title: HIV-1 superinfection is associated with an accelerated viral load increase but has a limited impact on disease progression.
abstract: OBJECTIVE
  HIV-1 superinfection occurs frequently in high-risk populations, but its clinical consequences remain poorly characterized. We undertook this study to determine the impact of HIV-1 superinfection on disease progression.
  
  
  METHODS
  In the largest prospective cohort study of superinfection to date, we compared measures of HIV-1 progression in women who acquired superinfection with those who did not. Clinical and laboratory data were collected at quarterly intervals. Linear mixed effects models were used to compare postacute viral load and CD4 T-cell counts over time in singly infected and superinfected women. Cox proportional hazards analysis was used to determine the effect of superinfection on time to clinical progression [CD4 cell count <200 cells/μl, antiretroviral therapy (ART) initiation or death].
  
  
  RESULTS
  Among 144 women, 21 of whom acquired superinfection during follow-up, the rate of viral load increase was higher in superinfected than in singly infected women (P = 0.0008). In adjusted analysis, superinfected women had lower baseline viral load before superinfection (P = 0.05) and a trend for increased viral load at superinfection acquisition (P = 0.09). We also observed a borderline association of superinfection with accelerated CD4 cell count decline (P = 0.06). However, there was no significant difference in time to clinical progression events.
  
  
  CONCLUSIONS
  These data suggest that superinfection is associated with accelerated progression in laboratory measures of HIV-1 disease, but has a limited impact on the occurrence of clinical events. Our observation that superinfected individuals have lower baseline viral load prior to superinfection suggests that there may be host or viral determinants of susceptibility to superinfection.
authors.affiliation: aHuman Biology Division bPublic Health Sciences Division cVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center dDepartment of Global Health eDepartment of Biostatistics fDepartment of Medicine gDepartment of Epidemiology, University of Washington, Seattle, Washington, USA hInstitute of Tropical and Infectious Diseases iDepartment of Medical Microbiology, University of Nairobi, Nairobi jCoast Provincial General Hospital, Mombasa, Kenya.
authors.forename: Keshet
authors.initials: K
authors.lastname: Ronen
authors.forename: Barbra A
authors.initials: BA
authors.lastname: Richardson
authors.forename: Susan M
authors.initials: SM
authors.lastname: Graham
authors.forename: Walter
authors.initials: W
authors.lastname: Jaoko
authors.forename: Kishor
authors.initials: K
authors.lastname: Mandaliya
authors.forename: R Scott
authors.initials: RS
authors.lastname: McClelland
authors.forename: Julie
authors.initials: J
authors.lastname: Overbaugh
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000473:pathology* / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D011446:Prospective Studies; D015163:Superinfection / Q000821:virology*; D019562:Viral Load
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