From April 2023, everyone with HIV who is older than four weeks (and who weighs more than 3kg) will be able to go on a treatment plan that includes the antiretroviral (ARV) drug dolutegravir, according to Thato Chidarikire, the Health Department’s acting head of HIV programmes.

Chidarikire was speaking during a Bhekisisa webinar on 7 December, during which the Southern African HIV Clinicians Society (SAHCS) previewed its 2023 (private sector) treatment guidelines for adults and children, which should also be available to the public early in 2023. 

Dolutegravir, which was first recommended as first-line treatment in South Africa in 2019, is one of the ARV drugs in a three-in-one pill for first-line treatment. The others are tenofovir and lamivudine.

First-line treatment is the combination of ARVs that works the best, and has the fewest side-effects, as initial treatment for HIV infection. If it starts to work less well (if the virus in their bodies becomes resistant to the treatment), a patient is switched to second-line treatment. 

Dolutegravir, which belongs to a group of ARVs called integrase inhibitors, replaces efavirenz in first-line treatment. Research shows it’s better than efavirenz at dropping the amount of HIV in someone’s blood to levels low enough so that it can no longer be passed on to other people through sex (called viral suppression). Dolutegravir is also more forgiving of skipped doses, reducing patients’ risk of developing drug resistance.  

Last, dolutegravir is cheaper than efavirenz and has fewer side-effects. 

The Health Department started to gradually phase in dolutegravir in December 2019.

From next year, the SAHCS will recommend dolutegravir not only for patients who start taking ARVs for the first time, but also for second- and third-line treatment, says Jeremy Nel, an infectious diseases specialist based at the Helen Joseph Hospital in Johannesburg. 

This is good news, says Nel, because doctors often had to opt for pricier, more complicated drug prescriptions when patients had to go onto second- and third-line treatment. 

But getting people to buy into the new guidelines could prove tricky for health workers, Nel argues, since they’ll have to undo the bad press dolutegravir has received since the World Health Organization (WHO) first backed its use in 2018. 

Researchers initially cautioned that the medicine could cause birth defects if taken by pregnant women and that it leads to considerable weight gain. 

Later data have, however, cleared up both concerns, although people remain uninformed and therefore fearful, says Luckyboy Mkhondwane, who leads the Treatment Action Campaign’s education projects for HIV treatment and prevention. 

The reputational damage could be behind the slow uptake of dolutegravir in the private sector, Nel says, which has lagged behind government facilities. 

But poor communication and a lack of training might be to blame as well. Health workers in the private sector had less information about dosing guidelines for dolutegravir and possible side-effects than their peers in government facilities, according to a 2022 study published in the South African Medical Journal. 

Mkhondwane explains: “If a doctor prescribes or talks about medication a patient has never heard of, it can intimidate patients and prevent them from asking questions.”

From strawberry-flavoured HIV medicine for children to undoing dolutegravir’s bad rap, the updated guidelines promise positive changes to treatment for the 7.8 million people in South Africa living with HIV. 

Here’s what you need to know. 

Why do the Health Department and SAHCS both have guidelines? 

Guidelines consolidate the newest, science-backed evidence for treating a disease into a standardised package, explains SAHCS chief executive Juliet Houghton. This means health workers can give all patients the care that’s best for them, she says.

Because the public and private health sectors cater for different markets, they each have their own guidelines — the department’s for state patients and SAHCS’s document for the private sector. 

The department may, for instance, have a tighter budget that could affect its guidelines, explains Houghton.

But Nel stresses that the two sets are very similar, so that people can get standardised care at whichever facility they use and know that their treatment won’t change dramatically should they switch sectors. In cases where the two documents differ, the SAHCS will explain its thinking. 

For the new guidelines, says Houghton, the SAHCS and the department are trying to align public and private-sector guidelines closer. 

Why do treatment guidelines change? 

Treatment guidelines evolve as better medicines and treatment plans emerge, Chidarikire says. 

Under the country’s first set of treatment rules from 2004, for instance, people could only get HIV treatment if their CD4 count had dropped to 200 or lower. This is a measure of how strong their immune system is. 

