P19. Antibody profiling of HIV-1 proteomes signifies decreasing antibody profile during long term antiretroviral therapy

Mohammed M. Morshed1*, Wang Zhang1*, Kajsa Noyan1, Jan Vesterbacka1, Anders Sönnerborg1, Ujjwal Neogi1
Affiliates: 1Karolinska Institutet *Equal Contribution

Background
The major challenge in evaluation the success of HIV eradication approaches is the need for accurate measurement of persistent HIV during effective antiretroviral therapy (ART). Previous studies have claimed that the anti-HIV antibody assay can distinguish HIV-infected individuals with different sizes of the viral reservoirs. In this study we performed antibody profiling of HIV-1 proteomes using the sensitive method Luciferase Immuno-precipitation system (LIPS) in well-characterized groups of Swedish patients.

Method
Plasma samples were obtained from HIV negative individuals (n=17), therapy naïve HIV-1 progressors (n=31), elite controllers (EC; n=19) with undetectable virus and stable CD4 cells according the EuroCoord definition and long term ART suppressors (n=19). LIPS was applied to quantify IgG against six HIV-1 fusion proteins: p24, gp41, reverse transcriptase (RT), trans-activator of transcription (Tat), integrase and protease.

Results
The median time since HIV diagnosis for the EC was 9 years (IQR: 2.7 – 32.8) with a median CD4 count of 950 cells/mm3 (IQR: 480 to 1655) at sampling. For the long term ART patients the median duration of ART was 19 years (IQR: 17-20) without any detectable viral blips. The LIPS assay using six HIV-1 fusion proteins identified significant lower antibody levels to gp41 in EC (p=0.01), but higher p24 levels (p=0.02) compared to normal progressors. While comparing the normal progressors and long term ART, there was significantly (p<0.001) lower levels to p24, gp41, integrase, tat and protease (but not to RT) in treated patients. However, collectively gp41, p24 and RT antibody levels were associated with the category of patients (Fig 1B, Heat map and Fig 1C, principle component analysis).

Conclusions
Our findings show that anti-HIV antibody responses decrease substantially with a very long duration of successful ART, which could indicate limited antigen expression due to a decreased reservoir of replication-competent virus. The heterogeneity in antibody levels among EC suggests that this category of patients is not a homogenous group. Further studies aim at correlating antibody levels with the size of the HIV reservoirs using novel molecular biological techniques.

P19-mohammed_m_morshed