Low AIDS Attack Rate Among Dutch Haemophiliacs Compared to Homosexual Men: A Correlate of HIV Antigenaemia Frequencies

Wolfs, Tom F. W.; Wolf, F de; Breederveld, C.; Sjamsjoedin-Visser, L. J. M.; Roos, M. T. L.; Bakker, Margreet; Goudsmit, Jaap

doi:10.1111/j.1423-0410.1989.tb01149.x

Cited by 3 publications

(1 citation statement)

References 41 publications

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“…The similar estimates of variability for peak and set-point plasma viral loads as well as for clinical endpoints we observed between intrarectal and intravenous SIVmac239 suggest that SIV replicates in an overall similar lymphoid compartment regardless the entry routes of infecting virus. Although it has been suggested that humans infected with HIV-1 through different routes of viral transmission (such as heterosexual or homosexual contact, needle-sharing among injecting drug users, or blood transfusion) might have different rates of disease progression [25], [26], the reasons for such differences have not-yet been clarified.…”

Section: Discussionmentioning

confidence: 99%

Variability of Bio-Clinical Parameters in Chinese-Origin Rhesus Macaques Infected with Simian Immunodeficiency Virus: A Nonhuman Primate AIDS Model

Chen

Lai

et al. 2011

PLoS ONE

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BackgroundAlthough Chinese-origin Rhesus macaques (Ch RhMs) infected with simian immunodeficiency virus (SIV) have been used for many years to evaluate the efficacy of AIDS vaccines and therapeutics, the bio-clinical variability of such a nonhuman primate AIDS model was so far not established.Methodology/Principal FindingsBy randomizing 150 (78 male and 72 female) Ch RhMs with diverse MHC class I alleles into 3 groups (50 animals per group) challenged with intrarectal (ir) SIVmac239, intravenous (iv) SIVmac239, or iv SIVmac251, we evaluated variability in bio-clinical endpoints for 118 weeks. All SIV-challenged Ch RhMs became seropositive for SIV during 1–2 weeks. Plasma viral load (VL) peaked at weeks 1–2 and then declined to set-point levels as from week 5. The set-point VL was 30 fold higher in SIVmac239 (ir or iv)-infected than in SIVmac251 (iv)-infected animals. This difference in plasma VL increased overtime (>100 fold as from week 68). The rates of progression to AIDS or death were more rapid in SIVmac239 (ir or iv)-infected than in SIVmac251 (iv)-infected animals. No significant difference in bio-clinical endpoints was observed in animals challenged with ir or iv SIVmac239. The variability (standard deviation) in peak/set-point VL was nearly one-half lower in animals infected with SIVmac239 (ir or iv) than in those infected with SIVmac251 (iv), allowing that the same treatment-related difference can be detected with one-half fewer animals using SIVmac239 than using SIVmac251.Conclusion/SignificanceThese results provide solid estimates of variability in bio-clinical endpoints needed when designing studies using the Ch RhM SIV model and contribute to the improving quality and standardization of preclinical studies.

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Section: Discussionmentioning

confidence: 99%

Variability of Bio-Clinical Parameters in Chinese-Origin Rhesus Macaques Infected with Simian Immunodeficiency Virus: A Nonhuman Primate AIDS Model

Chen

Lai

et al. 2011

PLoS ONE

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The balance of power between HIV and the immune system

McLean

1993

Trends in Microbiology

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Rapid Dissemination of SIV Follows Multisite Entry after Rectal Inoculation

et al. 2011

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Receptive ano-rectal intercourse is a major cause of HIV infection in men having sex with men and in heterosexuals. Current knowledge of the mechanisms of entry and dissemination during HIV rectal transmission is scarce and does not allow the development of preventive strategies. We investigated the early steps of rectal infection in rhesus macaques inoculated with the pathogenic isolate SIVmac251 and necropsied four hours to nine days later. All macaques were positive for SIV. Control macaques inoculated with heat-inactivated virus were consistently negative for SIV. SIV DNA was detected in the rectum as early as four hours post infection by nested PCR for gag in many laser-microdissected samples of lymphoid aggregates and lamina propria but never in follicle-associated epithelium. Scarce SIV antigen positive cells were observed by immunohistofluorescence in the rectum, among intraepithelial and lamina propria cells as well as in clusters in lymphoid aggregates, four hours post infection and onwards. These cells were T cells and non-T cells that were not epithelial cells, CD68+ macrophages, DC-SIGN+ cells or fascin+ dendritic cells. DC-SIGN+ cells carried infectious virus. Detection of Env singly spliced mRNA in the mucosa by nested RT-PCR indicated ongoing viral replication. Strikingly, four hours post infection colic lymph nodes were also infected in all macaques as either SIV DNA or infectious virus was recovered. Rapid SIV entry and dissemination is consistent with trans-epithelial transport. Virions appear to cross the follicle-associated epithelium, and also the digestive epithelium. Viral replication could however be more efficient in lymphoid aggregates. The initial sequence of events differs from both vaginal and oral infections, which implies that prevention strategies for rectal transmission will have to be specific. Microbicides will need to protect both digestive and follicle-associated epithelia. Vaccines will need to induce immunity in lymph nodes as well as in the rectum.

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Low AIDS Attack Rate Among Dutch Haemophiliacs Compared to Homosexual Men: A Correlate of HIV Antigenaemia Frequencies

Cited by 3 publications

References 41 publications

Variability of Bio-Clinical Parameters in Chinese-Origin Rhesus Macaques Infected with Simian Immunodeficiency Virus: A Nonhuman Primate AIDS Model

Variability of Bio-Clinical Parameters in Chinese-Origin Rhesus Macaques Infected with Simian Immunodeficiency Virus: A Nonhuman Primate AIDS Model

The balance of power between HIV and the immune system

Rapid Dissemination of SIV Follows Multisite Entry after Rectal Inoculation

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