Abstract
Human immunodeficiency virus (HIV), the main contributor of the ongoing AIDS epidemic, remains one of the most challenging and complex viruses to target and eradicate due to frequent genome mutation and immune evasion. Despite the development of potent antiretroviral therapies, HIV remains an incurable infection as the virus persists in latent reservoirs throughout the body. To innovate a safe and effective cure strategy for HIV in humans, animal models are needed to better understand viral proliferation, disease progression, and therapeutic response. Nonhuman primates infected with simian immunodeficiency virus (SIV) provide an ideal model to study HIV infection and pathogenesis as they are closely related to humans genetically and express phenotypically similar immune systems. Examining the clinical outcomes of novel treatment strategies within nonhuman primates facilitates our understanding of HIV latency and advances the development of a true cure to HIV.
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References
Ahlenstiel CL, Symonds G, Kent SJ, Kelleher AD (2020) Block and lock HIV cure strategies to control the latent reservoir. Front Cell Infect Microbiol 10. Available at https://doi.org/10.3389/fcimb.2020.00424 [Accessed December 20, 2022]
Ahn K, Lee SJ, Mook-Jung I (2022) White matter-associated microglia: new players in brain aging and neurodegenerative diseases. Ageing Res Rev 75:101574. https://doi.org/10.1016/j.arr.2022.101574
Alkhatib G, Combadiere C, Broder CC, Feng Y, Kennedy PE, Murphy PM et al (1996) CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science 272:1955–1958. https://doi.org/10.1126/science.272.5270.1955
Alzahrani J, Hussain T, Simar D, Palchaudhuri R, Abdel-Mohsen M, Crowe SM et al (2019) Inflammatory and immunometabolic consequences of gut dysfunction in HIV: parallels with IBD and implications for reservoir persistence and non-AIDS comorbidities. EBioMedicine 46:522–531. https://doi.org/10.1016/j.ebiom.2019.07.027
Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M et al (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–1799. https://doi.org/10.1212/01.WNL.0000287431.88658.8b
Antiretroviral Drug Discovery and Development | NIH: National Institute of Allergy and Infectious Diseases (2023). Available at https://www.niaid.nih.gov/diseases-conditions/antiretroviral-drug-development [Accessed May 12, 2023].
Archin NM, Kirchherr JL, Sung JAM, Clutton G, Sholtis K, Xu Y et al (2017) Interval dosing with the HDAC inhibitor vorinostat effectively reverses HIV latency. J Clin Invest 127:3126–3135. https://doi.org/10.1172/JCI92684
Ash MK, Al-Harthi L, Schneider JR (2021) HIV in the brain: identifying viral reservoirs and addressing the challenges of an HIV cure. Vaccines 9:867. https://doi.org/10.3390/vaccines9080867
Bailon L, Mothe B, Berman L, Brander C (2020) Novel approaches towards a functional cure of HIV/AIDS. Drugs 80:859–868. https://doi.org/10.1007/s40265-020-01322-y
Bar KJ, Coronado E, Hensley-McBain T, O’Connor MA, Osborn JM, Miller C et al (2019) Simian-human immunodeficiency virus SHIV.CH505 infection of rhesus macaques results in persistent viral replication and induces intestinal immunopathology. J Virol 93:e00372–e419. https://doi.org/10.1128/JVI.00372-19
Barnes CB, Schoofs T (2022) Sequential immunization of macaques elicits heterologous neutralizing antibodies targeting the V3-glycan patch of HIV-1 Env. https://doi.org/10.1126/scitranslmed.abk1533
