Talkin’
’Bout a Revolution

The mid 1990s -- specifically the two-year period beginning in December 1995 during which five revolutionary, lifesaving protease inhibitor medications were approved --mark the single biggest turning point in the global battle against HIV and AIDS. For millions of HIV-positive men, women, and children around the world, the arrival of these medications and the triple-drug combination therapy era they ushered in changed AIDS from a virtual death sentence to the possibility of living to fight another day, month, year, or more.

The Advocate welcomed the medications with a cover story simply -- and appropriately -- titled "Hope."

What many LGBT people may not know is that a second significant treatment revolution has been under way during the past year, with some leading HIV experts calling it second in importance only to the introduction of protease inhibitors. And for HIVers with difficult-to-treat drug-resistant virus, the three medications approved since August 2007 (Selzentry, Isentress, and Intelence) are no less miraculous those unveiled in the 1990s.

"There's a lot of excitement out there," says Rowena Johnston, Ph.D., vice president of research at the American Foundation for AIDS Research. "People sometimes lose sight of why we need more. The reason is that HIV can so rapidly develop resistance to the drugs we already have and we lose people who run out of options to treat their infection. So we're always in a race against time to find new and better ways to attack HIV."

Here is more information about these three newly approved medications and the novel -- and powerful -- ways in which they attack the virus.

Selzentry (maraviroc)

Drug Class: Entry Inhibitor

Approved: August 2007

Pfizer's Selzentry works by disabling the CCR5 receptors on the surface of T cells that HIV uses to latch onto the cells. Blocking the receptors prevents the virus from attaching to -- and subsequently infecting -- the cells.

Roche's Fuzeon (T-20) was the first entry inhibitor ever to receive Food and Drug Administration approval, in 2003, but that medication inhibits a protein in the virus itself. Selzentry is the first entry inhibitor -- actually, the only antiretroviral medication at all -- that targets human cells instead of HIV. Fuzeon also must be injected, while Selzentry is a tablet taken twice daily.

"Because it focuses on a previously untargeted infection step, Selzentry in combination with other antiretrovirals is useful in treating HIV resistant to other medications that focus on the virus itself," says Kenneth Mayer, MD, medical research director of Boston's Fenway Community Health Center.

But before Selzentry can be prescribed, a pricey diagnostic test -- called a tropism assay -- must be given to patients to confirm that they carry only virus that uses CCR5 cellular receptors; some substrains of HIV use the cells' CXCR4 portal or both types.

Isentress (raltegravir)

Drug Class: Integrase Inhibitor

Approved: October 2007

Isentress, developed by Merck, is the first integrase inhibitor to reach the consumer market. It works by blocking HIV's integrase enzyme, which inserts viral genetic information into cellular DNA, a process that turns the cell into a virus-making factory.

Because it targets a new enzyme in the replication cycle of the virus that no other drug has ever attacked, Isentress is useful in fighting virus that has mutated and developed resistance to existing meds, says Tony Mills, MD, a Los Angeles HIV specialist.

Isentress is taken orally in tablet form twice daily.

Intelence (etravirine)

Drug Class: Second-generation Nonnucleoside Reverse Transcriptase Inhibitor

Approved: January 2008

Intelence's chief advantages over existing NNRTI drugs include a better ability to thwart HIV's attempts to develop resistance to it and an ability to fight HIV resistant to its sister medications, says Brian Risley, lead treatment educator at AIDS Project Los Angeles.

The drug, marketed by Tibotec Therapeutics, has far less toxicity than other NNRTIs, particularly less of the central nervous system side effects associated with Bristol-Myers Squibb's Sustiva, which include dizziness, sleep disturbances, trouble concentrating, and vivid dreams. Another rare, but serious, Sustiva side effect not yet seen among Intelence users is the developing or worsening of major depression.

"I was really depressed and pretty much as nutty as you can get," says Craig Allen Lawver of West Hollywood, who took Sustiva for six months. "There was no way I could continue taking that drug."

Intelence is dosed orally in tablet form, taken twice daily.

Selzentry, Isentress, and Intelence are all currently approved only to treat drug-resistant infections and are not yet endorsed for first-line therapy, although the drugs' makers are now conducting studies to gauge their effectiveness among treatment-naive HIVers. But even though their use is currently limited, the medications are so revolutionary that treatment advocates have warmly welcomed their arrivals.

"Of course, no drug is perfect for everyone, and continued monitoring of side effects is essential for any new drug, but these three -- Selzentry, Isentess, and Intelence -- could revitalize the treatment regimens of many people with multidrug-resistant HIV," says Reilly O'Neal, editor of San Francisco AIDS Foundation's Bulletin of Experimental Treatments for AIDS.