Reduced inflammation and CD4 loss in acute SHIV infection during oral pre-exposure prophylaxis.

Abstract

BACKGROUND:

The impact of pre-exposure prophylaxis (PrEP) with antiretrovirals on breakthrough HIV or SHIV infection is not fully documented. We addressed the hypothesis that SHIV(SF162P3) infection despite active PrEP results in altered early immune parameters, compared with untreated infection.

METHODS:

Eleven rhesus macaques were infected during repeated, rectal, low-dose SHIV(SF162P3) exposures while receiving concurrent oral PrEP (Truvada [n = 2] or GS7340 [n = 4]) or as untreated controls (n = 5). We measured SHIV RNA, inflammatory cytokines, CD4 cells, and SHIV-specific and memory T cells until 20 weeks after peak viremia.

RESULTS:

SHIV infection during PrEP resulted in 100-fold lower peak viremia and lower IL-15, IL-18, and IL-1Ra levels, compared with controls (P < .05; Wilcoxon rank-sum test). Unlike controls, PrEP-treated macaques showed no significant CD4 cell count reduction during acute infection and developed more SHIV-specific central memory T cells, relative to controls. After in vivo CD8 cell depletion, viral load increased to similar levels, indicating that CD8 cells were critical for viral control in both groups.

CONCLUSIONS:

PrEP with antiretrovirals has beneficial effects on early SHIV infection even when infection is not prevented. Although long-term immune control could not be examined in this SHIV infection model, our results suggest that PrEP results in improved early disease parameters in breakthrough infections.

• Authors: Ellen N Kersh, Wei Luo, Qi Zheng, Debra R Adams, Debra Hanson, Ae S Youngpairoj, Mian-er Cong, Katherine Butler, R Michael Hendry, Janet M McNicholl, Walid Heneine, J Gerardo Garcia-Lerma
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 206 Issue 5 Pg. 770-9 (Sep 01 2012) ISSN: 1537-6613 [Electronic] United States
• PMID: 22740713 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-HIV Agents
• Cytokines
• Drug Combinations
• Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Organophosphorus Compounds
• RNA, Viral
• Deoxycytidine
• Tenofovir
• tenofovir alafenamide
• Adenine
• Alanine

Topics

• Adenine (analogs & derivatives, pharmacology)
• Alanine
• Animals
• Anti-HIV Agents (pharmacology)
• CD4 Lymphocyte Count
• CD4-Positive T-Lymphocytes (immunology, virology)
• Cytokines (blood, immunology)
• Deoxycytidine (analogs & derivatives, pharmacology)
• Drug Combinations
• Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Longitudinal Studies
• Macaca mulatta
• Male
• Organophosphorus Compounds (pharmacology)
• RNA, Viral (chemistry, genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Simian Acquired Immunodeficiency Syndrome (immunology, prevention & control, virology)
• Simian Immunodeficiency Virus (immunology)
• Statistics, Nonparametric
• Tenofovir (analogs & derivatives)
• Viremia (immunology, virology)