A big buzz-maker at this year’s Retrovirus confab? The HIV-meds pipeline is fuller than it’s been in a loooong time. “I think the next few years will see a plethora of new meds, bringing our total up to more than two dozen [from today’s 19],” says ace Los Angeles HIV doc Mark Katz, MD. Let’s look at ’em—from new nukes and PIs likely to get the FDA go-ahead this year or next to more sci-fi ideas that could transform treatment—if they survive R&D’s rocky road!

By the Time You Read This...

...two newbies may already have their FDA-OK. First there’s Reyataz (atazanavir, formerly branded Zrivada), the once-daily protease inhibitor (PI)that, in trials, squashed viral load as low or lower than PI Viracept—without boosting cholesterol, a prime PI problem. And get this: HIV that grows resistant to “Taz” may then become newly vulnerable to older PIs. And speaking of those oldies—between now and mid-’04, look for new versions of saquinavir (currently in Fortovase and Invirase) and Viracept to cut down those killer pill counts, plus power-PI tipranavir: In trials it KO’d HIV with heavy PI resistance—and could be a “salvage superhero.”

Next up No. 2? Gilead’s new NRTI (nuke) Coviracil (FTC), “little cousin” to 3TC (Epivir)—after all, they “tied” in trials, both fight hep B, both come in a once-daily, and if you’re resistant to 3TC, you likely won’t win with FTC. But it does stay in your system longer, so it may protect against resistance better than 3TC in the first place. Plus, Gilead might put FTC in one pill with fellow HIV/hep B–fighter Viread—which, says Project Inform’s Martin Delaney, would be a “somewhat superior alternative to Combivir,” a longtime lord of nuke-ville.

Yes More Nukes (and Non-Nukes)!

There’s a gaggle of both farther back in the pipeline (good news if you’re resistant to the current gang), but it’s still anyone’s bet which will make it to their FDA debut. Nuke-wise, keep your eye on Achillion’s elvucitabine (in Phase II trials for HIV and hep B), Parker Hughes’ stampidine and Gilead’s GS-7340 (a souped-up Viread). Meanwhile, Glaxo glamorized the way-wonky confab with news of three “benzophenonenon-nukes (NNRTIs) unaffected by K103N, the mutation that by itself allows HIV to wiggle around our three non-nukes. New “nons,” says POZ science editor David Gelman, MD, would mean more choices before resorting to PIs, with all their side-effect baggage. And capravirine, a possible godsend against Sustiva resistance, is now in Phase III trials (one trial short of the FDA-OK), rejiggered after canine studies showed it caused blood-vessel inflammation in some unlucky lil’ pups.

Point of (No) Entry

Even before Fuzeon (T-20) was finally approved, Retrovirus was singing about other in-the-works entry inhibitors (EIs), which stop HIV from getting inside a T cell—but Roche’s Fuzeon follow-up T-1249 was not high on the list (Gelman calls it “an average sequel to T-20’s bad movie”—with the same limited seating and high admission price). The real EI starlet was Tanox’s monoclonal antibody TNX-355, which vanquished viral load in the lab, seems pretty easy on the system and could require just one shot a week or less. To Marty Markowitz, MD, of the Aaron Diamond AIDS Research Center, it shows “good proof of concept.” But “human testing of all prior monoclonals has been disappointing,” a dampening Delaney says.

The Future of the Future

The buzzword on everyone’s lips? RNA interference (just RNAi if you’re really cool)—using bits of genetic material to “silence” or “shut off” the production of HIV genes. At the confab, a flurry of reports that RNAi had suppressed the virus (in the lab and early animal studies) had the mainstream press nearly crowing “Cure!” A more moderate Markowitz remarks, “Whether it will translate into clinical benefit remains to be seen,” while doubting Delaney calls RNAi fever “one of the most hyped stories of the year. If it ever comes to anything, it’s a good eight to 10 years away.” That’s likely true. But, hey, if it does, it will be the closest thing in HIV therapy to a “magic bullet”—precision-bombing the virus with no collateral damage. But right now it’s just another spoonful of alphabet soup.