Beck SE, Queen SE, Metcalf Pate KA, Mangus LM, Abreu CM, Gama L et al (2018) An SIV/macaque model targeted to study HIV-associated neurocognitive disorders. J Neurovirol 24:204–212. https://doi.org/10.1007/s13365-017-0582-4
Bell JE (1998) The neuropathology of adult HIV infection. Rev Neurol (paris) 154:816–829
Bimber BN, Ramakrishnan R, Cervera-Juanes R, Madhira R, Peterson SM, Norgren RB et al (2017) Whole genome sequencing predicts novel human disease models in rhesus macaques. Genomics 109:214–220. https://doi.org/10.1016/j.ygeno.2017.04.001
Blassel L, Zhukova A, Villabona-Arenas CJ, Atkins KE, Hué S, Gascuel O (2021) Drug resistance mutations in HIV: new bioinformatics approaches and challenges. Curr Opin Virol 51. https://doi.org/10.1016/j.coviro.2021.09.009
Bleul CC, Wu L, Hoxie JA, Springer TA, Mackay CR (1997) The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes. Proc Natl Acad Sci 94:1925–1930. https://doi.org/10.1073/pnas.94.5.1925
Borrajo A, Spuch C, Penedo MA, Olivares JM, Agís-Balboa RC (2020) Important role of microglia in HIV-1 associated neurocognitive disorders and the molecular pathways implicated in its pathogenesis. Ann Med 53:43–69. https://doi.org/10.1080/07853890.2020.1814962
Bricker KM, Chahroudi A, Mavigner M (2021) New latency reversing agents for HIV-1 cure: insights from nonhuman primate models. Viruses 13:1560. https://doi.org/10.3390/v13081560
Burdo TH, Soulas C, Orzechowski K, Button J, Krishnan A, Sugimoto C et al (2010) Increased monocyte turnover from bone marrow correlates with severity of SIV encephalitis and CD163 levels in plasma. PLoS Pathog 6:e1000842. https://doi.org/10.1371/journal.ppat.1000842
Busman-Sahay K, Starke CE, Nekorchuk MD, Estes JD (2021) Eliminating HIV reservoirs for a cure: the issue is in the tissue. Curr Opin HIV AIDS 16:200–208. https://doi.org/10.1097/COH.0000000000000688
Carlon-Andres I, Malinauskas T, Padilla-Parra S (2021) Structure dynamics of HIV-1 Env trimers on native virions engaged with living T cells. Commun Biol 4:1–14. https://doi.org/10.1038/s42003-021-02658-1
Chang WLW, Gonzalez DF, Kieu HT, Castillo LD, Messaoudi I, Shen X et al (2017) Changes in circulating B cell subsets associated with aging and acute SIV infection in rhesus macaques. PloS One 12:e0170154. https://doi.org/10.1371/journal.pone.0170154
Chawla A, Wang C, Patton C, Murray M, Punekar Y, de Ruiter A et al (2018) A review of long-term toxicity of antiretroviral treatment regimens and implications for an aging population. Infect Dis Ther 7. https://doi.org/10.1007/s40121-018-0201-6
Cicconi P, Cozzi-Lepri A, Castagna A, Trecarichi EM, Antinori A, Gatti F et al (2010) Insights into reasons for discontinuation according to year of starting first regimen of highly active antiretroviral therapy in a cohort of antiretroviral-naïve patients. HIV Med 11:104–113. https://doi.org/10.1111/j.1468-1293.2009.00750.x
Clifford DB, Ances BM (2013) HIV-associated neurocognitive disorder (HAND). Lancet Infect Dis 13:976–986. https://doi.org/10.1016/S1473-3099(13)70269-X
Collier AC, Coombs RW, Schoenfeld DA, Bassett R, Baruch A, Corey L (1996) Combination therapy with zidovudine, didanosine and saquinavir. Antiviral Res 29:99. https://doi.org/10.1016/0166-3542(95)00928-0
