HIV elite controllers as a key to novel strategies in treatment of HIV infection

Purpose of the study: To identify and primarily characterize the elite controllers (EC) in Moscow Regional HIV Living People Cohort (Russia). Methods: 2682 HIV-1-positive individuals with A1 (asymptomatic) stage of HIV infection were under regular physician observation continuously for at least 5 years. Verification antibody testing was performed with “New Love Blot” and “Autoblot 2000” (Biorad). Patients underwent scheduled HIV viral load and T-lymphocyte subpopulation measurement (twice a year) and did not have indications to HAART (viral load less then 5 log10/ml, CD4+ counts more then 500 cells/mm3). HIV viral load was detected by PCR m2000rt Abbott Biosystems analyzer, “RealTime HIV-1” sets with 20 copies per ml sensitivity) and major subpopulation of T-lymphocytes were analyzed by flow cytometer BD FACSCount, sets of antibodies D3/CD4/CD8/CD45) [1]. Summary of results: Average log10 viral load was defined in each patient for 5-year period, and the distribution appeared to have a bimodal character (Figure 1). 106 EC were primarily identified as having average viral load less then 1.7 log10 (50) HIV copies/ml.The incidence of EC appeared to be 3.95% (95% CI: 3.2%; 4.7%) of population with A1 (asymptomatic) disease with no indications to HAART, that corresponds to literary data [2]. Belonging to EC was then proved by laboratory dynamics. In EC 3 types of viral load dynamics were identified: 1) absence of detectable viremia, 2) single spikes, 3) episodic temporary elevation(s) (at mean 500-900 copies) lasting half a year. All these emphasize the control of virus. In EC 3 types of D4+ T-lymphocyte dynamics were defined: 1) CD4+ elevation (in case beginning from the acute stage of the disease), 2) stable D4+ cells, 3) CD4+ cell depletion with very small velocity. 12 EC had “minimal change disease” defined additionally by the absence or trace appearance of pol 68/66, 52/51, 34/31 antibodies (Table 1) and non-detectable PCR levels in all measurements. These represent 11.32% (95% CI: 5.17%; 17.47%) from EC and 0.45% (95% CI: 0.19%; 0.71%) from population with A1 (asymptomatic) HIV-disease. Conclusions: Among EC patients with “minimal change disease” were identified. They may represent: (i) primarily persistent HIV infection (with reduced productive cycle), (ii) low dose (localized) HIV-infection, (iii) rare successful immune-mediated elimination of HIV that could be the model for novel elimination strategies.