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Official websites use. Share sensitive information only on official, secure websites. Corresponding Author Contact: Alexander R. Bazazi, M. Participants completed rapid HIV testing and behavioral assessments. Estimates of HIV prevalence were computed for each of the three recruitment sites and the overall sample. HIV prevalence was Recruitment extended to locations far from initial interview sites but was concentrated around discrete geographic regions. Keywords: HIV prevalence, people who inject drugs, Malaysia, surveillance, respondent-driven sampling. The HIV epidemic in Malaysia is concentrated among marginalized populations, including people who inject drugs PWID , sex workers, and men who have sex with men. After initially pursuing a strictly punitive approach toward PWID, Malaysia introduced evidence-based harm reduction programs in , including needle exchange and opioid maintenance therapy 2. Supported primarily by the Ministry of Health and the Global Fund, needle exchange programs have been opened in all states in peninsular Malaysia 3. Methadone maintenance therapy is primarily provided by the Ministry of Health through specialist and primary care clinics supported by the National Anti-Drug Agency, which has scaled back its system of compulsory drug detention centers and increased access to subsidized methadone maintenance therapy in the community 4 - 6. Drug injection is often hidden from public view because of stigma and criminalization, particularly in Malaysia, where even traces of illegal drugs in the urine can result in arrest and detention 7 - 9. Ministry of Health surveillance data suggest that HIV prevalence could be as high as Respondent-driven sampling RDS was developed to recruit members of hidden populations such as PWID for which traditional probability sampling is not possible 10 - Participants in RDS studies are given a small number of coupons that they use to recruit other subjects who meet study inclusion criteria. Subjects are remunerated for participation and for successful recruitment. Traits, such as HIV status, of subjects recruited by RDS may not be statistically independent, so statistical approaches have been developed to estimate population prevalence from RDS data 10 , 11 , 16 - Estimation of population prevalence from subjects recruited by RDS remains controversial, and researchers continue to disagree about whether and how estimates should be adjusted for possible differences in sampling probability 12 , 19 - Statistical diagnostics have been proposed to help researchers determine whether data obtained by RDS conform to the assumptions made by statistical techniques for prevalence estimation We present for the first time in the peer-reviewed literature estimates of HIV prevalence among non-institutionalized PWID in Malaysia, use diagnostic tools to evaluate whether some key sampling assumptions for RDS are likely to hold, and document heterogeneity in HIV prevalence across geographic regions. Eligibility criteria were i injecting drugs in the previous 30 days verified by examination of injection sites and knowledge of drug preparation methods , ii age 18 years or older, iii possessing a valid RDS coupon, and iv spending time in Greater Kuala Lumpur. One interview site was located in a central urban area Kampung Baru and the other two were located in peri-urban areas approximately 30km west Shah Alam and south Kajang of the city center. After meeting with local harm reduction and addiction treatment experts, these particular sites were selected to maximize the chance of reaching PWID from all regions of Greater Kuala Lumpur. These experts confirmed a sizeable presence of PWID in these regions. Participants at each site were recruited using RDS Each participant was given three coupons that could be used to recruit eligible peers and 50RM 16USD for participating and 25RM 8USD for each eligible individual they recruited and who was successfully enrolled. Coupons were uniquely numbered to allow tracking of who recruited whom. To discourage repeat participation, we communicated to subjects that they could be uniquely identified from biometric measurements ulnar length, wrist circumference , but these measurements were ultimately not used because the number of participants at each site was relatively small and research staff were confident they could identify those attempting to participate multiple times. No discordance between tests was observed. All participants received pre-test and post-test counseling. Individuals with reactive test results were referred to local specialists at clinics where fully subsidized antiretroviral therapy was available. To verify the validity of self-reported drug use, urine samples were collected from all participants and tested for opioids. Tests usually indicate use within the prior two to three days. To avoid encouraging drug use to gain access to the study, urine test results were not used to determine eligibility. Participants completed a minute interviewer-administered questionnaire in their choice of Bahasa Malaysia or English that included a range of validated instruments and study-specific questions. Participants were asked a series of questions on personal network size, which is used in the RDS estimators Network size was defined as the number of PWID from Greater Kuala Lumpur that participants knew by name, who also knew their name, and whom they had seen in the prior three months. Injection-related risk behaviors were assessed in multiple ways: participants were asked about receptive sharing episodes—using a needle or syringe that had been used previously by someone else—as well as whether they had any needle or syringe sharing partners. To protect the privacy of participants, we collected data on what neighborhood participants lived in rather than exact addresses. Since neighborhoods vary greatly in size, the spatial resolution of our location data also varies greatly. To achieve the same level of spatial resolution for all participants, we coarsened the residential data by classifying each individual into one of three geographic regions based on which interview site was closest to their place of residence. No identifying information was collected. All participants gave their informed consent to participate. This study was approved by institutional review boards at University of Malaya and Yale University. Several estimators of population prevalence have been proposed for RDS data 16 , 17 , In the online appendix , we describe the population size estimate used as an input for the RDS-SS estimator and the insensitivity