A method for inhibition of retroviral replication by manipulation of enzyme adenosine diphosphoribosyl transferase which endogenously inhibits retroviral reverse transcriptase. The method is useful for prevention and treatment of retroviral infections, including HIV. The inhibition of the viral replication is achieved by administration to a mammal susceptible to or infected with a retrovirus drugs which specifically inhibit poly-ADP-ribosylation of adenosine diphosphoribosyl transferase.