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Previous treatment failures induce resistance to newer HIV drugs

NEW YORK (Reuters Health) – Nearly a fifth of HIV patients who failed treatment with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen turn out to carry mutations that make them resistant to the newer agent rilpivirine, too, even though they were never exposed to it, Spanish researchers say.

First-generation NNRTIs, such as nevirapine (NVP) and efavirenz (EFV), have been “limited by side effects, low barrier to resistance and broad cross resistance,” the researchers wrote online July 26 in AIDS.

Because of a paucity of research on the transfer of resistant mutations to the newer NNRTI rilpivirine (Edurant), Dr. Lourdes Anta’s team from the Spanish AIDS Research Network evaluated the prevalence of rilpivirine resistance-associated mutations in 1,064 viral samples from HIV patients with NNRTI treatment failures.

Rilpivirine resistance was defined as the presence of at least two drug resistant mutations from the International Antiviral Society-USA panel.

Overall, 776 viral samples (72.9%) harbored NNRTI resistance-associated mutations, and 206 (19.3%) were rilpivirine-resistant.

Among the rilpivirine-resistant genotypes, 51.5% were prior nevirapine treatment failures, 40.8% were efavirenz failures, and 7.8% were etravirine failures.

The most common resistance mutations were Y181C (21.8%), V108I (10.2%), K101E (9.1%), V90I(7.9%), and V179I (6.1%).

L1001 and V1081 were more prevalent with efavirenz treatment failures and Y181C, Y181I, V106A, H221Y and F227L with nevirapine failures.

Cross-resistance to rilpivirine was detected in 27% of etravirine failures.

E138K+M184I, the most prevalent rilpivirine resistant genotype in previous studies(ECHO and THRIVE), was not detected in any patient in this study.

“There is still scarce information about the distinct weight of mutations leading to resistance,” the research team acknowledges.

Although rilpivirine is now recommended for first-line and rescue regimens, “the sequential use of rilpivirine in patients that had failed other NNRTIs should not be done in the absence of drug resistance testing excluding cross-resistance,” the researchers conclude.


AIDS 2012.