Although the WHO recently reported that drug resistance to the gold-standard antiretroviral medicine, dolutegravir, “exceeded levels observed in clinical trials”, it has since elaborated, saying this was mainly linked to patients not adhering to treatment properly – rather than growing resistance to the medicine.
The resistance had ranged from 3.9% to 19.6%, reports Kerry Cullinan for Health Policy Watch.
Dolutegravir has been the recommended first- and second-line HIV treatment since 2018, being “more effective, easier to take, and with fewer side effects”, with “a high genetic barrier to developing drug resistance”, the agency said.
Used in combination with tenofovir and lamivudine, its use has led to “high levels of viral load suppression …often exceeding 90% or even 95%”.
The reports on resistance come from surveys in Uganda, Ukraine, Malawi and Mozambique, in the first three, resistance levels of dolutegravir ranging from 3.9% to 8.6% in adults, and including those who had never taken ART to those with some exposure to the drugs.
But in Mozambique, the survey involved people experienced with treatment who had transitioned to a dolutegravir-containing regimen while having high HIV viral loads. Here, resistance reached 19.6%.
“Overwhelmingly, data suggest that non-adherence to treatment is the primary reason for viral non-suppression – not drug resistance,” said the WHO.
Dolutegravir and TB medication
Meanwhile, a new clinical trial has found that people newly diagnosed with HIV did well if they were given preventative treatment for TB at the same time as dolutegravir.
The Aurum Institute, a research partner in the trial, said that annually, there were around 670 000 new TB cases among people with HIV, and an estimated 167 000 deaths from TB-related HIV.
The trial – called DOLPHIN-TOO – focused on whether the efficacy of dolutegravir in people with HIV who had never previously been treated with ARVs was affected by prophylactic TB treatment – either the standard isoniazid (6H) or the newer regimen: a weekly dose of isoniazid and rifapentine for three months (referred to as 3HP).
The results showed that while people in the 3HP group did have lower levels of dolutegravir in their bloodstream than those in the 6H group, they achieved an undetectable level of HIV virus in blood by eight weeks and maintained this for the six-month study.
Minimal side effects were seen, none severe, and most were resolved with continuation of therapy.
“This study points to the use of short course TB preventive treatment in people newly diagnosed with HIV who are at highest risk of active TB disease,” said Aurum.
“For patients with HIV, the best time to start TB preventive treatment is when they are first starting ART,” said Prof Gavin Churchyard, group CEO of the Aurum Institute.
“This is when patients are most closely monitored and are in regular contact with clinics and healthcare providers, making it easier to monitor them for any potential side effects.
“Seeing how safe and effective simultaneous initiation of 3HP and DTG-based ART is, this approach needs to be adopted in every country where TB is prevalent. The only way we will end TB is if we systematically prevent new TB cases in people with HIV up front, and we now have the recipe to do so.”
See more from MedicalBrief archives:
Adult doses of dolutegravir can be used with children of 20k or more
Dolutegravir associated with hyperglycaemia in people switching first-line ART in Uganda
Dolutegravir and raltegravir cause changes to fat cells
Once-daily Dolutegravir-based regimen safe and effective for people taking rifampicin for TB