Effect of acyclovir and phosphonoformate on cytomegalovirus infection in guinea pigs

Adult Hartley guinea pigs infected with guinea pig cytomegalovirus (CMV) develop a mononucleosis syndrome with a brief viremia, splenomegaly, lymphadenopathy, and peripheral lymphocytosis with circulating atypical lymphocytes. The present study used this experimental model to evaluate in vivo the therapeutic efficacy of acyclovir (ACV) and phosphonoformate (PFA) during CMV infection. Guinea pigs were treated with ACV or PFA from day 3 to day 7 postinoculation. The course of the mononucleosis syndrome and the spread of virus in various tissues were similar in drug- and sham-treated infected guinea pigs. Infected animals treated with ACV or PFA developed disseminated CMV disease with severe interstitial pneumonia, whereas sham-treated infected and drug-treated noninfected animals did not. In addition, mortality rates in infected animals treated with ACV were significantly higher than those in sham-treated animals. Furthermore, the normal lymphoproliferative response to CMV infection appeared to be reduced in ACV-treated as compared to sham-treated animals, with fewer peripheral lymphocytes, less lymphoid tissue in the spleen and lymph nodes, and less mononuclear inflammation around the inclusion-containing cells of the liver and salivary gland. These results show that ACV and PFA are not useful in the treatment of CMV infection in guinea pigs but instead may have harmful effects.