|
|
Abstract
GENOTYPIC ANALYSES AND HIV RNA RESPONSES IN PATIENTS AFTER 96 WEEKS OF TENOFOVIR DF (TDF) THERAPY
MILLER M, JOHNSON A, ISAACSON E, MARGOT N
Background: Study 902 was a placebo-controlled, 48-wk phase II study of 3 doses of TDF when added to stable ART in 189 treatment-experienced pts (mean 4.6 yrs prior ART, 94% with NRTI-associated mutations). There was a statistically significant reduction in HIV RNA at wk 24 (-0.58 log10 DAVG24) with 300 mg TDF qd that was durable through wk 48 (-0.62 log10 DAVG48). At wk 48, 135 pts entered an extension phase receiving 300 mg TDF.
Methods: Genotypic analyses of plasma HIV was performed for all pts completing 96 wks of extension phase dosing to-date (n=71) and compared to their wk 48 genotype. Final genotypic analyses of remaining pts will be included.
Results:Among the 71 analyzed pts, 59% switched from lower doses of TDF to 300 mg at wk 48 and there was a mean -0.92 log10 decrease in HIV RNA at wk 96 from baseline. At wk 96, HIV from 46 pts was successfully genotyped and 25 were unsuccessful due to insufficient HIV RNA (16 pts <50 c/mL). One pt (1.4%) developed the K65R RT mutation (selected by tenofovir in vitro) but maintained HIV RNA suppression (-0.4 log10). 28 pts (39%) developed new NRTI mutations, 20 of whom developed thymidine analog mutations while taking AZT or d4T. These 96-wk results are analogous to the 48-wk results, in which 2.1% (n=4) and 42% (n=63) of pts developed K65R or NRTI mutations, respectively. Although most pts maintained HIV RNA suppression, an analysis of pts with >0.5 log10 increase in HIV RNA from wk 48-96 was performed. Most of these pts developed NNRTI-, 3TC- or PI-associated mutations. No new mutations potentially associated with TDF therapy were identified.
Conclusions:Adding TDF 300 mg to existing ART in highly treatment-experienced pts with preexisting resistance mutations shows significant and durable HIV RNA reductions through wk 96. After 2 yrs of TDF therapy, as observed after 1 yr, there is an infrequent development of RT mutations associated with TDF therapy, consistent with the durability of the observed HIV RNA responses.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
128
Suggested Citation
"MILLERM, et al.
GENOTYPIC ANALYSES AND HIV RNA RESPONSES IN PATIENTS AFTER 96 WEEKS OF TENOFOVIR DF (TDF) THERAPY.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
128"
|
|
|