Wits Research on HIV patient’s viral loads reveals new cohort at risk of therapy failure
-
Wits Reproductive Health and HIV Institute publishes new research on Low Level Virema Co-hort
In a large South African cohort study, a team of researchers from the Wits Reproductive Health and HIV Institute (Johannesburg, Gauteng, South Africa) collaborating with the Ndlovu Research Consortium (Groblersdal, Limpopo, SA), the National Health Laboratory Service (SA), the University of California San Diego (USA), and the University Medical Center Utrecht (The Netherlands) found that low-level viremia in treated HIV-patients is an important risk factor for treatment failure.
The findings of the study indicate that the current WHO-defined threshold for virological failure fails to identify a large subset of patients who are at increased risk of poor outcomes of ART and that clinical interventions should take place at lower viral loads than those proposed by the current WHO guidelines. Results from this study were published in Lancet Infectious Diseases Saturday Nov 18, 2017.
“Sustainable virological suppression is an important part of the 90-90-90 targets defined by UNAIDS. This study shows that patients with LLV are at risk for therapy failure.” says Dr. Francois Venter, WHRI, Witwatersrand University. “A strong message from WHO regarding the risk of virological failure after LLV could motivate clinicians to act when LLV is encountered. “
The monumental response to the global HIV epidemic has led to an unprecedented amount of patients on antiretroviral therapy (ART). The goal of antiretroviral therapy (ART) in HIV positive patients is to suppress the amount of HIV in the blood (also known as viral load).
From the start of the ART roll-out, South Africa has invested in laboratory capacity enabling routine viral load monitoring of all patients on ART. The implementation of viral load monitoring was largely done in accordance with WHO ART guidelines, which advice annual routine monitoring and a threshold of 1000 copies/mL to define virological failure.
In clinical guidelines for high-income settings, cut-offs for therapy failure are lower and clinical intervention is already required above 50 copies/mL. Suppression below 50 copies prevents disease progression towards AIDS, prevents selection of resistance and lowers the risk of transmission of the virus to others.
The uniquely South African large-scale programmatic viral load monitoring program yields unique insights into crucial aspects of WHO ART guidelines, such as their current definition for virological failure. A study of over 70 000 patients attending 57 HIV treatment facilities has shown that patients presenting with detectable viral loads below the lenient 1000 copies/mL threshold are at an increased risk to develop virological failure that is, >1000 copies/mL.
A quarter of the patients in this cohort who were on first-line ART experienced one or more episodes of LLV. Compared to patients with virological suppression, that is with <50 copies/ml, patients with LLV were threefold more prone to develop failure of ART. In patients with LLV of the highest range (400-999 copies/mL) this risk increased to nearly fivefold, the risk to change to second-line therapy was even more pronounced to 13 times.
Important conclusions can be drawn from this study. The findings indicate that the current WHO-defined threshold for virological failure fails to identify a large subset of patients who are at an increased risk of poor outcomes of ART.
Dr Sergio Carmona, National Health Laboratory Services at Witwatersrand University, Johannesburg, adds that viral load monitoring remains key to determining ART success. “This study provides clear evidence that clinical interventions should take place at lower viral loads than those proposed by the current WHO guidelines. We need to support the scale-up of viral load testing in low- and middle-income countries as well as encourage adherence to ARVs and close follow-up of viral load results.”
A more active approach to low-level viremia is essential to prevent virological failure and subsequent selection of resistance. Such an approach should be implemented prior the introduction of integrase inhibitors which are the cornerstone of ART globally to preserve this powerful treatment for the coming decades.