Nancy L. Haigwood (ONPRC) and R. Paul Johnson (YNPRC)

Improved therapies to treat HIV patients, as well as an effective vaccine to protect uninfected individuals from future HIV infection, are both urgent public health priorities. Important information has come from studying HIV infection and AIDS in humans over the last 30 years, as well as from studying nonhuman primate (NHP) models for AIDS.

HIV infects and kills millions globally. In 2017, about 36.9 million people worldwide were living with HIV, and about 940,000 have died of AIDS-related illnesses. Globally, there were about 1.8 million new cases of HIV, with about 180,000 new infections in children (Global HIV & AIDS statistics — 2018 fact sheet). In the United States, AIDS disproportionately affects Hispanics, African Americans, and other ethnic minorities (

One of the major issues with HIV, in contrast to viruses that infect their hosts for a few days or weeks, is that it establishes a persistent infection that has been so far impossible to eradicate in humans (with a single notable exception, see below). Combinations of antiretroviral medications can lengthen lives by keeping viral loads at or near undetectable levels in many HIV patients. However, many HIV-infected patients do not have access to antiretroviral medications or are not able to stay on treatment. In addition, these drugs are not curative and progression to AIDS resumes if drug treatment is interrupted. Thus treatment that is started as soon as infection is detected is now the recommended approach to limit disease progression and damage to immune cells (UCSF news article). Drug treatment in mothers prior to delivery of newborns has greatly reduced transmission from mother to child, but children born to HIV-infected mothers still have a high risk of contracting the infection during birth or via breastfeeding in areas of the world where drug therapy is not available.

African primates are naturally infected with over 40 different simian immunodeficiency viruses (SIV), two of which have infected humans and generated HIV-1 and HIV-2. Chimpanzees are known to be the source of HIV-1 [1], and they, like humans, are variably susceptible to disease [2]. A few HIV patients have been found with genetic variations or other biological mechanisms that appear to naturally control the virus post-infection. These “elite controllers” are extremely uncommon, however, and scientists can only study them in limited ways.

For the last 30 years, the NPRCs have led the way by hosting research programs using NHP models for AIDS that have resulted in critical breakthroughs, as noted in the Key Publications listed below. All NPRCs have active NHP AIDS research programs serving researchers throughout the United States and impacting research progress worldwide. Genetically well-characterized NHPs used in controlled research and animal care settings at the NPRCs have informed researchers about early viral infection, viral escape from host immune responses, and potential vaccine targets. Asian monkeys, such as rhesus, cynomolgus and pig-tailed macaques have served as the flagship, lifesaving models for understanding the basics of infection routes, timing and doses that SIV requires to set up productive, lifelong infections mimicking HIV in humans and providing fundamental information on how SIV and HIV cause disease.

Some of the key lessons learned include knowledge that the immune systems in these animals are analogous to ours, which opens the door to exploring vaccines and immune-based therapies in NHPs. A lab-modified SIV incorporating parts of HIV– simian human immunodeficiency virus (SHIV) – has proved to be a useful tool in the NHP researchers’ arsenal to develop today’s medicines to treat HIV, as well as in the hunt for a vaccine [3]. NPRC researchers have also contributed to the development of using antiviral drugs for pre-exposure and post-exposure prophylaxis, vaginal microbicides [4] to help prevent sexual transmission of HIV to women [5] and safer medicines to prevent HIV transmission from a pregnant woman to her fetus or newborn [6].

There is still a great need for research into more effective treatments for people who already have HIV. Millions of people around the world cannot afford to take antiretroviral drugs to treat HIV, and many countries do not have the resources to provide their citizens with these medicines. Ultimately, researchers aim to find treatments that will result in long-term suppression of HIV infection or a cure for AIDS. Studies in NHP and other animal models have played an important role in showing promising leads in this effort [7]. The single report of an HIV-infected patient who has remained off antiretroviral medication and apparently free of HIV after undergoing a bone marrow transplant to treat leukemia (the Berlin patient—(#15 Hutter NEJM 2009)) has prompted a renaissance of efforts to develop strategies to eradicate HIV and SIV from infected individuals, and testing in NHP models will undoubtedly play a major role in moving these studies forward to human clinical trials.

