After thirty-two years since the first domestic outbreak of human immunodeficiency virus (HIV)/ acquired immune deficiency syndrome (AIDS) among injection drug users (IDUs) and almost two decades of comprehensive response efforts by the Chinese government, HIV/AIDS remains a major public health problem. The increasing burden of HIV/AIDS and comorbidities, the emergence of new HIV subtypes and/or circulating recombinant forms and drug mutations, the changing transmission networks, and the urgency of immediate antiretroviral therapy initiation upon an HIV diagnosis are increasingly challenging and altogether likely to have significant impact on the HIV epidemic in China. Upon the call for the global AIDS response to end AIDS by 2030, China needs to develop an innovative and pragmatic roadmap to address these challenges. This review is intended to provide a succinct overview of what China has done in efforts to achieve the global goal of ending AIDS by 2030 and the recently proposed “95-95-95-95” target (95% combination prevention, 95% detection, 95% treatment, 95% viral suppression), and to summarize the most recent progresses in the epidemiological research of HIV/AIDS in China with the aim of providing insights on the next generation of HIV control and prevention approaches and to shed light on upgrading the national strategy to end AIDS in this country.

Research Progress in the Epidemiology of HIV/AIDS in China

INTRODUCTION: The COVID-19 pandemic is impacting HIV care globally, with gaps in HIV treatment expected to increase HIV transmission and HIV-related mortality. We estimated how COVID-19-related disruptions could impact HIV transmission and mortality among men who have sex with men (MSM) in four cities in China, over a one- and five-year time horizon. METHODS: Regional data from China indicated that the number of MSM undergoing facility-based HIV testing reduced by 59% during the COVID-19 pandemic, alongside reductions in ART initiation (34%), numbers of all sexual partners (62%) and consistency of condom use (25%), but initial data indicated no change in viral suppression. A mathematical model of HIV transmission/treatment among MSM was used to estimate the impact of disruptions on HIV infections/HIV-related deaths. Disruption scenarios were assessed for their individual and combined impact over one and five years for 3/4/6-month disruption periods, starting from 1 January 2020. RESULTS: Our model predicted new HIV infections and HIV-related deaths would be increased most by disruptions to viral suppression, with 25% reductions (25% virally suppressed MSM stop taking ART) for a three-month period increasing HIV infections by 5% to 14% over one year and deaths by 7% to 12%. Observed reductions in condom use increased HIV infections by 5% to 14% but had minimal impact (<1%) on deaths. Smaller impacts on infections and deaths (<3%) were seen for disruptions to facility HIV testing and ART initiation, but reduced partner numbers resulted in 11% to 23% fewer infections and 0.4% to 1.0% fewer deaths. Longer disruption periods (4/6 months) amplified the impact of disruption scenarios. When realistic disruptions were modelled simultaneously, an overall decrease in new HIV infections occurred over one year (3% to 17%), but not for five years (1% increase to 4% decrease), whereas deaths mostly increased over one year (1% to 2%) and five years (1.2 increase to 0.3 decrease). CONCLUSIONS: The overall impact of COVID-19 on new HIV infections and HIV-related deaths is dependent on the nature, scale and length of the various disruptions. Resources should be directed to ensuring levels of viral suppression and condom use are maintained to mitigate any adverse effects of COVID-19-related disruption on HIV transmission and control among MSM in China.

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The impact of disruptions due to COVID-19 on HIV transmission and control among men who have sex with men in China.

