Changes in Plasma Human Immunodeficiency Virus Type 1 RNA Associated with Herpes Simplex Virus Reactivation and Suppression

Abstract

In early trials of antiretroviral therapy, acyclovir was associated with increased survival by an unknown mechanism. The hypothesis that subclinical herpes simplex virus (HSV) reactivation was associated, in vivo, with increased plasma human immunodeficiency virus (HIV) RNA and suppression with a reduced plasma HIV RNA load was investigated. HSV cultures were performed daily on HSV-2-positive/HIV-positive patients, and plasma HIV-1 RNA loads were measured at regular intervals. A subset of patients prior to, during, and after HSV suppression with high-dose acyclovir was measured to determine whether HSV suppression was associated with a decrease in HIV replication. Most (25/27 HSV-2-positive/HIV-positive persons) reactivated HSV. Total HSV shedding rate was strongly correlated with plasma HIV-1 RNA load (R=0.54; P=.004), and the plasma HIV-1 RNA level at a given CD4 cell count was 48% lower when treated with acyclovir. These data indicate that frequent mucosal HSV reactivation influences HIV replication in vivo and daily HSV suppression may be important in the management of HSV-positive/HIV-positive persons.

HIV infection of dendritic cells subverts the IFN induction pathway via IRF-1 and inhibits type 1 IFN production

“…by guest www.bloodjournal.org From shown to coexist in the same recurrent herpetic lesion. 44 Thus, coinfection or adjacent infection of epidermal and perhaps dermal DCs in these lesions with these viruses is probable. In these studies highly purified viral preparations and similar multiplicities of each virus were used over a range of 1-10 per cell.…”

Herpes Simplex Virus Type 2–Infected Dendritic Cells Produce TNF-α, Which Enhances CCR5 Expression and Stimulates HIV Production from Adjacent Infected Cells

“…Doubts about this HSV-2-HIV-1 relationship, engendered by failure of antiviral suppression of recurrent genital herpes to affect HIV-1 acquisition, are now being understood in terms of the failure of antivirals to completely suppress HSV-2 shedding and epithelial microulcers (7)(8)(9). Conversely HIV-1 + , HSV-2 + individuals also shed HIV-1 more frequently than those without HSV-2, because of increased viral shedding through genital ulcers (10).…”

Consistent Inhibition of HIV-1 Replication in CD4 + T Cells by Acyclovir without Detection of Human Herpesviruses

“…There is evidence of more rapid HIV-1 disease progression in dually infected individuals (6,15,29) as well as in vitro data demonstrating that HSV-2 proteins can activate the HIV-1 long terminal repeat, leading to increased HIV-1 replication (10,18,23). Recent trials of acyclovir monotherapy for HSV-2 infection in HSV-2/HIV-1-coinfected individuals showed an approximately 0.33 to 0.5 log 10 decrease in HIV-1 plasma levels, but the overall benefits of this approach remain unclear (24,30,36). One study reported that acyclovir therapy in HSV-2/HIV-1-coinfected patients did not prevent transmission of HIV-1 to uninfected partners (4).…”