnAbs of interest in NCT05001373 may be the key to protecting uninfected people from HIV. Whereas other prophylactic vaccines contain a series of the same antigen to induce an immune response, the phase 1 trial tests whether a sequence of immunogens may guide the immune system’s antibody response as it develops naive B cells into mature bnAbs. Mature bnAbs can be traced back to a germline-targeting antigen; vaccine sequencing might then begin with germline targeting and shepherd antibody response to produce mature HIV-fighting cells.

NCT05001373, which is a collaboration principally between International AIDS Vaccine Initiative (IAVI) and ModernaTx, Inc, builds upon the success of NCT03547245, the results of which IAVI and Scripps Research announced in February 2021. The trial demonstrated that the eOD-GT8 60mer vaccine could, indeed, stimulate germline B cells, a first step in bnAb production.

FUTURE DIRECTIONS: OTHER HIV RESEARCH AND VACCINES IN DEVELOPMENT

The vaccine sequence that investigators are studying in NCT05001373 may become a tool to ending the AIDS epidemic. However, researchers are investigating other exciting anti-HIV strategies and vaccines, too.

One such strategy is described by Williams et al in a study published in 

in May 2021. The study investigators examined how glycan-reactive B cells in rhesus macaques and humans evolved in the presence of HIV-1 envelope (Env). They discovered and described what they call Fab-dimerized glycan-reactive (FDG) antibodies, which bind to HIV-1 Env glycans. FDG antibodies neutralize HIV-1 and offer hope that another prophylactic vaccine for humans might be developed.

Therapeutic HIV vaccines also show promise. A prophylactic HIV vaccine would prepare the immune system to recognize and effectively fight HIV in uninfected patients.

 By contrast, therapeutic HIV vaccines are designed to improve the immune response in a person who is already infected. Theoretically, this could slow progression from HIV to AIDS and keep a patient’s viral load at undetectable levels without antiretroviral therapy (ART).

 Research has shown that patients with an undetectable viral load are unable to transmit the virus to others through sexual transmission, a concept known as “U = U” for “Undetectable = Untransmittable.”

Institutions like IAVI and the HIV Vaccine Trials Network (HVTN), headquartered at the Fred Hutchinson Cancer Research Center, are at the forefront of HIV vaccine development.

 A global, publicly funded, multidisciplinary collaborative that facilitates HIV vaccine development, HVTN has conducted over 50 HIV-vaccine-related clinical trials over the past decade.

lists the 8 HIV-vaccine-related studies that are part of the HVTN, currently recruiting, and available on ClinicalTrials.gov.

NCT05001373 represents an important step toward having a widely available HIV preventive vaccine available to the general public. Public health and HIV advocates are patiently awaiting the results of this and other groundbreaking trials with the hopes that ending the HIV epidemic is right around the corner.

Christina M. Madison, PharmD, FCCP, AAHIVP, 

is the founder and CEO of The Public Health Pharmacist, PLLC, in Las Vegas, Nevada.

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What is a therapeutic HIV Vaccine? NIH Office of AIDS Research. Accessed September 9, 2021. https://hivinfo.nih.gov/understanding-hiv/fact-sheets/what-therapeutic-hiv-vaccine

A phase 1 study to evaluate the safety and immunogenicity of eOD-GT8 60mer mRNA vaccine (mRNA-1644) and Core-g28v2 60mer mRNA vaccine (mRNA-1644v2-Core). ClinicalTrials.gov. Updated August 19, 2021. Accessed September 9, 2021. https://clinicaltrials.gov/ct2/show/NCT05001373

First-in-human clinical trial confirms novel HIV vaccine approach developed by IAVI and Scripps Research. News release. International AIDS Vaccine Initiative. February 3, 2021. Accessed September 16, 2021. https://www.iavi.org/news-resources/ press-releases/2021/first-in-human-clinical-trial-confirms-novel-hiv-vaccine-approach-developed-by-iavi-and-scripps-research

Moderna provides business update and announces three new development programs in infectious disease vaccines. News release. ModernaTx. January 11, 2021. Accessed September 16, 2021. https://investors.modernatx.com/news-releases/news-release-details/moderna-provides-business-update-and-announces-three-new

A phase 1 study to evaluate the safety and immunogenicity of eOD-GT8 60mer mRNA vaccine, Adjuvanted. ClinicalTrials.gov. Updated February 5, 2020. Accessed September 16, 2021. https://clinicaltrials.gov/ct2/show/NCT03547245

Williams WB, Meyerhoff RR, Edwards RJ, et al. Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies. 

