NATAP -
www.natap.orgReport from 6th Intl Congress on Drug Therapy in HIV
written by Graeme Moyle, MD, Chelsea & Westminster Hospital, London, UK
This report is excerpted from a more comprehensive report from Dr Moyle which
will be available later today. All conferences reports archived at NATAP
website.
Under the cold grey skies of Glasgow around 2500 HIV researchers meant to
discuss the hot topics in HIV therapeutics over 17 - 21 November 2002. There
was only modest amount of new data presented much of the discussion being
developed by plenary speakers.
Gilead 903 study: resistance outcomes
The Gilead 903 study is a 600 patients randomised placebo-controlled study
comparing tenofovir 245 mg once daily with d4T 40 mg twice daily (weight
adjusted, immediate release formulation) combined with efavirenz and
lamivudine, which has thus far completed 48 weeks of follow-up. By intention
to treat missing equals they are analysis 82 percent of tenofovir recipients
and 81 percent of d4T recipients had viral load is less than 50 copies/ml at
week 48. CD for benefits have also been similar in the two groups.
Individuals meeting definition for virological failure were described. In
the tenofovir group 29 individuals (9.7% of those randomised) and in the d4T
group 25 individuals (8.3%) were defined as virological failure. Mutations
associated with efavirenz resistance were found in 16 tenofovir failures and
12 d4T failures. The 3 TC signature mutations 184 V was found in 12
tenofovir failures and eight d4T failures. While time virus was detected in
10 tenofovir failures and 12 d4T failures. In vitro tenofovir is known to
select for the K65R mutation, a mutation which may be associated with reduced
viral fitness but when combined with other mutations may affect the activity
of 3 TC, abacavir and ddI. No patient in either group had the K65R mutation.
However, K. 65 was found in association with an efavirenz resistance
mutation alone in 2 tenofovir failures and one d4T failure, and in
combination with both an efavirenz resistance mutation and 184V in five
tenofovir failures and one d4T failure. Overall, this meant that seven
individuals in the tenofovir group of 29 with virological failure had the
K65R mutation and to other 25 virological failures in the d4T group had this
mutation. Assessment of the seven isolates from the tenofovir group using
both the Virco and ViroLogic phenotype assays was performed. Using the Virco
assay, three of the isolates with K65R were resistant to ddI, three resistant
to abacavir and four resistant to tenofovir. A number of the isolates showed
modest increases in susceptibility to AZT via both phenotypic assay.
Follow-up information on all seven individuals with K65R associated failure
in the tenofovir group were reported. All patients changed therapy, in
general to regimens that contained a thymidine analog and protease inhibitor
or ddI and a protease inhibitor. Five of these individuals had achieved
viral load is less than 50 copies/ml at last follow-up the other two
individuals had detectable virus below 2000 copies, with one individual lost
to follow-up and a second individual known to be incompletely adherence to
medication. These data would suggest that re-establishment of an optimal
virological response is achievable in individuals who experience viral
rebound associated with resistance mutations including the K65R mutation.
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