HIV TYPE-1 V3 SEROTYPING OF TANZANIAN SAMPLES - PROBABLE REASONS FOR MISMATCHING WITH GENETIC SUBTYPING

HIV-1 V3 serotyping is used to classify immunodeficiency viruses on th e basis of antibody binding to V3 peptides derived from env genetic su btypes. Although it shows a reasonable overlap, it has been reported t o be distinct from viral genetic subtypes. The aim of this study is to determine the feasibility of HIV-1 serotyping to predict genetic subt ypes in an East African setting, where multiple HIV-1 subtypes have co existed for many years. HIV-1 genetic subtypes of 86 AIDS patients in Mbeya Town, southwest Tanzania, mere determined, using env nucleic aci d sequencing as the basis for comparison. Those data were compared wit h V3 serotyping results obtained by four different methodologies. Four HIV-1 genetic subtypes were identified, including A (25, 29%), C (47, 55%), D (13, 15%), and G (1, 1%). The sensitivity and specificity of those serotyping assays varied considerably: sensitivity for genetic s ubtype A (40-48%), C (52-96%), and D (9-31%); and specificity for gene tic subtype A (77-95%), C (46-63%), and D (97-100%). We further tried to identify reasons for the discrepancies between serotyping results a nd genetic subtypes. By means of logistic regression analysis three am ino acid residues within the V3 loop (positions 12, 13, and 19; V, H, and A for serotype A, I, R, and T for serotype C) were found to be mos t important for antibody binding; a deviation from the subtype-specifi c amino acids was highly related to mismatched results. In addition, w e have shown that phenetic analysis of V3 amino acid sequence data cou ld be used to predict the majority of V3 serotypes (93-94%). Our data demonstrated that for the majority of specimens HIV-1 V3 serotyping re sults closely match the subtype of the analyzed sample as revealed by the V3 loop amino acid sequence. However, our data demonstrate that HI V-1 serotyping is not sufficiently accurate to predict genetic subtype s in Tanzania, where subtypes A, C, D, and G are circulating. This was due to highly similar amino acid sequences throughout the prevalent g enetic subtypes, which caused the inability of HIV-1 V3 serotyping to differentiate subtype A from C as well as D from C. Instead, the serot yping results reflect the frequency distribution of V3 serotypes. To i nvestigate HIV-1 genetic subtypes in population-based studies in this African setting additional or modified algorithms are needed.