Human immunodeficiency virus (HIV) testing is a crucial strategy for HIV prevention. HIV testing rates remain low among men who have sex with men (MSM) in China. Digital network-based secondary distribution is considered as an effective model to enhance HIV self-testing (HIVST) among key populations. Digital platforms provide opportunities for testers to apply for HIVST kits by themselves, and secondary distribution allows them to apply for multiple kits to deliver to their sexual partners or members within their social network. We describe a three-arm randomized controlled trial to examine the effect of monetary incentives and peer referral in promoting digital network-based secondary distribution of HIVST among MSM in China. Three hundred MSM in China will be enrolled through a digital platform for data collection. The eligibility criteria include being biological male, 18 years of age or over, ever having had sex with another man, being able to apply for kits via the online platform, and being willing to provide personal telephone number for follow-up. Eligible participants will be randomly allocated into one of the three arms: standard secondary distribution arm, secondary distribution with monetary incentives arm, and secondary distribution with monetary incentives plus peer referral arm. Participants (defined as “index”) will distribute actual HIV self-test kits to members within their social network (defined as “alter”) or share referral links to encourage alters to apply HIV self-test kits by themselves. All index participants will be requested to complete a baseline survey and a 3-month follow-up survey. Both indexes and alters will complete a survey upon returning the results by taking a photo of the used kits with the unique identification number. HIV testing rates remain suboptimal among MSM in China. Innovative interventions are needed to further expand the uptake of HIV testing among key populations. The findings of the trial can provide scientific evidence and experience on promoting secondary distribution of HIVST to reach key populations who have not yet been covered by existing testing services. The study was registered in the Chinese Clinical Trial Registry (ChiCTR1900025433) on 26, August 2019, http://www.chictr.org.cn/showproj.aspx?proj=42001. Prospectively registered.

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Monetary incentives and peer referral in promoting digital network-based secondary distribution of HIV self-testing among men who have sex with men in China: study protocol for a three-arm randomized controlled trial.

China's national guidelines call for increasing HIV pre-exposure prophylaxis (PrEP) use to reverse the epidemic in populations at highest risk. However, few data exist on PrEP awareness and willingness among trans women in China. Our research aim was to fill this data gap through a cross-sectional survey among trans women in Nanjing and Suzhou cities of Jiangsu province. Respondent-driven sampling (RDS) was used to recruit participants to gauge their awareness of and willingness to use PrEP. Logistic regression analysis was used to characterize associations with awareness of PrEP and willingness to use PrEP. Of 222 HIV-negative/unknown serostatus trans women, 33.3% were aware of PrEP and 49.1% were willing to use PrEP. PrEP awareness was associated with a university degree or above (adjusted odds ratio [AOR] 2.77, 95% CI 1.31-5.89) and not using alcohol with sex (AOR 2.02, 95% CI 1.00-4.09). Willingness to use PrEP was higher among trans women with one (AOR 3.56, 95% CI 1.68-7.54) or multiple sexual partners (AOR 2.53, 95% CI 1.24-5.15) compared to those with no partners. This study witnessed low awareness of PrEP, yet substantial willingness to use PrEP. Implementation research to identify ways to promote, scale up access, and assess effectiveness of PrEP for trans women is urgently needed in China.

Awareness and Willingness to use HIV Pre-exposure Prophylaxis (PrEP) Among Trans Women in China: A Community-Based Survey.

This study aimed to determine the change in mental health (depression and anxiety) among HIV-positive gay and bisexual men (GBM) one year after diagnosis and the disparities in trajectories of mental health between them. The potential factors contributing to the disparities were also investigated. This was a one-year follow-up study focusing on the mental health of newly diagnosed HIV-positive individuals. Participants rated their depression, anxiety, stress, and social support levels at baseline and one year later. Information on the utilization of mental healthcare and the initiation of antiretroviral therapy (ART) after diagnosis was collected at one-year follow-up. A total of 171 and 87 HIV-positive gay and bisexual men, respectively, completed two-time points surveys in this study. The depressive and anxiety symptoms experienced by HIV-positive GBM improvement one year after diagnosis. These improvements tended to be smaller in gay participants. Other factors including mental health care utilization and ART status during the one-year follow-up period, changes in social stress scores and objective social support scores were also associated with the changes in depression and anxiety, and all these factors, except for change in objective support, were found to be statistically different between HIV-positive GBM. Special attention should be given to the mental health of HIV-positive gay men. Promoting HIV-positive gay men to assess to mental health services and ART may be important for these populations to improve mental health. Enhancing social support and reducing stress levels may also be necessary for the vulnerable HIV-positive sexual minority groups.

https://www.mdpi.com/1660-4601/17/10/3414/pdf

The Disparities in Mental Health Between Gay and Bisexual Men Following Positive HIV Diagnosis in China: A One-Year Follow-Up Study