The ultimate goal of HIV vaccination is to stimulate immunity that will either prevent the virus from getting established or will help to control it, so that drug therapy is not required [8]. Many candidate HIV vaccines have been tested in preclinical NHP models, and the most promising are moving into human clinical trials. The challenge is to find a vaccine that is safe and effective against all strains of the virus. This is critically important because the virus often mutates as it jumps from person to person. HIV not only incorporates itself into the hosts’ genetic material and hijacks their immune system, but viral mutations from infections of a previous host may allow it to overcome drug therapies and immune responses that have previously controlled it. One new approach to vaccination—and possibly treatment-- includes using powerful human HIV-specific monoclonal antibodies [9] or other protective artificial proteins [10] as “gene therapy.” These proteins can be given “passively” or expressed continuously in nonhuman primates and have been shown to prevent infection when these animals are exposed to SHIV or SIV. Human trials of monoclonal antibodies have been proposed [11] and are underway in the setting of pre-exposure and post-exposure [12], based on the success of some of these antibodies in preventing infection in NHP models [13, 14].

Access to better and safer medicines, a prophylactic vaccine, and continuing preventive strategies are all still urgently needed to achieve the goal of and AIDS-free generation. Strategies known to reduce transmission include educating people about condom use, avoiding contaminated needles, using pre-exposure prophylaxis (PrEP), and treating HIV-infected mothers with drugs during labor to limit virus exposure [11]. With effective deployment of prevention and treatment strategies, many experts in the field believe it will be possible to control and stop the AIDS pandemic.

Article References

1. Gao F, Bailes E, Robertson DL, Chen Y, Rodenburg CM, Michael SF, et al.
Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes.
Nature. 1999;397(6718):436-41. doi: 10.1038/17130. PubMed PMID: 9989410.

2. Keele BF, Jones JH, Terio KA, Estes JD, Rudicell RS, Wilson ML, et al.
Increased mortality and AIDS-like immunopathology in wild chimpanzees infected with SIVcpz.
Nature. 2009;460(7254):515-9. Epub 2009/07/25. doi: nature08200 [pii]10.1038/nature08200. PubMed PMID: 19626114.

3. Hessell AJ, Haigwood NL.
Animal models in HIV-1 protection and therapy.
Curr Opin HIV AIDS. 2015. doi: 10.1097/COH.0000000000000152. PubMed PMID: 25730345.

4. Veazey RS.
Microbicide safety/efficacy studies in animals: macaques and small animal models.
Curr Opin HIV AIDS. 2008;3(5):567-73. Epub 2009/04/18. doi: 10.1097/COH.0b013e32830891bb01222929-200809000-00008 [pii]. PubMed PMID: 19373023.

5. Abdool Karim Q, Abdool Karim SS, Frohlich JA, Grobler AC, Baxter C, Mansoor LE, et al.
Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women.
Science. 2010;329(5996):1168-74. doi: 10.1126/science.1193748. PubMed PMID: 20643915; PubMed Central PMCID: PMCPMC3001187.

6. Van Rompay KK, Berardi CJ, Aguirre NL, Bischofberger N, Lietman PS, Pedersen NC, et al.
Two doses of PMPA protect newborn macaques against oral simian immunodeficiency virus infection.
AIDS. 1998;12(9):F79-83. PubMed PMID: 9662190.

7. Hansen SG, Piatak M, Jr., Ventura AB, Hughes CM, Gilbride RM, Ford JC, et al.
Immune clearance of highly pathogenic SIV infection.
Nature. 2013;502(7469):100-4. Epub 2013/09/13. doi: 10.1038/nature12519. PubMed PMID: 24025770; PubMed Central PMCID: PMC3849456.

