Michael Remington

Persistence of HIV-1 receptor-positive cells after HSV-2 reactivation is a potential mechanism for increased HIV-1 acquisition.

To explore the mechanism by which herpes simplex virus (HSV)-2 infection is related to HIV-1 acquisition, we conducted in situ analysis of the cellular infiltrate from sequential biopsies of HSV-2 lesions from patients on and off antiviral therapy. CD4+ and CD8+ T cells and a mixed population of plasmacytoid and myeloid dendritic cells (DCs), including cells expressing the C-type lectin receptor DC-SIGN, persisted at sites of HSV-2 reactivation for months after healing, even with daily antiviral therapy. The CD4+ T cells that persisted reacted to HSV-2 antigen, were enriched for expression of the chemokine receptor CCR5, and were contiguous to DCs expressing the interleukin-3 receptor CD123 or DC-SIGN. Ex vivo infection with a CCR5-tropic strain of HIV-1 revealed greater concentrations of integrated HIV-1 DNA in cells derived from healed genital lesion biopsies than in cells from control skin biopsies. The persistence and enrichment of HIV receptor–positive inflammatory cells in the genitalia help explain the inability of anti–HSV-2 therapy to reduce HIV acquisition.

Two-Day Regimen of Acyclovir for Treatment of Recurrent Genital Herpes Simplex Virus Type 2 Infection

The standard course of antiviral therapy for recurrent genital herpes requires administration of multiple doses of medication for 5 days. To assess the efficacy of a shorter course of antiviral therapy, patients with recurrent genital herpes simplex virus type 2 (HSV-2) infection were enrolled in a randomized, double-blind, placebo-controlled study of acyclovir (800 mg given by mouth 3 times per day [t.i.d.]) for 2 days. Of 131 people enrolled in the study, 84 (51 women and 33 men) were observed for >/=1 recurrence and 65 were observed for 2 recurrences, for which the patient was administered the same study drug (acyclovir or placebo). Acyclovir therapy (800 mg given by mouth t.i.d. for 2 days) significantly reduced the duration of lesions (median for acyclovir versus placebo, 4 days versus 6 days; P=.001), episode (4 days versus 6 days; P<.001), and viral shedding (25 hours versus 58.5 hours; P=.04), and it increased the proportion of aborted episodes (P=.029). A 2-day course of acyclovir is a convenient alternative for treatment of recurrent genital herpes.

Phase I Dose-Escalation Study of a Monovalent Heat Shock Protein 70-Herpes Simplex Virus Type 2 (HSV-2) Peptide-Based Vaccine Designed To Prime or Boost CD8 T-Cell Responses in HSV-Naïve and HSV-2-Infected Subjects

ABSTRACT This was a phase I study to assess the safety, tolerability, and immunogenicity of escalating doses of AG-702, a noncovalent complex of an HLA A*0201-restricted epitope in the glycoprotein B protein of herpes simplex virus type 2 (gB2) and truncated human constitutive heat shock protein 70. Similar vaccines have been immunogenic in animals. Three injections of 10 to 250 μg were administered intradermally to HLA A*0201-bearing subjects who were either herpes simplex virus type 2 (HSV-2)-infected or HSV uninfected. Sixty-two participants received the vaccine, 60 completed the protocol, and T-cell data were accrued for 56 subjects. The vaccine was safe and well tolerated. New or boosted responses to the HSV-2 CD8 epitope were not detected. Baseline responses to an epitope in virion proteins 13/14 were higher than responses to the gB2 epitope. A heat shock protein vaccine with an HSV-2 peptide appears to be safe at the doses studied in healthy adults with or without HSV infection. Modifications of the dose, adjuvant, route, schedule, or HSV antigen may be required to improve responses.