Caring for the whole person: transgender-competent HIV pre-exposure prophylaxis as part of integrated primary healthcare services in Vietnam.

INTRODUCTION: Although HIV prevalence among transgender women who have sex with men in Vietnam is high (16-18%), uptake of pre-exposure prophylaxis (PrEP) is low compared to other populations. When PrEP was initiated in 2017, gender-affirming healthcare was largely unavailable. Lack of access to competent, stigma-free healthcare is a well-documented barrier to transgender women's uptake of PrEP and primary healthcare (PHC). We aimed to demonstrate the utility of a PrEP quality improvement intervention in pinpointing and addressing barriers to PrEP use among transgender women in Vietnam. METHODS: We applied a real-world participatory continuous quality improvement (CQI) and Plan-Do-Study-Act (PDSA) methodology to ascertain barriers to PrEP uptake among transgender women and determine priority actions for quality improvement. A CQI team representing transgender women leaders, key population (KP)-clinic staff, public-sector HIV managers and project staff applied PDSA to test solutions to identified barriers that addressed the primary quality improvement outcome of the monthly change in PrEP uptake among transgender women and secondary outcomes, including month-3 PrEP continuation, the impact of offering PHC on PrEP uptake and unmet PrEP need. We utilized routine programmatic data and a descriptive cross-sectional study enrolling 124 transgender women to measure these outcomes from October 2018 to September 2021. RESULTS: Five key barriers to PrEP uptake among transgender women were identified and corresponding solutions were put in place: (1) offering gender-affirming care training to KP-clinics and community-based organizations; (2) integrating gender-affirming services into 10 KP-clinics; (3) offering PHC through five one-stop shop (OSS) clinics; (4) implementing a campaign addressing concerns related to hormone use and PrEP interactions; and (5) developing national HIV and transgender healthcare guidelines. New PrEP enrolment and month-3 PrEP continuation increased significantly among transgender women. Of 235 transgender women who initially sought healthcare other than PrEP at OSS clinics, 26.4% subsequently enrolled in PrEP. About one-third of transgender women reported unmet PrEP need, while two-thirds indicated an interest in long-acting cabotegravir. CONCLUSIONS: Offering gender-competent, integrated PHC can increase PrEP enrolment and continuation, and can be an entry-point for PrEP among those seeking care within PHC clinics. More work is needed to expand access to transgender women-led and -competent healthcare in Vietnam.

Prepped for PrEP? Acceptability, continuation and adherence among men who have sex with men and transgender women enrolled as part of Vietnam's first pre-exposure prophylaxis program.

Background HIV prevalence among men who have sex with men (MSM) and transgender women (TGW) in Vietnam is high, whereas coverage of effective HIV prevention services has been inadequate. Studies have measured MSM and TGW demand for pre-exposure prophylaxis (PrEP) services, which led to the design of the first ever PrEP program in Vietnam, Prepped for PrEP (P4P). METHODS: In March 2017, PrEP services were offered in Ho Chi Minh City as part of the P4P demonstration project, enabling same-day enrolment in three key population (KP)-led clinics and four public clinics. P4P aimed to assess acceptability and feasibility of PrEP services through calculating the rate of PrEP enrolment over time, and quarterly measures of continuation and adherence over an 18-month period. RESULTS: A total of 1069 MSM and 62 TGW were enrolled in P4P. Average monthly PrEP enrolment among MSM increased five-fold from the first 3 months (March-June 2017) to the last 3 months of active enrolment (March-June 2018), whereas for TGW, no increased trend in PrEP enrolment per quarter was seen. Self-reported PrEP adherence was >90% at all time points among MSM, but varied from 11.1% to 88.9% among TGW. PrEP continuation was calculated at months 3, 6, 9, 12, 15 and 18. For MSM, it was 88.7% at month 3, 68.8% at month 12 and 46.6% at month 18, whereas for TGW, it was 87.1%, 54.8% and 52.8%, respectively. Multivariable regression identified that MSM with lower-than-average income (adjusted odds ratio (aOR) 2.38 (95% confidence interval (CI): 1.59-3.54), P = 0.000), aged >30 years (aOR 2.03 (95% CI: 1.30-3.40), P = 0.007) and with an increasing number of sex partners (aOR: 1.06 (1.01-1.11), P = 0.011) had greater odds of remaining on PrEP. For TGW, being aged >30 years was associated with continuing on PrEP (aOR 5.62 (95% CI: 1.05-29.9), P = 0.043). CONCLUSIONS: We found PrEP to be highly acceptable among MSM and moderately acceptable among TGW. Continuation rates were relatively high for the first roll-out of PrEP; however, those aged ≤30 years were much more likely to discontinue services. Scaling-up PrEP through differentiated and community-led and engaged PrEP service delivery will be key to effectively increase access and uptake over the next 5 years.

Metformin reverses prostate cancer resistance to enzalutamide by targeting TGF-ß1/STAT3 axis-regulated EMT.

Although the newly developed second-generation anti-androgen drug enzalutamide can repress prostate cancer progression significantly, it only extends the survival of prostate cancer patients by 4-6 months mainly due to the occurrence of enzalutamide resistance. Most of the previous studies on AR antagonist resistance have been focused on AR signaling. Therefore, the non-AR pathways on enzalutamide resistance remain largely unknown. By using C4-2, CWR22Rv1 and LNCaP cell lines, as well as mice bearing CWR22Rv1 xenografts treated with either enzalutamide or metformin alone or in combination, we demonstrated that metformin is capable of reversing enzalutamide resistance and restores sensitivity of CWR22Rv1 xenografts to enzalutamide. We showed that metformin alleviated resistance to enzalutamide by inhibiting EMT. Furthermore, based on the effect of metformin on the activation of STAT3 and expression of TGF-ß1, we propose that metformin exerts its effects by targeting the TGF-ß1/STAT3 axis. These findings suggest that combination of metformin with enzalutamide could be a more efficacious therapeutic strategy for the treatment of castration-resistant prostate cancer.