In the Journals

Researchers: WHO HIV guidelines miss patients with low-level viremia

Under current WHO HIV guidelines, many patients in lower income countries fall below the threshold for virologic failure but nevertheless face significant risks for treatment failure, according to a recent study.

The data suggest that WHO should lower that threshold and clinicians should intervene at lower viremia levels, researchers wrote in The Lancet Infectious Diseases.

“This large-scale study shows that low-level viremia occurs frequently and represents an important threat to virologic success,” researcher Lucas E. Hermans, MD, of the department of medical microbiology at the University of Utrecht, the Netherlands, and colleagues wrote. “Current WHO-guided clinical practice in low-income and middle-income countries is not geared toward early recognition and management of low-level viremia. We urge policy makers and clinicians to incorporate management of low-level viremia in their efforts to control the HIV epidemic.”

The researchers noted that low-level viremia (LLV) in HIV falls between 50 and 999 copies per mL when the patient is on ART. The definition of virologic failure, however, differs according to geography.

In high-income countries, an HIV RNA load of more than 200 copies per mL denotes virologic failure. But for low- and middle-income countries, WHO guidelines are more lenient, and viral load must meet or exceed a threshold of 1,000 copies per mL to indicate virologic failure.

Hermans and colleagues sought to assess the effect of LLV in South Africa, a lower income country where the WHO threshold is higher.

They conducted an observational study that included more than 70,000 patients on ART. The patients were registered at 57 clinics between January 2007 and May 2016.

Altogether, 69,454 of the patients received first-line ART. Of those patients, 1,810 also received second-line ART. The remaining 1,476 received only second-line ART.

LLV occurred in 16,013 (23%) of patients receiving first-line ART and in 855 (26%) of those on second-line ART. Virologic failure was documented in 14,380 (22%) of the patients receiving first-line ART and in 1,092 (33%) of those on second-line ART.

Any LLV between 51 and 999 copies per mL was associated with a more than twofold risk for virologic failure in both first-line and second-line ART patients (adjusted HR = 2.6 and 2.1, respectively), the researchers said. That risk increased at an LLV of 200 to 399 copies per mL (aHR = 3.2 and 3.7) and at an LLV of 400 to 999 copies per mL (aHR = 4.7 and 6.8).

In addition, LLV quintupled a patient’s chances of switching from first-line to second-line ART (aHR = 5.2).

In a related commentary, Antonella Castagna, MD, and Laura Galli, MD, both from the infectious diseases clinic at San Raffaele University in Milan, Italy, called for a change in the WHO LLV threshold, among other considerations.

“Findings from this study suggest a revision of WHO guidelines to incorporate low-level viremia as an early warning indicator of virologic failure,” they wrote. “Furthermore, results from this study should prompt us to reconsider the definition of virologic failure, the frequency of viral load monitoring and the timing of switching to second-line regimens to reduce the exposure to detectable viremia, the risk of clinical progression and development of HIV drug resistance and, ultimately, the loss of therapeutic options.” – by Joe Green

Disclosures: Hermans reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. Castagna reports receiving personal fees from Bristol-Myers Squibb, Gilead Sciences, ViiV Healthcare, Merck and Janssen-Cilag. Galli reports no relevant financial disclosures.

Under current WHO HIV guidelines, many patients in lower income countries fall below the threshold for virologic failure but nevertheless face significant risks for treatment failure, according to a recent study.

The data suggest that WHO should lower that threshold and clinicians should intervene at lower viremia levels, researchers wrote in The Lancet Infectious Diseases.

“This large-scale study shows that low-level viremia occurs frequently and represents an important threat to virologic success,” researcher Lucas E. Hermans, MD, of the department of medical microbiology at the University of Utrecht, the Netherlands, and colleagues wrote. “Current WHO-guided clinical practice in low-income and middle-income countries is not geared toward early recognition and management of low-level viremia. We urge policy makers and clinicians to incorporate management of low-level viremia in their efforts to control the HIV epidemic.”

The researchers noted that low-level viremia (LLV) in HIV falls between 50 and 999 copies per mL when the patient is on ART. The definition of virologic failure, however, differs according to geography.

In high-income countries, an HIV RNA load of more than 200 copies per mL denotes virologic failure. But for low- and middle-income countries, WHO guidelines are more lenient, and viral load must meet or exceed a threshold of 1,000 copies per mL to indicate virologic failure.

Hermans and colleagues sought to assess the effect of LLV in South Africa, a lower income country where the WHO threshold is higher.

They conducted an observational study that included more than 70,000 patients on ART. The patients were registered at 57 clinics between January 2007 and May 2016.

Altogether, 69,454 of the patients received first-line ART. Of those patients, 1,810 also received second-line ART. The remaining 1,476 received only second-line ART.

LLV occurred in 16,013 (23%) of patients receiving first-line ART and in 855 (26%) of those on second-line ART. Virologic failure was documented in 14,380 (22%) of the patients receiving first-line ART and in 1,092 (33%) of those on second-line ART.

Any LLV between 51 and 999 copies per mL was associated with a more than twofold risk for virologic failure in both first-line and second-line ART patients (adjusted HR = 2.6 and 2.1, respectively), the researchers said. That risk increased at an LLV of 200 to 399 copies per mL (aHR = 3.2 and 3.7) and at an LLV of 400 to 999 copies per mL (aHR = 4.7 and 6.8).

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In addition, LLV quintupled a patient’s chances of switching from first-line to second-line ART (aHR = 5.2).

In a related commentary, Antonella Castagna, MD, and Laura Galli, MD, both from the infectious diseases clinic at San Raffaele University in Milan, Italy, called for a change in the WHO LLV threshold, among other considerations.

“Findings from this study suggest a revision of WHO guidelines to incorporate low-level viremia as an early warning indicator of virologic failure,” they wrote. “Furthermore, results from this study should prompt us to reconsider the definition of virologic failure, the frequency of viral load monitoring and the timing of switching to second-line regimens to reduce the exposure to detectable viremia, the risk of clinical progression and development of HIV drug resistance and, ultimately, the loss of therapeutic options.” – by Joe Green

Disclosures: Hermans reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. Castagna reports receiving personal fees from Bristol-Myers Squibb, Gilead Sciences, ViiV Healthcare, Merck and Janssen-Cilag. Galli reports no relevant financial disclosures.