HIV Monitoring Strategy Uses Drug Levels to Guide Resistance Testing

HIV viral load can rise during antiretroviral therapy for reasons that do not necessarily indicate drug resistance. Clinicians must distinguish between treatment nonadherence and resistance before deciding whether to reinforce adherence or switch therapy. This distinction is particularly important in resource-limited settings, where unnecessary resistance testing can add laboratory costs. A new study now shows that targeted drug exposure testing may help identify patients most likely to benefit from HIV-1 drug resistance testing.

Researchers at Wits University (Johannesburg, South Africa), South Africa’s National Health Laboratory Service, and University Medical Center Utrecht (Utrecht, The Netherlands) developed the Intensified Treatment Evaluation and Monitoring Approach 2 (ITREMA-2). The approach is intended for people with HIV whose viral load rises while receiving the standard antiretroviral treatment dolutegravir. By helping distinguish likely nonadherence from possible drug resistance, ITREMA-2 is designed to reduce the accumulation and spread of HIV-1 resistance in resource-limited settings.

The strategy uses a blood exposure test to determine whether dolutegravir is present in a patient’s blood. If the drug is absent, the result suggests recent nonadherence and a lower likelihood of resistant virus. If dolutegravir is detected but viral replication continues, resistance may be more likely, indicating a greater need for HIV-1 drug resistance testing.

The ITREMA-2 study included 288 people with HIV treated at Hillbrow Community Health Centre and Helen Joseph Hospital, two large public HIV clinics in Johannesburg. Conducted as a prospective, two-center implementation study in South Africa, the research also evaluated how the strategy could be incorporated into routine care after virologic failure was confirmed.

When incorporated into the care pathway, estimated laboratory monitoring costs were 23% lower than with the previous standard approach because unnecessary resistance tests could be avoided. The South African Department of Health has recently implemented an adapted version of the reflex testing strategy in public HIV care. The study was published in The Lancet HIV on September 2.

“An increased viral load does not automatically mean that treatment is failing because of drug resistance. Measuring dolutegravir in the same sample helps identify who needs resistance testing and provides clinicians and nurses with objective information to better support medication intake,” said Professor Annemarie Wensing of Wits Ezintsha and University Medical Center Utrecht.

“We have worked with the National Department of Health since the onset of the project and kept them informed on the study results as the project progressed. By doing this, we have been able to include an adapted version of ITREMA-2 into the national guidelines, which means the people who need resistance testing the most can be easily identified,” said Dr. Kim Steegen, co-principal investigator of the ITREMA-2 study at the National Health Laboratory Service and Wits University.

Related Links
Wits University
University Medical Center Utrecht