At least six provinces are running low on antiretrovirals (ARVs), according to a report on Wednesday.
One patient had to switch medication because the regular ARVs were unavailable, The New Age reported.
The life-prolonging drugs that were in short supply included tenofovir and abacavir.
About 1.7 million people in South Africa were on the state's ARV treatment programme.
Health department spokesman Fidel Hadebe told the newspaper the matter was getting "high-level attention".
"Discussions have taken place among all the concerned parties and the way forward has been charted," Hadebe was quoted as saying.
He said he could not comment further on the situation.
"A media statement is due to be released... by the minister [of health] on what exactly is going to happen moving forward," Hadebe said.
"I wouldn't want to be ahead of the minister in this regard."