HIV Reactivation from Latency after Treatment Interruption Occurs on Average Every 5-8 Days—Implications for HIV Remission

• DOI: 10.1371/journal.ppat.1005000
• Publication Date: 2015-07-02T18:05:21Z
• Authors: Mykola Pinkevych; Deborah Cromer; Martin Tolstrup; Andrew J. Grimm; David A. Cooper; Sharon R. Lewin; Ole S. Søgaard; Thomas A. Rasmussen; Stephen J. Kent; Anthony D. Kelleher; Miles P. Davenport
• Keywords: Latency stage; Virus latency

HIV infection can be effectively controlled by anti-retroviral therapy (ART) in most patients. However must continued for life, because interruption of ART leads to rapid recrudescence from long-lived latently infected cells. A number approaches are currently being developed 'purge' the reservoir cells order either eliminate completely, or significantly delay time viral after interruption. fundamental question research is how frequently virus reactivates latency, and thus much might need reduced produce a prolonged antiretroviral-free remission. Here we provide first direct estimates frequency interruption, combining data four independent cohorts patients undergoing treatment comprising 100 total. We estimate that replication initiated on average once every ≈6 days (range 5.1- 7.6 days). This rate around 24 times lower than previous thought, very similar across cohorts. In addition, analyse ratios different 'reactivation founder' viruses separate cohort ART-interruption, successful reactivation 3.6 days. suggests reduction size 50-70-fold would required increase time-to-recrudescence about one year, achieve at least short period free Our analyses studies will large detect modest changes reservoir, macaque models SIV latency may have higher frequencies seen human infection. Understanding mean an important step prolong remission HIV.