Poor response with tenofovir and ddI backbone causes early study termination
31 January 2005. Related: Conference reports, Antiretrovirals, ICAAC 44th Washington 2004.
Simon Collins, HIV i-Base
A study from the Chelsea and Westminster Hospital, London, presented data indicating a poorer response when tenofovir and ddI are used together as dual nucleoside backbone.
This open-label study planned to randomise 100 treatment naïve patients to either tenofovir/ddI/efavirenz or 3TC/ddI/efavirenz but the study closed early following an unplanned interim safety analysis of the first 73 patients. The reduced dose of ddI (250/200mg >/<60kg) was used throughout this study.
Although patients in each group were evenly matched by baseline CD4 and viral load, the tenofovir arm produced reduced virological responses and significantly greater earlier failure, defined as VL >0.5 log above nadir or development of new resistant mutations.
Efficacy of tenofovir/ddI/efavirenz v 3TC/ddI/efavirenz
| 3TC | tenofovir | |
|---|---|---|
| Mean baseline CD4 | 160 | 173 |
| Mean baseline VL | 5 log | 5 log |
| Results week 4 | ||
| n | 33 | 33 |
| mean (SD) change VL | -2.7 (0.57) | -2.8 (0.87) |
| %pt >1 log | 32/33 (97%) | 29/38 (88%) |
| Results week 12 | ||
| n | 23 | 29 |
| mean (SD) change VL | -1.88 (0.4) | -2.04 (0.9) |
| n (%) pts VL rebound or new RT mutations | 0/23 (0%) | 4/29 (14%) |
All patients failing the tenofovir arm had baseline VL >100,000 copies/mL and CD4 counts < 200 cells/mm3.
MEMS caps adherence monitoring confirmed 100% adherence in all the failing patients.
The poor performance of tenofovir/ddI, even when supported by efavirenz was clearly unexpected by these researchers. Although the combination failed in more advanced patients, together with other reports (see below) this should caution reliance on this dual nucleoside pairing in any three-drug combination,
No theoretical mechanism was suggested for the results of this study.
Reference:
Moyle G et al. Early virological failure in persons with viral loads >100,000 cps/ml and CD4 counts <200cells/mm3 receiving ddI/tenofovir/efavirenz as initial therapy: results from a randomised comparative trial. 44th ICAAC, Washington, 2004. Abstract H-566.