This issue of the Journal continues the dialogue on the interaction between HIV and herpes simplex virus type 2 (HSV-2). Two articles in this issue, one by Kapiga et al., describing a cohort of women in Tanzania, and the other by Cachay et al., describing a cohort of largely men who have sex with men (MSM) in San Diego, are devoted to the interaction between the 2 agents. Each of the studies evaluates very different regions in the spatial and temporal dynamics between the 2 organisms. Superficial reading of these articles suggests an even draw: one showing and the other not showing a significant interaction between the 2 infections.
The article by Kapiga et al. continues to strengthen the burgeoning number of studies indicating that both past and recently acquired HSV-2 infection are major factors, on both a population and individual basis, for increasing the risk of HIV acquisition. Since initially reported by our group and other researchers in San Francisco in cohorts of highly sexually active MSM studied in the early 1980s, >35 studies detailed in 2 separate meta analyses have shown that prevalent HSV-2 increases the risk of HIV-1. The study by Kapiga et al. adds to this body of work, showing that this association is relevant in sub-Saharan African women and that the risk is marked by HSV-2 infection itself and not whether there is recognizable genital ulcer disease. The underlying biological mechanisms by which HSV-2 is a plausible factor for an increased risk of HIV-1 acquisition has been strengthened considerably in the past several years by studies that indicated that subclinical genital mucosal reactivations occur in ∼90% of HSV-2—seropositive women and 80% of seropositive men, that such reactivations are common (20% of days with daily sampling), and that these “shedding episodes” are associated with microscopic ulcerations and the influx of activated CD4+ T cells to the ulcerative region. The even higher risk between incident HSV-2 and HIV acquisition, as shown by Kapiga et al. in the present issue and by Reynolds et al. in a prior issue of the Journal, can be explained by the even higher rates of subclinical reactivation (35%–40% of days) in early versus more-chronic HSV-2 infection. What makes for epidemiological/population-based concern about the interaction between these 2 agents versus those of other genital ulcer diseases is the much higher prevalence of HSV-2 versus that of Treponema pallidum or Haemophilus ducreyi in most populations throughout the worl. HSV-2 appears to be rapidly acquired after coital activity in sub-Saharan Africa, especially in young women, and the seroprevalence of HSV-2 is >50% in most high-risk populations throughout the world.