October 26, 2012
Failure rates are high for HIV-infected people on second-line combination antiretroviral therapy, even among those who have suppressed viral loads when they switch, according to a study presented at IDWeek 2012. However, second-line failures decreased by 60% between 1996 and 2010, which testifies to the improvements in potency, convenience and safety of antiretrovirals during that period.
"Whether it's due to pre-existing drug resistance, toxicity or tolerance, first ART [antiretroviral therapy] has its limits," said study presenter Joseph J. Eron, M.D., a professor of medicine at the University of North Carolina-Chapel Hill and the director of the clinical core of the University of North Carolina Center for AIDS Research. In the U.S., 20% of people with HIV who begin treatment modify or discontinue their first-line therapy within six months, Eron said; at two years, 50% of patients have done so. However, there have been no strong trials of second-line ART in resource-rich settings, he said.
In their study, Eron and colleagues analyzed data from patients in HIV clinical programs at Johns Hopkins University, the University of North Carolina and Vanderbilt University who had received both first- and second-line ART between 1996 and 2010. "These people had to at least switch their anchor drug and be followed at least eight weeks; all of these patients had to fail their first-line therapy to be included in the study," Eron explained. Of about 15,000 patients among all three cohorts, only 488 qualified to have their data analyzed in the study, he said.
Of the 488 HIV-infected patients, 67% were black, 32% were women, and 34% had a history of AIDS diagnosis. Of the patients, 49% received an NNRTI-based first regimen, 34% received an unboosted protease inhibitor-based regimen and 19% received a boosted protease inhibitor-based regimen.
Of the patients, 305 had switched to a second-line regimen with a viral load of 400 copies or more, while 183 (37.5%) switched with a viral load below 400 copies (considered "undetectable" for the purposes of this study), Eron reported. Among those who had a detectable viral load at the time of the switch, 17% experienced virological failure within six months, he said. Surprisingly, failure rates were also relatively high among patients with an undetectable viral load at the time of the switch: 12% of those patients experienced virological failure within six months of the switch, Eron said.
However, experience improved over the lengthy course of the study. Between June of 1996, the first year of the study, and June of 2010, the rate of second-line cART failure decreased by almost 60%, Eron said.
It did not appear to make a difference if patients with an undetectable viral load switched regimens when their viral load was 50 or 200 rather than 400, nor did the sequence of regimens used by the patient affect time to virological failure on second-line ART, he said.
Second-line failure occurred considerably earlier if viral load was detectable at the time of switching therapies. For those with detectable viral load at the time of the switch, patients had an average of 605 days to virological failure, compared to more than 1,500 days if their disease was undetectable at the time of the switch to second-line ART, Eron said. The finding was statistically significant (P = 0.001).
The timing of the switch to second-line ART occurred earlier in those who switched with viral loads of 400 and higher: an average of 520 days, compared to 670 days in those with lower viral (P = 0.01). Of the patient population, 38% had viral loads below 400 copies when they switched regimens.
"The study was limited by the difficulty of finding eligible patients," Eron said. "We had hoped to look at the effect of switching from one regimen to the other, but it was futile due to the limited sample size, so very large collaborations will be necessary" to confirm the findings.