HIV Testing and HIV Positivity Among People Who Inject Drugs (PWIDs) With and Without History of High-Risk Behaviors: Findings From a Respondent-Driven Sampling (RDS) Survey in Southern Thailand

People who inject drugs (PWIDs) may engage in other behaviors with high risk of HIV transmission to various extents. However, data are scarce regarding differences in HIV testing and HIV positivity among PWIDs with and without high-risk behaviors. Such data can help inform stakeholders with regard to program prioritization. The objective of this study was to assess the extent that lifetime and past-year histories of HIV tests and HIV positivity varied by history of high-risk behaviors among PWIDs. We conducted a cross-sectional study with respondent-driven sampling (RDS) in the deep south provinces of Thailand during late 2019 thru early 2020. Data collection was done using structured questionnaire with face-to-face interviews. We analyzed data using descriptive statistics and multivariate logistic regression analyses. A total of 283 PWIDs gave verbal informed consent, and 282 PWIDs participated in the interview (n = 282 PWIDs). Approximately 44.6% of the participants never had an HIV test. Participants with history of high-risk behaviors had significantly higher odds of lifetime HIV testing than participants with no history of high-risk behaviors (Adjusted OR = 2.94; 95% CI [1.11, 7.78]). Among participants with lifetime history of HIV tests, those with history of high-risk behaviors had significantly higher odds of being HIV-positive than those with no history of high-risk behaviors (Adjusted OR = 2.44; 95% CI [0.73, 8.17]). Stakeholders should consider encouraging those without history of high-risk behaviors not to be complacent about HIV testing, and ensure that those with high-risk behaviors have full access to HIV care when they test positive.


Introduction
There are more than 15 million persons who inject drugs (PWIDs) globally, the majority of whom are men (Degenhardt et al., 2017).Use of injection drugs may involve use of shared needles and syringes (Korthuis et al., 2012), which contributes to the 18% prevalence of HIV positivity among PWIDs worldwide (Degenhardt et al., 2017).In addition to use of shared needles, PWIDs may also engage in other behaviors with high risk of HIV transmission, including sex acts that involve mucosal tear (Billock et al., 2018;Duong et al., 2018), engaging in commercial sex work (Chen et al., 2014), and having sex without condom (Damas et al., 2021;Gangi et al., 2020).
Current guidelines for HIV prevention and control recommend that individuals at high risk of HIV infection are tested for HIV at least once per year (CDC, 2020).However, as little as three-fifths of all PWIDs undergo HIV testing (Handanagic et al., 2021).Furthermore, empirical data suggest that the extent that PWIDs engage in high-risk behaviors (e.g., needle-sharing or having unprotected sex) vary greatly (Baluku et al., 2019;Chen et al., 2014;Gangi et al., 2020;Korthuis et al., 2012), making it difficult to assess the needs for HIV testing and treatment in this marginalized group.
Yet despite the recommendation for annual HIV testing in the guidelines and variation in behaviors with high risk of HIV transmission, data are scarce regarding the extent that HIV testing and HIV positivity differ between PWIDs with high-risk behaviors and PWIDs without such behaviors.This lack of data also occurs in Southern Thailand, a region with high prevalence of HIV among PWIDs (Visavakum et al., 2016).We hypothesize that PWIDs with high-risk behaviors would have higher history of HIV screening and testing than PWIDs without such behaviors (Marson et al., 2021), and that PWIDs with high-risk behaviors would have higher prevalence of HIV positivity than PWIDs without such behaviors (Nyirenda et al., 2022).The objective of this study is to assess the extent that lifetime and past-year histories of HIV tests and HIV positivity varied by history of highrisk behaviors among PWIDs in the Thai-Malaysian border area.Such data can inform stakeholders in HIV prevention and harm reduction among substance users on the sub-group that may require additional promotion of HIV-testing behavior, and the priority group for ensuring timely and continued HIV treatment.

Study Design and Setting
This study was a cross-sectional study with respondentdriven sampling (RDS).Data collection sites included two locations.The first location was a clinical laboratory center located in the middle of Songkhla City that did not serve as a service location for PWIDs.The second site was an unmarked building next to a district hospital, approximately 1 hour distance by car from the first site.The second site was opened because of the rapid decline in participation at the first site, thus the investigators decided to recruit more participant from the district of the second site where there was high density of PWIDs and the nearby district hospital also operated a methadone clinic with voluntary counseling and testing for sexually-transmitted and blood-borne diseases.