Crise B, Li Y, Yuan C, Morcock DR, Whitby D, Munroe DJ et al (2005) Simian immunodeficiency virus integration preference is similar to that of human immunodeficiency virus type 1. J Virol 79:12199–12204. https://doi.org/10.1128/JVI.79.19.12199-12204.2005
Cummins NW, Sainski AM, Dai H, Natesampillai S, Pang Y-P, Bren GD et al (2016) Prime, shock, and kill: priming CD4 T cells from HIV patients with a BCL-2 antagonist before HIV reactivation reduces HIV reservoir size. J Virol 90:4032–4048. https://doi.org/10.1128/JVI.03179-15
Daniel M, King N, Letvin N, Hunt R, Seghal P, Desrosiers R (1984). A New Type D Retrovirus Isolated from Macaques with an Immunodeficiency Syndrome. https://doi.org/10.1126/science.6695172
Delery EC, MacLean AG (2019) Chronic viral neuroinflammation: speculation on underlying mechanisms. Viral Immunol 32:55–62. https://doi.org/10.1089/vim.2018.0093
Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M et al (1996) Identification of a major co-receptor for primary isolates of HIV-1. Nature 381:661–666. https://doi.org/10.1038/381661a0
Didier ES, MacLean AG, Mohan M, Didier PJ, Lackner AA, Kuroda MJ (2016) Contributions of nonhuman primates to research on aging. Vet Pathol 53:277–290. https://doi.org/10.1177/0300985815622974
Dock JN, Effros RB (2011) Role of CD8 T cell replicative senescence in human aging and in HIV-mediated immunosenescence. Aging Dis 2:382–397
Dos Santos SE, Medeiros M, Porfirio J, Tavares W, Pessôa L, Grinberg L et al (2020) Similar microglial cell densities across brain structures and mammalian species: implications for brain tissue function. J Neurosci 40:4622–4643. https://doi.org/10.1523/JNEUROSCI.2339-19.2020
Dragic T, Litwin V, Allaway GP, Martin SR, Huang Y, Nagashima KA et al (1996) HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature 381:667–673. https://doi.org/10.1038/381667a0
Eggers C, Arendt G, Hahn K, Husstedt IW, Maschke M, Neuen-Jacob E et al (2017) HIV-1-associated neurocognitive disorder: epidemiology, pathogenesis, diagnosis, and treatment. J Neurol 264. https://doi.org/10.1007/s00415-017-8503-2
Elliott JH, McMahon JH, Chang CC, Lee SA, Hartogensis W, Bumpus N et al (2015) Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study. Lancet HIV 2:e520–e529. https://doi.org/10.1016/S2352-3018(15)00226-X
El-Sadr WM, Lundgren JD, Neaton JD, Abrams D, Arduino RC (2006) CD4+ count–guided interruption of antiretroviral treatment. N Engl J Med 355. https://doi.org/10.1056/NEJMoa062360
Estes JD, Kityo C, Ssali F, Swainson L, Makamdop KN, Del Prete GQ et al (2017) Defining total-body AIDS-virus burden with implications for curative strategies. Nat Med 23:1271–1276. https://doi.org/10.1038/nm.4411
Estes JD, Wong SW, Brenchley JM (2018) Nonhuman primate models of human viral infections. Nat Rev Immunol 18:390–404. https://doi.org/10.1038/s41577-018-0005-7
Eugenin EA, Osiecki K, Lopez L, Goldstein H, Calderon TM, Berman JW (2006) CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected Leukocytes across the blood–brain barrier: a potential mechanism of HIV–CNS invasion and NeuroAIDS. J Neurosci 26:1098–1106. https://doi.org/10.1523/JNEUROSCI.3863-05.2006
Excision BioTherapeutics (2022) A phase 1/2a, sequential cohort, single ascending dose study of the safety, tolerability, biodistribution, and pharmacodynamics of EBT 101 in aviremic HIV-1 infected adults on stable antiretroviral therapy. clinicaltrials.gov Available at https://clinicaltrials.gov/ct2/show/NCT05144386 [Accessed January 11, 2023].
