Aspects of human papillomavirus (HPV) disease in human immunodeficiency virus (HIV) infection

Abstract

Cutaneous and genital human papillomavirus (HPV) infection in HIV patients, on suppressive anti-retroviral therapy (ART), poses under-investigated clinical challenges. HPV in HIV may represent a form of immune reconstitution associated disease (IRAD). HPV disease and IRADs have been separately correlated with human leucocyte antigen (HLA) genotype. HLA might also influence HPV in HIV. Comprehensive HPV typing of persistent warts obtained from HIV infected and healthy subjects was performed. Cutaneous HPV types were detected using nested PCR/sequencing and newly developed (Luminex based) HSLPCR/ MPG; genital and beta HPV types were identified using a reverse hybridisation line probe assay. Real time PCR was employed to determine HPV DNA viral loads. HLA alleles were defined in HIV infected and healthy patients by Luminex-based molecular typing using DNA derived from blood. The HPV profile of cutaneous and genital HIV warts differs significantly from warts from healthy individuals. In HIV, HPV 7 has been confirmed to be an important HPV type in cutaneous warts (p=0.001). In genital warts in HIV, HPV 11 is the predominant HPV type (p=0.15) and HPV 6 is less common (p=0.002), contrasting with the usual finding that HPV 6 is the principal type in the general population. Cross-over of HPV types between cutaneous and genital sites suggests that HPV tropism is less important than previously thought. An excess of beta HPV types, predominantly as mixed infections, is seen in cutaneous warts in HIV (p<0.0005). The HLA class I allele group HLA-B*44 (as the allele HLA-B*44:02 and the haplotype HLA-B*44, -C*05) has been identified more frequently in HIV than in controls (p=0.004, allele group; p=0.0006, allele; p=0.001, haplotype). The class II allele HLA-DQB1*06 may also be of interest (p=0.03). However, the differences are reduced after correction for multiple testing. Further work is required to ascertain if these HPV types and alleles are of importance.