United States Military HIV Research Program

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The United States Military HIV Research Program (USMHRP or MHRP) was initiated by the United States Congress in 1986, in reaction to the threat of lost effectiveness of U.S./Allied troops due to HIV infection. The mission of MHRP is to develop an HIV-1 vaccine, provide prevention, care, and treatment, and conduct meaningful HIV/AIDS research for the global community through the President's Emergency Plan for AIDS Relief (PEPFAR). It is centered at the Walter Reed Army Institute of Research (WRAIR), and has established five international research sites in Africa and Asia (Tanzania, Kenya, Nigeria, Uganda, and Thailand). MHRP also partners with the Armed Forces Research Institute of Medical Sciences (AFRIMS) in Thailand. MHRP works closely with The Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF), most notably in the development of the RV144 HIV vaccine in Thailand. MHRP is the largest research program supported by the HJF. [1]

Contents

Funding

The MHRP is a $175 million program which receives funding for research and treatment endeavors from the Department of Defense ($28 million), PEPFAR, and other organizations such as the Bill and Melinda Gates Foundation and the National Institute of Allergy and Infectious Diseases. [2] [3] Some of MHRP's collaborative vaccine-as-treatment research is funded by Janssen, a division of Johnson & Johnson. MHRP studies in combination approaches to HIV are made possible by a competitive grant that they competed for from a NIH-funded Martin Delaney Collaboratorive. [4]

In 2012, a MHRP scientist named Dr. Gary R. Matyas proposed a vaccine to treat heroin addiction and prevent those who received this vaccine from contracting HIV. Matyas was awarded the NIDA Avant-Garde Award for Medications Development for this proposition, which gave him $1 million per year for five years to continue his research at MHRP on the dual vaccine. [5]

International vaccine research

The program's most notable contribution to HIV/AIDS medical research was the RV 144 vaccine study of over 16,000 volunteers in Thailand. In September 2009, the MHRP and the Thai Ministry of Health conducted the first successful HIV/AIDS vaccine trial to show effective prevention in humans, with a final prevention rate of 31%. [6] [7] [8] [9] [10] [11] [12] [13] Although the efficacy is modest, this trial is significant because it proved that it is possible to develop an HIV vaccine.[ citation needed ]

The breakthrough led to increased interest in research on RV144 and the foundation of partnerships such as the Pox-Protein Public-Private Partnership (P5), a mosaic of public and private entities that focus on building on the success of RV144. [14] MHRP also provides study leadership, and is working with researchers around the globe to dissect the results from the RV144 trial and to design future clinical trials to translate a scientific milestone into an eventual public health tool. RV144 remains the only instance of successful preventative HIV vaccination. [15]

MHRP scientists are also pursuing other strategies to target multiple sub-types of HIV, including modified vaccinia virus Ankara (MVA) vaccines, which were initially developed by collaborating scientists from WRAIR, NIAID, the National Institutes of Health, and the Laboratory of Viral Diseases (LVD). MHRP has ongoing studies and clinical trials using different types of MVA vaccines in Uganda and Thailand, with progress milestones including partial protection and viral load reduction in monkeys being infected with Simian Immunodeficiency Virus (SIV). [16] [17]

Prevention, care, and treatment

In addition to vaccine research, the MHRP provides prevention, care, and treatment services to the communities where they conduct research. [18] According to the Henry M. Jackson Foundation for the Advancement of Military Medicine's 2016 annual report, MHRP works with local programs around the world to support more than 240,000 patients on antiretroviral therapy and to make HIV testing/advising accessible to more than 1.1 million people. [19]   Using existing in-country technical expertise and administrative infrastructure, MHRP expands partnerships with local researchers, health care services and NGOs in Africa to implement PEPFAR activities. Goals include providing counseling, testing, prevention of mother to child transmission, full access to antiretroviral therapy, home-based care, and care for orphans and vulnerable children. MHRP also conducts therapeutic research, tracks the HIV epidemic in active-duty forces, assesses the risk of HIV exposure to deployed U.S. and allied forces overseas, and conducts all HIV-1 testing for the Army.[ citation needed ]

In 2008, MHRP helped evaluate the efficacy of new Rapid Diagnostic Tests (RDT) for HIV types 1 and 2. [20] They were developed to be able to quickly test the blood of soldiers who transfuse blood to wounded soldiers in battle situations. This technology prevents transmission of HIV, HCV, and HBV from soldier to soldier and helps keep these diseases from weakening the fighting force further. Additionally, MHRP conducted the first study to characterize that current clinical testing methods can have difficulty detecting HIV viral presence in persons with acute infections. [21] [22]