Ferrucci L, Fabbri E (2018) Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol 15:505–522. https://doi.org/10.1038/s41569-018-0064-2
Fischl MA, Richman DD, Grieco MH, Gottlieb MS, Volberding PA, Laskin OL et al (1987) The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med 317:185–191. https://doi.org/10.1056/NEJM198707233170401
Gardner MR, Kattenhorn LM, Kondur HR, von Schaewen M, Dorfman T, Chiang JJ et al (2015) AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges. Nature 519:87–91. https://doi.org/10.1038/nature14264
Ghosh AK, Sarkar A, Mitsuya H (2017) HIV-associated neurocognitive disorder (HAND) and the prospect of brain-penetrating protease inhibitors for antiretroviral treatment. Med Res Arch 5:1113
Global HIV & AIDS statistics — Fact sheet (2023) Available at https://www.unaids.org/en/resources/fact-sheet [Accessed December 15, 2022]
Guaraldi G, Orlando G, Zona S, Menozzi M, Carli F, Garlassi E et al (2011) Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis off Publ Infect Dis Soc Am 53:1120–1126. https://doi.org/10.1093/cid/cir627
Gupta RK, Abdul-Jawad S, McCoy LE, Mok HP, Peppa D, Salgado M et al (2019) HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation. Nature 568:244–248. https://doi.org/10.1038/s41586-019-1027-4
Hatziioannou T, Evans DT (2012) Animal models for HIV/AIDS research. Nat Rev Microbiol 10:852–867. https://doi.org/10.1038/nrmicro2911
Heaton RK, Clifford DB, Franklin DR, Woods SP, Ake C, Vaida F et al (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER study. Neurology 75:2087–2096. https://doi.org/10.1212/WNL.0b013e318200d727
Heigele A, Joas S, Regensburger K, Kirchhoff F (2015) Increased susceptibility of CD4+ T cells from elderly individuals to HIV-1 infection and apoptosis is associated with reduced CD4 and enhanced CXCR4 and FAS surface expression levels. Retrovirology 12:86. https://doi.org/10.1186/s12977-015-0213-1
Heusinger E, Kirchhoff F (2017) Primate lentiviruses modulate NF-κB activity by multiple mechanisms to fine-tune viral and cellular gene expression. Front Microbiol 8. Available at https://doi.org/10.3389/fmicb.2017.00198 [Accessed January 17, 2023]
HIV clinical guidelines: Adult and adolescent ARV - what’s new in the guidelines | Clinicalinfo.HIV.gov (2023) Available at https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/whats-new [Accessed May 12, 2023].
Holkmann Olsen C, Mocroft A, Kirk O, Vella S, Blaxhult A, Clumeck N et al (2007) Interruption of combination antiretroviral therapy and risk of clinical disease progression to AIDS or death. HIV Med 8:96–104. https://doi.org/10.1111/j.1468-1293.2007.00436.x
Humes D, Emery S, Laws E, Overbaugh J (2012) A species-specific amino acid difference in the macaque CD4 receptor restricts replication by global circulating HIV-1 variants representing viruses from recent infection. J Virol 86:12472–12483. https://doi.org/10.1128/JVI.02176-12
Hütter G, Ganepola S, Schneider T, Blau O, Thiel E (2009) Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med
Ilyinskii PO, Simon MA, Czajak SC, Lackner AA, Desrosiers RC (1997) Induction of AIDS by simian immunodeficiency virus lacking NF-kappaB and SP1 binding elements. J Virol 71:1880–1887
Jiang G, Dandekar S (2015) Targeting NF-κB signaling with protein kinase C agonists as an emerging strategy for combating HIV latency. AIDS Res Hum Retroviruses 31:4–12. https://doi.org/10.1089/AID.2014.0199
Jiang Y, Tian B, Saifuddin M, Agy MB, Emau P, Cairns JS et al (2009) RT-SHIV, an infectious CCR5-tropic chimeric virus suitable for evaluating HIV reverse transcriptase inhibitors in macaque models. AIDS Res Ther 6:23. https://doi.org/10.1186/1742-6405-6-23
