Tenofovir (TFV) and Didanosine (ddI) are potent once daily reverse transcriptase inhibitors, effective against HIV-1 infection. Pharmacokinetic studies have demonstrated that when TFV is co-administered with ddI 400mg, ddI plasma concentrations are

1
The Durability of Tenofovir (TFV) and Didanosine
(ddI) When Dosed Together Using Low Dose
Didanosine 250mg. Tung M, Mandalia S, Bower M,
Nelson MR, Gazzard BGSt. Stephens Centre,
Chelsea and Westminster Hospital 369 Fulham
Road, London SW10 9NH, UK.

• TOLERABILTY AND SIDE EFFECTS
• Figure 3
• The majority of treatment discontinuations were
  due to toxicity and side effects probably
  relating to increased mitochondrial toxicity.

INTRODUCTION Tenofovir (TFV) and Didanosine (ddI)
are potent once daily reverse transcriptase
inhibitors, effective against HIV-1 infection.
Pharmacokinetic studies have demonstrated that
when TFV is co-administered with ddI 400mg, ddI
plasma concentrations are increased by up to 60.
These results led to concerns regarding side
effects and toxicity. Current recommendations
suggest reducing ddI dosage to 250mg when used in
combination with TFV, to minimise this
interaction. OBJECTIVES To look at the
virological efficacy and clinical tolerability of
highly active antiretroviral therapy (HAART)
combinations containing Tenofovir and Didanosine
250mg or Didanosine 400mg. METHODS A
retrospective analysis was performed of patients
who commenced an antiviral regimen containing TFV
with either ddI 250mg or ddI 400mg for the first
time. All patients were previously antiviral
experienced, with a mean number of 4 previous
HAART regimens. 78 patients, with a viral load
less than 50 copies/ml, receiving an antiviral
regimen containing TFV and ddI were identified.
33 Individuals were taking TFV and ddI 250mg
taken simultaneously with a light meal. 45
individuals were taking TFV and ddI 400mg taken
separately at least 2 hours apart and in a fasted
state. RESULTS VIROLOGICAL IMMUNOLOGICAL
SUCCESS 33 patients were taking TFV and ddI
250mg and the median duration of treatment was
356 days (range 302 434 days). This compares to
45 patients taking TFV and ddI 400mg for a median
time of 215 days (range 127 308 days). We
analysed the time from the start of the study to
treatment failure defined as either virological
failure or switch of therapy off TFV or ddI due
to toxicity. The survival distribution curve
demonstrates that time to treatment failure is
significantly slower in individuals receiving TFV
and ddI 250mg, p value 0.005. Figure 1
Looking at median CD4 count change
over 6 months, there was no significant
difference between the two groups. Figure 2

Table of treatment discontinuations
Reason for discontinuation TFV ddI 250 N 33 TFV ddI 400 N 45
Toxicity 2 12
Virological Failure 2 3
Patient Request 0 1
Starting Hep C treatment 1 0
Table of toxicity related discontinuations
Toxicity TFV ddI 250 TFV ddI 400
Pancreatic toxicity 0 3
Lactic Acidosis 0 1
Hyperlactataemia 0 2
Peripheral neuropathy 1 2
GI side effects 0 4
Hypophosphataemia 1 0
Table of median CD4 count (cells/mm³)
TFV ddI 250mg TFV ddI 400mg
Baseline Median CD4 count 328 373
6/12 treatment Median CD4 count 320 359