Efficacy and adverse effects of (R)-9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine in feline immunodeficiency
Background:
(R)-9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine (PMPDAP) is active against feline immunodeficiency virus (FIV) in vitro, and is less toxic than other acyclic nucleoside phosphonates. Its efficacy in naturally infected cats has not been evaluated in large controlled studies.
Hypothesis/Objectives:
PMPDAP is effective in naturally FIV-infected cats with minimal adverse effects.
Animals:
Forty-five privately owned cats naturally infected with FIV.
Methods:
Prospective, randomized, placebo-controlled, double-blinded clinical study. Cats were randomly assigned to be treated with PMPDAP (25 mg/kg) daily, PMPDAP 3 times a week, or placebo for a period of 6 weeks.
Results:
Administration of PMPDAP to FIV-infected cats did not lead to detectable improvements in clinical, virological, or immunological variables. Proviral load (FIV copies/10(6) cells) did not change significantly during treatment (placebo group: from 9505 ± 10119 to 8564 ± 8615; PMPDAP 3 times a week: from 4818 ± 4426 to 5041 ± 6197; PMPDAP daily: from 3525 ± 5038 to 3167 ± 5824). There was a significant decrease of red blood cell counts (×10(12) /L) (from 8.91 ± 1.82 to 7.34 ± 1.79 in cats treated 3 times per week (P < .001), and from 8.96 ± 1.13 to 6.01 ± 1.36 in cats treated daily (P < .001)), as well as of packed cell volume, and hemoglobin in both groups receiving PMPDAP.
Conclusions And Clinical Importance:
Administration of PMPDAP was not associated with significant improvements in clinical, immunological, or virological parameters, but treatment was associated with adverse effects, mainly anemia. Thus, PMPDAP, as administered in this study, cannot be recommended for treatment of FIV-infected cats.
Insights
The antiviral (R)-9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine (PMPDAP) did not improve feline immunodeficiency virus (FIV) in cats. Treatment with PMPDAP also led to adverse effects, primarily anemia.
Area of Science:
- Veterinary Medicine
- Virology
- Pharmacology
Background:
- Feline immunodeficiency virus (FIV) is a significant pathogen in cats.
- (R)-9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine (PMPDAP) showed in vitro activity against FIV.
- Previous studies indicated PMPDAP has lower toxicity compared to other acyclic nucleoside phosphonates.
Purpose of the Study:
- To evaluate the efficacy of PMPDAP in naturally FIV-infected cats.
- To assess the safety and adverse effects of PMPDAP treatment in cats.
- To determine if PMPDAP can improve clinical, virological, or immunological parameters in FIV-infected cats.
Main Methods:
- A prospective, randomized, placebo-controlled, double-blinded clinical study was conducted.
- Forty-five FIV-infected cats were enrolled and randomly assigned to receive daily PMPDAP, PMPDAP three times a week, or a placebo for six weeks.
- Clinical, virological, and immunological variables were monitored throughout the study.
Main Results:
- PMPDAP administration did not result in significant improvements in clinical, virological, or immunological parameters.
- Proviral load (FIV copies/10(6) cells) remained unchanged in all treatment groups.
- Significant decreases in red blood cell counts, packed cell volume, and hemoglobin were observed in cats treated with PMPDAP, indicating anemia.
Conclusions:
- PMPDAP treatment was not effective in improving the condition of FIV-infected cats.
- Adverse effects, primarily anemia, were associated with PMPDAP administration.
- PMPDAP, at the dosages and schedule used in this study, is not recommended for treating FIV-infected cats.