Joag SV, Li Z, Foresman L, Stephens EB, Zhao LJ, Adany I et al (1996) Chimeric simian/human immunodeficiency virus that causes progressive loss of CD4+ T cells and AIDS in pig-tailed macaques. J Virol 70. https://doi.org/10.1128/JVI.70.5.3189-3197.1996
Kim Y, Anderson JL, Lewin SR (2018) Getting the “kill” into “shock and kill”: strategies to eliminate latent HIV. Cell Host Microbe 23:14–26. https://doi.org/10.1016/j.chom.2017.12.004
Kirschner DE, Webb GF (1997) Understanding drug resistance for monotherapy treatment of HIV infection. Bull Math Biol 59:763–785. https://doi.org/10.1007/BF02458429
Kovalevich J, Langford D (2012) Neuronal toxicity in HIV CNS disease. Future Virol 7:687–698. https://doi.org/10.2217/fvl.12.57
Kwan TH, Chan CP, Wong NS, Lee SS (2022) Awareness of HIV functional cure and willingness in participating in related clinical trials: comparison between antiretroviral naïve and experienced men who have sex with men living with HIV. BMC Infect Dis 22:383. https://doi.org/10.1186/s12879-022-07346-x
Lambros K, Jens V, Stefan E (2014) Shift of HIV tropism in stem-cell transplantation with CCR5 Delta32 mutation. N Engl J Med 371. https://doi.org/10.1056/NEJMc1405805
Lepri AC, Sabin CA, Staszewski S, Hertogs K, Müller A, Rabenau H et al (2000) Resistance profiles in patients with viral rebound on potent antiretroviral therapy. J Infect Dis 181:1143–1147. https://doi.org/10.1086/315301
Li H, Wang S, Lee F-H, Roark RS, Murphy AI, Smith J et al (2021) New SHIVs and improved design strategy for modeling HIV-1 transmission, immunopathogenesis, prevention, and cure. J Virol 95:e00071–e121. https://doi.org/10.1128/JVI.00071-21
Liu Y, Cao W, Sun M, Li T (2020) Broadly neutralizing antibodies for HIV-1: efficacies, challenges and opportunities. Emerg Microbes Infect 9:194–206. https://doi.org/10.1080/22221751.2020.1713707
MacLean AG, Rasmussen TA, Bieniemy D, Lackner AA (2004) Activation of the blood-brain barrier by SIV (simian immunodeficiency virus) requires cell-associated virus and is not restricted to endothelial cell activation. Biochem Soc Trans 32:750–752. https://doi.org/10.1042/BST0320750
Magness CL, Fellin PC, Thomas MJ, Korth MJ, Agy MB, Proll SC et al (2005) Analysis of the Macaca mulatta transcriptome and the sequence divergence between Macaca and human. Genome Biol. 6. https://doi.org/10.1186/gb-2005-6-7-r60
Mallard J, Williams K (2018) An SIV macaque model of SIV and HAND: the need for adjunctive therapies in HIV that target activated monocytes and macrophages. J Neurovirol 24:213–219. https://doi.org/10.1007/s13365-018-0616-6
Mamik MK, Asahchop EL, Chan WF, Zhu Y, Branton WG, McKenzie BA et al (2016) Insulin treatment prevents neuroinflammation and neuronal injury with restored neurobehavioral function in models of HIV/AIDS neurodegeneration. J Neurosci off J Soc Neurosci 36:10683–10695. https://doi.org/10.1523/JNEUROSCI.1287-16.2016
Mancuso P, Chen C, Kaminski R, Gordon J, Liao S, Robinson JA et al (2020) CRISPR based editing of SIV proviral DNA in ART treated non-human primates. Nat Commun 11:6065. https://doi.org/10.1038/s41467-020-19821-7
Mattison JA, Vaughan KL (2017) An overview of nonhuman primates in aging research. Exp Gerontol 94:41. https://doi.org/10.1016/j.exger.2016.12.005
McBrien JB, Wong AKH, White E, Carnathan DG, Lee JH, Safrit JT et al (2020) Combination of CD8β depletion and interleukin-15 superagonist N-803 induces virus reactivation in simian-human immunodeficiency virus-infected, long-term ART-treated rhesus macaques. J Virol 94:e00755–e820. https://doi.org/10.1128/JVI.00755-20
