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