Background: HIV controllers (HICs) display spontaneous long-term control of HIV replication. Some HICs show a decline in their CD4 T cell count or lose the ability to control the virus. The aim of this study was to investigate the rate and determinants of immunological and/or virological progressions in a large cohort of HICs.
Methods: HICs from the French ANRS CO21/CODEX study are ART-naive HIV-1-infected patients diagnosed for > 5 years with 5 last consecutive HIV viral loads (VL) < 400 copies/mL. Immunological progression during follow-up was suspected if CD4 T cell count fell < 350/mm3 or declined by more than 200/mm3 from a last CD4 count < 600/mm3. Viral progression was suspected if HIV VL rose > 2000 copies/ml. The events of immunological and virological were confirmed if similar CD4 counts or VL were found on a consecutive measurement. Clinical characteristics were analysed at inclusion in the cohort and prior to the event. Immune activation and inflammatory parameters (% of HLADR+CD38+ T cells, IP10 levels), ultrasensitive HIV VL and total HIV DNA were compared using non parametric tests with the non-progressor HICs.
Results: Out of 217 patients followed in the cohort between 2009 and 2013, 37 patients experienced at least one suspicion of progression. Progression was confirmed in 15 patients (immunological progression, n=10; viral progression, n=5). Compared with non-progressor HICs, viral progressors (VP) were enrolled younger (p<0.01). No differences in terms of HLA B57 status or HCV coinfection were observed. Unprotected sexual intercourse and sexually transmitted infections were reported in the recent history of some HICs, but not more frequently in progressors. Relative to non-progressors, immunological progressors HICs had lower CD4 T cell nadir (median (IQR): 292 (236-373) vs. 516 (412-681)/mm3, p<0.001), as well as the CD4 count at inclusion, and viral progressors had higher ultrasensitive HIV RNA levels at inclusion (i.e., 1-2 years before progression) (p<0.01 for all). Interestingly, CD8 T cell activation and IP10 levels at inclusion in immunological progressors were significantly higher than in non-progressors (p<0.001), almost as elevated as observed in viremic non HICs patients.
Conclusions: CD4 T cell nadir, level of residual HIV replication and levels of basal immune activation seem major determinants to progression in HICs, and should be considered in order to adjust their follow-up and optimize the timing of cART initiation.