Risk Factors and Incidence of Syphilis in Human Immunodeficiency Virus (HIV)-Infected Persons: The HIV Outpatient Study, 1999-2015.

Background: Since 2000, the incidence of syphilis has been increasing, especially among gay, bisexual, and other men who have sex with men (MSM) in the United States. We assessed temporal trends and associated risk factors for newly diagnosed syphilis infections among human immunodeficiency virus (HIV)-infected patients during a 16-year period. Methods: We analyzed data from the HIV Outpatient Study (HOPS) cohort participants at 10 US HIV clinics during 1999-2015. New syphilis cases were defined based on laboratory parameters and clinical diagnoses. We performed Cox proportional hazards regression analyses of sociodemographic, clinical, and behavioral risk factors for new syphilis infections. Results: We studied 6888 HIV-infected participants; 641 had 1 or more new syphilis diagnoses during a median follow-up of 5.2 years. Most participants were male (78%), aged 31-50 years, and 57% were MSM. The overall incidence was 1.8 (95% confidence interval [CI], 1.6-1.9) per 100 person-years (PY) and it increased from 0.4 (95% CI, .2-.8) to 2.2 (95% CI, 1.4-3.5) per 100 PY during 1999-2015. In multivariable analyses adjusting for calendar year, risk factors for syphilis included age 18-30 years (hazard ratio [HR], 1.3 [95% CI, 1.1-1.6]) vs 31-40 years, being MSM (HR, 3.1 [95% CI, 2.4-4.1]) vs heterosexual male, and being non-Hispanic black (HR, 1.6 [95% CI, 1.4-1.9]) vs non-Hispanic white. Conclusions: The increases in the syphilis incidence rate through 2015 reflect ongoing sexual risk and highlight the need for enhanced prevention interventions among HIV-infected patients in care.

In vitro antiretroviral activity and in vivo toxicity of the potential topical microbicide copper phthalocyanine sulfate.

BACKGROUND: Copper has antimicrobial properties and has been studied for its activity against viruses, including HIV. Copper complexed within a phthalocyanine ring, forming copper (II) phthalocyanine sulfate (CuPcS), may have a role in microbicide development when used intravaginally. METHODS: CuPcS toxicity was tested against cervical epithelial cells, TZM-BL cells, peripheral blood mononuclear cells (PBMC), and cervical explant tissues using cell viability assays. In vivo toxicity was assessed following intravaginal administration of CuPcS in female BALB/C mice and measured using a standardized histology grading system on reproductive tract tissues. Efficacy studies for preventing infection with HIV in the presence of various non-toxic concentrations of CuPcS were carried out in TZM-BL, PBMC, and cervical explant cultures using HIV-1BAL and various pseudovirus subtypes. Non-linear regression was applied to the data to determine the EC50/90 and CC50/90. RESULTS: CuPcS demonstrated inhibition of HIV infection in PBMCs at concentrations that were non-toxic in cervical epithelial cells and PBMCs with EC50 values of approximately 50 µg/mL. Reproductive tract tissue analysis revealed no toxicity at 100 mg/mL. Human cervical explant tissues challenged with HIV in the presence of CuPcS also revealed a dose-response effect at preventing HIV infection at non-toxic concentrations with an EC50 value of 65 µg/mL. CONCLUSION: These results suggest that CuPcS may be useful as a topical microbicide in concentrations that can be achieved in the female genital tract.