Disulfiram reactivates latent HIV-1 in a Bcl-2-transduced primary CD4+ T cell model without inducing global T cell activation.

Highly active antiretroviral therapy (HAART) can reduce plasma HIV-1 levels to below the detection limit. However, due to the latent reservoir in resting CD4(+) cells, HAART is not curative. Elimination of this reservoir is critical to curing HIV-1 infection. Agents that reactivate latent HIV-1 through nonspecific T cell activation are toxic. Here we demonstrate in a primary CD4(+) T cell model that the FDA-approved drug disulfiram reactivates latent HIV-1 without global T cell activation. The extent to which disulfiram reactivates latent HIV-1 in patient cells is unclear, but the drug alone or in combination may be useful in future eradication strategies.

Improvements in the continuum of HIV care in an inner-city emergency department.

OBJECTIVE: The Johns Hopkins Hospital Emergency Department has served as a window on the HIV epidemic for 25 years, and as a pioneer in emergency department-based screening/linkage-to-care (LTC) programs. We document changes in the burden of HIV and HIV care metrics to the evolving HIV epidemic in inner-city Baltimore. DESIGN/METHODS: We analyzed seven serosurveys conducted on 18 ,144 adult Johns Hopkins Hospital Emergency Department patients between 1987 and 2013 as well as our HIV-screening/LTC program (2007, 2013) for trends in HIV prevalence, cross-sectional annual incidence estimates, undiagnosed HIV, LTC, antiretrovirals treatment, and viral suppression. RESULTS: HIV prevalence in 1987 was 5.2%, peaked at more than 11% from 1992 to 2003 and declined to 5.6% in 2013. Seroprevalence was highest for black men (initial 8.0%, peak 20.0%, last 9.9%) and lowest for white women. Among HIV-positive individuals, proportion of undiagnosed infection was 77% in 1987, 28% in 1992, and 12% by 2013 (P < 0.001). Cross-sectional annual HIV incidence estimates declined from 2.28% in 2001 to 0.16% in 2013. Thirty-day LTC improved from 32% (2007) to 72% (2013). In 2013, 80% of HIV-positive individuals had antiretrovirals ARVs detected in sera, markedly increased from 2007 (27%) (P < 0.001). Proportion of HIV-positive individuals with viral suppression (<400 copies/ml) increased from 23% (2001) to 59% (2013) (P < 0.001). CONCLUSION: Emergency department-based HIV testing has evolved from describing the local epidemic to a strategic interventional role, serving as a model for early HIV detection and LTC. Our contribution to community-based HIV-screening and LTC program parallels declines in undiagnosed HIV infection and incidence, and increases in antiretroviral use with associated viral suppression in the community.