StemCell Therapy

Drugs currentlyused to keep the HIV virus in check also cause immune-system changesthat mightmake humans better able toresist viral infectionsbutmight also cause harmful inflammation, according to a study published today in Cell Reports Medicine.

The UW Medicine-led studyby Dr.Florian Hladik and Sean Hughes examined the effects ofa commonly prescribed drug cocktail of drugs on the body.

Sold under the brand name Truvada, tenofovir disoproxil fumarate and emtricitabine (TDF/FTC)are prescribed in tandem formost HIV/AIDS patients to suppress viral loads to undetectable levels. First allowed for use in the United States 20 years ago, the drugs haveenabledpeopleto live for decades beyond their initial diagnosis.

However, Hladik said,"the virus itself never goes away."

In this research, the investigatorsstudied the effect of TDF/FTC in patients who were using the drugto prevent HIV, and in the absence of active HIV infection. The researchers observed patientsover the past five yearsand also includeddata from two earlier studies.

We wanted to know how the drugs themselves affect the immune system, Hughes said. We found that they stimulated type I / III interferon responses, a part of the immune system that is crucial for the bodys ability to fight off viruses. This only happened in the gut.

The clinical consequences of the findings are uncertain and merit further study.

Increased type I / III interferons could be a good thing and actually make the drugs more effective at suppressing viral infections, including HIV. However, they could also cause inflammation, which could contribute to conditions such as cardiovascular disease that are common in people living with HIV, Hladik said. These effects might even make it harder to find a cure for HIV if they make cells silently infected with HIV (called latent cells) more likely to survive or even cause them to proliferate.

Hladik and Hughesalso want to look for those same effects in people infected with HIV.

New drug regimens have just become available that highly suppress the HIV virus in patients and dont contain TDF/FTC or other drugs of thatclass. Bothhope to conduct a trial comparing immunity in HIV-infected individuals using TDF/FTC to others using these newer regimens to determine whether their findings are true in HIV-infected individuals. The researchers hypothesize that the newer regimens will avoid chronic immune activation and decrease the number of latent cells.

The most important next step is to repeat our studies in HIV-infected individuals, and to find out if replacing drugs such as TDF/FTC with newer regimens has clinically relevant effects on reducing chronic inflammation and persistence of latent HIV, Hladik said.

This work was funded by the National Institutes of Health(R01AI116292, R01AI111738,R01AI134293,AI027757,AI069481,R01DK112254);the Bill and Melinda Gates Foundation;the Microbicide Trials Network (UM1AI068633); the Canadian Institutes for Health Research;the Emory University-CDC HIV/AIDS Clinical Trials Unit (UM1AI069418, from the NIAID). The ddPCR work was supported by a grant from the James B. Pendleton Charitable Trust. A National Cancer Institute grant supported the Fred Hutchinson Cancer Research Center Experimental Histopathology core facility.

Read the original:
Common HIV drugs increase a type of immunity in the gut - UW Medicine Newsroom

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