Viral persistence vs viral eradication

After starting ART, HIV levels in the body decrease as viral replication is suppressed and infected cells die off. At first this decrease is rapid due to the loss of relatively short-lived, activated CD4 T-cells. Viral load then declines more slowly as other infected cells with longer life-spans, such as resting CD4 T-cells and macrophages, die off.

In 1998, David Ho and his team at the Aaron Diamond Research Centre estimated that latently HIV-infected CD4 T-cells had a half-life of about six months with fully suppressive therapy.¹ Using mathematical models based on this and other estimates, they predicted that complete HIV eradication might be possible with three years or more of totally suppressive antiretroviral therapy.²

Others, including researchers at the US National Institutes of Health (NIH), contested this theory, noting that intermittent bursts of localised HIV replication continue despite antiretroviral treatment.³ More recently, researchers suggested that sporadic immune activation replenishes virus reservoirs and could explain viral load ‘blips’ in people on HAART.⁴

Robert Siliciano and colleagues from Johns Hopkins Medical School put forward an alternative theory, suggesting that the body naturally maintains a pool of long-lived HIV-infected ‘memory’ CD4 T-cells even when there is no ongoing HIV replication.⁵ This is the immune system’s normal mechanism for sustaining life-long immunity against pathogens encountered in the past.

Studies by Anthony Fauci’s team at the NIH showed that in addition to these long-lived memory cells, HIV genetic material also persists in active CD4 T-cells, and can continue producing new viral particles even when treatment is keeping viral load at an undetectable level.⁶ Thus, despite having ‘undetectable’ viral load – below 50 copies/ml using the current standard test – a person may have steady low-level virus replication.