Sexual Acquisition of HCV in Women Living with HIV: Biological Plausibility,Epidemiological Signals,and Implications for Enhanced Testing and Treatment Strategies

Abstract

Hepatitis C virus (HCV) is transmitted primarily through parenteral exposure to infected blood, and sexual transmission in heterosexual couples has generally been considered inefficient. However, this conclusion is based largely on studies of immunocompetent monogamous couples and may not fully apply to women living with human immunodeficiency virus (HIV). This narrative review integrates biological, virological, and epidemiological evidence relevant to sexual acquisition of HCV in women with HIV, with particular attention to heterosexual exposure, women without injection drug use, genital tract shedding, and partner-related cofactors. Baseline heterosexual transmission risk appears to be very low in low-risk couples, yet the epidemiological evidence in women is sparse, mostly observational, and often underpowered. Even so, converging biological and epidemiological signals suggest that this risk may be underestimated in selected settings. In women living with HIV, chronic cervicovaginal inflammation, sexually transmitted infections, HPV-related cervical abnormalities, genital bleeding, and impaired local immune defenses may create a mucosal environment more permissive to the acquisition of blood-borne viruses during sex. HCV RNA has also been detected in the female genital tract, particularly in the presence of blood. Current evidence does not demonstrate that HIV is a definitive causal risk factor for sexual HCV transmission in women, but it does support the view that HIV may act as a clinically relevant risk modifier in selected exposure settings, particularly when the male partner is coinfected with HIV and HCV and has injection-related risk. In the direct-acting antiviral era, this issue has practical implications for enhanced testing, partner management, and treatment of current HCV infection in discordant partnerships.