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 log 10 /ml, CD4 + counts more then 500 cells/mm 3 ). 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 ÑD3/CD4/CD8/CD45) [1].Summary of results Average log 10 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 log 10 (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 ÑD4 + T‐lymphocyte dynamics were defined: 1) CD4 + elevation (in case beginning from the acute stage of the disease), 2) stable ÑD4 + 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.Env Env Env Gag Gag Gag Gag Pol Pol PolPatient number 160 120 41 55 40 24/25 18 68/66 52/51 34/31 1 + * + + + + − − − − 2 + + + + * + − * * + 3 + * + * ‐ * − * * * 4 + + + + + + − + * + 5 + + + + − + − + + − 6 + + + + + + * + + * 7 + + + + + + * * * + 8 + * + * ‐ * * * − * 9 + + + + ‐ + * − − − 10 + ‐ + * ‐ + − − − − 11 + + + + + + * − − − 12 + * + + + + − * − −Signs of antibodies: +, presence; *, traces; −, absenceConclusions 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.