Mediouni S, Kessing CF, Jablonski JA, Thenin-Houssier S, Clementz M, Kovach MD et al (2019) The Tat inhibitor didehydro-cortistatin A suppresses SIV replication and reactivation. FASEB. J off Publ Fed Am Soc Exp Biol 33:8280–8293. https://doi.org/10.1096/fj.201801165R
Meir-Shafrir K, Pollack S (2012) Accelerated aging in HIV patients. Rambam Maimonides Med J 3:e0025. https://doi.org/10.5041/RMMJ.10089
Meng TC, Fischl MA, Boota AM, Spector SA, Bennett D, Bassiakos Y et al (1992) Combination therapy with zidovudine and dideoxycytidine in patients with advanced human immunodeficiency virus infection. A phase I/II study. Ann Intern Med 116:13–20. https://doi.org/10.7326/0003-4819-116-1-13
Mittelbronn M, Dietz K, Schluesener HJ, Meyermann R (2001) Local distribution of microglia in the normal adult human central nervous system differs by up to one order of magnitude. Acta Neuropathol (berl) 101:249–255. https://doi.org/10.1007/s004010000284
Moretti S, Virtuoso S, Sernicola L, Farcomeni S, Maggiorella MT, Borsetti A (2021) Advances in SIV/SHIV non-human primate models of NeuroAIDS. Pathogens 10:1018. https://doi.org/10.3390/pathogens10081018
Naif HM (2013) Pathogenesis of HIV infection. Infect Dis Rep 5. https://doi.org/10.4081/idr.2013.s1.e6
Navia BA, Jordan BD, Price RW (1986) The AIDS dementia complex: I. Clinical Features Ann Neurol 19:517–524. https://doi.org/10.1002/ana.410190602
Okoye AA, Hansen SG, Vaidya M, Fukazawa Y, Park H, Duell DM et al (2018) Early antiretroviral therapy limits SIV reservoir establishment to delay or prevent post-treatment viral rebound. Nat Med 24:1430–1440. https://doi.org/10.1038/s41591-018-0130-7
Perez S, Johnson A-M, Xiang S, Li J, Foley BT, Doyle-Meyers L et al (2018) Persistence of SIV in the brain of SIV-infected Chinese rhesus macaques with or without antiretroviral therapy. J Neurovirol 24:62–74. https://doi.org/10.1007/s13365-017-0594-0
Peterson CW, Wang J, Deleage C, Reddy S, Kaur J, Polacino P et al (2018) Differential impact of transplantation on peripheral and tissue-associated viral reservoirs: implications for HIV gene therapy. PLoS Pathog 14:e1006956. https://doi.org/10.1371/journal.ppat.1006956
Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, Paris R et al (2009) Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 361:2209–2220. https://doi.org/10.1056/NEJMoa0908492
Robertson KR, Smurzynski M, Parsons TD, Wu K, Bosch RJ, Wu J et al (2007) The prevalence and incidence of neurocognitive impairment in the HAART era. AIDS Lond Engl 21:1915–1921. https://doi.org/10.1097/QAD.0b013e32828e4e27
Rumbaugh JA, Tyor W (2015) HIV-Associated Neurocognitive Disorders Neurol Clin Pract 5:224–231. https://doi.org/10.1212/CPJ.0000000000000117
Saylor D, Dickens AM, Sacktor N, Haughey N, Slusher B, Pletnikov M et al (2016) HIV-associated neurocognitive disorder — pathogenesis and prospects for treatment. Nat Rev Neurol 12:234–248. https://doi.org/10.1038/nrneurol.2016.27
Scarlatti G, Tresoldi E, Björndal A, Fredriksson R, Colognesi C, Deng HK et al (1997) In vivo evolution of HIV-1 co-receptor usage and sensitivity to chemokine-mediated suppression. Nat Med 3:1259–1265. https://doi.org/10.1038/nm1197-1259
Seitz R (2016) Human immunodeficiency virus (HIV). Transfus Med Hemotherapy 43:203–222. https://doi.org/10.1159/000445852
Sharma S, Thomas PG (2014) The two faces of heterologous immunity: protection or immunopathology. J Leukoc Biol 95:405–416. https://doi.org/10.1189/jlb.0713386
