The Spleen Is an HIV-1 Sanctuary During Combined Antiretroviral Therapy.

TitleThe Spleen Is an HIV-1 Sanctuary During Combined Antiretroviral Therapy.
Publication TypeJournal Article
Year of Publication2018
AuthorsNolan, DJ, Rose, R, Rodriguez, PH, Salemi, M, Singer, EJ, Lamers, SL, McGrath, MS
JournalAIDS Res Hum Retroviruses
Date Published2018 01
KeywordsAdult, Aged, Anti-Retroviral Agents, Antiretroviral Therapy, Highly Active, Genes, gag, HIV Infections, HIV Seropositivity, HIV-1, Humans, Male, Middle Aged, Phylogeny, Polymerase Chain Reaction, Proviruses, RNA, Viral, Spleen, Viral Load, Viral Proteins

Combined antiretroviral therapy (cART) does not eradicate HIV, which persists for years and can re-establish replication if treatment is stopped. The current challenge is identifying those tissues harboring virus through cART. Here, we used HIV env-nef single genome sequencing and HIV gag droplet digital PCR (ddPCR) to survey 50 tissues from five subjects on cART with no detectable plasma viral load at death. The spleen most consistently contained multiple proviral and expressed sequences (4/5 participants). Spleen-derived HIV demonstrated two distinct phylogenetic patterns: multiple identical sequences, often from different tissues, as well as diverse viral sequences on long terminal branches. Our results suggested that ddPCR may overestimate the size of the tissue-based viral reservoir. The spleen, a lymphatic organ at the intersection of the immune and circulatory systems, may play a key role in viral persistence.

Alternate JournalAIDS Res Hum Retroviruses
PubMed ID29084441
PubMed Central IDPMC5771542
Grant ListR01 MH100984 / MH / NIMH NIH HHS / United States
R01 NS063897 / NS / NINDS NIH HHS / United States
U24 MH100929 / MH / NIMH NIH HHS / United States