A new report documents an increase in HIV drug resistance to dolutegravir

The latest World Health Organization (WHO) report on HIV drug resistance (HIVDR) tells us where drug resistance is growing and offers recommendations for countries to monitor and respond to potential challenges.

The report brings some good news and some troubling news. It highlights the high levels of HIV viral load suppression (>90%) in the population receiving antiretroviral therapy (ART) containing dolutegravir (DTG). However, observational and survey data generated in the country indicate that HIVDR levels according to DTG exceed those observed in clinical trials.

As of 2018, WHO recommends the use of dolutegravir as the preferred first- and second-line HIV treatment for all population groups. It is more effective, easier to take and has fewer side effects than other drugs currently in use. It also has a high genetic barrier to developing drug resistance.

However, among four published studies, levels of resistance to dolutegravir ranged from 3.9% to 8.6% and reached 19.6% among treatment-experienced people who switched to DTG-containing ART while having a high viral load. HIV burden. To date, only a few countries have reported research data to the WHO.

“The worrying evidence of resistance in individuals with unreduced viral loads despite treatment with dolutegravir highlights the need for increased vigilance and increased efforts to optimize the quality of HIV care,” said Dr Meg Doherty, Director of the Global HIV, Hepatitis and WHO STI Programmes. . “Standardized surveillance of HIV drug resistance is essential to effectively prevent, monitor and respond to these challenges”.

Haiti was the only country to report HIVDR survey data among ART-naïve or ART-initiating infants. One infant, whose mother was receiving DTG-based ART, was found to have resistance to DTG. Effective management of high viral load among pregnant and lactating women is essential to prevent HIV transmission to infants. Increasing routine HIVDR surveillance among newborns newly diagnosed with HIV and not yet on HIV treatment will be important to guide appropriate ART options going forward.

Global goals derailed

In 2022, more than 75% of the 39 million people living with HIV worldwide were receiving HIV treatment. Countries have implemented WHO recommendations, with 116 out of 127 adopting WHO first-line DTG-based treatment for adults and adolescents, and 74% of reporting low- and middle-income countries have adopted viral load monitoring for adults and adolescents.

But progress towards the SDG targets stalled as there were still an estimated 1.3 million new HIV infections and 630,000 deaths from HIV-related causes. Between 2017 and 2022, for the majority of countries reporting through the Global AIDS Monitoring System (GAM), programmatic quality indicators for HIV treatment did not achieve established global targets, further highlighting the need to proactively improve the quality of treatment and care services for HIV.

In 2022, only 12 of the 45 WHO focus countries reported conducting surveys or integrated monitoring of HIVDR early warning indicators into routine monitoring and evaluation systems. Many countries continue to miss the mark when it comes to optimizing retention in care, suppressing viral load at the population level, and transitioning people with virologic failure to different regimens. In addition, antiretroviral drug supply shortages continue to occur, which can negatively impact patient adherence to treatment.

WHO recommends that countries routinely conduct standardized HIVDR surveillance to monitor the prevalence and patterns of resistance among people who do not achieve a reduced viral load. This is critical because information and data from surveys influence the development of treatment guidelines and inform the quality of treatment programs.

Recommended guidelines for action in the country

The report also documents cases of resistance to integrase strand transfer inhibitors (INSTIs) following recent exposure to cabotegravir (CAB-LA). Delayed detection and confirmation of HIV infection may increase the risk of developing resistance to INSTIs. From 2022, WHO recommends the use of long-acting CAB-LA injection as an additional HIV prevention option for people at significant risk of HIV infection.

Despite the potential risk, the WHO recommends the introduction of CAB-LA for pre-exposure prophylaxis (PrEP) and calls for the scaling-up of PrEP to be accompanied by standardized drug resistance surveillance among HIV-positive individuals while receiving PrEP.

Routine monitoring of quality of care indicators at both clinical and national levels, followed by addressing any suboptimal performance, remains a cornerstone of ART program success. Key indicators of quality of care include timely ART uptake, ART retention, viral load testing coverage, timely second viral load testing, ARV drug supplies, and timely transition to second-line ART.

A new HIVDR report highlights the importance of strengthening data reporting systems so that countries can effectively monitor and report on quality of care indicators. It highlights the active engagement of ART clinics and programs in using indicator data to develop locally appropriate and sustainable solutions. These efforts are critical to optimizing the quality of service delivery, thereby reducing the emergence of drug-resistant HIV.

Minimizing the spread of HIV drug resistance is a critical part of the broader global response to antimicrobial resistance that requires coordinated action across all government sectors and levels of society.