The addition of ddI to the HAART regimens of individuals with detectable viral load despite therapy and NRTI resistance, can lead to a significant reduction in viral load in the short term, according to French research presented to the 43rd ICAAC in Chicago on September 14th. However, the strategy is less likely to be effective in individuals with high level NRTI resistance, raising questions over the likely utility of ddI in salvage therapy.
In the double-blind, multi-centre, randomised, placebo controlled A1454-176 Jaguar study, 110 individuals were randomised to receive the appropriate once-daily weight-determined dose of enteric coated ddI (400mg or 250mg) in addition to their existing HAART. A placebo was given to 58 patients.
All the study participants were on stable anti-HIV therapy, but had an HIV viral load between 1,000 and 100,000 copies/mL. Median viral load at baseline was 6,310 copies and median CD4 cell count was 378 cells/mm3. Patients had a median of three resistance mutations to thymidine analogues and four nucleoside mutations. A total of 68% of individuals had previous experience of ddI treatment.
HIV viral load was monitored at baseline and then at weeks two and four. The primary outcome of the study was the mean change in viral load by week four.
Mean HIV viral load fell to 1,500 copies/mL in the ddI-treated patients by week four (median reduction -0.59 log10 copies/ml), but increased to approximately 8,000 copies in the placebo arm (+0.05 log10 copies/ml) (p
Adding ddI proved most effective for individuals with either no thymidine analogue mutations (median reduction in viral load -0.8 log10 copies/ml), or just one (1.0 log10 copies/ml). In patients with three thymidine analogue mutations. the median reduction at week 4 was -0.4 log 10 copies/ml), whilst the reduction recorded in patients with four or more thymidine analogue mutations or four or more nucleoside analogue mutations (including M184V) was not statistically significant.
The median fall in viral load was 0.6 log10 for patients with the M184V mutation and 0.1 log10 for those with resistance at L74V (the mutation which confers high level resistance to ddI).
On the basis of these data, the investigators concluded that ddI retains significant antiviral activity in treatment-experienced individuals with resistance mutations. However, further follow-up will be needed to determine whether the antiviral impact of adding ddI is sustained, especially in patients with several thymidine analogue mutations.
Further information on this website
Changing treatment - Overview of key issues and research on the subject of choosing new regimens for treatment-experienced patients.
Resistance to NRTIs - includes information on resistance to ddI.
ddI - key research - summaries of key studies
ddI - overview - overview of use of ddI in HIV treatment.
Molina J et al. Didanosine in treatment-experienced HIV-infected patients: results from a randomised double-blind study (A1454-176 Jaguar). 43rd ICAAC, abstract H-447, Chicago, September 14 – 17th, 2003.