8. Picker LJ, Hansen SG, Lifson JD.
New paradigms for HIV/AIDS vaccine development.
Annu Rev Med. 2012;63:95-111. Epub 2011/09/29. doi: 10.1146/annurev-med-042010-085643. PubMed PMID: 21942424.

9. Johnson PR, Schnepp BC, Zhang J, Connell MJ, Greene SM, Yuste E, et al.
Vector-mediated gene transfer engenders long-lived neutralizing activity and protection against SIV infection in monkeys.
Nat Med. 2009. Epub 2009/05/19. doi: nm.1967 [pii]10.1038/nm.1967. PubMed PMID: 19448633.

10. Gardner MR, Kattenhorn LM, Kondur HR, von Schaewen M, Dorfman T, Chiang JJ, et al.
AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges.
Nature. 2015;519(7541):87-91. doi: 10.1038/nature14264. PubMed PMID: 25707797; PubMed Central PMCID: PMCPMC4352131.

11. Voronin Y, Mofenson LM, Cunningham CK, Fowler MG, Kaleebu P, McFarland EJ, et al.
HIV monoclonal antibodies: a new opportunity to further reduce mother-to-child HIV transmission.
PLoS Med. 2014;11(4):e1001616. doi: 10.1371/journal.pmed.1001616. PubMed PMID: 24714363; PubMed Central PMCID: PMCPMC3979646.

12. Ledgerwood JE, Coates EE, Yamshchikov G, Saunders JG, Holman L, Enama ME, et al.
Safety, Pharmacokinetics, and Neutralization of the Broadly Neutralizing HIV-1 Human Monoclonal Antibody VRC01 in Healthy Adults.
Clin Exp Immunol. 2015. doi: 10.1111/cei.12692. PubMed PMID: 26332605.

13. Barouch DH, Whitney JB, Moldt B, Klein F, Oliveira TY, Liu J, et al.
Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys.
Nature. 2013;503(7475):224-8. doi: 10.1038/nature12744. PubMed PMID: 24172905; PubMed Central PMCID: PMCPMC4017780.

14. Shingai M, Nishimura Y, Klein F, Mouquet H, Donau OK, Plishka R, et al.
Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia.
Nature. 2013;503(7475):277-80. doi: 10.1038/nature12746. PubMed PMID: 24172896; PubMed Central PMCID: PMCPMC4133787.

15. Hutter G, Nowak D, Mossner M, Ganepola S, Mussig A, et al. (2009)
Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation.
The New England journal of medicine 360: 692–698. doi: 10.1056/nejmoa0802905. PubMed PMID: 19213682

Recent NPRC Publications


Arunachalam PS, Charles TP, Joag V, Bollimpelli VS, Scott MKD, Wimmers F, Burton SL, Labranche CC, Petitdemange C, Gangadhara S, Styles TM, Quarnstrom CF, Walter KA, Ketas TJ, Legere T, Jagadeesh Reddy PB, Kasturi SP, Tsai A, Yeung BZ, Gupta S, Tomai M, Vasilakos J, Shaw GM, Kang CY, Moore JP, Subramaniam S, Khatri P, Montefiori D, Kozlowski PA, Derdeyn CA, Hunter E, Masopust D, Amara RR, Pulendran B
T cell-inducing vaccine durably prevents mucosal SHIV infection even with lowerneutralizing antibody titers.
Nat Med. 2020 May 11. pii: 10.1038/s41591-020-0858-8. doi:10.1038/s41591-020-0858-8. 2020.

Bauer AM, Ziani W, Lindemuth E, Kuri-Cervantes L, Li H, Lee FH, Watkins M, Xu H, Veazey R, Bar KJ
Novel transmitted/founder SHIVs for HIV latency and cure research.
J Virol. 2020 Jan 22. pii: JVI.01659-19. doi: 10.1128/JVI.01659-19. 2020.

