title: Roles of clinical and subclinical reactivated herpes simplex virus type 2 infection and human immunodeficiency virus type 1 (HIV-1)-induced immunosuppression on genital and plasma HIV-1 levels.
abstract: BACKGROUND
  Few longitudinal studies have described the interactions between reactivation of herpes simplex virus type 2 (HSV-2) infection (hereafter, "HSV-2 reactivation") and genital and systemic replication of human immunodeficiency virus type 1 (HIV-1).
  
  
  METHODS
  Women in Burkina Faso who were seropositive for both HIV-1 and HSV-2 were enrolled in a randomized placebo-controlled trial of therapy to suppress reactivation of HSV-2 infection (hereafter, "HSV suppressive therapy"). During the baseline phase, 6 enriched cervicovaginal lavage specimens were obtained over 12 weeks to detect and quantify the HIV-1 RNA and HSV-2 DNA loads.
  
  
  RESULTS
  Women with genital ulcer disease (GUD) detected at least once were more likely than women in whom GUD was not detected (risk ratio [RR], 1.23; 95% confidence interval [CI], 1.09-1.37) to have genital HIV-1 RNA detected during >or=1 visit. Similarly, women with genital HSV-2 DNA detected during >or=1 clinic visit were more likely than women in whom genital HSV-2 DNA was not detected (RR, 1.17; 95% CI, 1.01-1.34) to have genital HIV-1 RNA detected at least once. In addition, the mean genital HIV-1 RNA loads for women with GUD detected during >or=1 visit and women with HSV-2 genital shedding detected during >or=1 visit were greater than that for women in whom genital HSV-2 DNA or GUD was never detected. The plasma HIV-1 RNA load was increased among women for whom >or=1 visit revealed GUD (+0.25 log(10) copies/mL; 95% CI, -0.05-0.55) or genital HSV-2 DNA (+0.40 log(10) copies/mL; 95% CI, 0.15-0.66), compared with women who did not experience GUD or HSV-2 genital shedding, respectively. The association of HSV-2 reactivations on HIV-1 replication tended to be stronger in patients with a higher CD4(+) cell count (i.e., >500 cells/microL). The contribution of HSV-2 to HIV-1 replication among women with CD4(+) cell count of <or=500 cells/microL was reduced because almost all experienced HIV-1 genital shedding.
  
  
  CONCLUSIONS
  Both clinical and subclinical HSV-2 reactivations play a role in increasing the rate of HIV-1 replication. HSV suppressive therapy is a promising tool for HIV control. Initiation of such therapy when the CD4(+) cell count is >500 cells/microL deserves further investigation.
  
  
  BACKGROUND
  The ANRS 1285 Study is registered with the National Institutes of Health (registration number NCT00158509).
authors.affiliation: Centre Muraz, Burkina Faso. n_nagot@hotmail.com
authors.forename: N
authors.initials: N
authors.lastname: Nagot
authors.forename: A
authors.initials: A
authors.lastname: Ouedraogo
authors.forename: I
authors.initials: I
authors.lastname: Konate
authors.forename: H A
authors.initials: HA
authors.lastname: Weiss
authors.forename: V
authors.initials: V
authors.lastname: Foulongne
authors.forename: M C
authors.initials: MC
authors.lastname: Defer
authors.forename: A
authors.initials: A
authors.lastname: Sanon
authors.forename: P
authors.initials: P
authors.lastname: Becquart
authors.forename: M
authors.initials: M
authors.lastname: Segondy
authors.forename: A
authors.initials: A
authors.lastname: Sawadogo
authors.forename: P
authors.initials: P
authors.lastname: Van de Perre
authors.forename: P
authors.initials: P
authors.lastname: Mayaud
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000276:immunology*; D002050:Burkina Faso; D005260:Female; D015497:HIV-1 / Q000302:isolation & purification*; D006558:Herpes Genitalis / Q000150:complications* / Q000517:prevention & control*; D006561:Herpes Simplex / Q000150:complications* / Q000517:prevention & control*; D018258:Herpesvirus 2, Human / Q000302:isolation & purification*; D006801:Humans; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load; D014775:Virus Activation / Q000502:physiology*
chemical_list: D012367:RNA, Viral