Study Population and Participants
Inclusion criteria included: (1) age of 15 years or older; (2) residing in the study area; (3) having used injecting drugs within the past 6 months; (4) Thai citizenship; (5) presenting to the investigators with the project's authentic and unexpired coupons on the day of study; and (6) not being under the influence of substance or a state of psychosis that precluded providing informed consent or giving interview data independently.
Investigators performed sample size calculation for estimation of proportion of PWIDs who were tested for HIV during the year prior to the survey at 30%, with assumed design effect of 2, at 95% level of confidence.Investigators thus obtained a sample size of 325 participants.

Study Variables
For our study, history of high-risk behaviors included self-reported history of sharing needles for injecting drug use with any individual within 6 months prior to the survey, or history of sex without condom use with a casual partner or a transactional sex partner (a partner to whom the participant paid for sex, or a partner who paid the participant).
History of participant in HIV testing was assessed based on two questions: (1) lifetime history of HIV testing and (2) time since last HIV test among those who were tested.Considering the recommended period of testing at least once a year, we categorized the participants into three groups according to their HIV test history: (1) participants who never tested for HIV; (2) participants who tested in lifetime but before the past 12 months; and (3) participants who tested within the past 12 months.Among those who had tested for HIV, we also inquired about their test results as well as history of receiving treatment among those who tested positive.Details of the variable definitions can be found in Table 1.

Study Instruments
The instrument in this study was a standardized questionnaire that was adapted to the context of PWIDs in Thailand.Research staff recorded the interview data into an electronic device.

Participant Recruitment and Data Collection
Recruitment of study participants started with four seed participants.The number of seed participants was determined based on the 1:100 ratio between seeds and samples.Seed participants were selected based on suggestions from local partners who served or were otherwise involved with local PWIDs.Seed participants included four male PWIDs with the age range of 39 to 44 years.Two seed participants were HIV-positive at the time of study.After the investigators finished data collection with seed participants, investigators gave three voucher coupons to the seeds and asked each seed to recruit three peers and give three coupons to the peer.Each of the peers who participated would then receive three voucher coupons to give to three other peers.Each voucher consisted of two parts: (1) recruitment (upper part) where the new recruits would bring to the study sites to enroll in the study; (2) compensation (bottom part), where the participant who made the referral would bring to the study standardized to receive their recruitment compensation.The voucher did not contain any stigmatizing information.
After a potential participant arrived at the study site, a research staff would assess the potential participant's eligibility, provided the participants with details of the study, and asked for verbal informed consent.A research staff then interviewed the participant with the study questionnaire.After the interview, research staff would provide the participants with three voucher coupons to recruit three peers, as per the above-mentioned details.

Data Management and Analysis
Data management and processing prior to analyses included creation of a data dictionary, modification of variable names into a form that was more user-friendly for statistical packages, translation of cell contents from Thai to English, transformation of variables into appropriate classes.We also deleted data from participants from whom data was not collected.
Data analyses included exploratory data analyses and descriptive statistics.In addition, we used multivariate logistic regression to assess the difference in likelihood of HIV testing in lifetime (tested within past 12 months or tested but not within past 12 months vs. never tested) and HIV testing within past 12 months (vs.tested but not within past 12 months or never tested) between those with high versus low risk of HIV infection.In multivariate analyses, we adjusted for age, completion of high school versus less than high school or no answer, being unemployed versus unemployed or no answer, and monthly personal income above poverty line of 3,000 THB versus below poverty line or no answer, based on known predictors of HIV testing identified a priori in the literatures (Allen et al., 2023;Centre for SDG Research and Support, 2021).In the covariates, we decided to (1) whether the participant had been tested for HIV in lifetime (ever vs. never); (2) time since last HIV test for those with lifetime history of testing (categorized as more than 12 months prior vs. within 12 months prior) HIV test results Self-reported HIV test results among those who were informed of their HIV test, based on two questions among participants who reported having been testing for HIV in their lifetime: (1) whether they had received their test results; (2) their test results (positive vs. negative); those who refused to answer were excluded from the analyses group together missing responses with the reference group in order to maximize statistical power, based on the assumption that those who refused to answer all had the same characteristics as those in the response group.

Ethical Considerations
An application for full ethical approval was made to the Research Ethics Committee for Science, Technology and Health Science at Prince of Songkla University, Pattani Campus, and ethical approval was received on 11 April 2019.The ethics approval number is psu.pn.1-011/2561.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Verbal informed consent was obtained from all individual participants involved in the study.Written informed consent was not obtained because use of injecting drug was a stigmatized and illegal activity.In order the reduce the anxiety of the participants when revealing themselves or their names, investigators obtained verbal informed consent in lieu of written informed consent by stating the participant's voucher number, and asking the research staff who conducted the interview to sign the form as a record of informed consent.

