Intensification of a Failing Regimen with Zidovudine May Cause Sustained Virologic Suppression in the Presence of the K65R Mutation
Schlomo Staszewski*1, B Dauer1, L Locher2, M Moesch1, P Gute2, and M Stuermer1
1JW Goethe Univ, Frankfurt, Germany and 2Gemeinschaftspraxis Grueneburgweg, Frankfurt, Germany
K65R mutation is seldom selected with current treatment strategies. It has been
selected with sub-optimal therapies such as tenofovir/didanosine/abacavir
(TDF/ddI/ABC) regimens. The K65R limits the number of nucleoside reverse
transcriptase inhibitor (NRTI) options. However, it has the potential to
decrease phenotypic zidovudine (AZT)-resistance and rarely occurs concurrently with thymidine analogue mutations (TAM).
Thus, patients with the K65R mutation usually maintain AZT as options.
studied 3 patients who experienced virologic failure associated with the K65R
and other resistance mutations. Their drug regimens were then intensified with
AZT without changing any other drugs despite genotypic resistance.
1 was experiencing therapy failure with ABC/ddI/lamivudine (3TC); Patient 2,
who never attained undetectable viremia in 4 years
of treatment, failed while taking ABC/ddI/TDF. Genotype testing at virologic
failure showed K65R, L74V, M184V, and the Y115F mutations to be present in both
patients. Patient 3, who failed on TDF/3TC+nevirapine (NVP), demonstrated the
K65R, G190S, and Y181C mutations. Their failing regimens were intensified with
AZT while the other drugs were continued, despite resistance mutations to all
the drugs in their regimens. All 3 patients had an immediate viral load
reduction to undetectable levels within 4 weeks: Patient 1 dropped more than 2 logs from 5300
copies/mL to <50 copies, patient 2 dropped > 3 logs from 48,000 to <20
copies, and patient 3 had a 1.4 log reduction from 1130 to <50 copies/mL.
Follow-up time ranged from 15 months to 2 years. All 3 patients have maintained
<50 copies/mL and all 3 remain on their regimens.
these patients with the K65R mutation and no TAM, AZT was added to regimens in
which genotypic testing showed resistance to all their drugs. AZT was the only
active drug, but this addition was enough to achieve sustained viral load
reductions to >50 copies/mL.