Direct stringency comparison of two macaque models (single-high vs. repeat-low) for mucosal HIV transmission using an identical anti-HIV chemoprophylaxis interventin

Backgroud In our previous work, oral chemoprophylaxis with tenofovir disoproxil fumarate (TDF) provided partial protection in rhesus macaques against repeated low-dose (RL) intrarectal SHIV162p3 exposure. Methods Here, we make a direct comparison of these previous findings with data generated using a single high (SH)-dose challenge strategy. Results All 5 (100%) control macaques were infected after a SH challenge and only three of five (60%) TDF-treated macaques became infected. The remaining two TDF-treated macaques remained virus-negative and were susceptible to virus infection upon re-challenge in the absence of oral TDF. Thus, two of five (40%) TDF-treated macaques were protected by the pre-exposure chemoprophylaxis regimen. By comparison with the RL challenge system, only one of four (25%) of TDF-treated macaques were protected from infection, whereas four of four (100%) control macaques became infected using RL challenges. Conclusion Taken together, these findings indicate that the stringency of the RL challenge model for testing antiretroviral interventions is not lower and possibly greater than that of the SH challenge model.