de Oliveira Medeiros S, Abreu CM, Delvecchio R, Ribeiro AP, Vasconcelos Z, et al. Follow-up on long-term antiretroviral therapy for cats infected with feline immunodeficiency virus. J Feline Med Surg. 2016 Apr;18(4):264-72.
Therapy with antiretroviral drugs has been the mainstay of management of humans with HIV. In humans, combinations of multiple antiretrovirals are generally used to effect low viral loads and long term survival. In feline medicine, Antiretroviral therapy has been much less commonly utilized, in part because of cost concerns and dosing issues, but also due to the relatively low severity of FIV infection.
In some cases, however, FIV may lead to major clinical signs such as stomatitis, encephalitis, or feline Acquired Immunodeficiency Syndrome. In these cases, therapy with an antiretroviral medication may help to improve or resolve clinical signs. The most commonly utilized antiretroviral in feline medicine have been the “nucleoside reverse transcriptase inhibitors”, specifically zidovude (AZT) and lamivudine (3TC). These are often administered together in a “fixed dose combination”. A major complication of long term anti-retroviral therapy in humans is the development of resistance to the drugs used.
This study investigated the use of long term AZT followed by 3TC in FIV infected cats, and monitored for the development of resistance.
4 cats naturally infected with FIV were followed for a several year period. Cats were indoor only and tested FeLV negative. AZT treatment was initiated at a rate of 5mg/kg every 12 hours. This was maintained for 5-6 years, and then transitioned to AZT+3TC for an additional 3 years. FIV positive untreated cats and FIV negative cats were used as controls. Hematologic parameters, FIV viral load, and CD4 and CD8 T-Cell counts were trended during this time period. Viral sequencing was also undertaken.
Response to therapy among cats was highly variable. While some animals responded to treatment with a reduced viral load, others showed no effect. Overall, treated cats exhibited lower CD4:CD8 ratios than treated cats; the opposite of what would be expected.
An interesting finding was the development of several “resistance mutations” in the RNA of FIV viruses in long term treated cats. These mutations were similar to recognized variations in HIV associated with resistance to antiretrovirals.
While there are several flaws in this study- inconsistent testing, long delays prior to follow up, and very small sample sizes, it does raise some interesting points. The data from this study suggests that, while AZT and other antiretrovirals may be able to improve symptoms in some cats with AZT< there is a risk of long term resistance occurring to therapy. This indicates that multi-drug therapies (similar to the human “Highly Active Anti Retroviral Therapy”) may be needed to effect long term control of FIV. (MRK)