Background
The HIV/AIDS epidemic persists, with among men who have sex with men (MSM) disproportionately affected. Globally, as of 2022, an estimated 39 million people were living with HIV, with MSM prevalence at 7.7%, markedly exceeding the general population's rate of 0.7% [
1]. In China, HIV/AIDS cases reached 1.2 million by 2022’s end, with MSM prevalence surpassing 7%, significantly higher than the 0.1% in the broader population [
2]. Pre-exposure prophylaxis (PrEP), an innovative biomedical intervention employing antiviral drugs, has proven highly effective in preventing HIV [
3], slashing the risk by about 99% during sexual exposure [
4]. The China Real-World Oral Intake of PrEP (CROPrEP) study observed no new HIV infections among highly adherent MSM over a 12-month period [
5]. Adherence plays a crucial role in ensuring the effectiveness of PrEP, which can be influenced by various factors, including stigma, discrimination, side effects, and compromised mental well-being [
6].
Due to their unique social identity, MSM often encounter different forms of stigma, leading to emotional distress, social isolation, and physiological reactivity [
7]. Individual, interpersonal (intimate partner violence and low social support), community-level and structural (gender inequality) factors at different levels can contribute to elevated risk of depression and HIV acquisition among MSM [
8]. A meta-analysis revealed that the overall prevalence of anxiety symptoms among Chinese MSM was 32.2% [
9]. Several studies have established a connection between anxiety, depression, and reduced PrEP adherence [
10‐
12]. A study in China also found that psychological factors had significant effects on the willingness to use and adherence to PrEP [
13]. However, these studies mainly focus on the relationship between anxiety/depression scores at one or multiple time points and PrEP adherence, overlooking the fluctuations in anxiety/depression scores experienced by study participants during PrEP use.
The Group-based trajectory model (GBTM) aims to identify distinct clusters of individual trajectories within a population and analyze the characteristics of individuals within each group [
14]. In the HIV Prevention Trials Network 082, GBTM was used to identify a significant inverse relationship between elevated depressive symptoms and PrEP use during the follow-up period among adolescent girls [
15]. Wu et al. used GBTM and observed that the proportions of MSM in the low, moderate, and high anxiety groups were 32.56%, 56.12%, and 11.32%, respectively [
16]. Li et al. categorized young and middle-aged MSM in Beijing into three groups based on trajectories of depressive symptoms after new HIV-diagnosis [
17]. Despite the positive outcomes of GBTM in assessing the influence of depressive symptom trajectories on PrEP adherence, few studies have explored this topic among MSM [
18]. Therefore, there is an urgent need to understand the fluctuations in anxiety and depression among MSM on PrEP, as well as the factors that contribute to varying levels of anxiety and depression.
During the implementation of the CROPrEP project, we collected data on anxiety and depression scores, as well as PrEP adherence [
5]. This study employed GBTM to examine the fluctuations in anxiety and depression scores among MSM using PrEP, investigated the factors that influence the levels of anxiety and depression, and assessed the characteristics in PrEP adherence across different subgroups.
Discussion
In this study, GBTM delineated three distinct anxiety and depression trajectories among MSM using PrEP: consistently low, consistently moderate, and high but bell-shaped. Higher anxiety and depression levels were associated with monthly income, psychological gender identity, and sexual role with men. Notably, increased anxiety undermined PrEP adherence, while depression did not exert a measurable impact. To the best of our knowledge, few studies identify varied trajectories of anxiety and depression among MSM using PrEP in China. This study indicates that when promoting PrEP among MSM, attention should be paid to their mental health during the medication process to enhance medication adherence and prevention efficacy.
In a novel application of GBTM, this research assessed mental health fluctuations among MSM on PrEP. A prior study in China also utilized the GBTM to classify MSM into low, moderate, and high anxiety groups, as well as low and high depression groups based on the trajectory analysis [
16]. Our research indicated that participants in the high but bell-shaped anxiety and depression group tend to exhibit an increasing trend in their mean scores from the beginning of the study to the sixth month, which then decreases from six to twelfth months. This could be attributed to initial concerns about PrEP efficacy and side effects, resulting in increased levels of anxiety and depression. However, after a period of use, the realization of PrEP’s role in reducing the risk of HIV infection leads to a decrease in these levels [
24]. Contrary to our findings, another study in Amsterdam found no significant temporal changes in the proportion of individuals diagnosed with anxiety or depressive mood disorders across both regimens [
25]. However, it should be noted that this study assessed anxiety and depression on an annual basis, potentially overlooking short-term fluctuations. We found that, within the high but bell-shaped anxiety and depression group, up to 78.0% and 60.3% of individuals may exhibit symptoms of anxiety and depression, respectively. Therefore, future research should not only focus on behavioral changes among MSM on PrEP but also regularly monitor their mental health, ensuring appropriate monitoring intervals.
