Compositions and methods for treating disordered and/or prodromal stage tissue infected with by a virus in a mammal by co-administering a systemic anti-virus drug and topically administered anti-infective composition. The systemic anti-virus drug is internally administered and disrupts or inhibits virus replication systemically within the mammal. Examples include nucleoside analogues, nucleoside analogue precursors, and nucleotide analogues. The topically administered anti-infective composition includes at least one anti-infective agent, such as an organohalide (e.g., benzalkonium chloride), and is formulated to penetrate below the skin surface and allow the anti-infective agent to kill viruses at a treatment site. The topical anti-infective composition enhances efficacy of the systemic anti-virus drug and reduces the time and/or number of dosages otherwise required for the systemic anti-virus drug to treat the viral infection. The topical anti-infective composition can be more beneficial than the systemic anti-virus drug in killing viruses and can reduce or eliminate post-herpetic neuralgia.