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.


  1. Ramratnam B et al. The decay of the latent reservoir of replication-competent HIV-1 is inversely correlated with the extent of residual viral replication during prolonged anti-retroviral therapy. Nat Med 6: 82-85, 2000
  2. Ho D Toward HIV eradication or remission: the tasks ahead. Science 280: 1866-1867, 1998
  3. Grossman Z et al. Ongoing HIV dissemination during HAART. Nat Med 5: 1099-1104, 1999
  4. Jones LE et al. Transient viremia, plasma viral load, and reservoir replenishment in HIV-infected patients on antiretroviral therapy. J Acquir Immune Defic Syndr, 2007
  5. Blankson JN et al. The challenge of viral reservoirs in HIV-1 infection. Ann Rev Med 53: 557-593, 2002
  6. Chun TW et al. HIV-infected individuals receiving effective antiviral therapy for extended periods of time continually replenish their viral reservoir. J Clin Invest 115: 3250 – 3255, 2005
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.