Long-lived macrophages might explain unsuppressible low-level viraemia on ART

A paper published in April in JID proposes that macrophages could be a newly-identified source of clonally expanded HIV that could explain low-level viraemia in people who are otherwise on effective ART. [1]

This is important because there is generally low awareness of research that can help manage low-level viraemia in people who have excellent adherence; ART might already be maximally suppressive and intensification will not achieve an undetectable viral load.

The paper reports four cases of people with advanced HIV who were adherent to ART but who took longer than a year to become undetectable. The researchers were able to track the source of this residual viraemia to drug-sensitive HIV from a diverse pool of long-lived HIV-infected macrophages.

The cases were men aged 29 to 47 with subtype B HIV and very low CD4 counts of 90, 10, 16 and 12 cells/μL. Viral load when starting ART ranged from >800,000 to 2.1 million copies/mL and after 6 months in the four cases was 1500, 700, 13000 and >14 million copies/mL. Although CD4 counts increased to 232, 186 and 139 in the first three cases, this remained at 22 in the fourth case who was an immunological non-responder, who remained at high clinical risk and whose viral load remained at high levels out to week 57.

The study reported that genetic defects in vpr in three of these cases may affect survival or HIV produced from macrophages.

Full details of these responses, including treatment changes are included in the full paper.

This is a different mechanism to the previously reported cases from other research groups where the source of low-level viral load – sometimes sustained at several thousand copies/mL – has been traced to the pool of latently infected T-cells in the viral reservoir. [2]

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The clinical importance of these findings is that switching or intensifying ART will not lead to further viral suppression for low-level viraemia in this setting.

However, intensification for a month might be a practical way to confirm in such cases that current ART is maximally suppressive, after adherence has been discounted.

This could reduce the anxiety and stress for both people living with HIV and the doctors managing their care, given the importance of achieving and maintaining undetectable viral load on ART.