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Updated: Jul 13, 2026
Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
Direct stringency comparison of two macaque models (single-high vs. repeat-low) for mucosal HIV transmission using an
Shambavi Subbarao1, Artur Ramos, Caryn Kim
1Laboratory Branch, Division of HIV/AIDS Prevention, NCHHSTP, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Background:
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.
Insights
Tenofovir disoproxil fumarate (TDF) chemoprophylaxis showed partial protection against repeated low-dose SHIV challenges. A single high-dose challenge model revealed TDF protected 40% of macaques, suggesting varying model stringency.
Area of Science:
- Virology
- Primate Models
- Antiretroviral Therapy
Background:
- Previous studies demonstrated oral tenofovir disoproxil fumarate (TDF) offered partial protection against repeated low-dose (RL) intrarectal SHIV162p3 exposure in rhesus macaques.
- This research directly compares TDF efficacy using a single high (SH)-dose challenge strategy against prior RL challenge findings.
Purpose of the Study:
- To compare the efficacy of oral TDF chemoprophylaxis in rhesus macaques under two different SHIV challenge models: single high-dose (SH) versus repeated low-dose (RL).
- To evaluate the relative stringency of the SH and RL challenge models for assessing antiretroviral interventions.
Main Methods:
- Rhesus macaques received oral TDF chemoprophylaxis.
- Animals were challenged intrarectally with SHIV162p3 using either a single high (SH)-dose or repeated low-dose (RL) strategy.
- Infection rates and protection efficacy of TDF were compared between the two challenge models.
Main Results:
- Under the SH challenge, 60% of TDF-treated macaques became infected, with 40% protection observed.
- Under the RL challenge, only 25% of TDF-treated macaques were protected.
- Control groups showed 100% infection rates in both SH (5/5) and RL (4/4) challenge models.
Conclusions:
- The repeated low-dose (RL) challenge model appears to be as stringent, if not more stringent, than the single high-dose (SH) model for evaluating antiretroviral interventions.
- Findings highlight the importance of challenge model selection in assessing the efficacy of pre-exposure prophylaxis.