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Analytical treatment interruption (ATI) to assess the immune system’s ability to control HIV in participants who became HIV-infected during the HVTN 704/HPTN 085 AMP study. ClinicalTrials.gov. Updated September 14, 2021. Accessed September 17, 2021. https://clinicaltrials.gov/ct2/show/NCT04801758?term=HVTN&recrs=a&cond=HIV&draw=2&rank=1

Analytical treatment interruption (ATI) to assess the immune system’s ability to control HIV in participants who became HIV-infected during the HVTN 703/HPTN 081 AMP study. ClinicalTrials.gov. Updated September 5, 2021. Accessed September 17, 2021. https://clinicaltrials.gov/ct2/show/NCT04860323

Evaluating safety and immune response to the HIV-1 CH505 transmitted/founder gp120 adjuvanted with GLA-SE in Healthy, HIV-exposed uninfected infants (HVTN 135). ClinicalTrials. gov. Updated December 31, 2020. Accessed September 17, 2021. https://clinicaltrials.gov/ct2/show/NCT04607408

Evaluating the safety and immunogenicity of stabilized CH505 TF chTrimer in healthy, HIV-uninfected adult participants. ClinicalTrials.gov. Updated June 7, 2021. Accessed September 17, 2021. https://clinicaltrials.gov/ct2/show/NCT04915768

Evaluating the safety and immunogenicity of HIV-1 BG505 SOSIP.664 gp140 with TLR agonist and/or alum adjuvants in healthy, HIV-uninfected adults. ClinicalTrials.gov. Updated September 2, 2021. Accessed September 17, 2021. https://clinicaltrials.gov/ct2/show/NCT04177355

Evaluating the safety and immunogenicity of EnvSeq-1 and CH505 M5 gp120 Envs adjuvanted with GLA-SE in healthy, HIV-uninfected adults. ClinicalTrials.gov. Updated May 18, 2021. Accessed September 17, 2021. https://clinicaltrials.gov/ct2/show/ NCT03220724

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 subcutaneous infusions in healthy, HIV-uninfected adult participants. ClinicalTrials.gov Updated August 4, 2021. Accessed September 17, 2021. https://clinicaltrials.gov/ct2/ show/NCT04212091

A study of heterologous vaccine regimen of adenovirus serotype 26 Mosaic4 human immunodeficiency virus(ad26.Mos4.Hiv), adjuvanted Clade c gp140 and Mosaic gp140 to prevent HIV-1 infection among cis-gender men and transgender individuals who have sex with cis-gender men and/or transgender individuals (MOSAICO). ClinicalTrials.gov. Updated September 1, 2021. Accessed September 17, 2021. https://clinicaltrials.gov/ct2/show/ NCT03964415


Articles

The success of the COVID-19 messenger RNA (mRNA) vaccines from Pfizer/BioNTech and Moderna has given many HIV advocates hope that a preventive mRNA vaccine is on the horizon.

Using mRNA to Create the Elusive HIV Vaccine

Public health means “the health of the many versus the health of the one,” i.e., focusing on the health and wellness of the population rather than the individual patient. It's distinguishable from clinic medicine because of its emphasis on communicable disease prevention rather than curing disease.

One of the most successful examples of population health in modern medicine is the invention of routine recommended vaccinations for the prevention of communicable diseases. Prior to this modern miracle, thousands of children and adults died every year from vaccine-preventable diseases.

Pharmacists working in the community setting are practicing public health pharmacy practice on a daily basis, but probably just didn’t have a name for it. Preventing illness and disease by educating patients about preventive health screenings, chronic disease prevention, harm reduction strategies, and vaccinations.

Different types of public health interventions include epidemiology and surveillance, health teaching, outreach, policy development, screening, and social marketing.

