FSU study aids fight against HIV, hepatitis B

January 08, 2020

TALLAHASSEE, Fla. -- A discovery by Florida State University College of Medicine researchers is expected to open the door for new and more potent treatment options for many of the more than 36 million people worldwide infected with the HIV virus and for others chronically ill with hepatitis B.

Their work has established for the first time the mechanism responsible for how two widely used antiviral drugs inhibit viruses.

In a paper published by Communications Biology, an open-access journal from Nature Research, Professor Zucai Suo and colleagues also provide the key to understanding how a single HIV-1 mutation can inactivate the anti-HIV drugs emtricitabine and lamivudine. Those drugs are worth billions in annual sales for the companies that make them, and the frequency of patients who develop resistance creates serious and dangerous obstacles to controlling the disease.

Emtricitabine also is approved for use in patients with hepatitis B, which afflicts 270 million people worldwide, according to the World Health Organization.

The paper suggests new pathways for developing drugs able to avoid specific virus mutations that can render these two blockbuster L-nucleoside drug treatments ineffective for many patients.

It's not unusual for patients undergoing treatment to develop a resistance to their prescribed anti-HIV medications, leaving physicians with three options: adjust the treatment regimen, temporarily interrupt therapy or continue with an only partially effective regimen.

For patients who have failed their first treatment regimen, or even a second, doctors typically try to salvage the current course of treatment by adjusting the combination of drugs. But for patients who have failed multiple treatment regimens, there are limited options to suppress the incurable virus.

The number of drug choices available when one combination fails is limited. More than a million of those infected with HIV live in the U.S.

"In our paper, we suggest new chemical possibilities for more potent L-nucleoside analog drugs, which may possess different drug-resistance mutation profiles from the most widely used current anti-HIV drugs," said Suo, the study's co-lead author, and an Eminent Professor and the Dorian and John Blackmon Chair in Biomedical Science at the FSU College of Medicine. Eric Lansdon of Gilead Sciences Inc. is the co-lead author.

"Right now, there are a limited number of FDA-approved drugs available," Suo said. "New drugs need to be developed if doctors are to have other options when treating so many patients who may have developed resistance to most of the FDA-approved anti-HIV drugs."

The drugs remain highly effective in keeping the disease under control for most patients, but some patients develop a resistance due to mutations within the HIV virus.

Suo's paper explains how the class of HIV drugs known as L-nucleoside reverse transcriptase inhibitors (L-NRTIs) work. L-NRTIs block an enzyme that HIV needs to replicate, but they were discovered through blind trials. Important details about the underlying mechanism triggering L-NRTIs have remained a mystery, as well as a source of controversy among the scientists who study them.

"The enzyme has a unique pocket and supposedly recognizes NRTIs, but not their structural mirror images -- L-NRTIs," said Suo, who grew curious about the mechanism behind L-NRTI drugs as a graduate student. He's been motivated since then to understand and explain the mechanism involved, which he does in his paper -- one of six he has published involving L-NRTI research.

Suo's current paper also explains how a mutation found in some patient populations leads to developing resistance to antiviral L-NRTI drugs.

"Patients, HIV scientists and medical doctors all will benefit from this," Suo said. "HIV scientists and drug companies will now know how it works and will be able to design better drugs in the same class of medications. They will be able to build on the mechanism described in this paper to make slight adjustments for better and more powerful treatment options."
This work was supported by Gilead Sciences Inc. and a grant from the National Science Foundation.

Florida State University

Related HIV Articles from Brightsurf:

BEAT-HIV Delaney collaboratory issues recommendations measuring persistent HIV reservoirs
Spearheaded by Wistar scientists, top worldwide HIV researchers from the BEAT-HIV Martin Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy (BEAT-HIV Collaboratory) compiled the first comprehensive set of recommendations on how to best measure the size of persistent HIV reservoirs during cure-directed clinical studies.

The Lancet HIV: Study suggests a second patient has been cured of HIV
A study of the second HIV patient to undergo successful stem cell transplantation from donors with a HIV-resistant gene, finds that there was no active viral infection in the patient's blood 30 months after they stopped anti-retroviral therapy, according to a case report published in The Lancet HIV journal and presented at CROI (Conference on Retroviruses and Opportunistic Infections).

Children with HIV score below HIV-negative peers in cognitive, motor function tests
Children who acquired HIV in utero or during birth or breastfeeding did not perform as well as their peers who do not have HIV on tests measuring cognitive ability, motor function and attention, according to a report published online today in Clinical Infectious Diseases.

Efforts to end the HIV epidemic must not ignore people already living with HIV
Efforts to prevent new HIV transmissions in the US must be accompanied by addressing HIV-associated comorbidities to improve the health of people already living with HIV, NIH experts assert in the third of a series of JAMA commentaries.

The Lancet HIV: Severe anti-LGBT legislations associated with lower testing and awareness of HIV in African countries
This first systematic review to investigate HIV testing, treatment and viral suppression in men who have sex with men in Africa finds that among the most recent studies (conducted after 2011) only half of men have been tested for HIV in the past 12 months.

The Lancet HIV: Tenfold increase in number of adolescents on HIV treatment in South Africa since 2010, but many still untreated
A new study of more than 700,000 one to 19-year olds being treated for HIV infection suggests a ten-fold increase in the number of adolescents aged 15 to 19 receiving HIV treatment in South Africa, according to results published in The Lancet HIV journal.

Starting HIV treatment in ERs may be key to ending HIV spread worldwide
In a follow-up study conducted in South Africa, Johns Hopkins Medicine researchers say they have evidence that hospital emergency departments (EDs) worldwide may be key strategic settings for curbing the spread of HIV infections in hard-to-reach populations if the EDs jump-start treatment and case management as well as diagnosis of the disease.

NIH HIV experts prioritize research to achieve sustained ART-free HIV remission
Achieving sustained remission of HIV without life-long antiretroviral therapy (ART) is a top HIV research priority, according to a new commentary in JAMA by experts at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The Lancet HIV: PrEP implementation is associated with a rapid decline in new HIV infections
Study from Australia is the first to evaluate a population-level roll-out of pre-exposure prophylaxis (PrEP) in men who have sex with men.

Researchers date 'hibernating' HIV strains, advancing BC's leadership in HIV cure research
Researchers have developed a novel way for dating 'hibernating' HIV strains, in an advancement for HIV cure research.

Read More: HIV News and HIV Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.