Abrahams MR, Joseph SB, Garrett N, Tyers L, Moeser M, Archin N, et al. The replication-competent HIV-1 latent reservoir is primarily established near the time of therapy initiation. Sci Transl Med. 2019;11(513):eaaw5589.

Valcour V, Chalermchai T, Sailasuta N, Marovich M, Lerdlum S, Suttichom D, et al. Central nervous system viral invasion and inflammation during acute HIV infection. J Infect Dis. 2012;206(2):275–82.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Abdel-Mohsen M, Richman D, Siliciano RF, Nussenzweig MC, Howell BJ, Martinez-Picado J, et al. Recommendations for measuring HIV reservoir size in cure-directed clinical trials. Nat Med. 2020;26(9):1339–50. This paper reviews the limitations , advantages, and caveats of currently available options for measuring reservoir size and provides guidance.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Avalos CR, Abreu CM, Queen SE, Li M, Price S, Shirk EN, et al. Brain macrophages in simian immunodeficiency virus-infected, antiretroviral-suppressed macaques: a functional latent reservoir. mBio. 2017;8(4):e01186-17.

Bachmann N, von Siebenthal C, Vongrad V, Turk T, Neumann K, Beerenwinkel N, et al. Determinants of HIV-1 reservoir size and long-term dynamics during suppressive ART. Nat Commun. 2019;10(1):3193.

Article  PubMed  PubMed Central  Google Scholar 

Churchill MJ, Deeks SG, Margolis DM, Siliciano RF, Swanstrom R. HIV reservoirs: what, where and how to target them. Nat Rev Microbiol. 2016;14(1):55–60.

Article  CAS  PubMed  Google Scholar 

Henderson LJ, Reoma LB, Kovacs JA, Nath A. Advances toward curing HIV-1 infection in tissue reservoirs. J Virol. 2020;94(3):e00375-19.

Mitchell BI, Laws EI, Ndhlovu LC. Impact of myeloid reservoirs in HIV cure trials. Curr HIV/AIDS Rep. 2019;16(2):129–40. Excellent review of the history of growing evidence of importance of myeloid reservoirs (with emphasis on CNS) in HIV persistence, barrier to eradication, issues with quantifying myeloid reservoirs and thoughtful discussion of considerations for cure strategies.

Article  PubMed  PubMed Central  Google Scholar 

Chan P, Ananworanich J. Perspective on potential impact of HIV central nervous system latency on eradication. AIDS. 2019;33 Suppl 2:S123–S33. Thoughtful review of impact of CNS reservoirs on HIV eradication and considerations for cure strategies.

Article  PubMed  Google Scholar 

Honeycutt JB, Wahl A, Baker C, Spagnuolo RA, Foster J, Zakharova O, et al. Macrophages sustain HIV replication in vivo independently of T cells. J Clin Invest. 2016;126(4):1353–66.

Article  PubMed  PubMed Central  Google Scholar 

Honeycutt JB, Thayer WO, Baker CE, Ribeiro RM, Lada SM, Cao Y, et al. HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy. Nat Med. 2017;23(5):638–43.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cenker JJ, Stultz RD, McDonald D. Brain microglial cells are highly susceptible to HIV-1 infection and spread. AIDS Res Hum Retroviruses. 2017;33(11):1155–65.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Avalos CR, Price SL, Forsyth ER, Pin JN, Shirk EN, Bullock BT, et al. Quantitation of productively infected monocytes and macrophages of simian immunodeficiency virus-infected macaques. J Virol. 2016;90(12):5643–56.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Abreu C, Shirk EN, Queen SE, Beck SE, Mangus LM, Pate KAM, et al. Brain macrophages harbor latent, infectious simian immunodeficiency virus. AIDS. 2019;33 Suppl 2:S181–S8. This study is strongest evidence for replication competent HIV proviral DNA in brain myeloid cells – in SIV macaque model on suppressive ART. Also demonstrates the utility of macrophage adapted QVOA assay.

Article  PubMed  Google Scholar 

Winston A, Julie F, Fidler S. HIV cure strategies: response to ignore the central nervous system at your patients’ peril. AIDS. 2017;31(7):1051–2.

Article  PubMed  Google Scholar 

Lv T, Cao W, Li T. HIV-related immune activation and inflammation: current understanding and strategies. J Immunol Res. 2021;2021:7316456.

Article  PubMed  PubMed Central  Google Scholar 

Montoya JL, Campbell LM, Paolillo EW, Ellis RJ, Letendre SL, Jeste DV, et al. Inflammation relates to poorer complex motor performance among adults living with HIV on suppressive antiretroviral therapy. J Acquir Immune Defic Syndr. 2019;80(1):15–23.

Article  PubMed  PubMed Central  Google Scholar 

Zicari S, Sessa L, Cotugno N, Ruggiero A, Morrocchi E, Concato C, et al. Immune activation, inflammation, and non-AIDS co-morbidities in HIV-infected patients under long-term ART. Viruses. 2019;11(3):200.

Article  CAS  PubMed Central  Google Scholar 

van Zoest RA, Underwood J, De Francesco D, Sabin CA, Cole JH, Wit FW, et al. Structural brain abnormalities in successfully treated HIV infection: associations with disease and cerebrospinal Fluid Biomarkers. J Infect Dis. 2017;217(1):69–81.

