Besieged by unforgiving pill-popping schedules, many PWAs are wishing for a kinder, gentler regimen: if only drugs could be taken twice (b.i.d.) instead of three times (t.i.d.) daily…. But—bottom line—can less-frequent dosing maintain adequate blood levels of the drugs for virus-suppressing potency? Results from studies so far have been mixed.

First, the good news: A recent trial of 360 PWAs on combos containing nelfinavir (Viracept) found that equal proportions of patients (80 percent) on t.i.d. or b.i.d. had undetectable viral loads after 48 weeks. Side effects were also about equal, with slightly more cases of diarrhea in the b.i.d. group. And preliminary results from 242 patients in a 24-week saquinavir (Fortovase) combo study found roughly similar rates of undetectability among b.i.d.’ers and t.i.d.’ers (69 percent vs. 74 percent)—but whether these results will hold up in more people over the long term is unknown.

The bad news concerns indinavir (Crixivan). Expectations were raised last winter when a 90-person, 24-week study found roughly equal viral suppression in those on the drug (as part of a combo) either b.i.d. or t.i.d. for 24 weeks. But these hopes were dashed by a 400-person study, halted in September when researchers saw that after the same period, only 64 percent of b.i.d.’ers had undetectable viral loads, compared to 91 percent of t.i.d.’ers. Manufacturer Merck then issued a warning against using the b.i.d. regimen.

Meanwhile, research involving two-protease combos (plus nucleosides) taken b.i.d. is underway.