**Author details**

340 Immunodeficiency

[227-235].

**6. Summary and outlook** 

disease of our past, not of our future.

**Disclaimer** 

The initial safety and size guidelines to develop ring devices that are suitable for use in pig-tailed and rhesus macaques came from the administration of different sized rings and the close monitoring of the safety of these devices. Non-medicated silicone elastomer vaginal rings of 3 different sizes were administered to pig-tailed and Chinese rhesus macaques for a 28 day period [224]. No signs of inflammation or irritation were observed on colposcopic examinations and the animals showed no behavioral changes or other problems following insertion of the rings. Mucosal proinflammatory cytokines were unchanged in the presence of the rings (for 4 weeks) or upon removal (4 weeks post removal). Safety analyses of macaque-sized elastomeric silicone and polyurethane intravaginal rings (IVRs) loaded with candidate ARV drugs were tested in pig-tailed macaques in four studies ranging in duration from 49 to 73 days with retention of the IVR being 28 days in each study. The presence of IVRs not only made of silicone but other polymers such as, polyurethane in pig-tailed macaques does not cause an alteration longitudinally in the levels of the proinflammatory cytokines locally or systemically and in the vaginal microbiological patterns [225, 226]. Efficacy studies in the NHP model with IVRs are just beginning, but preliminary pharmacokinetic studies are very promising

As we move forward in our endeavors to prevent HIV infections, it is clear that having viable animal models are a vital component of a comprehensive approach to develop and test biomedical preventions. The field of HIV treatment and prevention has broadened to include not only vaccine discovery and treatment of infected individuals to PEP, PrEP, combination therapies, and discussions of eradication and cure. The pharmaceutical discoveries of recent years have increased our options for PEP and PrEP, and vaccine designs are becoming much more sophisticated. As the prevention field moves forward we are constantly modifying the macaque model to accommodate new combinations of interventions. The new SHIVs will have to incorporate the elements necessary to evaluate vaccines and other prevention modalities both singly and in combination. The likelihood that future clinical vaccine trials will be conducted in concert with PrEP trials is very high, and the recombinant viruses we use in the NHP models have to keep pace in evaluating promising candidates in the most rigorous way possible. The nonhuman primate model has adapted to aid researchers in answering ever more complex questions surrounding the interaction of the virus, host, and antiretroviral drugs. The coming years will be very interesting and fruitful as we move towards our common goal; to make HIV and AIDS a

The findings and conclusions are those of the author and do not necessarily represent the

official position of the Centers for Disease Control and Prevention.

Lara E. Pereira *LRRI, Albuquerque, NM, USA* 

Priya Srinivasan and James M. Smith *Laboratory Branch, Division of HIV/AIDs Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA* 
