Tag Archives: sexually transmitted

Study: Potent new drug candidate blocks HIV strains

U.S. scientists say they have created a novel drug candidate that is so potent and universally effective, it might work as part of an unconventional vaccine and could be used in the fight against HIV/AIDS.

The research, which involved scientists from more than a dozen research institutions, was published February 18 online ahead of print by the prestigious journal Nature.

The study shows that the new drug candidate blocks every strain of HIV-1, HIV-2 and SIV (simian immunodeficiency virus) that has been isolated from humans or rhesus macaques, including the hardest-to-stop variants. It also protects against much-higher doses of virus than occur in most human transmission and does so for at least eight months after injection.

“Our compound is the broadest and most potent entry inhibitor described so far,” said Michael Farzan, a TSRI professor who led the effort announced on Feb. 18 by The Scripps Research Institute in Jupiter, Florida. “Unlike antibodies, which fail to neutralize a large fraction of HIV-1 strains, our protein has been effective against all strains tested, raising the possibility it could offer an effective HIV vaccine alternative.”

Blocking a Second Site

When HIV infects a cell, it targets the CD4 lymphocyte, an integral part of the body’s immune system. HIV fuses with the cell and inserts its own genetic material — in this case, single-stranded RNA — and transforms the host cell into an HIV manufacturing site.

The new study builds on previous discoveries by the Farzan laboratory, which show that a co-receptor called CCR5 contains unusual modifications in its critical HIV-binding region and that proteins based on this region can be used to prevent infection.

With this knowledge, Farzan and his team developed the new drug candidate so that it binds to two sites on the surface of the virus simultaneously, preventing entry of HIV into the host cell.

“When antibodies try to mimic the receptor, they touch a lot of other parts of the viral envelope that HIV can change with ease,” said TSRI research associate Matthew Gardner, the first author of the study with Lisa M. Kattenhorn of Harvard Medical School. “We’ve developed a direct mimic of the receptors without providing many avenues that the virus can use to escape, so we catch every virus thus far.”

The team also leveraged preexisting technology in designing a delivery vehicle — an engineered adeno-associated virus, a small, relatively innocuous virus that causes no disease. Once injected into muscle tissue, like HIV itself, the vehicle turns those cells into “factories” that could produce enough of the new protective protein to last for years, perhaps decades, Farzan said.

Data from the new study showed the drug candidate binds to the envelope of HIV-1 more potently than the best broadly neutralizing antibodies against the virus. Also, when macaque models were inoculated with the drug candidate, they were protected from multiple challenges by SIV.

“This is the culmination of more than a decade’s worth of work on the biochemistry of how HIV enters cells,” Farzan said. “When we did our original work on CCR5, people thought it was interesting, but no one saw the therapeutic potential. That potential is starting to be realized.”

In addition to Farzan, Gardner and Kattenhorn, authors of the study, “AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges,” include Hema R. Kondur, Tatyana Dorfman, Charles C. Bailey, Christoph H. Fellinger, Vinita R. Josh, Brian D. Quinlan, Pascal Poignard and Dennis R. Burton of TSRI; Jessica J. Chiang, Michael D. Alpert, Annie Y. Yao and Ronald C. Desrosiers of Harvard Medical School; Kevin G. Haworth and Paula M. Cannon of the University of Southern California; Julie M. Decker and Beatrice H. Hahn of the University of Pennsylvania; Sebastian P. Fuchs and Jose M. Martinez-Navio of the University of Miami Miller School of Medicine; Hugo Mouquet and Michel C. Nussenzweig of The Rockefeller University; Jason Gorman, Baoshan Zhang and Peter D. Kwong of the National Institutes of Health; Michael Piatak Jr. and Jeffrey D. Lifson of the Frederick National Laboratory for Cancer Research; Guangping Gao of the University of Massachusetts Medical School; David T. Evans of the University of Wisconsin; and Michael S. Seaman of Beth Israel Deaconess Medical Center.

The work was supported by the National Institutes of Health through multiple grants.

