The next line of attack: the previous generation of anti-HIV drugs changed AIDS from an untreatable epidemic into a survivable disease. The next crop aims to get rid of the virus altogether.

We all know someone whose life was saved by protease inhibitors and reverse transcriptase inhibitors. In the early 1990s these wonder drugs transformed AIDS from a death sentence into a chronic, but manageable, disease.

Now, after a decade, two new classes of drugs--integrase inhibitors and CCR5 antagonists--are vying to be the next-generation breakthroughs.

"We haven't turned a corner with any radical paradigm shift in the way we treat HIV and AIDS, but still, the news is good," says Kenneth Mayer, MD, director of the Brown University AIDS Program in Providence, R.I., and medical research director at Boston's Fenway Community Health.

Mayer was one of many AIDS researchers who attended February's 14th annual Conference on Retroviruses and Opportunistic Infections in Los Angeles. It was there that encouraging study results concerning these new drugs were presented.

What excites physicians and researchers about these inhibitors is that they attack HIV earlier in the virus's life cycle than medications currently available. An older drug class, protease inhibitors, stops the virus from replicating once it's already inside the patient's T cells. Fusion inhibitors, first introduced in 2003, block HIV from ever entering a patient's T cells.

But among the new classes, integrase inhibiters step the enzyme that allows the virus into the host T cell's DNA, which means HIV can't reproduce itself. And while CCR5 antagonists are similar to fusion inhibitors, they act a step quicker--targeting the CCR5 T-cell corecepter, not the virus itself. Thus, it's difficult to become resistant to this class.

"They are not the answer to all of our problems, but they will be a great option for patients who have become resistant to the other drugs available and don't have other options," says James Tom Barrett, MD, chief medical officer at Chicago's Howard Brown Health Center, who also attended the L.A. conference.

The fusion inhibitor already on the market--enfuvirtide, developed in 2003 by Roche and Trimeris under the brand name Fuzeon--has proven effective, but many HIV-positive patients are turned off by its high cost and the fact that it must be injected with a syringe. Pfizer's answer to these complaints, maraviroc (part of the new CCR5 antagonists class), will likely get Food and Drug Administration approval this year.

As for integrase inhibitors, they're not as far along in development and approval, but early research shows promise. At the L.A. conference, Gilead Sciences, the makers of integrase inhibitor elvitegravir, touted study results that showed one oral dose of the drug reduces viral load in HIV-positive patients already on treatment.

So far there are no major side effects of CCR5 antagonists or integrase inhibiters, and the drugs are well-tolerated. "The data showed a little bit of gastric intestinal upset, but that was about it," says Barrett. "And the dosage data looks good--either once or twice a day."

He cautions, however, that researchers don't know the long-term effects of these new drugs, and won't until they are used by a larger population for a longer period of time.

In addition to anti-HIV drugs, the quest for an AIDS vaccine reached groundbreaking momentum earlier this year when scientists at the National Institute of Allergy and Infectious Diseases near Washington, D.C., found a chink in HIV's armor.

One of the biggest roadblocks to vaccine development has been the ability of HIV to constantly mutate. NIAID researchers discovered a protein on the surface of HIV that does not change, which could be a place vulnerable to attack with a particular antibody. Inserting the antibody at this weak point of HIV would, theoretically, neutralize the virus.

"This is similar to trying to knock down a wall," explains lead researcher Peter Kwong, Ph.D., of NIAID's Vaccine Research Center. "You could use a hammer and just start hammering away. But if you know where there's a weak spot in the wall, you could place a stick of dynamite in and just blow the wall away."

So, how does this get us closer to a vaccine?

"The news here is that for a long time we thought a vaccine was not possible," says Kwong. "We can focus on this one spot and this one antibody. Now, while some technical hurdles remain, a vaccine is not seen as an impossibility."

It's progress for sure, but until we have a vaccine, the development of better anti-HIV drugs remains vital.

"Until we have an active vaccine, we have to put as much as we can into new treatment options," says HIV clinical pharmacist Sarita Doshi of the Whitman-Walker Clinic in Washington, D.C.

The new inhibitors may not shake the ground like their progenitors, but Doshi still lauds their impact. "These new classes of drugs may not be part of the same turning point we had in the mid '90s, but they are giving some patients renewed hope," she says. "And this year, we may see up to three new drugs on the market, two using an entirely new mechanism for attacking HIV. That's huge."

Kuhr is editor at large of Boston-based In Newsweekly, a gay and lesbian newspaper.