Johannesburg - A simplified antiretroviral medication was introduced in Ga-Rankuwa, north west of Pretoria, on Monday.
It would see people with HIV taking one tablet a day instead of three, Health Minister Aaron Motsoaledi said.
"We believe that the roll-out of the fixed-dose combination (FDC) will assist a great deal in the management and treatment of HIV," he said in a statement.
"The FDC will improve compliance and reduce the risk of patients not complying with treatment dosage."
Motsoaledi said the "three drugs in one pill" was highly effective in reducing the viral load and would improve the patients' immune response.
Newly-diagnosed patients and HIV-positive pregnant women would be put on FDC's from the beginning of April.
Patients would be monitored monthly by their clinician for the first three months until they were stable.
From June, "non-complicated" patients would be switched to FDC on a permanent basis.
"We want all pregnant HIV-positive women to be on FDCs. We decided to introduce a pregnancy register at selected sites to conduct surveillance on adverse drug reactions," said Motsoaledi.
"We are doing this not because we don't trust these drugs but because this is a normal part of clinical practice which is done everywhere in the world."
Motsoaledi said more than 7000 doctors and nurses had been updated on the new guidelines.
About 389,857 units of the FDC had been supplied to the various provinces for the patients who would receive the medication in the first phase.
The SA National AIDS Council (SANAC) welcomed the change in treatment to just one tablet a day, saying the fixed-dose combination would make taking HIV/Aids treatment "convenient".
"We hope that it will result in patients complying with and adhering to their treatment," said CEO Dr Fareed Abdullah in a statement.
"We hope that this will enable many more patients to take their medication everywhere and anywhere they may be."
SANAC said it hoped the new treatment would encourage people to stay on their treatment and thus reduce non-compliance and non-adherance incidences.
The ARV tender of R5.9 billion over two years was announced in November.
By the end of 2014, the department wants the number of patients on ARV's to increase from 1.7 million to 2.5 million.