Siliciano RF, Greene WC (2011) HIV latency. Cold Spring Harb Perspect Med 1:a007096. https://doi.org/10.1101/cshperspect.a007096
Silva de Castro I, Gordon SN, Liu J, Bissa M, McKinnon K, Trinh HV et al (2020) Expression of CD40L by the ALVAC-simian immunodeficiency virus vector abrogates T cell responses in macaques. J Virol 94:e01933–e2019. https://doi.org/10.1128/JVI.01933-19
Sivanandham R, Kleinman AJ, Sette P, Brocca-Cofano E, Kilapandal Venkatraman SM, Policicchio BB et al (2020) Nonhuman primate testing of the impact of different regulatory T cell depletion strategies on reactivation and clearance of latent simian immunodeficiency virus. J Virol 94:e00533–e620. https://doi.org/10.1128/JVI.00533-20
Stone WH, Treichel RC, VandeBerg JL (1987) Genetic significance of some common primate models in biomedical research. Prog Clin Biol Res 229:73–93
Sugiyama R, Habu Y, Ohnari A, Miyano-Kurosaki N, Takaku H (2009) RNA interference targeted to the conserved dimerization initiation site (DIS) of HIV-1 restricts virus escape mutation. J Biochem (tokyo) 146:481–489. https://doi.org/10.1093/jb/mvp093
Sun T, Hevner RF (2014) Growth and folding of the mammalian cerebral cortex: from molecules to malformations. Nat Rev Neurosci 15:217–232. https://doi.org/10.1038/nrn3707
Thippeshappa R, Kimata JT, Kaushal D (2020) Toward a macaque model of HIV-1 infection: roadblocks, progress, and future strategies. Front Microbiol 11. Available at https://doi.org/10.3389/fmicb.2020.00882 [Accessed January 7, 2023].
Tsai CC, Follis KE, Benveniste RE (1988) Antiviral effects of 3’-azido-3’-deoxythymidine, 2’,3’-dideoxycytidine, and 2’,3’-dideoxyadenosine against simian acquired immunodeficiency syndrome-associated type D retrovirus in vitro. AIDS Res Hum Retroviruses 4:359–368. https://doi.org/10.1089/aid.1988.4.359
Tseng A, Seet J, Phillips E (2015) The evolution of three decades of antiretroviral therapy: challenges, triumphs and the promise of the future. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309625/
Valcour V, Chalermchai T, Sailasuta N, Marovich M, Lerdlum S, Suttichom D et al (2012) Central nervous system viral invasion and inflammation during acute HIV infection. J Infect Dis 206:275–282. https://doi.org/10.1093/infdis/jis326
Valcour V, Yee P, Williams AE, Shiramizu B, Watters M, Selnes O et al (2006) Lowest ever CD4 lymphocyte count (CD4 nadir) as a predictor of current cognitive and neurological status in human immunodeficiency virus type 1 infection–the Hawaii Aging with HIV Cohort. J Neurovirol 12:387–391. https://doi.org/10.1080/13550280600915339
Vallender EJ, Miller GM (2013) Nonhuman primate models in the genomic era: a paradigm shift. ILAR J 54:154–165. https://doi.org/10.1093/ilar/ilt044
Van Duyne R, Kuo LS, Pham P, Fujii K, Freed EO (2019) Mutations in the HIV-1 envelope glycoprotein can broadly rescue blocks at multiple steps in the virus replication cycle. Proc Natl Acad Sci 116:9040–9049. https://doi.org/10.1073/pnas.1820333116
Veazey RS, DeMaria M, Chalifoux LV, Shvetz DE, Pauley DR, Knight HL et al (1998) Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science 280:427–431. https://doi.org/10.1126/science.280.5362.427
Veazey RS, Lackner AA (2017) Nonhuman primate models and understanding the pathogenesis of HIV infection and AIDS. ILAR J 58:160–171. https://doi.org/10.1093/ilar/ilx032
Verheyen J, Thielen A, Lubke N, Dirks M, Widera M, Dittmer U et al (2019) Rapid rebound of a preexisting CXCR4-tropic human immunodeficiency virus variant after allogeneic transplantation with CCR5 Δ32 homozygous stem cells. https://doi.org/10.1093/cid/ciy565