The prevalence of HIV among men who have sex with men (MSM) has become a significant public health challenge. The aim was to comprehensively estimate the national prevalence of HIV among MSM and its time trends through a large-scale systematic analysis. Systematic search of Cochrane Library, PubMed, EMBASE, CNKI, VIP, and Wanfang Data databases without language restriction for studies on the prevalence of HIV among MSM published before Dec.31, 2018. Studies were eligible for inclusion if they were published in the peer-reviewed literature and used validated assessment methods to assess the prevalence of HIV among MSM. Estimates were pooled using random-effects analysis. Data were extracted from 355 cross-sectional studies (571,328 individuals) covered 59 cities from 30 provinces and municipalities of China. The overall national prevalence of HIV among MSM from 2001 to 2018 was estimated to be 5.7% (95% CI: 5.4–6.1%), with high between-study heterogeneity (I2 = 98.0%, P <  0.001). Our study showed an increased tendency in the HIV prevalence as time progressed by meta-regression analysis (I2 = 95.9%, P <  0.0001). HIV prevalence was the highest in those aged 50 years and older with HIV prevalence of 19.3% (95%CI: 13.1-27.4%, N = 13). HIV was more prevalent in the illiterate population (16.8%), than in those who had received an education. Although the internet was a major venue for Chinese MSM seeking male sex partners (35.6, 95%CI: 32.3-39.9%, N = 101), seeking MSM in bathhouses/saunas had the highest associated prevalence of HIV (13.4, 95%CI: 10.3-17.1%, N = 22). The HIV prevalence among MSM varied by location: compared with other regions in China, HIV was highly prevalent among MSM in the southwest (10.7, 95%CI: 9.3-12.2%, N = 91). Compared to participants who sometimes or always used condoms, participants who had never used a condom in the past 6 months had a higher risk of HIV infection, with odds ratios of 0.1 (95%CI: 0.08-0.14). Our analysis provided reliable estimates of China’s HIV burden among MSM, which appears to present an increasing national public health challenge. Effective government responses are needed to address this challenge and include the implementation of HIV prevention.

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The prevalence of HIV among MSM in China: a large-scale systematic analysis

Objective The present study was to explore the feasibility of developing positron molecular probes for the metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), to evaluate the distribution and pharmacokinetics, and to explore whether the probe can be used for the imaging of malignant tumours with high MALAT-1 expression in vivo. Methods [68Ga]Ga labelling of MALAT-1 antisense oligonucleotides ([68Ga]Ga-MALAT-1-ASO) was synthesized by the conjugation of MALAT-1-NOTA-ASO and [68Ga] Ga3+. The radiochemical purity was shown by radio-HPLC. Pharmacokinetic studies and cellular uptake studies were performed. The biodistribution and metabolism of [68Ga] Ga-MALAT-1-ASO in normal ICR and MHCC-LM3 xenograft-bearing nude mice were studied in vitro and in vivo. Results [68Ga]Ga-MALAT-1-ASO was obtained in 98% radiochemical yield from a 10-min synthesis with 100 ± 50 MBq/nmol specific activity and >99% radiochemical purity. The Log D was -2.53 ± 0.19. The tracer displayed excellent stability in vitro. 68Ga-MALAT-1 ASO showed satisfactory binding ability to MHCC-LM3 cells; the biodistribution of [68Ga]Ga-MALAT-1-ASO in MHCC-LM3 tumour-bearing mice demonstrated specific uptake of the radiotracer (3.04 ± 0.11%ID/g). Micro-PET images of the MHCC-LM3 cell xenograft mouse model provided further evidence to support the hypothesis that [68Ga]Ga-MALAT-1-ASO can target tumours in vivo. Conclusions We conclude that [68Ga]Ga labelling of MALAT-1 ASO is a convenient approach. The high accumulation of [68Ga]Ga-MALAT-1-ASO for tumours expressing MALAT-1 suggests that this radio compound may be used as a potential positron molecular probe. Molecular structure optimization studies need to be more in-depth to further reduce its background uptake and enhance tumour targeting.

Qian-ni Ye

Papers

The prevalence of HIV among MSM in China: a large-scale systematic analysis

Preclinical evaluation of [68Ga]Ga-MALAT-1-antisense oligonucleotides for specific PET imaging of MALAT-1 expressing tumours.