This study aims to use a social media mini-application-enabled intervention to successfully promote the initiation and persistence of pre-exposure prophylaxis (PrEP) among at-risk people 18 years and above (including men who have sex with men (MSM), transgender women, sex workers, and other key populations) in Wuhan and Guangzhou, China.

The China National Medical Products Administration (NMPA) recently approved TDF/FTC (Truvada) for PrEP making it the first HIV prevention medicine available in China. While this is a significant step in addressing the country's rising rates of new HIV diagnoses, implementation and scale-up of this resource will be the next challenge.

3200 at-risk adults will be engaged by word of mouth and social media. Individuals will be asked to complete a survey of risk and PrEP interest, to download the study mobile mini-application onto their cell phone, and will be offered an HIV and syphilis screen. One thousand two hundred of these subjects who are eligible and willing to start PrEP will be enrolled in the study. The first 700 participants enrolled in each site will complete an additional four-phased, WeChat-based adherence intervention through a stepped-wedge design, with each cluster starting at three-month intervals.

Enrolled participants will undergo baseline laboratory testing before brought to a collaborating hospital where an established physician will provide TDF/FTC and arrange follow-up. Rural and out-of-town enrollees may undergo testing at an outside lab. All subjects will be encouraged to keep using the mini-application for receiving constant health education and counseling support on HIV/STI prevention, PrEP initiation and/or adherence management. Subjects on PrEP will be contacted every three months over the course of two years to answer questions on adherence including number of missed pills and/or sex events not covered by on-demand PrEP, adverse effect, and utilization of the mini-application. 120 enrollees in Guangdong will additionally participate in a pill count adherence sub study that counts the number of unused pills at each clinical follow-up

A PrEP messaging open contest will be organized to assess the best images and videos to enhance PrEP adherence among those who start PrEP. New content will be developed using crowdsourcing and introduced into the mini-application at staggered times. The effect of this content will be evaluated through a stepped wedge approach nested within this single arm study.

Inclusion Criteria:

• Age 18+
• Engaged in at-risk sex. At risk sex is defined as sex with >1 partner in the past 90 days, inconsistent condom use with vaginal or anal sex, ongoing sexual relationship with an HIV-positive partner, participation in commercial sex work, or any bacterial STI diagnosed or reported in the past 6 months.

Exclusion Criteria:

• History renal dysfunction
• Chronic hepatitis B (HBV) infection
• HIV infection
• Indication for HIV post-exposure prophylaxis
• Signs and symptoms consistent with acute HIV infection
• Under the age range of 18