World's first Cat to be Treated with HAART

August 2015

By Joel Kehler

FIV HealthScience Newsletter

On August 22, 2015, Charlie, a cat from Maryland, became the world's  first cat with FIV to be treated with HAART, or Highly Active  Antiretroviral Therapy.  HAART is the current standard of therapy for  HIV infection and is defined as treatment with at least three  antiretroviral drugs drawn from at least two different classes.  The  classes themselves are based on which part of the viral replication  process is being inhibited.  The three drugs Charlie is receiving are  tenofovir (TDF), emtricitabine (FTC), and raltegravir (RAL).  The last,  raltegravir, is an inhibitor of the integrase enzyme that FIV requires  to insert its DNA into the host genome and was recently written about here because of  a study that found it effective at inhibiting replication of the feline  leukemia virus, a retrovirus like FIV.  TDF and FTC are inhibitors of  the viral enzyme called reverse transcriptase needed to transform the  virus's RNA into DNA. The appeal of all three of these drugs is that  cats tolerate them well with little evident toxicity.  This is not the case with most other HIV drugs.

It's not as if this same combination of drugs (and others like it)  has never before been given to animal test subjects as part of research  projects.  They have.  In recent years, a number of studies making use  of macaques have done just that.  One recent study,  for instance, used the same drugs that Charlie is getting along with  others, including auranofin (a gold salt occasionally used to control  feline stomatitis) and BSO (buthionine sulfoximine, an inhibitor of  certain enzymes), to counteract retrovirally-induced immune activity.   These drug combinations succeeded not only in inhibiting viral  replication, but in strongly impacting the pool of inactive Memory T  cells responsible for making retroviral infections impossible so far to  eradicate.  Macaques are liable to infection with SIV, the simian  immunodeficiency virus. Why have they and not cats been singled out for  the highest order of therapeutic interventions?  Because SIV is more  closely related in most particulars to HIV than FIV is, and helping  people, not animals, is the goal of the overwhelming proportion of  animal antiretroviral research.

Three-drug combinations have been tried before in cats with FIV.  The pioneer effort occurred a dozen or so years ago by a German cat owner and involved  TDF, FTC, and a third drug, abacavir (ABC).  Abacavir belonged to the  same class of reverse-transcriptase inhibiting drugs as the other two.   Consequently, the combination did not qualify as a true HAART regimen.   At the time, no drugs in other classes were both available and known to  be effective at inhibiting FIV.  In vitro research had shown that the combination of zidovudine, lamivudine, and abacavir  had strong FIV-inhibiting power, but zidovudine (AZT, now ZVD) is a  difficult drug for cats, causing significant side-effects.  Some human  HIV patients had actually begun to use the all-"nuke" combination of  TDF/FTC/ABC because of its lack of side effects by comparison to the  AZT-based combination and many HAART combinations.  The optimism was  short-lived, as it was eventually shown that TDF and ABC were liable to a  common mutation that led to eventual treatment failure.

A 2007 modeling study with a sister drug to raltegravir denominated L-870,810, the  development of which was eventually abandoned, laid the groundwork for a  true FIV HAART regimen.  The drug inhibited FIV.  Later, after  raltegravir had been licensed for production (trade name Isentress) it  was confirmed almost as a sidelight to another study of SIV that it too inhibited FIV, although not quite as strongly as it  did SIV or HIV.  The pieces were now in place for investigation of a  multi-drug combination of tenofovir, emtricabine, and raltegravir in an  FIV study.  That study has yet to happen.

The 2007 study by an Italian team concluded with these words.  "FIV  is not only an interesting animal model for retrovirologists, but is  also an important pathogen in veterinary practice. Therefore, the  present study may also provide the bases for providing a potential  treatment to alleviate disease and prolong survival time of infected pet  cats. For example, L-870,810, an INSTI successfully tested in humans,  used in combination with NRTIs active on FIV could lead to an ART  equivalent for feline AIDS." Well the time has come for a true FIV HAART  study.  Let's hope the will to do it follows in the near future.

Meanwhile, Charlie is showing the way. Charlie was a very sick cat  when he began his HAART regimen, his white cells existing in critically  low numbers.  It remains to be seen whether HAART will provide a salvage  therapy for him.  Immune reconstitution is not an overnight process, so  Charlie will have to hang in there for awhile, and his dedicated owner  is doing the best to see that happens. Charlie's case history appears on  the Reports page of this site.  Whatever the outcome, it is to be hoped, at the  very least, that Charlie's experience supplies "proof of concept" for a  therapy that is long overdue for a legitimate try out.

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