1987 Retrovir (AZT), the first drug to fight HIV, is approved. It’s a nuke (short for nucleoside analog). But pretty soon it’s clear that by itself, AZT can’t prevent HIV from mutating to get around it.
1994-95 Studies show that the handful of nukes on the market work better when used together. Combination therapy—the idea of getting more action against HIV by teaming meds up—is born.
1995-96 Approval of the first protease inhibitors (PIs): Invirase (saquinavir), Crixivan (indinavir) and Norvir (ritonavir).‑Combin-ing PIs and nukes improves their punch, ushering in triple-drug therapy.
1996-98 More weapons against the virus: The --non-nukes (NNRTIs) debut, hitting HIV in a slightly different way than nukes.
1997 Drug makers put two nukes into a single pill (Combivir), creating the first ever fixed-dose combination.
1998-99 Oops. We notice bizarre side effects like body-fat accumulation and loss, and spiking levels of blood fats. These come to be known as lipodystrophy.
1999 It turns out PIs sometimes increase the levels of other meds. Small amounts of Norvir (ritonavir) can be used to “boost” other PIs so they work better and can be taken less often and in lower doses.
2000 Some non-nukes and Norvir-boosted PIs combine nicely with selected nukes into once-daily regimens.
2002 A new nuke named Viread (tenofovir) comes on the scene. It’s chemically different from other nukes but acts against HIV in the same way.
2003 The entry inhibitor Fuzeon (T-20) is approved—the first in a new class of HIV meds. Twice-daily injections are a drawback, so pharma gets to work developing a pill.
2003 Some newer PIs such as Reyataz (atazanavir) are less linked to lipo.
2004 Fixed-dose, once-daily combo pills (Epzicom and Truvada) become available.
2004-05 New classes of HIV meds—including CCR5 antagonists, HIV integrase inhibitors and maturation inhibitors—are in development.
2006 Drug makers announce that they’ve successfully combined two nukes (Emtriva and Viread) with the non-nuke Sustiva (efavirenz) in a single pill. If approved, it will be the first one-pill, once-a-day HIV regimen.