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Although the transport of human immunodeficiency virus type 1 (HIV-1) through the epithelium is critical for HIV-1 colonization, the mechanisms controlling this process remain obscure. In the present study, we investigated the transcellular migration of HIV-1 as a cell-free virus through primary genital epithelial cells (PGECs). The absence of CD4 on PGECs implicates an unusual entry pathway for HIV-1. We found that syndecans are abundantly expressed on PGECs and promote the initial attachment and subsequent entry of HIV-1 through PGECs. Although CXCR4 and CCR5 do not contribute to HIV-1 attachment, they enhance viral entry and transcytosis through PGECs. Importantly, HIV-1 exploits both syndecans and chemokine receptors to ensure successful cell-free transport through the genital epithelium. HIV-1-syndecan interactions rely on specific residues in the V3 of gp120 and specific sulfations within syndecans. We found no obvious correlation between coreceptor usage and the capacity of the virus to transcytose. Since viruses isolated after sexual transmission are mainly R5 viruses, this suggests that the properties conferring virus replication after transmission are distinct from those conferring cell-free virus transcytosis through the genital epithelium. Although we found that cell-free HIV-1 crosses PGECs as infectious particles, the efficiency of transcytosis is extremely poor (less than 0.02% of the initial inoculum). This demonstrates that the genital epithelium serves as a major barrier against HIV-1. Although one cannot exclude the possibility that limited passage of cell-free HIV-1 transcytosis through an intact genital epithelium occurs in vivo, it is likely that the establishment of infection via cell-free HIV-1 transmigration is a rare event.

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Introduction It has been reported in an open-label study that the combination of alkalinized lidocaine and heparin can immediately relieve the symptoms of urinary urgency, frequency, and pain associated with interstitial cystitis (IC). This combination has also been reported to relieve pain associated with sex in patients with IC. Aim The aim of this study was to corroborate these findings in a multicenter setting. Methods The study design was a multicenter prospective, double-blind, crossover, placebo-controlled trial. Each participant met all of the clinical National Institute of Diabetes and Digestive and Kidney Diseases criteria (excluding cystoscopy) for IC. Each patient received drug and control, in random order, within 48 hours of enrolling in the study. Main Outcome Measures The primary outcome measure was percent change in pain score (11-point analog pain scale) 12 hours after receiving the drug or control. Secondary measures were the global assessment response (GAR) of symptoms and 12-hour average urgency reduction determined from 11-point urgency scales. Results Eighteen (18) patients completed the trial. The average reduction of pain over 12 hours was 21% for control and 42% for active drug (P = 0.0363). GAR was 13% for control and 50% for drug (P = 0.0137). Average urgency reduction was 13% for control and 35% for drug (P = 0.0328). Conclusions The combination of alkalinized lidocaine and heparin provides up to 12 hours of relief from urgency and pain associated with IC. This combination provides significant immediate relief of symptoms for patients with IC.