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P2.091 A Repeated Low Dose Co-Challenge Model of SHIV-RT and HSV-2 in Rhesus Macaques
  1. J Kenney1,
  2. N Derby1,
  3. M Aravantinou1,
  4. S Rana1,
  5. J D Lifson2,
  6. Jr M Piatak2,
  7. A Gettie3,
  8. J Blanchard4,
  9. M Robbiani1
  1. 1Population Council, New York, NY, United States
  2. 2SAICFrederick, Inc., NCI Frederick, Frederick, MD, United States
  3. 3Aaron Diamond AIDS Research Center, New York, NY, United States
  4. 4Tulane National Primate Research Center, Covington, LA, United States

Abstract

Background HIV acquisition is facilitated by HSV-2 infection, making microbicides that block both viruses desirable for limiting HIV transmission. We have tested microbicides in a stringent efficacy model: vaginal co-challenge with a single high dose of SHIV-RT (103 TCID50) and HSV-2 (2 × 108 pfu) in DepoProvera (DP)-treated macaques. Here we established a model mimicking real world exposure: repeated low dose SHIV/HSV-2 co-challenge in non-DP-treated animals.

Methods Two groups of macaques were co-challenged weekly for 11wks with SHIV (10 or 50 TCID50) and HSV-2 (107 pfu) after which the SHIV dose was increased to 200 TCID50 in all animals for 9 more co-challenges. HSV-2 shedding in vaginal swabs and SHIV plasma viremia were determined. Antibodies (Abs) to SIV and HSV-2, HSV-2-specific T cell responses and the hormones estradiol and progesterone were measured in the blood.

Results After 11 co-challenges, SHIV infections were detected in 1/3 animals from the 10 TCID50 SHIV group and 1/3 from the 50 TCID50 SHIV group (after 2 and 8 challenges, respectively). Upon increasing the SHIV dose, two more animals became infected (after 1 and 5 more co-challenges), but the last two remained uninfected. SHIV viremia was similar in all infected animals, which all developed SIV-specific Abs. All animals (6/6) became HSV-2 infected. Initial analyses suggest that the frequency of HSV-2 shedding was greater in non-DP-treated animals repeatedly exposed to 107 pfu than we previously observed for DP-treated animals that received a single 2 × 108 pfu dose of HSV-2 with SHIV (p < 0.0001). HSV-2-specific IgG responses were not detected; T cell responses are being analysed.

Conclusion We have developed a repeated low dose co-challenge model to evaluate microbicides against SHIV and HSV-2. SHIV infection frequency was 67% in this model, similar to the single high dose co-challenge. HSV-2 infection was enhanced compared to the single high dose model.

  • HIV
  • HSV-2
  • microbicide

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