title: Twelve-Month Antiretroviral Therapy Suppresses Plasma and Genital Viral Loads but Fails to Alter Genital Levels of Cytokines, in a Cohort of HIV-Infected Rwandan Women.
abstract: BACKGROUND
  Genital viral load (GVL) is the main determinant of sexual transmission of human immune-deficiency virus (HIV). The effect of antiretroviral therapy (ART) on local cervico-vaginal immunological factors associated with GVL is poorly described. We aimed to identify the risk factors of detectable GVL, and the impact of ART on HIV genital shedding and its correlates in a cohort of HIV-infected women, attending HIV care in Kigali, Rwanda.
  
  
  METHODS
  All participants were evaluated for GVL, plasma viral load (PVL), CD4 count, various sexually-transmitted infections (STIs) at baseline and at month 12. Genital concentration of 19 cytokines and mRNA expression of APOBEC3G and BST2, two host HIV restriction factors, were evaluated at baseline in all participants. Cytokine levels were re-assessed at month 12 only in participants eligible for ART at baseline. Risk factors of GVL ≥ 40 copies/mL at baseline and month 12 were assessed using logistic regression. Effect of 12-month ART on various local and systemic immunological parameters was examined using a paired t-test and McNemar as appropriate.
  
  
  RESULTS
  96 of the 247 women enrolled in the study were eligible for ART. After 12 months of ART, PVL and GVL decreased to undetectable level in respectively 74 and 88% of treated participants. ART did not affect cytokine levels. HIV genital shedding occurred only when PVL was detectable. At baseline, GVL was independently associated with IL-1β after controlling for PVL, age and N. gonorrhea infection (95% CI 1.32-2.15) and at month 12 with MIP-1β (95% CI 0.96-21.32) after controlling for baseline GVL, PVL and month 12 IL-8.
  
  
  CONCLUSIONS
  Suppressive ART does not necessarily reduce genital level of immune activation. Minimizing all conditions favoring genital inflammation, including active detection and treatment of STIs, might reduce the risk of HIV transmission as supplement to the provision of potent ART.
authors.affiliation: Amsterdam Institute of Global Health and Development (AIGHD), Department of Global Health of the Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Pascale
authors.initials: P
authors.lastname: Ondoa
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Raju
authors.initials: R
authors.lastname: Gautam
authors.affiliation: INTERACT Program, Kigali, Rwanda; National Reference Laboratory, Kigali, Rwanda.
authors.forename: John
authors.initials: J
authors.lastname: Rusine
authors.affiliation: Department of Respiratory Medicine of the Academic Medical Center, Amsterdam, The Netherlands; Department of Experimental Immunology of the Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Rene
authors.initials: R
authors.lastname: Lutter
authors.affiliation: Department of Medical Microbiology of the Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Jurriaans
authors.affiliation: Department of Experimental Immunology of the Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Neeltje
authors.initials: N
authors.lastname: Kootstra
authors.affiliation: Project San Francisco, Kigali, Rwanda.
authors.forename: Etienne
authors.initials: E
authors.lastname: Karita
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Janneke
authors.initials: J
authors.lastname: van de Wijgert
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D000998:Antiviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count / Q000379:methods; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D010949:Plasma / Q000821:virology*; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D012307:Risk Factors; D012432:Rwanda; D014621:Vagina / Q000821:virology*; D019562:Viral Load / Q000187:drug effects*; D017201:Virus Shedding / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D012333:RNA, Messenger; D012367:RNA, Viral