Estep RD, Govindan AN, Manoharan M, Li H, Fei SS, Park BS, Axthelm MK, Wong SW
Molecular analysis of lymphoid tissue from rhesus macaque rhadinovirus-infectedmonkeys identifies alterations in host genes associated with oncogenesis.
PLoS One. 2020 Feb 4;15(2):e0228484. doi: 10.1371/journal.pone.0228484.eCollection 2020. 2020.

Felber BK, Lu Z, Hu X, Valentin A, Rosati M, Remmel CAL, Weiner JA, Carpenter MC, Faircloth K, Stanfield-Oakley S, Williams WB, Shen X, Tomaras GD, LaBranche CC, Montefiori D, Trinh HV, Rao M, Alam MS, Vandergrift NA, Saunders KO, Wang Y, Rountree W, Das J, Alter G, Reed SG, Aye PP, Schiro F, Pahar B, Dufour JP, Veazey RS, Marx PA, Venzon DJ, Shaw GM, Ferrari G, Ackerman ME, Haynes BF, Pavlakis GN
Co-immunization of DNA and Protein in the Same Anatomical Sites Induces Superior Protective Immune Responses against SHIV Challenge.
Cell Rep. 2020 May 12;31(6):107624. doi: 10.1016/j.celrep.2020.107624. 2020.

Fuchs SP, Martinez-Navio JM, Rakasz EG, Gao G, Desrosiers RC
Liver-Directed but Not Muscle-Directed AAV-Antibody Gene Transfer Limits Humoral Immune Responses in Rhesus Monkeys.
Mol Ther Methods Clin Dev. 2019 Nov 26;16:94-102. doi:10.1016/j.omtm.2019.11.010. eCollection 2020 Mar 13. 2020.


Other Key HIV/AIDS Publications (NPRC and Non-NPRC)

Recent News Articles

June 19, 2020
Emory Researchers Show New Adjuvant Successful in Extending Immunity Against HIV

May 11, 2020
New HIV Vaccine Combination Strategy Provides Better and More Durable Protection

March 17, 2020
Immunotherapy Combo Achieves Reservoir Shrinkage in HIV Model

February 26, 2020
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January 22, 2019
In animal models, a 'shocking' step toward a potential HIV cure

January 7, 2020
OHSU study shows promise for preventing mother-to-baby HIV transmission

January 7, 2020
Antibody HIV therapy for primate newborns shows potential as therapy

January 7, 2020
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January 7, 2020
Single dose of antibodies can knock out HIV in newborns

November 21, 2019
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September 11, 2019
Texas Biomed Researchers Pinpoint Why HIV Patients Are More Likely to Develop Tuberculosis

July 29, 2019
Breakthrough at Texas research institute may hold key to managing HIV infections

July 24, 2019
Scientists Pinpoint New Mechanism that Impacts HIV Infection

June 26, 2019
NIH Funds Creation of New Lab Model for TB/HIV Research

May 15, 2019
Shelby O’Connor Part of $6m International Grant to Study HIV/TB Coinfection

April 30, 2019
Tulane University awarded $6.1 million to study HIV, tuberculosis in infants

April 29, 2019
Huge step in HIV fight is happening in San Antonio

April 29, 2019
International Collaboration between Texas Biomedical Research Institute and Mymetics Corporation in Switzerland Receives Funding from NIH for Novel HIV Vaccine Study

April 9, 2019
TXBioBytes from Texas Biomed Episode 032 — TB and HIV: Battling Back Against a One-Two Punch

March 19, 2019
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February 11, 2019
New Discovery Could Lead to Ways to Protect HIV Patients from Deadly Tuberculosis

November 20, 2018
TX BioBytes from Texas Biomed Episode 022 – Promising Protection Against a Killer

October 31, 2018
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October 9, 2018
TX BioBytes from Texas Biomed Podcast Episode 019 — HIV and the Genome: The Other 97%

September 28, 2018
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September 26, 2018
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September 18, 2018
TXBioBytes from Texas Biomed Episode 017 — Promising Protection Against HIV

July 29, 2018
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July 27, 2018
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July 24, 2018
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November 30, 2017
Scientists are getting close to a new HIV vaccine after warnings of a European epidemic

