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.