Virologic Failure on Rilpivirine May Lead to Broad NNRTI Resistance

Charles B. Hicks, MD


AIDS Clinical Care 

In This Article

Abstract and Introduction


In the ECHO and THRIVE trials, 10% of the patients who received rilpivirine-based regimens experienced treatment failure. Nearly half of these patients developed resistance to multiple nonnucleoside reverse transcriptase inhibitors.


As enthusiasm for "one-pill-once-daily" antiretroviral regimens grows, it is becoming increasingly important to distinguish between the available options — currently, tenofovir/FTC/efavirenz (Atripla) and tenofovir/FTC/rilpivirine (Complera). One factor to consider is the resistance consequences of treatment failure with these regimens, as was recently characterized in the ECHO and THRIVE trials.

In these two trials, treatment-naive, HIV-infected patients were randomized to receive rilpivirine or efavirenz, each in combination with two nucleoside reverse transcriptase inhibitors (NRTIs), predominantly tenofovir and FTC. Rates of treatment response were comparable overall, but the reasons for failure differed substantially between the groups: Treatment failures in the rilpivirine arm were mainly due to virologic failure (especially among patients with baseline viral loads >100,000 copies/mL), whereas treatment failures in the efavirenz arm were due mainly to adverse events (JW AIDS Clin Care Aug 1 2011). In the current analysis (sponsored by the maker of rilpivirine), investigators compared the resistance profiles of viruses obtained following rilpivirine versus efavirenz failure.

Overall, 10% of patients in the rilpivirine arm and 6% of those in the efavirenz arm were categorized as having experienced virologic failure (VF). Viral isolates were available from 62 of the 72 rilpivirine failures and 28 of the 39 efavirenz failures. Treatment-emergent nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance–associated mutations (RAMs) were detected in 63% of rilpivirine failures versus 54% of efavirenz failures. For NRTI RAMs, the difference was even more striking: 68% versus 32%. The most common NNRTI RAM detected in the rilpivirine failures was E138K, identified in 45% of failures, most often together with M184I/V, which primarily affects susceptibility to FTC and 3TC. E138K was associated with cross-resistance to all other clinically available NNRTIs (efavirenz, nevirapine, etravirine). In contrast, the most common NNRTI RAM in the efavirenz failures was K103N, which caused cross-resistance to nevirapine only.


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