Walker EM, Slisarenko N, Gerrets GL, Kissinger PJ, Didier ES, Kuroda MJ et al (2019) Inflammaging phenotype in rhesus macaques is associated with a decline in epithelial barrier-protective functions and increased pro-inflammatory function in CD161-expressing cells. GeroScience 41:739–757. https://doi.org/10.1007/s11357-019-00099-7
Wei J, Hou J, Su B, Jiang T, Guo C, Wang W et al (2020) The prevalence of Frascati-criteria-based HIV-associated neurocognitive disorder (HAND) in HIV-infected adults: a systematic review and meta-analysis. Front Neurol 11. https://doi.org/10.3389/fneur.2020.581346
Wei X, Decker JM, Wang S, Hui H, Kappes JC, Wu X et al (2003) Antibody neutralization and escape by HIV-1. Nature 422:307–312. https://doi.org/10.1038/nature01470
Welles HC, Jennewein MF, Mason RD, Narpala S, Wang L, Cheng C et al (2018) Vectored delivery of anti-SIV envelope targeting mAb via AAV8 protects rhesus macaques from repeated limiting dose intrarectal swarm SIVsmE660 challenge. PLoS Pathog 14:e1007395. https://doi.org/10.1371/journal.ppat.1007395
Williams DW, Eugenin EA, Calderon TM, Berman JW (2012) Monocyte maturation, HIV susceptibility, and transmigration across the blood brain barrier are critical in HIV neuropathogenesis. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3289493/
Wing EJ (2017) The aging population with HIV infection. Trans Am Clin Climatol Assoc 128:131–144
Wu F, Ourmanov I, Riddick N, Matsuda K, Whitted S, Plishka RJ et al (2015) TRIM5α restriction affects clinical outcome and disease progression in simian immunodeficiency virus-infected rhesus macaques. J Virol 89:2233–2240. https://doi.org/10.1128/JVI.02978-14
Xiao X, Chen W, Feng Y, Zhu Z, Prabakaran P, Wang Y et al (2009) Germline-like predecessors of broadly neutralizing antibodies lack measurable binding to HIV-1 envelope glycoproteins: implications for evasion of immune responses and design of vaccine immunogens. Biochem Biophys Res Commun 390:404–409. https://doi.org/10.1016/j.bbrc.2009.09.029
Yu S, Ou Y, Xiao H, Li J, Adah D, Liu S et al (2020) Experimental Treatment of SIV-infected macaques via autograft of CCR5-disrupted hematopoietic stem and progenitor cells. Mol Ther Methods Clin Dev 17:520–531. https://doi.org/10.1016/j.omtm.2020.03.004
Zerbato JM, Serrao E, Lenzi G, Kim B, Ambrose Z, Watkins SC et al (2016) Establishment and reversal of HIV-1 latency in naive and central memory CD4+ T cells in vitro. J Virol 90:8059–8073. https://doi.org/10.1128/JVI.00553-16
Zheng H-Y, Wang X-H, He X-Y, Chen M, Zhang M-X, Lian X-D et al (2022) Aging induces severe SIV infection accompanied by an increase in follicular CD8+ T cells with overactive STAT3 signaling. Cell Mol Immunol 19:1042–1053. https://doi.org/10.1038/s41423-022-00899-6
Ziani W, Bauer A, Lu H, Wang X, Wu X, Bar KJ et al (2021) Immune responses and viral persistence in simian/human immunodeficiency virus SHIV.C.CH848-infected rhesus macaques. J Virol 95:e02198–e2220. https://doi.org/10.1128/JVI.02198-20
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NHP studies in the MacLean Lab are currently supported by R21-MH113517, R01-HL152804, R01-NS104016, R21-MH125716, U42OD024282, U42OD010568, and the TNPRC base grant P51-OD11104.
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Van Zandt, A.R., MacLean, A.G. Advances in HIV therapeutics and cure strategies: findings obtained through non-human primate studies. J. Neurovirol. 29, 389–399 (2023). https://doi.org/10.1007/s13365-023-01162-y
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DOI: https://doi.org/10.1007/s13365-023-01162-y