Danish
researchers have recommended that the combination of ddI/d4T and abacavir
should not be used, following the results of a randomised trial conducted by
the University of Copenhagen.
The
study randomized 178 antiretroviral naïve HIV infected patients to receive either a
triple nucleoside analogue regimen of ddI/d4T/abacavir (n=60) or
AZT/3TC/ritonavir/saquinavir (400/400mg) (n=60) or
AZT/3TC/nevirapine/nelfinavir (n=58). The study was open label. The median baseline
CD4 cell count was 161 cells/mm3 and median viral load was 100,000 copies/ml
After 48 weeks, participants in the ddI/d4T/abacavir group were
significantly more likely to have discontinued any of the study drugs when
compared to the AZT/3TC/nevirapine/nelfinavir group (63% vs 45%; p=0.04),
although there was no difference in discontinuations between the triple
nucleoside group and the ritonavir/saquinavir group (57%).
Participants in the triple nucleoside arm of the study were also
significantly less likely to have viral load below 20 copies when compared with
the AZT/3TC/nelfinavir/nevirapine group (41% vs 66%; p=0.01, intent to treat
analysis) – but once again, there was no difference between the triple nuke arm
and the ritonavir/saquinavir arm (41% vs 56%, p=0.12). Virological response in
people with baseline viral load above 20,000 copies/ml or AIDS was superior in
both the ritonavir/saquinavir and the nevirapine/nelfinavir groups.
The following significant differences in adverse events emerged:
style='font-size:10.0pt;mso-bidi-font-size:10.0pt'>
DdI/d4T/abacavir
NVP/NFV
RTV/SQV
Neurological
events
16**
2
3
GI
complications
7
9
21**
Triglycerides
2.2mmol/L(trend)
1.5
1.9
Total
cholesterol
4.8mmol/L*
5.5
5.5
Lactate
1.8mmol/L*
1.1
1.3
Note:
discontinuations due to hypersensitivity reactions not reported
- P=0.003
* P<0.05
What
does this study show?
The
authors concluded that a triple regimen of ddI/d4T/abacavir could not be
recommended due to a higher adverse event rate and poorer virological
performance. This is the second randomised study this year to have presented ddI/d4T
in a poor light – at the International AIDS Conference in July, results of ACTG
384 showed that starting treatment with ddI/d4T/efavirenz resulted in a less
sustained virologic response than starting with AZT/3TC/efavirenz.
This study
was not designed to compare the nucleoside backbones, but instead looked at
three different strategies for starting treatment – triple nucleosides, a
boosted protease inhibitor or use of a single protease inhibitor with a
non-nucleoside reverse transcriptase inhibitors.
Currently
most UK clinicians would not endorse the strategy of starting treatment with a
PI and an NNRTI in the same regimen, on the grounds that it could use up more
treatment options than necessary when there is no evidence that such a regimen
is superior to using two nucleoside analogues and an NNRTI. Indeed, the ACTG
384 study found that whilst starting treatment with two nucleoside analogues
and nelfinavir/efavirenz delayed the failure of the first regimen when compared
with AZT/3TC or ddI/d4T with nelfinavir, the four drug regimen did not outlast
two sequential three drug regimens.
Gerstoft J et al. Abacavir, didanosine and stavudine versus
ritonavir, saquinavir, zidovudine and lamivudine or nelfinavir, nevirapine,
zidovudine and lamivudine in antiretroviral naïve HIV patients. 42nd
ICAAC, San Diego, astract H-164, 2002.