Work Outside of HIV

Zika, Ebola, and Middle East Respiratory Syndrome (MERS) outbreaks were responded to by MHRP, as they used their infrastructure and research experience to help develop vaccines for both local people and military personnel living in regions where those diseases were endemic. [23]

In 2014, MHRP's Uganda site conducted the first vaccine trial for Ebola and Marburg virus ever done in Africa. Using combination DNA vaccines, it was shown that it is safe for people to receive both vaccines in combination. The antigens conduced by these vaccines were critical in the future development of stronger Ebola vaccines in Africa. [24] In 2015, the Uganda site conducted a uniquely extensive study of Ebola survivors, finding that many were suffering from chronic malaise including hearing and vision loss up to 21 months post-infection. [25]

MHRP scientists under WRAIR developed a Zika vaccine called ZIKV in only ten months, [26] beginning clinical trial in 2016. This vaccine is not only important to maintain troop health when deploying to foreign regions where Zika is prevalent, but also for those servicemen stationed domestically because there are clusters of military bases in the southern United States where people are at risk for Zika. [27] Preliminary data from a phase 1 clinical trial indicate that 92% of participants would be protected from Zika infection. [28]

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<span class="mw-page-title-main">Uganda Virus Research Institute</span>

The Uganda Virus Research Institute (UVRI) is a medical research institute owned by the Uganda government that carries out research on communicable diseases in man and animals, with emphasis on viral transmitted infections. UVRI is a component of Uganda National Health Research Organization (UNHRO), an umbrella organization for health research within Uganda.

The Division of Acquired Immunodeficiency Syndrome (DAIDS) is a division of the National Institute of Allergy and Infectious Diseases, which is part of the National Institutes of Health. It was formed in 1986 as a part of the initiative to address the national research needs created by the advent and spread of the HIV/AIDS epidemic. Specifically, the Division's mission is to increase basic knowledge of the pathogenesis, natural history, and transmission of HIV disease and to support research that promotes progress in its detection, treatment, and prevention. DAIDS accomplishes this through planning, implementing, managing, and evaluating programs in (1) fundamental basic research, (2) discovery and development of therapies for HIV infection and its complications, and (3) discovery and development of vaccines and other prevention strategies.

<span class="mw-page-title-main">Walter Reed Army Institute of Research</span> Biomedical research facility administered by the U.S. Department of Defense

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RV 144, or the Thai trial, was an HIV vaccine clinical trial that was conducted in Thailand between 2003 and 2006. It used a combination of two HIV vaccines that had each failed in earlier trials. Participants were vaccinated over the course of 24 weeks beginning in October 2003 and were then tested for HIV until July 2006. The results of the study were publicized in September 2009. The initial report showed that the rate of HIV infection among volunteers who received the experimental vaccine was 31% lower than the rate of HIV infection in volunteers who received the placebo. This reduction was not large enough for the Ministry of Public Health in Thailand to support approving the vaccine; it would have licensed it if the reduction had been 50% or more.

