Why resistance rarely develops with viral suppression <50 copies/mL

Simon Collins, HIV i-Base

American and Israeli researchers have used a conceptual model to consider the distinct patterns of the virological and immunological response to antiretroviral therapy. They interpret recent data in terms of ‘proximal immune activation and virus transmission’ (PAT) and believe it may explain why resistance mutations are rarely observed below 50-100 copies RNA/mL despite clear evidence of ongoing viral replication.

The researchers write in their abstract: “We suggest that below this threshold, virus generated in the course of an infection burst rarely sparks new bursts in unrelated target cells, thus precluding gradual increase in the repertoire of infected memory cells; viral replication remains local and resistant variants that may emerge are prevented from spreading. However, above threshold, HIV-specific memory cells are generated and are capable of spreading new resistant variants within the memory pool. Thus, both direct spreading and anti-HIV response dependent ‘mixing’ become insignificant when infection bursts are sufficiently reduced. Consistent with mixing, we previously observed that resistance mutations did develop in patients with intermittent viraemia episodes, who showed limited evidence of generalised T cell activation but had large numbers of HIV-specific T cells. Importantly, PAT predicts that in the absence of rapid spreading and mixing, wild-type HIV and resistant variants can coexist, actively replicating in relative isolation.”


Grossman Z, Grossman Z, Hunt PW et al. Distinct patterns of the virological and immunological response to antiretroviral therapy interpreted in terms of the dynamics of immune activation and HIV transmission. XII International HIV Drug Resistance Workshop, Los Cabos, Mexico, 10-14 June 2003. Abstract 57. Published as part of Antiviral Therapy Volume 8 Issue 3.

Links to other websites are current at date of posting but not maintained.