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Home > Treatment > HIV Meds Quarterly > Winter/Spring 2011 > Rilpivirine
Rilpivirine Redux
Rilpivirine Redux

The primary results of the Phase III studies of the NNRTI rilpivirine, presented this summer at the International AIDS Conference, showed that the overall efficacy of rilpivirine and efavirenz (each given with 2 NRTIs) in treatment-naive patients was the same (see "Rilpivirine [TMC278] in Initial Therapy"). However, rates of virologic failure were higher in the rilpivirine arm, whereas rates of adverse events were higher in the efavirenz arm. Additional analysis of the data, presented at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), helps to characterize the causes and consequences of virologic failure in rilpivirine recipients.

Efficacy data from the week 48 pooled ECHO and THRIVE studies show that rates of virologic failure (HIV RNA level <50 copies/mL) were higher in rilpivirine recipients with baseline HIV RNA >100,000 copies/mL than in those with lower viral loads (77% vs 90%), whereas, in efavirenz recipients, the differences according to baseline HIV RNA were much more modest (81% vs 84%, respectively). Not surprisingly, suboptimal adherence (assessed by pill count) also was associated with virologic failure, but the effect was seen more strongly in the rilpivirine treatment arm. In patients with pretreatment HIV RNA >100,000 copies/mL, the effect of suboptimal adherence was particularly striking in those treated with rilpivirine: virologic failure was seen in 50% of study subjects, compared with 17% of those taking efavirenz. (Note: The numbers of patients in these subanalyses are small; statistical comparisons could not be made.)

Of the patients with virologic failure on rilpivirine, about two thirds had NNRTI resistance and two thirds had NRTI resistance (mostly M184I or M184V), and more than half had resistance involving both classes. Decreased susceptibility to rilpivirine was associated with the following mutations: E138K/G/Q/R, K101E/P, H221Y, and Y181C/I/V.

Clinical Bottom Line
These data help to characterize patients who are at greater risk of treatment failure with rilpivirine--specifically those with high baseline viral loads and those who are not closely adherent to their ARV regimens, with the highest risk involving those who fit both categories. For many patients, however, rilpivirine is likely to offer a reasonable alternative to efavirenz for initial therapy, and one with less risk of adverse effects. If it receives FDA approval, it is expected to be available in a coformulation with tenofovir/emtricitabine, as a 1-pill once-daily regimen.


Rimsky L, Eron J, Clotet B, et al. Characterization of the resistance profile of TMC278: 48-week analysis of the Phase III studies ECHO and THRIVE. In: Program and abstracts of the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 12-15, 2010; Boston. Abstract H-1810.