Monitor health status to identify and solve community health needs.

Diagnosis and investigate health problems and health hazards in the community.

Inform and educate the community about public health problems.

Mobilize community partners to identify and solve health problems.

Develop polices and plans that support individual and community health efforts.

Enforce laws and regulations that protect health and ensure safety.

Link people in need to personal health services.

Assure competent public and personal health care workforce.

Evaluate the effectiveness, accessibility, and quality of personal and population-based health services.

Research for new insight and innovative solutions to health problems.

Traditional pharmacists’ roles in public health have been associated with the federal government as a commissioned pharmacist officer with the US Public Health Services through the US Department of Health and Human Services and in other federal agencies and programs, Indian Health Services, and the US Federal Bureau of Prisons. There are also pharmacists who work directly for the Centers for Disease Control and Prevention as a Public Health Fellow, FDA, and Drug Enforcement Agency.

With the expanded scope of pharmacy practice authorized by the US Department of Health and Human Services (HHS) via the Public Readiness and Emergency Preparedness Act (PREP Act) for pharmacists, pharmacy technicians, and pharmacy interns, the need for ambulatory care, community pharmacists, and outpatient pharmacists to be more involved in the provision of public health interventions became even more of a priority.

The Expanded Access to COVID-19 Therapeutics HHS PREP Act Declaration 9th Amendment adds coverage to include trained professionals to administer covered COVID-19 therapeutics, providing a pathway for increased access to COVID-19 therapeutics, particularly in surge states with rising numbers of COVID-19 cases and in rural areas where access to inpatient and outpatient services may be more limited. This is in addition to previous amendments that allowed pharmacists, qualified pharmacy interns, and pharmacy technicians to provide pediatric vaccination administration (3 years of age and up) in all 50 states, as well as ordering/administration of COVID-19 testing and vaccinations.

Misinformation has been declared a “Public Health Threat” by the US Surgeon General Vivek Murthy, MD, MBA. Unfortunately, there have been too many lives that have been lost during this pandemic due to misinformation, including anti-vaccine and anti-mask rhetoric. Pharmacists are in a unique position to help with this public health threat as a pillar of the community who patients like, know, and trust. This doesn’t have to end at the pharmacy counter and can be shared community advocacy and outreach.

There are many examples of ways that pharmacists can help with public health or population health. These include adult and pediatric vaccination services; disaster preparedness (mass prophylaxis and vaccination); COVID-19 testing and vaccination; HIV prevention (PEP and PrEP); hormonal contraceptive services, which include emergency contraceptives and medical abortion; maternal child health through prenatal care and lactation/breastfeeding support services; harm reduction strategies (needle exchange and access to condoms, *which are covered by Medicaid); LGBTQ care (gender affirmation and hormone therapy); substance use disorder services (Naloxone education and dispensing); viral hepatitis management (testing and treatment for hepatitis C viral infection); and tuberculosis prevention (latent tuberculosis infection management).

The COVID-19 pandemic has brought renewed attention to the practice of public health and why it’s so important that we get it right. This has shed more light on existing health disparities and inequities. Public health works best when you don’t know that it’s there.

Public health advocates work behind the scenes to prevent the transmission of communicable diseases, advocating for safe streets, clean air, and clean water. Pharmacists are one of the most trusted and accessible health care professionals. Most patients can access COVID-19 vaccination/testing less than 5 miles from their home because of the efforts that pharmacies and pharmacists have made during this pandemic.

Public health is not only good medicine, but is also good for the community. Improving access to health care and preventative care services will improve health outcomes and decrease overall health care costs.

Health equity should be a priority for the underserved and the most vulnerable of our population to address the health disparities that the pandemic has exacerbated. Most public health services are billable and reimbursable through Medicaid billing codes that have been updated to keep up with the expansion of telehealth, telemedicine, and remote patient monitoring.

There are so many possibilities for the profession of pharmacy and for pharmacists to be able to practice at the top of their licensure while making a lasting and meaningful impact in their communities. Public health matters and should be prioritized.

Pharmacists working in the community setting are practicing public health pharmacy practice on a daily basis, but probably just didn’t have a name for it. 