Impact of individuals choosing to stop ART could be considerable, and data are needed on subsequent viral EX 527 rebound to better inform future transmission models. Furthermore, final results from SPARTAC suggested that ART initiated in primary HIV infection was associated with a change in pVL set-point out to 60 weeks after stopping therapy whilst the SMART trial reported that interruption of ART in chronic infection was associated with an increased risk of all-cause mortality The level of viral rebound following interruption of ART commenced in at different stages of HIV infection is, therefore, highly relevant from both a clinical and public health perspective and warrants further investigation. We, therefore, wanted to compare the pVL changes observed after cessation of ART initiated in chronic HIV infection with those in PHI by comparing viral rebound between individuals enrolled in two protocol-indicated ART interruption studies; SPARTAC and SMART. Our findings support those from a smaller study which observed significantly shorter time to viral rebound following treatment interruption in participants who initiated treatment in PHI compared to chronic infection. However, they did not consider the stage of infection prior to commencing therapy. We found that, as anticipated, when participants with chronic infection were stratified by nadir CD4 at time of stopping ART, lower nadir CD4 was associated with higher pVL after stopping therapy. Compared to PHI, viral rebound was higher in chronically-infected participants with nadir CD4,500 cells/ mm3, but similar to levels experienced by those with nadir CD4$500 cells/mm3. Interestingly, in chronically-infected participants with CD4 nadir,200 cells/mm3, higher CD4 count at ART stop was associated with subsequent higher viral burden. Thus, it could be hypothesised that the degree of viral rebound may be related to the degree of immune reconstitution occurring during ART, or to the number of CD4 target cells available for viral infection at ART stop. The observed difference in virological impact of stopping ART in PHI versus chronic infection may reflect differences in viral reservoir size although no data were available from either trial on HIV reservoir size and we were, therefore, unable to directly examine this. A study of ART initiated during PHI found that 36 weeks of therapy reduced proviral HIV-1 DNA to levels comparable to those seen in long-term non-progressors whilst, although levels were also reduced in chronic infection, they remained significantly higher than in PHI and long-term nonprogressors. This was supported by others reporting evidence for decay of the reservoir in patients who initiated ART early in infection and a significant reduction in its size in those initiating ART early, compared to chronic, infection. However, others quantifying the viral reservoir in treated PHI participants reported that, although a reduction in reservoir size is observed after even short-course ART initiated in PHI, complete abolition of viral replication is not achieved and viral reservoir may be re-expanded even after short-term rebound of viraemia. As the majority of studies examining short-course ART in PHI are observational in nature, the reason for starting or stopping therapy may be related to prognosis. In our analysis, the protocolindicated ART cessation in both trial populations minimises the effect of this potential source of bias, although this study has some limitations. It was not possible to adjust for ART duration, which was longer for the chronically-infected compared to PHI participants, or for ART class.