of HIV prevalence estimates to a range of population size estimates Table A1. We use the full sample, including the six seeds, in all estimates. We stratify our estimates of HIV prevalence by recruitment site and present a pooled estimate for all three sites. We highlight the sample mean over RDS estimators, which differ little within each site in our study because HIV-infected and HIV-uninfected individuals have similar network sizes. Furthermore, assumptions about the sampling process necessary for the RDS estimators to be valid are controversial, and simulation and empirical studies have shown that even under ideal conditions these estimators can be biased with high sampling variance 20 , 21 , 23 , We present data visualizations to explore potential heterogeneity in HIV prevalence across recruitment sites and recruitment chains. The igraph package in R was used to plot recruitment graphs for each site Figure 2 Cumulative sample prevalence plots for each recruitment chain were created using the RDS package in R Figure 3 ; the x-axis in these plots is the set of participants ordered by when they were recruited 25 , We present our own cumulative prevalence plots for each site that show the cumulative HIV prevalence over time since beginning recruitment Figure 1. Cumulative prevalence plots can provide visual evidence for whether the sample exhibits dependence from initial seed selection and whether recruitment reaches individuals with different characteristics over time We recruited a total of participants, All participants reported using opioids in the prior six months, and nearly all The mean age was 39 years at all sites. The sample was predominantly male While Drug use varied by site, with methamphetamine use in the past 6 months reported by On average, participants at all sites reported injecting more than three times per day, and the vast majority were daily injectors Table I. More detailed data on drug use and drug treatment are reported elsewhere 35 , Engagement in HIV risk behaviors in the previous month was common. Unprotected sexual intercourse was reported by Engaging in any receptive sharing of needle or syringes occurred among nearly two thirds of participants from the Kampung Baru Yet more participants reported having any sharing partners in Shah Alam Needle exchange use varied widely by site, with HIV prevalence varied considerably by site of recruitment: estimated prevalence was Estimated confidence intervals from the sample mean and other RDS estimators were broadly overlapping, and point estimates from the different estimators did not differ appreciably within each site Table II. Given considerable recruitment across neighborhoods See Section 3. Using the sample mean, the estimated HIV prevalence overall was Cumulative sample prevalence and bootstrapped confidence intervals at different times in the sampling process are shown in Figure 1. Each point represents the HIV prevalence estimated with the sample mean using all people recruited up to that time. Plots are stratified by interview site. These plots show that the cumulative sample prevalence within each recruitment site remains relatively stable after the first two to three weeks of recruitment. Figure 2 shows the recruitment chains with HIV status indicated by color and network size proportional to node size. One of the sampling assumptions for the RDS estimators is that recruitment ties between subjects represent reciprocal relationships In our study, only 5 participants 1. All other respondents reported receiving the coupon from a friend, acquaintance, or relative, which supports the assumption of reciprocation. The longest recruitment chain extended 11 waves in Kampung Baru, 25 waves in Shah Alam, and 14 waves in Kajang. While recruitment was concentrated around the Kampung Baru site, in some cases recruitment extended over a broad geographic area. Supplementary Table A3 shows that while recruitment from each interview site extended to different neighborhoods across the city, recruitment was concentrated near recruitment sites, and recruitment in certain regions appears to have been structured geographically. There were very few recruitment events between individuals living near Kajang and those living near Shah Alam. Supplementary Figure A2 displaying the frequency of recruitments between disaggregated neighborhoods shows that recruitment occurred across many neighborhood pairs. Figure 3 is a plot showing the cumulative sample prevalence of HIV separately for each recruitment chain. Three of the chains, one from each recruitment site, grew to include more than 25 respondents. By the time these chains accumulated 50 participants, the cumulative prevalence of HIV was similar in the longer chain from Kajang and the longer chain from Shah Alam. The longer chain from Kampung Baru has a noticeably higher prevalence by the time this chain includes 50 participants. This plot suggests that the prevalence in the final sample may be heavily influenced by the selection of the initial seeds and that the chain resulting from the first Kampung Baru seed may have sampled from a social network with high HIV prevalence, which could bias our estimates. Network size reflects how many connections participants have to other PWID. Additionally, network size is incorporated in different ways by the RDS estimators, and differences in network size between HIV-infected and uninfected people are responsible for differences between adjusted and unadjusted estimates of HIV prevalence. With a median network size of 10 S. Self-reported network size is highly variable, and there is evidence of rounding to multiples of Red lines indicate medians. The confidence interval for our pooled HIV prevalence estimate of Since nearly half of our participants were sampled from the Shah Alam site, the site with the lowest HIV prevalence, our estimate of It is not possible to compare our estimates with these previous studies. The high proportion of participants engaging in HIV risk behaviors in our sample has important implications for the future of the HIV epidemic in Kuala Lumpur. High levels of risk behaviors in Kampung Baru have the potential to facilitate continued transmission among people in this already high-prevalence region and also potentially among PWID from other regions who might inject drugs in Kampung Baru. Furthermore, the frequency of recruitment events across neighborhood boundaries suggests that PWID are not geographically static. The potential for HIV transmission is augmented when PWID know other PWID in distant neighborhoods and are willing to travel significant distances to meet them, a behavior