Scientists have detected emerging drug resistance to dolutegravir, the cornerstone HIV treatment used across multiple Sub-Saharan African countries. While the WHO-recommended regimen maintains a high viral suppression rate above 90% for adherent patients, new data reveal resistance mutations in populations with prior treatment experience, prompting urgent calls for enhanced surveillance.
Antiretroviral therapy has transformed HIV care over the past decade, lifting the global number of people accessing treatment to 32.1 million by the end of December 2025, a dramatic increase from 7.6 million in 2010, according to World Health Organization figures. Yet this widespread expansion faces a rising biological challenge. Genetic changes in the virus are allowing it to replicate despite modern medications, threatening first- and second-line regimens.
The core medication under scrutiny is dolutegravir, commonly known as DTG. Adopted globally as the preferred first- and second-line treatment since 2018, DTG has been favored for its superior efficacy, manageable side-effect profile, and a historically strong genetic barrier against resistance. Programmatic evidence shows that over 95% of adults retained in care across low- and middle-income countries achieve viral suppression within 6 to 24 months. However, recent findings from clinical studies indicate that acquired resistance is surfacing more frequently than previously anticipated among specific patient groups.
Findings From the Ndovu Study Across East and Southern Africa
Researchers presented data from the Ndovu Study at the International AIDS Society summit in Rio de Janeiro, Brazil, highlighting resistance trends reported by the Nation among HIV-positive individuals in Kenya, Tanzania, Mozambique, and Lesotho. Dr. Loice Ombajo, the principal investigator and an infectious disease expert, shared outcomes after enrolling the initial 2,994 participants across 131 sites in Kenya who had been taking DTG-based regimens for at least six months.
While nearly nine in 10 patients respond well and achieve viral suppression, a minority fails to suppress the virus. Dr. Ombajo explained that adherence issues frequently drive initial treatment failure, noting that patients can experience fatigue, forget doses, or struggle with their diagnosis. When medication is taken intermittently, the virus mutates.
“The challenge with resistance is that it doesn’t matter whether you take the drug or not. The drug is unlikely to work. That is a concern because that is a drug we are using for HIV treatment.”
Dr. Loice Ombajo, Principal Investigator and CEMA Co-Director
When the research team worked with participants in the cohort to improve adherence, about 70 per cent achieved viral suppression. However, the remaining 30 per cent maintained high viral loads. Subsequent examination of that subset revealed that three out of every 10 individuals in that group exhibited resistance to the drug.
Global Surveillance Data and Regional Resistance Projections
Broader international data mirror these regional observations. According to World Health Organization surveillance data, DTG resistance has been documented in up to 4.8% of participants without viral suppression in published cohorts. Furthermore, studies supported by the United States President’s Emergency Plan for AIDS Relief across four low- and middle-income countries show prevalence estimates ranging from 3.9% in individuals without viral suppression on ART for at least nine months, up to 19.6% in patients with heavy prior treatment experience.
Mathematical modeling underscores the long-term stakes if mitigation strategies are not expanded. A projection from South Africa forecasts that HIV drug resistance linked to DTG-based treatment failure could surge from 18% in 2023 to 42% by 2035 in data published by the WHO. Public health authorities emphasize that routine surveillance through viral load laboratory methods or clinic-based sentinel surveys remains essential for tracking these patterns.
Clinical Management and Vulnerable Populations
The emergence of resistance poses severe risks for vulnerable demographics, including pregnant and breastfeeding mothers. The National Syndemic Disease Control Council notes that mother-to-child transmission remains a significant challenge, driven in part by drug resistance in mothers who may have taken medication inconsistently. Elevated viral loads significantly increase the likelihood of transmission to infants, while adults face risks of passing resistant strains to sexual partners.
Experts stress that resistance testing remains expensive, leaving many resource-limited nations without adequate diagnostic tools. Without timely detection, patients experiencing treatment failure face severe immunosuppression, making them highly susceptible to opportunistic infections such as meningitis and specific forms of pneumonia.
To combat the spread of resistant strains, public health guidelines emphasize maintaining patient retention in care, scaling up viral load testing access, and rapidly switching treatment regimens upon confirmed failure.
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