Article  PubMed  Google Scholar 

Li GH, Henderson L, Nath A. Astrocytes as an HIV reservoir: mechanism of HIV infection. Curr HIV Res. 2016;14(5):373–81.

Article  CAS  PubMed  Google Scholar 

Ding J, Liu Y, Lai Y. Knowledge from London and Berlin: finding threads to a functional HIV cure. Front Immunol. 2021;12:688747.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sengupta S, Siliciano RF. Targeting the Latent Reservoir for HIV-1. Immunity. 2018;48(5):872–95.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dufour C, Gantner P, Fromentin R, Chomont N. The multifaceted nature of HIV latency. J Clin Invest. 2020;130(7):3381–90.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Farber DL. Tissues, not blood, are where immune cells function. Nature. 2021;593(7860):506–9.

Article  CAS  PubMed  Google Scholar 

Gisslen M, Keating SM, Spudich S, Arechiga V, Stephenson S, Zetterberg H, et al. Compartmentalization of cerebrospinal fluid inflammation across the spectrum of untreated HIV-1 infection, central nervous system injury and viral suppression. PLoS ONE. 2021;16(5):e0250987.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kearney MF, Wiegand A, Shao W, Coffin JM, Mellors JW, Lederman M, et al. Origin of rebound plasma HIV includes cells with identical proviruses that are transcriptionally active before stopping of antiretroviral therapy. J Virol. 2016;90(3):1369–76.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yuan NY, Kaul M. Beneficial and adverse effects of cART affect neurocognitive function in HIV-1 infection: balancing viral suppression against neuronal stress and injury. J Neuroimmune Pharmacol. 2021;16(1):90–112.

Article  PubMed  Google Scholar 

Letendre S. Central nervous system complications in HIV disease: HIV-associated neurocognitive disorder. Top Antivir Med. 2011;19(4):137–42.

PubMed  Google Scholar 

Lin SP, Calcagno A, Letendre SL, Ma Q. Clinical treatment options and randomized clinical trials for neurocognitive complications of HIV infection: combination antiretroviral therapy, central nervous system penetration effectiveness, and adjuvants. Curr Top Behav Neurosci. 2021;50:517–45.

Article  PubMed  PubMed Central  Google Scholar 

Gutierrez J, Byrd D, Yin MT, Morgello S. Relationship between brain arterial pathology and neurocognitive performance among individuals with human immunodeficiency virus. Clin Infect Dis. 2019;68(3):490–7.

Article  PubMed  Google Scholar 

Lanman T, Letendre S, Ma Q, Bang A, Ellis R. CNS neurotoxicity of antiretrovirals. J Neuroimmune Pharmacol. 2021;16(1):130–43.

Article  PubMed  Google Scholar 

Mackiewicz MM, Overk C, Achim CL, Masliah E. Pathogenesis of age-related HIV neurodegeneration. J Neurovirol. 2019;25(5):622–33.

Article  CAS  PubMed  Google Scholar 

Fernandes N, Pulliam L. Inflammatory mechanisms and cascades contributing to neurocognitive impairment in HIV/AIDS. Berlin: Springer Berlin Heidelberg. p. 1–27.

Heaton RK, Clifford DB, Franklin DR Jr, Woods SP, Ake C, Vaida F, et al. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology. 2010;75(23):2087–96.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Akiyama H, Jalloh S, Park S, Lei M, Mostoslavsky G, Gummuluru S. Expression of HIV-1 intron-containing RNA in microglia induces inflammatory responses. J Virol. 2020:e01386-20.

Chivero ET, Guo M-L, Periyasamy P, Liao K, Callen SE, Buch S. HIV-1 Tat primes and activates microglial NLRP3 inflammasome-mediated neuroinflammation. J Neurosci. 2017;37(13):3599–609.

Article  CAS  PubMed  PubMed Central  Google Scholar 

de Oliveira MF, Gianella S, Letendre S, Scheffler K, Kosakovsky Pond SL, Smith DM, et al. Comparative analysis of cell-associated HIV DNA levels in cerebrospinal fluid and peripheral blood by droplet digital PCR. PLoS ONE. 2015;10(10):e0139510.

Article  PubMed  PubMed Central  Google Scholar 

Winston A, Antinori A, Cinque P, Fox HS, Gisslen M, Henrich TJ, et al. Defining cerebrospinal fluid HIV RNA escape: editorial review AIDS. AIDS. 2019;33 Suppl 2:S107–11.

Article  PubMed  Google Scholar 

Joseph SB, Kincer LP, Bowman NM, Evans C, Vinikoor MJ, Lippincott CK, et al. Human immunodeficiency virus type 1 RNA detected in the central nervous system (CNS) after years of suppressive antiretroviral therapy can originate from a replicating cns reservoir or clonally expanded cells. Clin Infect Dis. 2019;69(8):1345–52. This study shosw CSF escape can contain HIV DNA from clonally expanded cells trafficked into CSF or from replicating CNS reservoirs.

Article  PubMed  Google Scholar 

Spudich S, Robertson KR, Bosch RJ, Gandhi RT, Cyktor JC, Mar H, et al. Persistent HIV-infected cells in cerebrospinal fluid are associated with poorer neurocognitive performance. J Clin