Circumcision’s Place in the Vicious Cycle Involving Herpes Simplex Virus Type 2 and HIV

Abstract

Human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 2 (HSV-2) have caused two overlapping epidemics that pose major public health problems worldwide. The two viruses are involved in a vicious circle, with HSV-2 enhancing HIV-1 acquisition, replication and shedding, and HIV, in turn, facilitating acquisition, reactivation and shedding of HSV-2 (1). A high proportion of HIV-infected persons are also infected with HSV-2 – 30 to 70% of those in Europe and 50 to 90% of those in Africa (2, 3). A meta-analysis of 19 prospective observational studies found that HSV-2 infection increases the risk of acquiring HIV-1 by 2.7 in men and 3.1 in women. (4). More recently, cohort studies in Uganda and Zimbabwe found HSV-2 infected persons to be 2.8 and 4.4 times more likely to acquire HIV-1, respectively (5). Plasma and genital HIV levels are increased during both symptomatic and asymptomatic HSV-2 reactivations (6–8). That HSV-2 infection enhances both HIV-1 replication and shedding is further supported by studies of HSV-2 suppressive therapy with valacyclovir. Administration of valacyclovir reduces rectal and plasma HIV-1 levels in HIV positive men who have sex with men by 33% and 53%, respectively (9), and it reduces the quantity of detectable HIV-1 in Peruvian women by 45% (10) and African women by 0.71 log10 copies/ml (11). Certain HSV-2 proteins may increase HIV-1 expression and pro-inflammatory cytokines during HSV-2 reactivation, likely increasing HIV-replication (1).