929 Shedding of Multiple DNA Viruses in the Genital Tract of HIV-infected Women S. Calcaterra1, F. Carletti1, C. Minosse1, S. Zaniratti1, I. Abbate2, G. Cappiello2, D. Serraino1, P. Piselli1, C. Pavia1, M. L. Schaivone2, M. Peroni1, A. Ursitti2, C. Tucci-Nardi2, G. Pontani2, M. R. Capobainchi*1 1Inst Natl per le Malattie Infettive L Spallanzani IRCCS, Rome, Italy and 2S Pertini Hosp, Rome, Italy
Background: Virus shedding through the genital secretions represents an important source of infection. Since reactivation of persistent viral infections in immunosuppressed patients is very common, we investigated the presence of viruses associated with persistent infections in the cervico-vaginal secretions of HIV+ women .
Methods: We studied 182 HIV+, median age 35 yrs, range 18-50, attending the Hospital Gynecology Service in 1999-2000, and an age-matched group of 44 seronegative women (HIV-). DNA extracted from the cytobrush was used in specific PCR reactions for HPV, HSV1/2, CMV, and TTV. HPV+ samples underwent molecular characterization by probe hybridization, RFLP or nucleotide sequencing. In 26 HIV/HCV co-infected women, HCV shedding on cytobrush was detected by RT-PCR; HCV genotyping was performed by InnoLipa; quasispecies analysis was carried out by cloning and sequencing HVR-1 region. Phylogenetic analysis revealed in cervico-vaginal secretion, clusters of sequences distinct from those in blood.
Results: HPV infection was detected in 72 (39.6%) HIV+, 57 by high-middle risk, and 15 by low risk strains. Multiple HPV types were detected in 7 cases. HSV shedding was detected in 50 (27.5%) cases, 26% of which with HSV1 only, 38% HSV2 only, and 36% with both. CMV and TTV were detected in 28% and 19.8% of cases, respectively; HHV8 was detected occasionally (1.1%). Shedding of multiple viruses was observed in 36% HIV+. The most frequent association was HPV with CMV (29.8%), TTV (23.9%), HSV2 (20.9%), and HSV1 (17.9%). In 12.1% of cases, concomitant shedding of > 2 DNA viruses was detected. In the HIV- group, HPV shedding was less frequent (4.5%), and involved HPV56 and 59. Prevalence of CMV and TTV was 6.8% and 11.4%, respectively. Only one case of co-infection (CMV+TTV) was detected. HCV shedding was detected in a high proportion of viremic women (76.5%). By phylogenetic analysis, clusters of sequences distinct from those in blood, were revealed in cervico-vaginal secretion.
Conclusions: Differently from what has been observed in HIV-, multiple shedding of DNA viruses is very common in HIV+. In addition, HCV shedding has been demonstrated here for the first time, although it remained to be established whether shed HCV-RNA corresponds to infectious virion particles. Quasispecies analysis indicates an at least partial compartmentalization of HCV replication in the genital tract of HIV/HCV co-infected women.
