Our study demonstrated an association of HPV with anal LGSIL/HGSIL, which has been previously reported16–18
; but this is the first report that HIV DNA copy numbers were also associated with LGSIL/HGSIL. The identification of high-risk HPV genotypes with anal LGSIL/HGSIL is consistent with other published data.16,17
We previously described HIV DNA as an important factor in HIV disease progression.5–8
The significance of HIV DNA in disease pathogenesis lies in the fact that monocytes harboring HIV DNA persist in patients on cART in spite of having undetectable HIV RNA levels.5,7,8
The current study was limited to assessing HIV DNA from the pool of cells from anal cytology specimens. Since monocyte subsets may possibly be key players in the disease process, plans to measure HIV DNA from isolated cellular subsets will be considered for the future. The presence of these quiescent viral reservoirs in monocytes suggests that the cells appear to be more resistant to apoptosis and may be important factors in disease progression.19
The significance of the association of high-risk HPV genotypes with HIV DNA and LGSIL/HGSIL remains to be determined. However, the pattern may be similar to reports of HIV-associated disease progression being related to persistence of HIV DNA in circulating cells including monocytes.6,20
Limitations of the study are that we did not look at relationships between duration of cART or duration of HIV suppression and the level of HIV DNA in anal specimens, thus the association of HIV DNA that we describe could possibly be related to these factors in anal intraepithelial neoplasia pathogenesis.
The relationship or interaction of HPV and HIV DNA is unclear, but systemic immune activation occurs in the setting of chronic HIV infection, which may be a factor influencing the risk for coinfection by HIV and HPV.21
Immune activation and/or recruitment of cytokines could create an inflammatory environment perpetuated by continuous chronic infection. Recent data demonstrated higher levels of inflammatory cytokines from activated monocytes with high HIV DNA copies,6
which could establish a persistent inflammatory milieu for HIV and HPV that affects each other synergistically.
Our study was also limited by the number of participants enrolled as well as the cross-sectional design. Study enrollment is continuing as well as follow-up of repeat anal cytology and HPV genotyping and HIV DNA analysis, which will provide additional information on the persistence and importance of both pathogens in LGSIL/HGSIL. The conclusions are also limited because only anal LGSIL/HGSIL was compared to HPV genotypes and HIV DNA with no high-resolution anoscopy (HRA) and anal biopsy results available.22
HRA and anal biopsies were not part of the initial research study nor was the differentiation between LGSIL and HGSIL available from the cytopathology reports; both of these are planned for follow-up studies.
In the current cART era with effective reduction of HIV RNA to undetectable levels, the significance of persistent HIV DNA in cells may become an important factor in improving chronic HIV infection. Our unique findings of anal LGSIL/HGSIL associated with HIV DNA copy numbers and high-grade HPV genotypes highlight the importance of HIV and HPV in the pathogenesis of LGSIL/HGSIL. Future investigations warrant a study of a larger number of patients with follow-up HRA to determine the significance of HIV DNA and HPV in LGSIL/HGSIL pathogenesis.