Combination therapy treats latent HIV reservoirs

By TRISHA PARAYIL | October 18, 2018

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 PUBLIC DOMAIN

A newly developed combination therapy was proven successful in killing HIV-infected cells.

Medical researchers have determined a strategy that treats the latent reservoir in cells infected with human immunodeficiency virus (HIV), potentially dismantling one of the barriers to finding a cure for the virus. 

The current treatment for HIV is antiretroviral therapy (ART). ART involves the administration of a combination of drugs called antiretrovirals. Despite its success in reducing the number of deaths related to acquired immune deficiency syndrome (AIDS) over the past two decades, ART does not cure patients with HIV. Instead, it prevents the virus from replicating and reduces the risk of HIV transmission. 

ART does not cure HIV because the virus can ‘hide’ from the therapy by remaining dormant in infected cells. The collection of infected cells containing dormant HIV is called the latent reservoir. 

According to Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, the cells in the latent reservoir can become active and replicate HIV at any time. 

A team of scientists led by Dan Barouch recently published a study that offers a promising method of targeting the latent reservoir. Barouch is the director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center. 

The scientists first presented their findings from the early stages of the study in March at the 25th Conference on Retroviruses and Opportunistic Infections. 

Since the promising initial results, the study was conducted in full, and the results appeared in Nature

In the study, 44 rhesus monkeys were infected with an HIV-like virus and treated with ART for two-and-a-half years. After 96 weeks, the monkeys were divided into three experimental groups and one control group. 

The control group did not receive additional treatment. One group was treated with an immune stimulating agent. Another was treated with antibodies. The third experimental group was treated with both the immune stimulating agent and the antibodies. 

The monkeys continued to be treated with ART until week 130. After ending treatment, scientists began to monitor for viral rebound. Viral rebound is a period of persistent levels of HIV in the blood after a period of little HIV presence. 

The control group rebounded almost immediately and displayed high viral loads. The group which was only given the immune stimulant demonstrated similar effects. The monkeys given only the antibodies displayed less severe viral rebound, but the rebound was detectable nonetheless. 

Of the 11 monkeys which were given the combination therapy of the immune stimulating agent and the antibodies, five did not rebound in six months. The monkeys which did rebound had lower peak viral loads compared to the other groups. 

“The combination of the antibodies and the immune stimulant led to optimal killing of HIV-infected cells,” Barouch said in a press release. 

According to the authors of the study, the findings suggest that administering both broadly neutralizing antibodies and immune stimulants are a strategy to treat the viral reservoir.  

“Our data provide an initial proof-of-concept in primates showing the potential of innate immune activation with immune-based targeting of the viral reservoir,” the study reads. 

This treatment is promising for the more than 35 million people worldwide living with the virus and the two million people diagnosed annually. 

The authors note that, while the study is a significant first step, there is still work to be done. 

“Although we are still a long way off from having a cure for HIV, our data suggest a strategy for targeting the viral reservoir that can be further explored,” Barouch said in a press release. 

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