The impact of initial highly active antiretroviral therapy on future treatment sequences in HIV infection

To determine whether the initial use of non-nucleoside reverse transcriptase inhibitors (NNRTI) or protease inhibitors (PI) differentially influences subsequent HIV therapy. A cohort study using a prospective clinical database in a university-based HIV clinic. A total of 440 HIV-seropositive patients, naive or nucleoside experienced, initiating therapy with either an NNRTI or PI between January 1998 and July 2003 and followed to December 2003. Time until stopping the first regimen and until exposure to all antiretroviral classes (excluding tenofovir and enfuvirtide) according to the type of initial regimen. A total of 291 subjects initiated HAART with PI and 149 with NNRTI; median follow-up 3.1 and 2.3 years, respectively. Subjects starting NNRTI remained on their initial regimens longer (median time to change 2.1 versus 1.6 years; log rank P = 0.03). Overall, subjects initiating NNRTI-based regimens were less likely to alter their therapy. Previous nucleoside exposure was an important predictor of treatment modification. Subjects initiating NNRTI-based HAART were also less likely to experience virological failure than those initiating PI-based HAART. Individuals starting with NNRTI were exposed to fewer regimens (15 versus 25% received three or fewer regimens), and showed a trend towards lower rates of three-class exposure (7 versus 12%). There is a high rate of treatment modification among patients initiating HAART. The initial use of NNRTI-based HAART was associated with more durable treatment and lower rates of virological failure, which may translate into a reduced need for multiple salvage therapies.