Antibody Responses to Plasmodium Falciparum Antigens in Hiv Infected Adults in Bondo Sub County Hospital, Siaya County, Kenya

Abstract

Malaria and human immunodeficiency virus (HIV) are co-endemic in sub-Saharan Africa. Infection with HIV results in B cell anomalies. Antibodies are critical in protection against malaria and it is hypothesized that B cell anomalies resulting from HIV infection interfere with antibody responses contributing to severe and frequent malaria episodes. Individuals infected with HIV have elevated antibody and C-reactive protein (CRP) levels. However, it is unclear whether malaria-specific antibodies, particularly immunoglobulin M (IgM), total immunoglobulin G (IgG) and IgG subclasses levels would be increased or decreased, given the evidence of impaired B cell responses to other antigens due to HIV. Furthermore, how malaria-specific antibodies correlate with viral load (VL) and CRP levels in HIV infected individuals is unclear given their link in HIV disease progression. Plasmodium falciparum (Pf) vaccines studies have associated malaria protection with antibodies against apical membrane antigen-1 (AMA-1) and glutamate-rich protein-R0 (GLURP-R0). The current study aimed to: determine quantities and prevalence of antibody isotypes (IgG and IgM) against Pf antigens (AMA-1 and GLURP-R0); determine quantities and prevalence of IgG subclasses in response to Pf selected antigens and; measure the correlation of Pf specific antibody isotypes and subclasses with VL, CD4+ counts and CRP levels. A comparative cross-sectional study using a sample size of 181 comprising of 52 HIV negative and 129 HIV positive adult participants seeking care at Bondo sub-County Hospital was conducted. Data from Bondo Sub-County hospital have shown an overlap in malaria and HIV infections. Antibody and CRP levels were tested using ELISA. The CD4+ cell and VL counts were obtained using FACSCount and Abbott m2000 analyzer respectively. Medians and proportions of Pf-specific antibody levels were compared using Wilcoxon Rank-Sum and Chi-Square tests respectively. Correlations of Pf-specific antibodies with VL and CRP were obtained using Spearman correlation. The study found that IgM, IgG1 and IgG3 levels against both AMA-1 and GLURP-R0 were significantly high in HIV infected individuals (P<0.0001). Antibody responses against AMA-1 were lower in individuals having CD4+ counts ≤200 cells/ml (P =0.01). Levels of IgM and IgG1 against both AMA-1 and GLURP-R0 were associated with CRP levels (P=0.01, 0.05, 0.02 and 0.004 respectively) and IgM and IgG1 against both antigens were associated with VL (P=<0.001, 0.02, 0.02 and 0.01 respectively). The data suggest that HIV infection leads to increased IgM, IgG1 and IgG3 responses, but low CD4+ counts are associated with lower total IgG and IgG1 responses. These findings provide an insight into a better understanding of malaria-specific antibody responses due to HIV infection. Future studies should assess the cellular mechanisms leading to increased antibody levels in HIV-malaria co-infection.