Herpes simplex virus type 2 coinfection does not accelerate CD4 count decline in untreated HIV infection

Clin Infect Dis. 2013 Aug;57(3):448-57. doi: 10.1093/cid/cit208. Epub 2013 Apr 9.


Background: Herpes simplex virus type 2 (HSV-2) reactivations are associated with increased HIV load, but whether HSV-2 coinfection accelerates HIV disease is unclear. We compared rates of CD4 count decline according to HSV-2 status in untreated HIV-infected adults.

Methods: HIV-infected patients with a past period of antiretroviral therapy (ART)-untreated follow-up with initial CD4 count of 400-900 cells/mm(3) and no chronic anti-HSV therapy were included. HSV-2 status was determined by HerpeSelect enzyme-linked immunosorbent assay. Rates of CD4 count change were compared by HSV-2 status using mixed linear regression models, and time to the first of ART initiation or CD4 <350 cells/mm(3) using proportional hazards models.

Results: Of 218 patients included, 123 (56.4%) were seropositive for HSV-2 and 161 (73.8%) for HSV-1. In univariate analysis, the difference in the rate of CD4 count change associated with HSV-2 was not statistically significant at +13.6 cells/mm(3)/year (P = .12). Results were similar at -4.5 cells/mm(3)/year (P = .68) after adjustment for sex, HSV type 1, oral and genital herpes symptoms, immigrant status, and the interaction of immigrant status with time. However, HSV-2 seropositivity was associated with a shorter time to the first of ART initiation or CD4 <350 cells/mm(3), with an adjusted hazard ratio of 2.07 (95% confidence interval, 1.28-3.33).

Conclusions: HSV-2 coinfection was not associated with the rate of CD4 count decline during ART-untreated HIV infection, but was associated with an earlier combined endpoint of ART initiation or CD4 <350 cells/mm(3). Attenuating effects of acyclovir on HIV disease progression observed in recent clinical trials may result from direct anti-HIV activity rather than indirect benefits from HSV-2 suppression.

Keywords: CD4 count; HIV; cohort study; disease progression; herpes simplex virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology*
  • Coinfection / immunology*
  • Coinfection / virology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • HIV Infections / complications*
  • HIV Infections / immunology*
  • Herpes Genitalis / immunology*
  • Herpes Genitalis / virology
  • Herpesvirus 2, Human / isolation & purification*
  • Humans
  • Male