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Experts call for more training after study flags risks of commonly-used ARV

South African medical experts have issued an alert about the antiretroviral drug that has become this country’s first-choice treatment for HIV-positive people. Dolutegravir is less costly and works faster than other ARVs but it can also interact with some commonly used drugs including calcium, iron and rifampicin.

Compared with previous ARVs, dolutegravir is cheaper, swiftly effective, has fewer side-effects, and patients do not become resistant to its effects.

But in two papers in the SA Medical Journal, doctors and pharmacologists say there are downsides too, reports TimesLIVE.

One particularly affects HIV-positive patients in the private sector, where a survey of healthcare providers found that fewer than half knew about dolutegravir’s 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 approved the drug in 2019, dolutegravir has been viewed as a wonder drug for HIV-positive people, including the 20% of people aged 15 to 49 infected with the virus in this country, which has the world’s largest antiretroviral programme, so the findings are significant for 5m South Africans taking ARVs.

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.

The second paper, by University of KwaZulu-Natal pharmacist Varsha Bangalee and colleagues, says another potential side-effect 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. Notably, female patients and (people over 60) are more likely to experience neuropsychiatric toxicity with dolutegravir.”

Study 1 details

Training, guideline access and knowledge of antiretroviral interactions: Is the South African private sector being left behind?

BS Chisholm, AM Swart, M Blockman

Published in the South African Medical Journal in October 2022

Abstract

Background
South Africa (SA) has the largest antiretroviral therapy programme in the world. While the majority of the country accesses healthcare in the public sector, 15.2% access private healthcare. In 2019, dolutegravir was introduced as first-line treatment for HIV. Dolutegravir has clinically significant interactions with numerous commonly used medicines, e.g. rifampicin and cation-containing medicines such as calcium and iron. They require dosage adjustments, detailed in public and private HIV guidelines.

Objectives
To describe SA healthcare workers’ guideline access, training and knowledge of dolutegravir’s interactions, focusing on differences between the public and private sectors.

Methods
A cross-sectional, descriptive study was done using an online survey of healthcare workers in the field of HIV in SA, conducted by the National HIV and TB Healthcare Worker Hotline. Convenience sampling was used, with electronic dissemination to users of the hotline and by relevant HIV-focused organisations. Simple descriptive statistics and statistical analyses were used.

Results
A total of 1 939 surveys were analysed, with 22% from the private sector. Training on the dolutegravir guidelines was received by significantly fewer healthcare workers in the private sector v. the public sector: 42.4% (95% confidence interval (CI) 37 – 48) v. 67.5% (95% CI I 65 – 70), respectively. Significantly fewer healthcare workers in the private sector had access to the guidelines (63.8%; 95% CI 59 – 69 v. 78.8%; 95% CI 77 – 81). When asked if they were aware that dolutegravir has interactions, just over half (56.9%) of healthcare workers in the private sector responded ‘yes’, 24.6% responded ‘no’ and 18.5% did not answer. Of those who were aware that dolutegravir has interactions, 48.9% knew that dolutegravir interacts with calcium, 44.6% with iron and 82.0% with rifampicin. Private sector knowledge of dosing changes was lower for all interacting drugs, with the difference only significant for calcium and iron. Private sector healthcare workers reported significantly lower levels of counselling on dolutegravir use in all appropriate situations.

Conclusion
Private sector healthcare worker access to HIV training and guidelines requires attention. 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. Without these adjustments, there is a risk of treatment failure, increased mother-to-child transmission and morbidity and mortality

Study 2 details

Dolutegravir as first-line antiretroviral therapy in South Africa: Beware the one-size-fits-all approach

A Bangalee, S Hanley, V, Bangalee

Published in the South African Medical Journal in October 2022

Abstract

Dolutegravir (DTG) is a pivotal antiretroviral medicine that has become the backbone of several HIV programmes, especially in sub-Saharan African countries. It has recently replaced efavirenz as the preferred third drug for people initiating antiretroviral therapy in South Africa (SA). Its tolerability, cost-effectiveness and favourable resistance profile have had a global influence on HIV management, including the recent revision of the World Health Organization antiretroviral guidelines. As with any medicine, however, informed decisions are important. Despite the several advantages DTG offers, additional data informing risks over benefits have emerged that warrant clinical attention before DTG is prescribed. This article aims to give the primary care provider an overview of the benefits and risks associated with the roll-out of DTG in SA.

 

SAMJ article – Training, guideline access and knowledge of antiretroviral interactions: Is the South African private sector being left behind? (Open access)

 

SAMJ article – Dolutegravir as first-line antiretroviral therapy in South Africa: Beware the one-size-fits-all approach (Open access)

 

TimesLIVE article – Experts issue warnings about SA’s first-choice antiretroviral (Open access)

 

See more from MedicalBrief archives:

 

Further studies link dolutegravir to weight gain

 

Dolutegravir associated with hyperglycaemia in people switching first-line ART in Uganda

 

Once-daily Dolutegravir-based regimen safe and effective for people taking rifampicin for TB

 

Dolutegravir and raltegravir cause changes to fat cells

 

 

 

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