Guarding the gains: Africa moves to tackle rising HIV drug resistance

A major African-led research initiative is reshaping how the world detects and manages HIV treatment failure, as scientists warn that poor adherence and emerging drug resistance are quietly undermining progress in the global response. The multi-country Ndovu Study is generating critical real-world evidence expected to influence treatment guidelines across Africa and beyond, at a time when millions rely on modern antiretroviral therapy (ART) to survive and remain healthy.

Researchers in Kenya, Tanzania, Lesotho and Mozambique are collaborating on a landmark study to answer one of the most pressing clinical questions facing HIV programmes: what should be done when first-line therapy stops working, particularly when resistance develops to dolutegravir, the backbone of current treatment worldwide.

For more than a decade, ART has transformed HIV from a fatal infection into a manageable chronic condition. With consistent treatment, people living with HIV can suppress the virus, restore immune function, live long lives and prevent onward transmission. The rollout of dolutegravir-based regimens marked a major advance because the drug is potent, generally well tolerated and more robust against resistance than earlier medicines.

However, clinicians are confronting a troubling reality. When patients struggle with adherence, viral load rebounds and treatment can fail. In some cases, the virus adapts, reducing the effectiveness of available drugs. When failure occurs on dolutegravir-based regimens, switching options are limited in many low- and middle-income settings, placing patients at higher risk.

Monitor treatment failure

The Ndovu Study was launched to address this challenge. Now underway in four African countries, it focuses on people receiving dolutegravir-based treatment who present with high viral loads — a key warning sign of poor adherence or possible resistance. By closely monitoring these patients, strengthening adherence support and conducting resistance testing, researchers are building a detailed picture of how treatment failure occurs in real-world settings.

Importantly, investigators say the study goes beyond documenting failure; it is designed to transform how health systems respond.

HIV treatment suppresses viral replication. When medicines are taken as prescribed, viral load drops to very low levels, protecting the immune system. When doses are missed, the virus multiplies, increasing the risk of resistant strains emerging.

Poor adherence remains a leading driver of treatment failure. As more countries adopt dolutegravir-based regimens as first-line therapy, programme data show inconsistent treatment is closely linked to virological failure. Patients with failing regimens often present with weakened immunity and serious opportunistic infections, such as tuberculosis and cryptococcal meningitis, which are complex and costly to manage.

Until now, limited large-scale, programme-relevant evidence has guided how such patients should be managed, particularly in African settings where most people living with HIV reside.

Practical evidence

The Ndovu Study integrates clinical follow-up, laboratory resistance testing and structured adherence interventions within routine health systems. Its goal is to generate practical, policy-ready evidence to inform national and international guidelines.

According to the World Health Organisation (WHO), an estimated 40.8 million people were living with HIV in 2024, with 1.3 million new infections and approximately 630,000 deaths from HIV-related illnesses. While access to treatment has expanded, experts say the next phase must prioritise treatment quality, adherence support and rapid action when regimens fail.

Recently, investigators met in Naivasha for a three-day meeting hosted by the Centre for Epidemiological Modelling and Analysis (CEMA) to review enrolment, laboratory readiness and data systems. Participants emphasised aligning research with national HIV programmes so findings can quickly inform frontline practice.

One of the study’s defining features is that it is African-led and embedded within public health systems. This enables researchers to capture real-world patient behaviour, health system constraints and operational challenges often overlooked in tightly controlled clinical trials, producing evidence that is directly applicable to policymakers and programme managers.

Poor adherence

Dr Loice Ombajo, Chief Investigator of the Ndovu Study and Co-Director at CEMA, warned that rising treatment failure linked to poor adherence and potential dolutegravir resistance represents a serious clinical signal.

“We are observing a concerning pattern in which some patients are failing treatment primarily due to poor adherence, with a real risk of developing resistance to dolutegravir, the very drug that anchors current first-line HIV therapy. This endangers lives and limits future treatment options,” she said.

“We urgently require robust, programme-based evidence to guide how clinicians should respond when treatment fails or resistance is suspected,” she continued.

In Tanzania, Principal Investigator Dr Patricia Munseri of the Muhimbili University of Health and Allied Sciences said preparations for the clinical trial phase focus on scientific rigour, retention and ethical compliance to generate high-quality data for policy decisions.

In Lesotho, Dr Irene Ayakaka of SolidarMed highlighted the need for earlier resistance detection, routine viral load monitoring and structured adherence support.

In Mozambique, Dr Nalia Ismael said that although progress has been made, gaps remain in retention and resistance management, and the study will offer practical guidance for national programmes.

The Ndovu Study is sponsored by CEMA at the University of Nairobi and funded by the Bill & Melinda Gates Foundation. Across all four countries, teams are working closely with Ministries of Health to ensure findings are translated rapidly into practice, recognising that delays in responding to treatment failure can cost lives.