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References

  1. ↑ "HJF Annual Report 2016" (PDF). HJF. 2016. Retrieved 26 October 2018.
  2. ↑ "U.S. Military HIV Research Program (MHRP)". NIH: National Institute of Allergy and Infectious Diseases. Retrieved 2018-10-26.
  3. ↑ "Budget cuts threaten Military HIV Research Program". Science Speaks: Global ID News. 2011-12-13. Retrieved 2018-10-26.
  4. ↑ "HJF Annual Report 2016" (PDF). HJF. 2016. Retrieved 26 October 2018.
  5. ↑ "NIDA supports development of combined anti-heroin and HIV vaccine". 2012-07-25. Retrieved 2018-11-07.
  6. ↑ Karasavvas N, Billings E, Rao M, Williams C, Zolla-Pazner S, Bailer RT, et al. (November 2012). "The Thai Phase III HIV Type 1 Vaccine trial (RV144) regimen induces antibodies that target conserved regions within the V2 loop of gp120". AIDS Research and Human Retroviruses. 28 (11): 1444–57. doi:10.1089/aid.2012.0103. PMC   3484815 . PMID   23035746.
  7. ↑ "Efficacy trials - The RV144 trial" . Retrieved 2018-10-26.
  8. ↑ McNeil DG (2009-09-25). "For First Time, AIDS Vaccine Shows Some Success". New York Times. Retrieved 2009-09-24.
  9. ↑ Medical News Today (2009-09-25). "In Thailand Clinical Study, HIV Vaccine Regimen Demonstrates Modest Preventive Effect".
  10. ↑ Bob Grant (2009-09-24). "HIV vax testers react to Thai trial".
  11. ↑ "HIV Vaccine Study First to Show Some Effectiveness in Preventing HIV". US Military HIV Research Program. Archived from the original on September 27, 2009. Retrieved 2009-09-24. Also see Frequently asked questions regarding the RV144 Phase III HIV Vaccine Trial and Thailand MHRP site information Archived 2008-09-07 at the Wayback Machine .
  12. ↑ "Sanofi Pasteur Commends Results of First HIV Vaccine Study to Show Some Effectiveness in Preventing HIV" (PDF). Sanofi Pasteur. Archived from the original (PDF) on 2011-07-16. Retrieved 2009-09-24.
  13. ↑ "Prime-Boost Vaccine Study Shows Modest Effect in Preventing HIV" (PDF). Global Solutions for Infectious Diseases. Retrieved 2009-09-24.
  14. ↑ "P5 Partnership". Global HIV Vaccine Enterprise. Retrieved 2018-10-26.
  15. ↑ Hontelez JA, Nagelkerke N, Bärnighausen T, Bakker R, Tanser F, Newell ML, et al. (August 2011). "The potential impact of RV144-like vaccines in rural South Africa: a study using the STDSIM microsimulation model". Vaccine. 29 (36): 6100–6. doi:10.1016/j.vaccine.2011.06.059. PMC   3157643 . PMID   21703321.
  16. ↑ "HJF Annual Report 2016" (PDF). HJF. 2016. Retrieved 26 October 2018.
  17. ↑ "MVA Vaccine". MHRP | Military HIV Research Program. Retrieved 2018-10-26.
  18. ↑ Reilly L (July 2010). "U.S. Military HIV Research Program: successfully integrating HIV vaccine research with prevention, care, and treatment". Military Medicine. 175 (7 Suppl): 42–4. doi: 10.7205/MILMED-D-10-00168 . PMID   23634478.
  19. ↑ "HJF Annual Report 2016" (PDF). HJF. 2016. Retrieved 26 October 2018.
  20. ↑ Manak MM, Njoku OS, Shutt A, Malia J, Jagodzinski LL, Milazzo M, et al. (November 2015). "Evaluation of Performance of Two Rapid Tests for Detection of HIV-1 and -2 in High- and Low-Prevalence Populations in Nigeria". Journal of Clinical Microbiology. 53 (11): 3501–6. doi:10.1128/JCM.01432-15. PMC   4609716 . PMID   26311857.
  21. ↑ Robb ML, Eller LA, Kibuuka H, Rono K, Maganga L, Nitayaphan S, et al. (June 2016). "Prospective Study of Acute HIV-1 Infection in Adults in East Africa and Thailand". The New England Journal of Medicine. 374 (22): 2120–30. doi:10.1056/nejmoa1508952. PMC   5111628 . PMID   27192360.
  22. ↑ "HJF Annual Report 2016" (PDF). HJF. 2016. Retrieved 26 October 2018.
  23. ↑ "HJF Annual Report 2016" (PDF). HJF. 2016. Retrieved 26 October 2018.
  24. ↑ Kibuuka H, Berkowitz NM, Millard M, Enama ME, Tindikahwa A, Sekiziyivu AB, et al. (April 2015). "Safety and immunogenicity of Ebola virus and Marburg virus glycoprotein DNA vaccines assessed separately and concomitantly in healthy Ugandan adults: a phase 1b, randomised, double-blind, placebo-controlled clinical trial". Lancet. 385 (9977): 1545–54. doi: 10.1016/S0140-6736(14)62385-0 . PMID   25540891. S2CID   205975536.
  25. ↑ Clark DV, Kibuuka H, Millard M, Wakabi S, Lukwago L, Taylor A, et al. (August 2015). "Long-term sequelae after Ebola virus disease in Bundibugyo, Uganda: a retrospective cohort study". The Lancet. Infectious Diseases. 15 (8): 905–12. doi: 10.1016/S1473-3099(15)70152-0 . PMID   25910637.
  26. ↑ Blank C (November 30, 2016). "Human trials of Zika vaccine underway". Drug Topics.
  27. ↑ "Human Trials Begin for Army-Developed Zika Vaccine". U.S. Department of Defense. Retrieved 2018-11-07.
  28. ↑ Modjarrad (2018). "Preliminary aggregate safety and immunogenicity results from three trials of a purified inactivated Zika virus vaccine candidate: phase 1, randomised, double-blind, placebo-controlled clinical trials". The Lancet. 391 (10120): 563–571. doi:10.1016/S0140-6736(17)33106-9. PMC   5884730 . PMID   29217375.
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