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.