Results
The investigators and research staff were able to recruit a total of 283 participants.There was one participant whose answer status was ''FAILED,'' that is, the instrument failed to record the data.We subsequently excluded the participant from the analyses, and the final number of participants included was 282 individuals.
Participants were nearly all male, with mean age of 42.3 years (Table 2).Four-fifths of the participants did not finish high school, and two-fifths lived below the poverty line.The two most common injecting drugs that the participants reported using were heroin and amphetamine.Nearly 90% of the participants did not share needle in the past 6 months or had sex without condom with casual or transactional sex partners.Male participants were also asked about lifetime and past-year history of anal sex as an indicator of MSM behavior.Although 13 of 238 male participants (5.4%) who answered the question on lifetime history of anal sex reported history of such behavior, none reported past-year history of such behavior (data not shown in table).With regard to HIV testing, nearly half of the participants never had an HIV test.Among participants who had an HIV test, approximately one-fourth were HIV-positive.Participants with history of high-risk behaviors did not have a significantly higher odds of testing for HIV within the past 12 months compared to participants with no history of high-risk behaviors (Adjusted OR = 0.75; 95% CI [0.30, 1.91]; Table 3).However, participants with history of high-risk behaviors still had significantly higher odds of lifetime testing than participants with no history of high-risk behaviors (Adjusted OR = 2.94; 95% CI [1.11,7.78]).Among participants with lifetime history of HIV tests, those with history of high-risk behaviors had significantly higher odds of being HIV-positive than those with no history of high-risk behaviors (Adjusted OR = 2.44;95% CI [0.73,8.17];Table 4).

Discussion
People who inject drugs (PWIDs) have varying level of health behaviors that put them at high risk of HIV infection.Although HIV control guidelines recommend that PWIDs undergo HIV tests at least once a year, little is known about the extent that PWIDs with and without high-risk behaviors undergo HIV tests.We examined such differences among PWIDs in southern Thailand using respondent-driven sampling survey based on a standardized protocol.We found that lifetime history of HIV testing was more common among PWIDs with high-risk behaviors than among PWIDs without highrisk behaviors.HIV positivity was also higher among PWIDs with high-risk behaviors than among PWIDs without high-risk behaviors, although this difference was not statistically significant.
The prevalence of high-risk behaviors among our participants was lower than in previous studies.Shared needle use and history of risky sexual encounters were almost mutually exclusive (except for one person), this is vastly different from other studies which found these two behaviors to co-occur (Chen et al., 2014;Damas et al., 2021;Gangi et al., 2020).The history of shared needle use in our study was lower than in other respondentdriven sampling studies on behaviors of PWIDs (Chen et al., 2014;Korthuis et al., 2012).Considering that there could be a gap between obtaining sterile syringe and actual use (Gangi et al., 2020;Korthuis et al., 2012), access to clean needles among PWIDs in our study could have been close to 100 percent.This low prevalence of shared needle use seemed to reflect on-going changes in Thailand (Martin et al., 2019) and other parts of Asia (Khezri et al., 2022), which showed that shared needle use had dropped significantly in the past decades.History of high-risk sexual behavior was uncommon despite that our definition of risky sex in past 12 months included unprotected casual sex and engaging in paid sex act, which was (similar/more liberal) than in previous studies (Damas et al., 2021;Gangi et al., 2020).In previous studies, PWIDs also reported MSM behaviors (Billock et al., 2018;Duong et al., 2018) in addition to being commercial sex workers or clients.However, we did not include past-year history of anal sex (as proxy measure for being MSM) in the definition of unsafe sex in our study because none of the participants who reported lifetime history of anal sex reported anal sex within the past year.The influence of social desirability was possible, but unlikely, otherwise the participants would not have admitted to anal sex in the first place.In that regard, even if participants reported past-year history of anal sex, the inclusion of such behaviors would have been problematic because our measurement questions did not include details with regard to condom use, making definition of risky sex inconsistent (our other categories involved self-reported non-use of condom).
Prevalence of lifetime and repeated HIV testing among our participants was similar to previous studies (Burt et al., 2017;Schneider et al., 2020;Tempalski et al., 2019).The prevalence of HIV testing seems to be subject to fluctuations (Burt et al., 2017), and findings at the time of study may not be generalizable to other periods.However, our study questions only assessed the time of last examination, but did not capture the number of tests done per year, the context in which the tests were done (after potential exposure vs. routine test date as determined in advance by PWID or care provider), whether participants had been unable to take the HIV test when they desired to do so, and self-reported barriers to HIV testing.Future studies should consider including these questions to contextualize HIV testing, and further improve the relevance of the study findings for stakeholders who work in harm reduction.
Approximately one-fourth of the participants in our study who reported having received an HIV test result were HIV-positive.This prevalence was similar to another study conducted among PWIDs in Cambodia (Sopheab et al., 2018).These findings reflect the progress toward UHC in providing antiretroviral treatment in developing countries (Assefa et al., 2020).However, this study was conducted prior to the COVID-19 pandemic.Access to HIV testing and treatment during the pandemic seems to be very dynamics and heterogeneous (Magnani et al., 2022), and our findings may have limited generalizability to the pandemic and post-pandemic eras.
We found that PWIDs with history of high-risk behaviors were more likely to be HIV-positive than those without such history, although those with history of high-risk behaviors were also more likely to report history of testing for HIV.The findings of our study differed from a previous study, which found heterogeneity in HIV-risk behaviors: HIV-positive female PWIDs were more likely to use shared needle/syringe than HIV-negative female PWIDs, but we also more likely to use condom during sexual intercourse (Damas et al., 2021).However, our study showed that HIV-positive PWIDs were both more likely to report use of shared needle, and more likely to report history of risky sex in past 12 months, as self-reports of these two behaviors were almost mutually-exclusive.Although social desirability bias might have been present in our study, its likely misclassified HIV high-risk individuals as those with lowrisk, biasing the measure of association toward the null and making our study findings conservative.We also found that those with history of high-risk behaviors were more likely to test positive for HIV compared to those with no such history, which was as expected considering the nature of HIV transmission (Patel et al., 2014).The study findings concurred with our hypothesis.Despite the statistical non-significance in the prevalence of being HIV positive, the difference nonetheless should be taken into consideration.The policy implications of our findings are that stakeholders should encourage PWIDs without history of high-risk behaviors not to be complacent and undergo HIV testing at least once per year, and take measures to ensure that PWIDs with high-risk behaviors have full access to HIV care when they test positive.Furthermore, greater insights can be obtained from newly developed techniques in predictive mathematical modelling, including: the Kudryashov method (Ali Akbar et al., 2021), generalized auxiliary equation technique (Akinyemi et al., 2021), fractional Iteration algorithm (Ahmad, Khan, Ahmad, et al., 2020), Variational Iteration algorithm-I (Ahmad & Khan, 2019), Variational iteration algorithm-II (Ahmad, Khan, Stanimirovic´, et al., 2020), meshless techniques (Inc et al., 2020), and modified (G'/G)-expansion method (Ahmad et al., 2021).Future studies should consider incorporating these techniques into the study design and data analyses accordingly.

