One of the show's most closely-followed storylines is Dineo- a girl from a poor family who gets into a relationship with an older man to support herself through university and send money back home to her mother and two siblings.
Dineo's entwinement with a wealthy older man highlights South Africa's problem of "blessers": wealthy men who shower "blessings" of gifts and clothing on poor girls - and often expect unprotected sex in return.
"I was happy seeing... that season three is coming, I can't even lie, it teaches a lot about life," said fan Aphiwe Magcina on the show's Facebook page.
"Shuga" is expected to reach several million followers as its third South African series debuts, with an especially high audience among young women, who account for around quarter of all new HIV infections in Africa.
HIV campaigners have over the years played an important behind-the-scenes role in shaping the show's plots.
In 2018, Unitaid and other organisations teamed up with Shuga's producers, the music channel MTV's Staying Alive Foundation, to help highlight HIV risk.
Age-gap, transactional relationships and gender-based violence are "something that we have really consistently had to tackle" on the show, Georgia Arnold, the foundation's executive director, told AFP.
Shows like Shuga are not new to South African screens, for the country has widely turned to television over the years to try to combat HIV infection and stigma.
But anecdotal evidence of Shuga's effectiveness has been borne out by research.
A team from the London School of Hygiene and Tropical Medicine found that those who had watched the show were twice as likely to use condoms, know their HIV status and be on pre-exposure prophylaxis (PrEP), a HIV-preventing medication.
A World Bank study also found that in Nigeria, infections of chlamydia dropped 58 percent among women who had had watched the show at community screenings.
Shuga first premiered in Kenya in 2009 and has since had several series shot in Nigeria, Ivory Coast and Kenya, and two in South Africa.
The show's previous seasons reached almost three million views weekly in South Africa, and when it aired on the national terrestrial broadcast SABC reached 44.8 percent of the country's low income audiences.
"We were the number two drama when we premiered the series on SABC 1", Arnold told AFP, referring to South Africa's national broadcaster.
It reached a wider audience since streaming on Netflix since 2021 and expanded its outreach further on social media.
It's crucial "to be able to reach (young people) on the platforms where they are", she said.
The human immunodeficiency virus (HIV) has a long and tragic history in South Africa.
Through a tragic combination of cost and political denial, life-saving drugs that came onstream at the end of the 1990s were not available to poor South Africans -- several hundred thousand died, according to one estimate.
Today, fatalities have plummeted but new infections are still high.
Nearly one in seven of the population has the AIDS virus - one of the highest rates of prevalence in the world and a clear sign of the need for vigilance, say campaigners.
"One-thousand young women are infected every week in South Africa, which means we still need to ramp up awareness specifically targeted at them," Sibongile Tshabalala, chair of the HIV/AIDS organisation Treatment Action Campaign (TAC), told AFP.
"They're in transactional relationships not because they want to be, but poverty, high unemployment and gender based violence all contribute and once exposed to the virus they often don't know what to do," she said.