A landmark multi-country study is exposing a silent crisis as children and teenagers are failing their HIV treatment at alarming rates, raising fears of a resistance catastrophe that could unravel decades of progress against the epidemic.
When a child living with HIV misses doses of their antiretroviral medication, the consequences are not immediate. The virus does not announce its return with dramatic symptoms. Instead, it multiplies quietly in the bloodstream, adapting and evolving, until the drugs that once held it at bay no longer work.
This is the crisis that scientists across East and Southern Africa are now racing to document, understand, and stop. A groundbreaking multi-country study, the Ndovu Project, is generating critical evidence that children and adolescents on dolutegravir (DTG), the cornerstone antiretroviral drug now used across sub-Saharan Africa, are failing treatment at rates that researchers describe as deeply alarming.
The numbers are stark. Among a large Kenyan cohort of children and teenagers on DTG-based regimens, 41 per cent failed to suppress the virus after three full months of enhanced adherence counselling. This means that even after intensive support designed to help young patients stay on their medication, nearly half remained with detectable viral loads, a sign that the treatment was not working.
“It is deeply concerning that some people are experiencing treatment failure due to lack of adherence to therapy and potentially developing resistance to dolutegravir, placing their lives at risk,” said Dr Loice Ombajo, Chief Investigator of the Ndovu Study, infectious disease specialist, and Co-Director at the Centre for Epidemiological Modelling and Analysis (CEMA) at the University of Nairobi.
Dolutegravir was heralded as a game-changer when it was introduced. Paediatric DTG formulations rolled out across sub-Saharan Africa from 2019, offering children a simpler, more effective treatment. Yet, the Ndovu findings suggest that for a troubling proportion of young patients, the drug is failing, not because the medicine itself is inadequate, but because the conditions required to make it work are not being met.
Unlike adults who may have multiple treatment lines available, children who develop resistance to DTG face drastically narrowed choices
HIV treatment works through consistency. Antiretroviral drugs suppress the virus to undetectable levels, protecting the immune system and preventing transmission. When patients, especially children, miss doses, the viral load rises. A rising viral load gives the virus opportunities to mutate. And when mutations accumulate in the presence of a drug, resistance develops.
“When adherence stops, the viral load rises, the virus develops resistance, and limited treatment options leave patients vulnerable to death,” the Ndovu study notes.
For children, this chain reaction carries a particular weight. Unlike adults who may have multiple treatment lines available, children who develop resistance to DTG, which is currently the best first-line option, face drastically narrowed choices. They are, in the words of researchers, reliant on lifelong therapy with very little margin for error.
The barriers to adherence among young patients are numerous and, in many cases, structural. They include the stigma that surrounds HIV in communities across the region, long distances to clinics, side effects that go unaddressed, difficulty swallowing pills, and the simple fact that children depend on caregivers to administer their medication. When caregivers face poverty, illness, or competing pressures, a child’s treatment is often the first casualty.
Kenya’s Ministry of Health guidelines on HIV treatment already acknowledge these vulnerabilities, stressing enhanced adherence support through counselling and monitoring during the first three months of therapy. But the Ndovu findings suggest that even where such support is provided, it is not always enough.
The Ndovu Project spans Kenya, Tanzania, Lesotho, and Mozambique, enrolling HIV patients with high viral loads on DTG-based regimens. Funded by the Gates Foundation and conducted in partnership with Kenya’s Ministry of Health through the National AIDS/STI Control Program (NASCOP), the study is generating evidence to guide the management of treatment failures across the continent.
Sub-Saharan Africa bears 67 per cent of the world’s HIV burden, yet local evidence to guide treatment decisions remains far behind
It is operating against a backdrop of immense scale. The World Health Organization (WHO) estimates that 40.8 million people were living with HIV globally in 2024, with 1.3 million new infections recorded and 630,000 AIDS-related deaths. Sub-Saharan Africa bears 67 per cent of the world’s HIV burden, according to UNAIDS 2025 estimates, yet local evidence to guide treatment decisions remains far behind.
Dr Patricia Munseri, Principal Investigator in Tanzania and Associate Professor at Muhimbili University of Health and Allied Sciences (MUHAS), emphasised the importance of the study meeting the highest research standards.
“While we look forward to initiating the Ndovu clinical trial, we are confident in our ability to recruit and retain participants while being mindful to attain high-quality data that aligns with the study protocols, national and international ethical and regulatory standards,” she said. “This is an excellent opportunity for further collaboration within the continent and globally in addressing public health challenges.”
Among adults, the research is also yielding findings that challenge established clinical practice.
A second Ndovu analysis found that many adults with two consecutive high viral loads on DTG still achieved viral suppression without changing their treatment regimen. This directly challenges WHO guidance, which advises switching patients to protease inhibitors after two high viral loads without waiting for drug resistance testing, a strategy common in resource-limited settings.
The data suggests that such switches may be unnecessary for a significant proportion of patients, potentially exhausting treatment options without clear clinical benefit. “Many people who have two high viral load test results while on DTG are still able to suppress the virus without changing treatment,” researchers noted.
A companion study titled the Sungura trial; a 96-week open-label study at two Kenyan sites funded by ViiV Healthcare and sponsored by the University of Nairobi, is examining HIV treatment among adults over 60. Africa’s demographic shift means that HIV prevalence is rising among older populations, a group whose medical complexity is rarely reflected in global guidelines.
The Ndovu and Sungura studies expose the risk of applying uniform global guidelines across Africa’s diverse realities
In the Sungura cohort, 100 per cent of participants were virally suppressed at week 48 on a dual DTG/lamivudine (3TC) therapy, making it a striking result. Yet the same patients were living with high burdens of opportunistic and chronic conditions, including kidney disease, diabetes, hypertension, and osteoporosis, complicating long-term care and raising questions about how treatment guidelines account for ageing patients.
Taken together, the Ndovu and Sungura studies expose the risk of applying uniform global guidelines across Africa’s diverse realities, from children struggling with adherence, to adults who may not need regimen switches, to elderly patients managing multiple conditions.
“Dolutegravir-based treatment has transformed HIV care globally,” said Dr Ombajo. “But our findings show that we still lack critical data on interventions for key populations in Africa, including children, people with persistent viraemia, and older adults above 60 years. Without these data, treatment guidelines risk being insufficient.”
Researchers from the studies have proposed a set of urgent measures: strengthening laboratory systems for drug resistance testing through genotyping, scaling up routine viral load monitoring, reinforcing adherence support with interventions tailored specifically to children and adolescents, and aligning national policies with emerging local evidence rather than defaulting to one-size-fits-all global guidance.
The stakes are high. DTG is first-line therapy across much of the continent. If resistance to it becomes widespread, driven by inadequate adherence support, late detection, and delayed intervention, the consequences for millions of people, and especially children, could be catastrophic.
“From the Ndovu results, it is clear that a one-size-fits-all approach may not be optimal. We need better tools and data to distinguish who truly needs a switch and who can safely continue DTG with adherence support,” Dr Ombajo said.
With UNAIDS targeting the ambitious 95-95-95 goals by 2030, where 95 per cent of people living with HIV know their status, 95 per cent are on treatment, and 95 per cent are virally suppressed, the window for course correction is narrowing.
“Data saves lives,” Dr Ombajo said. “To end HIV as a public health threat in Africa, we must generate evidence that reflects the realities of the populations most affected.”
*The Ndovu and Sungura studies are ongoing. Findings are expected to directly inform national HIV treatment guidelines across participating countries.
