Back-burning to cure HIV: Temporary depletion of all CD4+ cells and elimination of the extracellular reservoir with HIV Immunotoxin Therapy

Zanin, Mary K.B.; Duvall, Marcus R.

doi:10.1016/j.mehy.2008.08.033

Cited by 5 publications

(1 citation statement)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pharmacologic depletion of the HIV reservoir is an underexplored but potentially effective component of HIV cure strategies. Other investigators have proposed temporary depletion of certain cells as a means to clear the reservoir, 44 using targeting molecules ranging from the very specific (CD32a 29 ) to broad (all CD4 + T cells). The results reported in this study demonstrate the feasibility of this approach in an NHP model and constitute a critical first step toward systematic evaluation of this strategy.…”

Section: Discussionmentioning

confidence: 99%

Depletion of Gut-Resident CCR5⁺Cells for HIV Cure Strategies

Merriam

Chen

Méndez-Lagares

et al. 2017

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

The HIV reservoir forming at the earliest stages of infection is likely composed of CCR5 cells, because these cells are the targets of transmissible virus. Restriction of the CCR5 reservoir, particularly in the gut, may be needed for subsequent cure attempts. Strategies for killing or depleting CCR5 cells have been described, but none have been tested in vivo in nonhuman primates, and the extent of achievable depletion from tissues is not known. In this study we investigate the efficacy of two novel cytotoxic treatments for targeting and eliminating CCR5 cells in young rhesus macaques. The first, an immunotoxin consisting of the endogenous CCR5 ligand RANTES fused with Pseudomonas exotoxin (RANTES-PE38), killed CCR5 lamina propria lymphocytes (LPLs) ex vivo, but had no detectable effect on CCR5 LPLs in vivo. The second, a primatized bispecific antibody for CCR5 and CD3, depleted all CCR5 cells from blood and the vast majority of such cells from the colonic mucosa (up to 96% of CD4CCR5). Absence of CCR5-expressing cells from blood endured for at least 1 week, while CCR5 cells in colon were substantially replenished over the same time span. These data open an avenue to investigation of combined early ART treatment and CCR5 reservoir depletion for cure of HIV-infected infants.

show abstract

Section: Discussionmentioning

confidence: 99%