Gay rights group endorses once-a-day pill intended to prevent HIV infection

The nation’s largest LGBT civil rights group over the weekend endorsed efforts to promote the use of a once-a-day pill to prevent HIV infection and called on insurers to provide more generous coverage of the drug.

Some doctors have been reluctant to prescribe the drug, Truvada, on the premise that it might encourage high-risk, unprotected sexual behavior. However, its preventive use has been endorsed by the U.S. Centers for Disease Control and Prevention, the World Health Organization and many HIV/AIDS advocacy groups.

The Human Rights Campaign joined those ranks with the release of a policy paper strongly supporting the preventive use of Truvada. It depicted the drug as “a critically important tool” in combatting HIV, the virus that causes AIDS.

“HRC does not take this position lightly,” the policy paper said. “We recognize there is still ongoing debate … and that there are those out there who will disagree with our stance.”

Truvada has been around for a decade, serving as one of the key drugs used in combination with others as the basic treatment for people with HIV. In 2012, the Food and Drug Administration approved it for pre-exposure prophylaxis, or PrEP – in other words, for use to prevent people from getting sexually transmitted HIV in the first place.

“Today, there is an unprecedented chance to end the HIV/AIDS epidemic, in part through PrEP’s aggressive prevention of new HIV infections,” said Chad Griffin, president of the Human Rights Campaign. “There is no reason – medical or otherwise – to discourage individuals from taking control of their sexual health and talking to their doctor about PrEP.”

The CDC says studies have shown that Truvada, when taken diligently, can reduce the risk of getting HIV by 90 percent or more. Research discussed at the International AIDS Conference in July found that use of the drug does not encourage risky sex and is effective even if people skip some doses.

As part of its announcement, the Human Rights Campaign called on insurers, regulators and Truvada’s manufacturer to take steps to reduce costs, raise public awareness, and make the option available to all medically qualified individuals who could benefit from it, regardless of ability to pay.

The cost of Truvada varies widely; a New York State Health Department fact sheet gives a range of $8,000 to $14,000 per year. The manufacturer, California-based Gilead Sciences Inc., has a program that provides assistance to some people who are eligible to use Truvada but cannot afford it.

The Human Rights Campaign urged all states to emulate Washington state, which implemented a program earlier this year offering assistance in paying for PrEP. The preventive option also was endorsed by New York Gov. Andrew Cuomo when he announced initiatives in June aimed at ending the state’s AIDS epidemic by 2020.

The HRC called on state insurance regulators to take action against any insurers who deny legitimate claims from patients who’ve been prescribed PrEP by their doctors.

A prominent provider of services to HIV-positive people, the Los Angeles-based AIDS Healthcare Foundation, remains a vocal critic of the preventive use of Truvada. In an ad campaign launched in August, the foundation says many gay men fail to adhere to Truvada’s once-a-day regimen and describes government promotion of the drug as “a public health disaster in the making.”

On Oct. 10, an alliance of about two-dozen HIV/AIDS organizations in New York released an open letter to the Healthcare Foundation, asking it not to extend the ad campaign to their state.

“We believe your campaign could prevent people at risk for HIV from using this potential lifesaving medication,” the letter said.

The Healthcare Foundation’s president, Michael Weinstein, said his organization did plan to run ads soon in New York City asserting there is data casting doubts on Truvada’s effectiveness.

“Censoring the discussion is not the answer,” he said.

Weinstein also noted that – according to figures from Gilead – only a few thousand people thus far have filled prescriptions for Truvada.

“If people really felt it was the answer, it’s hard to imagine it wouldn’t have spread like wildfire,” Weinstein said. “It’s obvious there is enormous ambivalence in the medical community.”

According to the CDC, there are about 50,000 new HIV infections annually, with gay and bisexual men accounting for nearly 63 percent of them.

On the Web…

Human Rights Campaign: http://www.hrc.org/

AIDS Healthcare Foundation: http://www.aidshealth.org/(hash)/

CDC factsheet: http://www.cdc.gov/hiv/pdf/PrEP-GL-Patient-Factsheet-PrEP-English.pdf