Risk of HIV infection is high in Chinese MSM, with an annual HIV incidence ranging from 3.41 to 13.7/100 person-years. Tenofovir-based PrEP is effective in preventing HIV transmission in MSM. This study evaluates the epidemiological impact and cost-effectiveness of implementing PrEP in Chinese MSM over the next two decades. A compartmental model for HIV was used to forecast the impact of PrEP on number of infections, deaths, and disability-adjusted life years (DALY) averted. We also provide an estimate of the incremental cost-effectiveness ratio (ICER) and the cost per DALY averted of the intervention. Without PrEP, there will be 1.1-3.0 million new infections and 0.7-2.3 million HIV-related deaths in the next two decades. Moderate PrEP coverage (50%) would prevent 0.17-0.32 million new HIV infections. At Truvada's current price in China, daily oral PrEP costs $46,813-52,008 per DALY averted and is not cost-effective; on-demand Truvada reduces ICER to $25,057-27,838 per DALY averted, marginally cost-effective; daily generic tenofovir-based regimens further reduce ICER to $3675-8963, wholly cost-effective. The cost of daily oral Truvada PrEP regimen would need to be reduced by half to achieve cost-effectiveness and realize the public health good of preventing hundreds of thousands of HIV infections among MSM in China.

Long-acting injectable (LAI) formulations of antiretrovirals (ARVs) as pre-exposure prophylaxis (PrEP) could be an attractive alternative for men who have sex with men (MSM) who are interested in ARV-based biomedical prevention but will not use a daily pill. This study investigated interest in LAI-PrEP in a cohort of MSM in China and characterized how MSM willing to use only injectable PrEP differed from MSM who would use PrEP regardless of modality or not at all. Demographic, behavioral, and risk perception measures were collected and associations investigated. A licensed LAI-PrEP agent would increase the proportion interested in PrEP by 24.5% over oral PrEP alone. Combining interest in oral and injectable PrEP, 78.5% of the sample could be covered if reported interest in PrEP translated into actual uptake. Partnership factors differentiated those who would be willing to use only LAI-PrEP versus any PrEP modality, while higher self-perception of risk was associated with interest in LAI-PrEP versus no PrEP. The addition of a second PrEP modality could yield increased population coverage of PrEP. Social and behavioral research should be undertaken in parallel with clinical development of injectable PrEP agents to identify characteristics of those who are not interested in oral PrEP but would take advantage of ARV-based prevention with the introduction of an injectable product.

The hepatitis B virus (HBV) infects 257 million people worldwide. HBV infection requires establishment and persistence of covalently closed circular (ccc) DNA, a viral episome, in nucleus. Here, we study cccDNA spatial localization in the 3D host genome by using chromosome conformation capture-based sequencing analysis and fluorescence in situ hybridization (FISH). We show that transcriptionally inactive cccDNA is not randomly distributed in host nucleus. Rather, it is preferentially accumulated at specialized areas, including regions close to chromosome 19 (chr.19). Activation of the cccDNA is apparently associated with its re-localization, from a pre-established heterochromatin hub formed by 5 regions of chr.19 to transcriptionally active regions formed by chr.19 and nearby chromosomes including chr. 16, 17, 20, and 22. This active versus inactive positioning at discrete regions of the host genome is primarily controlled by the viral HBx protein and by host factors including the structural maintenance of chromosomes protein 5/6 (SMC5/6) complex.