Early virological failure after tenofovir + didanosine + efavirenz combination in HIV-positive patients upon starting antiretroviral therapy.

A prospective, randomized pilot trial was conducted in
naive patients comparing three different combinations:
zidovudine+lamivudine+lopinavir/ritonavir (arm A) versus
tenofovir+lamivudine+efavirenz (arm B) versus tenofovir+
didanosine+efavirenz (arm C). HIV-RNA slope (days
1, 3, 7, 14 and 28) was slower in arm C with respect to
arm B (P<0.0001). Seven out of eight patients (87.5%)
reached undetectable HIV-RNA by week 28 in arm A,
10/10 (100%) in arm B and 6/10 (60%) in arm C. Among
arm C patients who failed at week 4, one HIV isolate
showed 67N and 219Q, and another one showed 210F
and 215D substitutions in the HIV reverse transcriptase
gene at baseline, respectively. Non-nucleoside reverse
transcriptase inhibitor resistance-related mutations
appeared first, followed by 65R mutations in all cases.
Efavirenz AUC0–24 values were lower in arm C with
respect to arm B, especially in patients who failed early.
A high virological failure rate after tenofovir+didanosine+
efavirenz correlated with a slower HIV-RNA
decrease and a peculiar accumulation of resistance
mutations. A constellation of factors could be correlated
with early failure events in patients receiving this combination
such as resistance mutations or polymorphisms
present at baseline, low CD4+ T-cell count or advanced
disease and unexpectedly low efavirenz plasma levels.