Human papillomavirus 16 (HPV16) and HPV52 E6-specific immunity in HIV-infected adults on combination antiretroviral therapy

C Y Leng; H C Low; L L Chua; M L Chong; H Sulaiman; I Azwa; J M Roberts; A Kamarulzaman; R Rajasuriar; Y L Woo

doi:10.1111/hiv.12432

Human papillomavirus 16 (HPV16) and HPV52 E6-specific immunity in HIV-infected adults on combination antiretroviral therapy

HIV Med. 2017 May;18(5):321-331. doi: 10.1111/hiv.12432. Epub 2016 Sep 20.

Authors

C Y Leng¹, H C Low¹, L L Chua², M L Chong¹, H Sulaiman^{1

3}, I Azwa^{1

3}, J M Roberts⁴, A Kamarulzaman^{1

3}, R Rajasuriar^{1

5

6}, Y L Woo^{1

2

7}

Affiliations

¹ Centre of Excellence for Research in AIDS (CERiA), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
² University of Malaya Cancer Research Institute (UMCRI), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
³ Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
⁴ Douglass Hanly Moir Pathology, Macquarie Park, New South Wales, Australia.
⁵ Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
⁶ Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
⁷ Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

PMID: 27649852
DOI: 10.1111/hiv.12432

Abstract

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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%).

Keywords: HIV; cancer; combination antiretroviral therapy; human papillomavirus; human papillomavirus-specific immune responses; immune recovery.

MeSH terms

Adult
Anti-Retroviral Agents / therapeutic use*
Antiretroviral Therapy, Highly Active*
Cross-Sectional Studies
Enzyme-Linked Immunospot Assay
Female
Genotype
HIV Infections / complications*
HIV Infections / drug therapy*
Humans
Interferon-gamma / metabolism
Leukocytes, Mononuclear / immunology
Longitudinal Studies
Male
Middle Aged
Oncogene Proteins, Viral / immunology*
Papillomaviridae / immunology*
Papillomavirus Infections / immunology*

Substances

Anti-Retroviral Agents
Oncogene Proteins, Viral
Interferon-gamma