But today, anyone who tests HIV positive can get treatment. 

Says Houghton: “The bottom line is that recommendations are updated to make sure that everyone in South Africa living with HIV gets the best care available to them.” 

What’s new for children? 

Caregivers of newborns and children can look forward to simpler HIV treatment plans.

The current guidelines say children from age 10 and up (and who weigh at least 30kg) should take the adult form of the medicine. 

But with the new plan, infants and kids can take a child-friendly form of dolutegravir from four weeks old (until the age of 10 years), instead of the older nevirapine and azidothymidine. 

The child-friendly version of dolutegravir holds huge promise. 

Why? 

It’s a four-in-one, strawberry-flavoured pill that will replace the series of syrups that caregivers and health workers currently have to give children but struggle to get them to take it.

The medicines taste bad so “children don’t always get the full dose they need because they spit it out”, explains James Nuttall of the University of Cape Town. They can also have side-effects and have to be given twice a day, which can be difficult for caregivers, he says.  

The new dolutegravir pill recommended for children from next year can be dissolved in water or sprinkled over soft food, and needs to be taken only once a day. South Africa’s medicines regulator, the South African Health Products Regulatory Authority, approved this form of the drug in June. 

Better treatment for children is a crucial step to get the HIV epidemic under control, Nuttall says.

Children fare far worse than adults when it comes to treatment. One way to see the difference is to look at their progress in reaching the United Nations-backed 95-95-95 targets. 

The goal is for countries to have diagnosed 95% of all HIV-positive people, provide ARV therapy to 95% of those diagnosed and to get the viral load of 95% of people being treated down to undetectable levels by 2030.

On the whole, South Africa stands at 94-78-89. But the picture changes dramatically for children: for those aged 0 to 15 years, we stand at only 80-69-64. 

Is it safe to use dolutegravir during pregnancy? 

“One word on that,” says Nel: “Yes.” 

He continues: “They [ARVs] are not only safe, they’re essential.” 

When a pregnant person has a lot of HIV in their blood, they pass on the virus to their baby, Nel says. 

But dolutegravir’s ability to cut someone’s viral load quickly means it can stop the HIV from spreading from a mom to an infant. That’s why the Health Department recommends that all HIV-positive mothers should be considered to be at high risk to transmit the virus to their babies until proven otherwise, and be on HIV treatment, explains Chidarikire.

Nuttall concludes: “It would be great if paediatric HIV could be something we read about in books, rather than a condition we treat every day.”

Does dolutegravir cause weight gain? 

No. A study has suggested people on dolutegravir gain more weight than those on efavirenz. But new research from South Africa shows that it’s not dolutegravir itself that makes people gain weight, Nel says, it’s the body’s normal reaction to returning to health (because the virus has been virtually thwarted).

The researchers also found that people not gaining weight while on efavirenz is likely because their bodies struggled to break down the drug quickly enough, which interferes with normal metabolism. 

Will any nurse be able to start people on HIV treatment and prevention? 

No. At the moment, only nurses who have completed the Nimart training programme (nurse-initiated management of antiretroviral treatment) can prescribe and administer ARVs and prevention medicines such as the HIV prevention pill (now available in South Africa) or the new two-monthly anti-HIV injection cabotegravir (not yet available in the country). 

That won’t change under the department’s new guidelines, says Chidarikire. 

Will testing guidelines for newborns change? 

No. In 2015, the department began using polymerase chain reaction (PCR) tests to determine a newborn’s HIV status, so that they could start treatment as soon as possible if they were infected during pregnancy, explains Nuttall.

Newborns have to be tested with PCR tests, rather than with antibody tests (which are cheaper), because with a positive antibody test it’s not clear whether it’s the mother or the baby who has HIV. Any infant born to an HIV-positive mother will test positive for the virus at first because the mom’s antibodies will be transferred to the foetus through the placenta. 

A positive PCR test means the virus itself is present. 

Nuttall says HIV-negative infants should be tested again in their first year of life, in case they become infected during breastfeeding, and treatment can start immediately. DM/MC

This story was produced by the Bhekisisa Centre for Health Journalism. Sign up for the newsletter.