In the mid-1990s, some experts thought it might be possible to eradicate HIV using then-new potent combination antiretroviral regimens. The theory was that over time, cells already infected with HIV would reach the end of their natural life-span and die off, to be replaced by freshly produced, uninfected cells.

After starting treatment with an effective combination regimen, HIV levels in the body decrease rapidly at first. During this first phase, the drugs primarily block HIV replication in activated CD4 T-cells with short life-spans. In the slower second phase, other infected cells with longer life-spans, such as resting CD4 T-cells and macrophages, gradually begin to die off and virus production declines further.

On the basis of mathematical models, David Ho and his team at the Aaron Diamond Research Centre initially estimated that complete HIV eradication might require three years or more of totally suppressive antiretroviral therapy ^[1]. They further estimated the half-life of latent HIV-infected CD4 T-cells to be about six months with fully suppressive 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 forth 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 being ‘undetectable’ viral load - below 50 copies/ml using the current standard test - a person may have steady low-level virus replication.

Today, the notion of HIV eradication is widely regarded with scepticism due to the growing evidence that the virus persists in the body despite long-term use of suppressive antiretroviral therapy.