Several factors influence the levels of anxiety and depression among MSM using PrEP. A comparative study conducted in Western China found that the high prevalence of anxiety and depression was linked to factors such as younger age and lower monthly income [
26]. This aligns with the results of our research. MSM and psychologically as female are more susceptible to stigma and violence because of their distinct social identity. This increased vulnerability can contribute to mental health issues such as anxiety and depression [
27‐
29]. Our findings suggest that playing the bottom role in male-to-male sex is associated with elevated levels of anxiety. A plausible explanation could be that MSM who exclusively assume a bottom role in sexual activities often adopt a passive and submissive position, which may not fulfill their psychological and physiological needs. This can lead to long-term frustrations that manifest as symptoms of anxiety and depression [
30]. Wu et al. found that MSM with syphilis were more likely to have a higher physical depression score [
31]. Therefore, to maximize the preventive effectiveness of PrEP among MSM, it is essential to prioritize attention on economically disadvantaged, young MSM who identify as female, play the bottom role in male-to-male sex, have multiple sexual partners, and test positive for syphilis.
In our research, we discovered a correlation between elevated levels of anxiety symptoms and decreased PrEP adherence. Previous studies have also evaluated the negative effect of symptoms of anxiety and depression on PrEP adherence [
10,
25,
32‐
34]. However, these investigations have predominantly overlooked the fluctuations in anxiety and depression among MSM throughout the entire PrEP utilization process. Young et al. discovered that 61.5% of participants exhibiting anxiety had protective tenofovir levels, in contrast to 81.8% of other participants [
12]. Conversely, an investigation among MSM in New York City revealed no significant correlation between depressive symptoms and PrEP adherence [
35]. In our research, it was observed that only elevated levels of anxiety at the 12th-month follow-up were correlated with decreased PrEP adherence, potentially related to the lockdown imposed during the COVID-19 pandemic. A study in France revealed that 58.8% of MSM reported discontinuing PrEP during the COVID-19 lockdown, and 15.4% were not utilizing PrEP at the time of the survey [
36]. It is imperative to closely monitor symptoms of anxiety and depression among MSM throughout the PrEP utilization process to enhance adherence and consequently improve its effectiveness.
There are consistent challenges in adhering to PrEP as prescribed. Four HIV seroconverters had adherence scores below 0.9, indicating poor adherence in our study. The adherence scores of the other three seroconverters at their last negative follow-up visits were all above 0.9. However, the duration between last negative result and initial positive result was relatively long, exceeding two months. The above results indicate the importance of PrEP adherence in preventing HIV infection. A recent study showed that short message service reminders were ineffective in promoting PrEP adherence among young Kenyan women [
37]. Therefore, it is crucial to evaluate and implement additional innovative interventions, such as real-time monitoring and just-in-time intervention, to support PrEP use among MSM [
38].
This study acknowledges several limitations. Primarily, apart from a lower proportion of PrEP adherence observed in the high but bell-shaped group of anxiety in the 12th month, no significant differences in PrEP adherence were found across different levels of anxiety and depression in other analyses. This might be attributed to the limitations of the HADS scale, which only measures anxiety and depression levels in the past month and does not reflect the anxiety and depression experienced by MSM over the course of the past three months while taking PrEP. Secondly, due to attrition during the follow-up process, the accuracy of GBTM results may be impacted. However, the attrition rate in this study is relatively low (11.7%, 120/1023), and the GBTM demonstrates resilience to data lost to follow-up, bolstering the credibility of the results. Thirdly, compared to other trajectory model studies, the BIC in this article is relatively high, which may be attributed to the skewed distribution of HADS scores. However, in addition to BIC, we also utilized AvePP for trajectory model selection, enhancing the credibility of the results. Fourth, adherence was evaluated based on self-reported questionnaires. Participants may underreport information about sexual behavior due to societal stigma. However, we cross-verified self-reported medication intake with pill dispensing records and pill counts at each follow-up to enhance adherence accuracy. Lastly, given that this study was conducted within a PrEP demonstration project, the PrEP adherence outcomes may not be extrapolatable to real-world scenarios where adherence support structures may not be as robust. Future studies conducted after the broader promotion of PrEP may yield improved results.
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