New animal model first to mimic HIV infection in infants

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Researchers have developed an animal model mimicking HIV in infants, termed the simian-human immunodeficiency virus (SHIV)-infected infant rhesus macaque model.

To-date all animal models that have been developed for testing novel HIV treatments have been in adult animals, however, it is known that infants have distinct differences in their immune system, making current models poor representations of pediatric infection. Moreover, the method of HIV acquisition is often different in infants when compared with adults.

Principal investigator, Sallie Permar (Duke Human Vaccine Institute, NC, USA) commented: “It is important to develop a model by which we can study infected infants and study the interventions that can be implemented to reduce the viral reservoir and delay time to rebound after stopping antiretroviral therapy.”

The study, published recently in mBio, describes a new model that can allow testing of immune interventions against the HIV envelope protein through the use of a SHIV. Moreover, the model takes advantage of recent advances in SHIV development that allows the virus to replicate the clade C HIV viruses, which are involved in the transmission of HIV in infants.

To produce the model, the team infected infant monkeys with SHIV in the first 1–2 months of life, simulating transmission from breast milk. They then administered antiretroviral therapy 12 weeks after infection, stopping treatment after a few months. Evaluation of plasma virus load demonstrated that the viral load reached its peak and responded quickly to therapy, simulating the pattern observed in human infants.

The researchers also compared their infant macaque model to adult macaques, discovering that adult monkeys had better virus control after rebound.

“There are going to be differences in the infant and adult-based therapies that are aimed at extending the time to viral rebound after stopping antiretroviral therapies,” stated lead author Ria Goswami (Duke Human Vaccine Institute). “Novel interventions that do not rely on daily adherence to antiretroviral therapy are needed to achieve sustained viral remission for perinatally infected children, who currently rely on lifelong antiretroviral therapy.”

The team would like to use this new model to test novel immune-based therapies for HIV in infants, such as monoclonal antibodies, to extend the time before viral rebound in infants. Permar concluded: “We are interested in having safer alternative strategies to antiretroviral drugs that will maintain virologic control for infected infants that are developed specifically for infants. This is the first infant SHIV model to model HIV treatment and rebound.”

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Source: Goswami R, Nelson AN, Tu JJ et al. Analytical treatment interruption after short-term antiretroviral therapy in a postnatally simian-human immunodeficiency virus-infected infant rhesus macaque model. mBio, doi:10.1128/mBio.01971-19 (2019); www.asm.org/Press-Releases/2019/September-1/Infant-Model-of-HIV-Opens-New-Avenues-for-Research


How can HIV pass from mother to child?

If a mother becomes infected with HIV before or while she is pregnant then the virus may spread to the infant during pregnancy, childbirth or breastfeeding. Women who are diagnosed as HIV positive and who adhere to antiretroviral treatment during pregnancy and beyond have a significantly lower risk of passing the virus on to their children.

What is the current treatment for HIV in infants?

The treatment for infants and adults with HIV is very similar, both are administered antiretroviral therapy, a combination of medications that act against HIV. However, there are challenges in infants, for examples some antiretroviral medications aren’t available in liquid formulations that young children can swallow, moreover, some side effects are serious in infants.

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