that is consistent with our data. Additionally, if participants underreported HIV risk behaviors due to social desirability bias, the prevalence of HIV risk behaviors could be even higher than our sample suggests. We found that the distribution of network size differed significantly among HIV-infected and HIV-uninfected individuals, with a lower median network size among HIV-infected individuals. One explanation is that since networks of PWID are not static 41 , 42 , HIV infections could be long-standing and not related to current network characteristics. Alternatively, it is possible that HIV-infected individuals, such as those from the densely populated area around Kampung Baru, have more turnover in their networks and thus more casual or newly-formed ties, which have been associated with increased risk behaviors and also may be underreported 40 - Different levels of coverage of HIV prevention interventions may be required to impact transmission rates in regions with different levels of HIV prevalence Regional differences in both HIV risk behaviors and prevalence in our sample may require different intervention strategies. The Kampung Baru recruitment site was close to the oldest harm reduction organization in Malaysia, which may explain why a large proportion of participants sampled there reported accessing a needle exchange. Primary prevention interventions in settings such as Shah Alam and Kajang, with moderate HIV prevalence and high levels of HIV risk behaviors, are urgently needed to keep prevalence from increasing. Many participants from Kajang reported accessing a needle exchange while very few from Shah Alam did, likely due to recent establishment of a needle exchange program in Kajang and the absence of one in Shah Alam. We observed frequent recruitment between coarsened geographic regions. Recruitment occurred within and between diverse geographic regions, though many neighborhoods were not linked by recruitment, which could be due to barriers to recruitment, or bottlenecks, across geographic space 25 , or to the limited sample size. Few recruitments occurred between people residing in Shah Alam and those residing in Kajang. This could have been due to our policy of allowing participants to be interviewed only at the site where the seed in their recruitment chain was interviewed. As recruitment chains extended to reach people who lived closer to other interview sites, greater geographic mixing might have occurred had we allowed interviews to be conducted at any research site. Limited recruitment between particular regions could be evidence of a violation of RDS sampling assumptions related to achieving a final sample that does not depend on the non-random initial selection of seeds Previous studies have also documented the influence of geography on RDS recruitment, including how recruitment can be concentrated around study sites and may not cross certain geographic boundaries 45 - Dependence within recruitment chains, of which we found evidence with respect to HIV status, also poses a threat to sampling assumptions Differences in reported drug use between sites also suggests that these samples may have been drawn from heterogeneous sub-populations that could be separated by network or geographical bottlenecks. This heterogeneity across interview sites and recruitment chains highlights the potential role of the location of research sites and the selection of seeds in influencing estimates of HIV prevalence. Our study has several additional limitations, some unique to our study and some shared by all RDS studies. In the absence of a sampling frame and with many aspects of the RDS recruitment process hidden to researchers, the source and magnitude of bias in estimates are difficult to characterize. In our study, it is possible that we undersampled women and non-Malay ethnic groups, but evaluating the representativeness of our sample is difficult without better data on the underlying population of PWID in Greater Kuala Lumpur. Few data are available on women who inject drugs in Malaysia or elsewhere There is added stigma around drug use for women in Malaysia, which may have made women less likely to enter a setting frequented by PWID for fear of revealing their membership in the population 50 , Additionally, underlying social networks of PWID may cluster by sex and participants may have been less able to recruit female members of their networks. Malays were overrepresented in our sample compared to their numbers in Greater Kuala Lumpur Malays are also overrepresented among PWID in the criminal justice system and compulsory drug detention centers 4 , 53 , but we may have undersampled ethnically Chinese and Indian Malaysians, possibly because of homophily in network formation or preferential recruitment by ethnicity. Additionally, although the vast majority of residents of Greater Kuala Lumpur can communicate in Bahasa Malaysia or English, not offering research interviews in any other language could have discouraged participation by non-Malay ethnic groups. In the absence of adequate HIV prevention efforts including sufficient access to safe injection equipment, however, social ties may also serve as injection equipment sharing partnerships, representing potential avenues of disease transmission. Regular active surveillance of community-dwelling PWID is necessary to effectively monitor the HIV epidemic in Malaysia and elsewhere, and surveillance data and methodology should be publicly available. Sustained support for expanding evidence-based HIV prevention interventions, including needle exchange, methadone maintenance therapy, and antiretroviral therapy for PWID, is needed to stem the epidemic of HIV in Malaysia. Site-specific differences in HIV prevalence may necessitate the implementation or expansion of different types of prevention efforts. OraSure Technologies, Inc. Funders had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. This section collects any data citations, data availability statements, or supplementary materials included in this article. As a library, NLM provides access to scientific literature. AIDS Behav. Find articles by Alexander R Bazazi. Forrest Crawford , Ph. Find articles by Forrest Crawford. Alexei Zelenev , Ph. Find articles by Alexei Zelenev. Robert Heimer , Ph. Find articles by Robert Heimer. Lembah Pantai, Kuala Lumpur, Malaysia. Find articles by Adeeba Kamarulzaman. Frederick L Altice , M. Find articles by Frederick L Altice. PMC Copyright notice. Open in a new tab. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel. Median network size SD , overall.

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