title: Human papillomavirus 16 (HPV16) and HPV52 E6-specific immunity in HIV-infected adults on combination antiretroviral therapy.
abstract: Human papillomavirus (HPV)-associated cancers disproportionately affect those infected with HIV despite effective combination antiretroviral therapy (cART). The primary aim of this study was to quantify HPV16 and HPV52 E6-specific interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) T-cell responses, a correlate of protective immunity, in the first year following cART initiation and subsequently in those patients with suboptimal (sIR) and optimal (oIR) immune reconstitution.
  
  
  
  Ninety-four HIV-infected patients were recruited to the study; a longitudinal cohort of patients recruited just prior to commencing cART and followed up for 48 weeks (n = 27), and a cross-sectional cohort (n = 67) consisting of patients with sIR (CD4 T-cell count < 350 cells/μL) and oIR (CD4 T-cell count > 500 cells/μL) after a minimum of 2 years on cART. Controls (n = 29) consisted of HIV-negative individuals. IFN-γ ELISPOT responses against HPV16 and HPV52 E6 were correlated to clinical characteristics, anal and oral HPV carriage, T-cell maturational subsets, markers of activation, senescence and T-regulatory cells.
  
  
  
  HPV16 and HPV52 E6-specific T-cell responses were detected in only one of 27 patients (3.7%) during the initial phase of immune recovery. After at least 2 years of cART, those who achieved oIR had significantly higher E6-specific responses (9 of 34; 26.5%) compared with those with sIR (2 of 32; 6.3%) (P = 0.029). Apart from higher CD4 T-cell counts and lower CD4 T-cell activation, no other immunological correlates were associated with the detection of HPV16 and HPV52 E6-specific responses.
  
  
  
  HPV16 and HPV52 E6-specific IFN-γ T-cell responses, a correlate of protective immunity, were detected more frequently among HIV-infected patients who achieved optimal immune recovery on cART (26.5%) compared with those with suboptimal recovery (6.3%).
authors.affiliation: Centre of Excellence for Research in AIDS (CERiA), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: C Y
authors.initials: CY
authors.lastname: Leng
authors.affiliation: Centre of Excellence for Research in AIDS (CERiA), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: H C
authors.initials: HC
authors.lastname: Low
authors.affiliation: University of Malaya Cancer Research Institute (UMCRI), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: L L
authors.initials: LL
authors.lastname: Chua
authors.affiliation: Centre of Excellence for Research in AIDS (CERiA), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: M L
authors.initials: ML
authors.lastname: Chong
authors.affiliation: Centre of Excellence for Research in AIDS (CERiA), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.|Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: H
authors.initials: H
authors.lastname: Sulaiman
authors.affiliation: Centre of Excellence for Research in AIDS (CERiA), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.|Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: I
authors.initials: I
authors.lastname: Azwa
authors.affiliation: Douglass Hanly Moir Pathology, Macquarie Park, New South Wales, Australia.
authors.forename: J M
authors.initials: JM
authors.lastname: Roberts
authors.affiliation: Centre of Excellence for Research in AIDS (CERiA), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.|Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: A
authors.initials: A
authors.lastname: Kamarulzaman
authors.affiliation: Centre of Excellence for Research in AIDS (CERiA), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.|Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.|Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Rajasuriar
authors.affiliation: Centre of Excellence for Research in AIDS (CERiA), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.|University of Malaya Cancer Research Institute (UMCRI), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.|Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Y L
authors.initials: YL
authors.lastname: Woo
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D003430:Cross-Sectional Studies; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology*
chemical_list: D044966:Anti-Retroviral Agents; D009856:Oncogene Proteins, Viral; D007371:Interferon-gamma
keywords: 
  HIV
  ; cancer; combination antiretroviral therapy; human papillomavirus; human papillomavirus-specific immune responses; immune recovery