1. INTRODUCTION OBJECTIVES METHODS RESULTS DISCUSSION
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 BG St. 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.
Figure 4
Looking more closely at the toxicity related discontinuations, lactic acidosis and hyperlactataemia related to mitochondrial toxicity, and pancreatitis were the common causes identified as shown in table 4. There have been documented reports of nephrotoxicity associated with the use of TNF. So far in this cohort there have been no cases of TFV related renal toxicity.
DISCUSSION
Time from virological suppression to treatment failure is significantly slower in patients receiving TFV and ddI 250mg
There were fewer toxicity related discontinuations in patients taking TFV + ddI 250
CONCLUSION
Our clinical cohort has shown that using TFV with ddI 250mg is a safe, well tolerated and effective combination.
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 =
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 3
Patient Request 1
Starting Hep C treatment
Table of toxicity related discontinuations
Toxicity
TFV + ddI 250
TFV + ddI 400
Pancreatic toxicity 3
Lactic Acidosis 1
Hyperlactataemia 2
Peripheral neuropathy
GI side effects 4
Hypophosphataemia
Table of median CD4 count (cells/mm³)
TFV + ddI 250mg
TFV + ddI 400mg
Baseline
Median CD4 count
328
373
6/12 treatment
320
359