October 17, 2017
Reservoir Explorers Find Extra HIV/SIV Pond

February 24th, 2017
CNPRC Core Scientist Tapped for Chancellor’s Achievement Award

January 31, 2017
Select Antiviral Cells Can Access HIV's Hideouts

December 1, 2016
2016 Was A Banner Year For HIV/AIDS Research

November 22, 2016

November 09, 2016
Scientists Achieve 'Functional Cure' for HIV in Monkey Model

October 14, 2016
New therapy 'cures' monkeys of HIV-like virus, could offer breakthrough for treatment in humans

October 13, 2016
A drug used to treat Crohn’s disease could suppress HIV, monkey study suggests

October 13, 2016
Experiment in Monkeys Raises Hopes of 'Functional Cure' for HIV

September 6, 2016
Other layers of immunity in TB/HIV co-infections discovered

September 6, 2016
Tulane researchers find other layers of immunity in TB/HIV co-infections

July 21, 2016
Immune-Enhancing Treatment May Destabilize HIV Reservoirs

July 21, 2016
Comprehensive HIV vaccine project funded at $23 million by NIH

June 15, 2016
No Monkeying Around With An HIV Vaccine

June 10, 2016
HIV Vaccine Developed Through Primate Centers Collaboration

June 7, 2016
NIH Awards Emory $35.6 Million Grant for Rresearch Aimed at HIV/AIDS Vaccine and Cure

May 31, 2016
News Release: Schistosome drug resistance study

May 31, 2016
HIV – Defense in Depth: Texas Biomedical Research Institute scientist creates a defense-in-depth strategy for HIV vaccine development

April 11, 2016
Mymetics’ HIV vaccine candidate confirms promise in preclinical study with the Texas Biomed

March 21, 2016
Giving antibodies to infant macaques exposed to an HIV-like virus could clear infection

March 21, 2016
OHSU study: Special antibodies may stop newborn HIV

January 14, 2016
Scientists uncover how part of a protein helps primates fight HIV

January 12, 2016
Cellular pathway discovered that may re-energize immune cells to eliminate HIV

December 22, 2015
Tulane receives $4.2 million to study cure for HIV

December 3, 2015
Texas Biomed receives $5 million grant to study possible functional cure for babies born with HIV

December 1, 2015
Designing an HIV Cure With Kenneth Cole and amfAR

November 9, 2015
IL-21 repairs immune function in primate model of HIV infection

August 11, 2015
SIV shrugs off antibodies in vaccinated monkeys

August 7th, 2015
Exposure to SIV in utero results in reduced viral loads and altered responsiveness to postnatal challenge

July 24, 2015
Animal research crucial to creating AIDS treatments

June 18, 2015
HIV-1 neutralizing antibodies induced by native-like envelope trimers

April 30, 2015
Texas Biomed scientist receives nearly $3.4 million NIH grant to study Papillomavirus-based AIDS vaccine for dual protection against HIV and HPV-induced Cancer

March 9th, 2015
Novel Tool Captures Total Body SIV Replication

February 20th, 2015
Gram of prevention, kilo of cure: UW-Madison plays key role in next phase of AIDS research

February 18th, 2015
AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges

February 18th, 2015
Molecule Shows Ability to Block AIDS Virus

February 18th, 2015
Scientists announce anti-HIV agent so powerful it can work in a vaccine

January 15th, 2015
Human mode of responding to HIV vaccine is conserved from monkeys

January 2nd, 2015
HIV vaccines should avoid viral target cells, primate model study suggests

November 25th, 2014
Masking HIV target cells prevents viral transmission in animal model

November 3, 2014
New research sheds light on future efforts to eradicate HIV from the body in human patients

November 1st, 2014
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October 31st, 2014
Immune cells proposed as HIV hideout don't last in primate model

October 30th, 2014
Early HIV infection and potential therapeutic targets

January 18, 2000
Updated treatment guidelines for HIV infection announced by international panel of AIDS experts