486 HIV-1 Superinfection with a CRF01_AE Strain: Cell-free RNA Levels are Significantly Lower than the Primary Infecting Subtype B Strain S.Subbarao*1, A.Ramos1, P.Srinivasan1, D.Hu1, S.Vanichseni2, K.Choopanya2, T.Chaowanachan3, J.Tappero1,3, T.Mastro1, T.Folks1 1CDC, Atlanta, GA; 2Bangkok Metropolitan Admin, Thailand; and 3Thai Ministry of Publ Hlth -U S CDC Collaboration, Nonthaburi, Thailand
Background: We have previously described 2 cases of HIV-1 intersubtype superinfection identified from an HIV vaccine preparatory cohort in Bangkok, Thailand. In one case described here, the super-infecting CRF01_AE strain was detected by molecular and serologic analyses approximately 11 months (mos) after complete seroconversion and the development of specific T-cell responses to the primary infection with a subtype B strain. Cross-subtype immune responses were absent prior to superinfection with the CRF01_AE strain. Our objective in this study was to measure cell-free viral RNA levels of the primary and super-infecting strains.
Methods: A real-time, PCR-based (TaqMan, Roche Diagnostic Systems, Branchburg, NJ) quantitative assay was developed to measure and compare subtype-specific cell-free viral loads at roughly 4 mo intervals, over 44 mos of follow-up since initial seroconversion.
Results: The subtype-specific TaqMan assay reproducibly amplified 50 copies of the same-subtype target RNA or DNA in a background of 13,000 copies of the other subtype. Cell-free subtype B RNA levels ranged from 7,484 to 237,649 copies/ml over the 44 mo follow-up period, while CRF01_AE RNA levels ranged from 3,320 to 18,348 copies/ml between mos 11 and 44. When CRF01_AE superinfection was first detected, the cell-free RNA level was determined to be 1.1-fold lower than the subtype-B RNA level at that sampling point. In 6/8 subsequent sampling points following super-infection, when both CRF01_AE and subtype-B cell-free RNA levels were detected and measured, CRF01_AE RNA levels remained 3- to 53-fold lower than the primary subtype B RNA levels.
Conclusions: Cell-free viral RNA levels of the super infecting virus remained much lower than the levels observed for the primary strain, suggesting that the immune response to the primary infection may be controlling the super-infecting strain. These findings suggest that if sterilizing immunity is not an immediately achievable goal with current HIV vaccines, perhaps vaccine-induced immunity can decrease viremia, reduce HIV transmission, and delay disease progression.