Short Communication: Viremic Control Is Independent of Repeated Low-Dose SHIV_SF162p3Exposures

Abstract

The repeat low-dose virus challenge model is commonly used in nonhuman primate studies of HIV transmission and biomedical preventions. For some viruses or challenge routes, it is uncertain whether the repeated exposure design might induce virus-directed innate or adaptive immunity that could affect infection or viremic outcomes. Retrospective cohorts of male Indian rhesus (n=40) and female pigtail (n=46) macaques enrolled in repeat low-dose rectal or vaginal SHIV(SF162p3) challenge studies, respectively, were studied to compare the relationship between the number of previous exposures and peak plasma SHIV RNA levels or viral load area under the curve (AUC), surrogate markers of viral control. Repeated mucosal exposures of 10 or 50 TCID50 of virus for rectal and vaginal exposures, respectively, were performed. Virus levels were measured by quantitative reverse-transcriptase real-time PCR. The cumulative number of SHIV(SF162p3) exposures did not correlate with observed peak virus levels or with AUC in rectally challenged rhesus macaques [peak: rho (ρ)=0.04, p=0.8; AUC: ρ=0.33, p=0.06] or vaginally challenged pigtail macaques (peak: ρ=-0.09, p=0.7; AUC: ρ=0.11, p=0.6). Infections in these models occur independently of exposure history and provide assurance that neither inoculation route nor number of exposures required for infection correlates with postinfection viremia. These data also indicate that both the vaginal and rectal repeated low-dose virus exposure models using SHIV(SF162p3) provide a reliable system for nonhuman primate studies.

Antiretroviral Drug Activity in Macaques Infected during Pre-Exposure Prophylaxis Has a Transient Effect on Cell-Associated SHIV DNA Reservoirs

“…In a large retrospective analysis of 40 rhesus macaques exposed repeatedly to SHIV 162p3 , we found no correlation between cumulative exposures to SHIV and peak plasma RNA levels or AUC values [22]. In our study we also found no correlation between cumulative SHIV exposures and SHIV DNA levels during the acute or the plateau phase, suggesting that previous virus exposures have little or no impact on cell-associated DNA levels in PBMCs.…”

Measuring immunity to SARS-CoV-2 infection: comparing assays and animal models

“…Serial challenges are often spaced by several days to prevent undue stress on animals and to identify which challenge resulted in infection. Although serial challenge implies a potential risk of ‘priming’ an endogenous response through multiple challenges, in practice this has not been observed in the setting of HIV 74 , 75 . A similar, parallel low-dose challenge approach involves challenge with multiple strains simultaneously (each at a low (typically 50%) infectious dose).…”

Animal Models of Human Viral Diseases

“…AIDs in such models is often defined as CD4+ T-cells that have dropped to less than 50% of the baseline values. Alternatively, repeated low dose challenges are often utilized, depending on the requirements of the model (Henning et al, 2014;Moldt et al, 2012;reynolds et al, 2012).…”