Experts issue cautionary warnings about SA’s first-choice antiretroviral

Experts have sounded a cautionary alarm about the drug that has become the first-choice treatment for HIV-positive people in SA.

Compared to previous antiretrovirals, dolutegravir is cheaper, works faster, has fewer side-effects, and patients do not become resistant to its effects.

But in two papers in the October edition of the SA Medical Journal, doctors and pharmacologists say there are downsides too. 

One particularly affects HIV-positive patients in the private sector, where a survey of healthcare providers found that less than half were aware of dolutegravir’s possibly serious interactions with drugs including calcium, iron and the antibiotic rifampicin. 

The other paper also warns about possible problems for patients taking diabetic and epilepsy medications. And it says weight gain and insomnia have been reported by patients on dolutegravir. 

Since the World Health Organisation gave it the green light in 2019, dolutegravir has been regarded as a wonder drug for HIV-positive people — including the 20% of South Africans between the ages of 15 and 49 infected with the virus. 

It is now the first-choice drug in SA for HIV-positive patients, which has the world’s largest antiretroviral programme, so the findings are significant for the 5-million South Africans taking ARVs.

Since the World Health Organisation gave it the green light in 2019, dolutegravir has been regarded as a wonder drug for HIV-positive people - including the 20% of South Africans between the ages of 15 and 49 infected with the virus. 

Only 42.4% of healthcare workers in the private sector had received training on dolutegravir guidelines, according to a survey reported by Briony Chisholm and colleagues in the University of Cape Town’s clinical pharmacology department. In the public sector, training had reached 67.5% of staff.

Chisholm, one of the people behind the National HIV and TB Healthcare Worker Hotline, said the lack of training meant many private sector doctors, nurses and pharmacists were unaware of dolutegravir’s potentially serious interactions with other drugs.

“In a high-burden HIV setting such as SA, it is vital that healthcare workers across all professions, in both the public and private sector, know how to adjust antiretroviral dosing due to clinically significant interactions,” says the paper.

“Without these adjustments, there is a risk of treatment failure, increased mother-to-child transmission and morbidity and mortality.”

Dolutegravir has interactions with calcium, iron and magnesium, the diabetes drug metformin, the antibiotic rifampicin and some anti-epileptic drugs. Chisholm said these require changes in the regimen or dose which are listed in the guidelines most private-sector workers have not seen.

“High computer proficiency and good internet access would be expected in the private sector, and HIV guidelines are available electronically, which begs the question: why is private sector guideline access poor?” says Chisholm’s paper.

The second paper, by University of KwaZulu-Natal pharmacist Varsha Bangalee and colleagues, says another potential pitfall for patients on dolutegravir is weight gain.

“Two clinical trials in Sub-Saharan Africa demonstrated that women on dolutegravir gained more weight than men,” it says.

“Clinically significant weight gain may increase the risk of adverse birth outcomes, diabetes, cardiovascular disease, cancer, and other serious non-Aids events. Moreover, body fat changes can be deleterious to self-perception and antiretroviral adherence.

“Weight gain in adolescents living with HIV is also of concern, particularly as this group represents a growing proportion of patients receiving ART in Sub-Saharan Africa.”

Insomnia and sleep disorders were the main neuropsychiatric symptoms reported by patients on dolutegravir, says Bangalee’s paper.

“Practitioners should be alert to dolutegravir’s spectrum of neuropsychiatric symptoms. These include dizziness, anxiety, depression, headache, [pins and needles], musculoskeletal pain, poor concentration and slow thinking.

“These side-effects may result in treatment discontinuation and poorer outcomes.[33] Notably, female patients and [people over 60] are more likely to experience neuropsychiatric toxicity with dolutegravir.”