Strengths and Limitations
The findings of this study add to the scarce literatures on characteristics of PWIDs who engaged in re-testing.However, a number of limitations should be considered in the interpretation of our study findings.Firstly, human behaviors are dynamic, and our definition of high-risk behaviors followed a rather rigid timeframe, and self-report of illegal or stigmatized behaviors are subject to social desirability, all of which could have introduced information bias due to misclassification into our study.Secondly, non-participation in HIV testing was differential between those with and without history of high-risk behaviors, thus potentially introducing selection bias into our study.Lastly, the study was conducted before the COVID-19 pandemic, which limited the generalizability of our findings to other contexts.Caveats are recommended in the interpretation of our study results.

Conclusion
We conducted a cross-sectional study using respondentdriven sampling among PWIDs to assess the extent that history of high-risk behaviors was associated with HIV testing and HIV positive status.We found that PWIDs with high-risk behaviors were more likely to be HIV-positive, but were also more likely to have engaged in HIV testing.However, limitations regarding measurement of high-risk behaviors, potential selection bias, and the study's limited generalizability should be considered as caveats in the interpretation of the study findings.
Stakeholders should consider encouraging those without history of high-risk behaviors not to be complacent and undergo testing, and ensure that those with high-risk behaviors have full access to HIV care when they test positive.

Table 1 .
Definition of Risky Behaviors Where HIV Testing Was Needed.

Table 2 .
General Characteristics of the Study Participants (n = 282 People Who Injected Drugs).

Table 3 .
History of HIV Test Among Study Participants According to Risky Behaviors (n = 262 participants; row percents).a a Adjusted for age, education (completed high school vs. less than high school), employment at time of study, and income above versus below poverty line (3,000 THB per person per month); excluded those who did not remember time of test.Bold texts denote statistical significance at 95% level of confidence.

Table 4 .
HIV Test Results by High Behaviors Among Study Participants Who Were Tested at Least Once and Were Informed of the Results (n = 136 Participants; Row Percents).aAdjustedfor age, education (completed high school vs. less than high school), employment at time of study, and income above versus below poverty line (3,000 THB per person per month); excluded those who did not remember test result. a