Hepatitis C virus quasispecies in HIV-infected women: role of injecting drug use and highly active antiretroviral therapy (HAART)

Abstract

Despite the high frequency of HCV and HIV coinfection, little is known about HCV quasispecies in HIV-positive patients. The current analysis included 236 HIV+/anti-HCV+ women enrolled in the Women's Interagency HIV Study (WIHS). Hypervariable region 1 of the second envelope gene was analyzed by single-strand conformation polymorphism (SSCP). The relationship between the HCV quasispecies and clinical and demographic features were analyzed in multivariate models. Age over 40 years and high HCV RNA load were the only factors significantly associated with quasispecies complexity, assessed as the number of SSCP bands. High HIV and HCV plasma loads were associated with quasispecies stability over time, as reflected by stable SSCP band patterns. However, women who were actively injecting drugs were 3 times more likely to experience quasispecies changes than their noninjecting counterparts. No affect on HCV quasispecies dynamics was noted in relation to CD4 count or highly active antiretroviral therapy (HAART).

Conclusion: among HIV/HCV coinfected patients, HCV quasispecies complexity and dynamics correlate more closely with HIV and HCV plasma loads than with CD4+ cell counts. Active drug use is associated with quasispecies changes probably due to repeated superinfections with new HCV strains. This needs to be considered when planning treatment and prevention strategies for HCV in coinfected individuals.

Fig. 1

SSCP analysis of hypervariable region 1 HCV RNA amplified from sequential plasma samples of 6 different WIHS patients. Three patients in the upper row showed changes in the position of SSCP bands (“shift”), indicating viral sequence changes. In 3 patients in the lower row the position of bands did not change, indicating stability of viral quasi-species. In patient 2010-1640 (lower row) new minor bands appeared at visit 6 (last lane); however, since position of the major bands did not change, for the purpose of this study patient’s quasispecies was classified as stable. Patients’ ID and visit numbers are shown above each gel.

Fig. 2

Phylogenetic reconstruction of evolutionary relationship of HVR1/E2 sequences in 6 patients. Bootstrap proportions of greater than 50% are shown at branch points. The taxa are labeled A, B, and C indicating sequential samples from each patient, which correspond to visit numbers shown in Fig. 1. In patients 1010-0432, 1010-1092, and 2010-1640 viral population was relatively monophyletic with intermingling of sequences from different visits, while in patients 1010-2070, 3051-2643, and 4051-2188 quasispecies from sequential visits tended to group separately.