HIV treatment drugs. Kenya and other African countries switched rapidly to
dolutegravir after the WHO recommended it as the
preferred first-line treatment in 2018.
Kenya has begun a year-long study to examine why some patients on dolutegravir, the world’s leading HIV drug, are not achieving viral suppression.
The work aims to find out whether these cases are mainly due to missed doses and adherence problems, or whether HIV is developing mutations that make the drug less effective.
The scientists will also evaluate whether these patients should be switched to another regimen.
The move follows troubling reports from Kenya and neighbouring countries, where signs of resistance to the drug have been detected. The results could shape how Kenya and other African nations manage HIV treatment in future.
The “Ndovu study”, supported by the Ministry of Health and
the Gates Foundation, will run for 12 months. It will enroll participants
across eight treatment sites in Kenya, Mozambique, Tanzania and Lesotho.
“The Ndovu study seeks to provide critical evidence for the management of DTG failure… whether and when viremia with DTG resistance requires regimen switch… and, whether switch to a protease inhibitor is the most appropriate option after failure on DTG,” said the researchers, led by Dr Loice Ombajo, an infectious disease specialist and a senior lecturer in internal medicine at the University of Nairobi.
Recruitment of the total 6,600 participants with unsuppressed virus began in March and will end in December. The researchers said 362 of these participants will be part of a randomised controlled trial (RCT). These are patients with major dolutegravir-associated drug-resistant mutations who will be randomised to switch to ritonavir-boosted darunavir (DRV/r) or continue with dolutegravir with follow-up for 12 months.
“Initial results from the cohort are expected in March 2026 and from the RCT in February 2027,” the scientists said in a study protocol titled, ‘The dolutegravir failure cohort: a multi-country longitudinal cohort with a randomised clinical trial of continued dolutegravir versus switch to darunavir in people with viraemia while on dolutegravir in Sub-Saharan Africa (The Ndovu Study) protocol.’
The Ndovu researchers said they want to see how many patients keep the virus under control. For the group being followed over 12 months, the main goal is to check how many achieve a viral load below 200 copies by the end of the year. For the randomised trial, the key measure is how many reach that same level of suppression after six months. The study will also look at which drug resistance mutations appear in patients who are not suppressed, how adherence affects outcomes, and how both patients and health workers feel about staying on dolutegravir versus switching to another drug, darunavir/ritonavir.
Health authorities and HIV programme managers are watching closely, as these results could inform national treatment guidelines.
Kenya and other African countries switched rapidly to dolutegravir after the World Health Organization recommended it as the preferred first-line treatment in 2018.
The drug is highly potent, has fewer side effects than older regimens, and was thought to have a “high barrier” to resistance. By 2019, Kenya had adopted the dolutegravir-based combination TLD (tenofovir, lamivudine and dolutegravir) as the backbone of its national programme.
Trials that led to the WHO endorsement were conducted under
tightly controlled conditions. However, real-world data from programmes in
Africa are beginning to show a more complicated picture.
Dr Loice Ombajo, an infectious disease specialist and a senior lecturer in internal medicine at the University of Nairobi.
The WHO last year warned that its research in Mozambique, Malawi, Uganda and Ukraine found that resistance to dolutegravir ranged from around four to 20 per cent among sampled treatment-experienced who transitioned to a DTG-containing ART while having high HIV viral loads.
“The worrying evidence of resistance in individuals with unsuppressed viral load despite dolutegravir treatment underscores the necessity for increased vigilance and intensified efforts to optimize the quality of HIV care delivery,” said Dr Meg Doherty, Director, WHO Department of the Global HIV, Hepatitis and STI Programmes. “Standardized surveillance of HIV drug resistance is essential for effectively preventing, monitoring, and responding to these challenges”.
In Kenya, surveillance samples from patients with viral non-suppression show a resistance prevalence of up to 22.6 per cent in ART-experienced patients (on DTG as second or third line regimens) and 8.3 per cent in those failing a first line DTG-based regimen.
Dr Ombajo’s team noted there is insufficient data to inform the management of dolutegravir failure, with the WHO and various countries adopting different approaches.
They hope their study will support a standard evidence-based management approach.
Kenya’s HIV guidelines recommend that patients with treatment failure be switched to a protease inhibitor regimen (medications that prevent viruses from making more copies of themselves), but without resistance testing. The Ndovu study questions this assumption, which treats treatment failure and resistance as one thing.
Treatment failure means the HIV is not being suppressed, mostly because of missed doses, drug interactions, resistance or other health factors.
But drug resistance means the virus has actually mutated so that the drug no longer works effectively, even if the patient takes it correctly.
The Ndovu study protocol says: “The WHO recommendation to switch to PI-based therapy is based on the untested assumptions that people failing DTG have selected for clinically relevant integrase inhibitor drug resistance mutations.”
The scientists said if most patients failing dolutegravir have not actually developed resistance, then switching them prematurely could expose them to more complex and costly therapies without clear benefit. Conversely, if resistance is more common than expected, then failing to detect it could allow the virus to spread in forms that are harder to treat.
