Prevalence and correlates of prescription drug diversion and misuse among people living with HIV in the eThekwini district, KwaZulu-Natal, South Africa

Background Prescription drug diversion, and misuse has increased over the past decade and is notably in high-income-countries and significantly contributes to the opioid epidemic. People living with HIV (PLWH) are particularly vulnerable to prescription drug diversion, and misuse as most experience chronic pain, mental health problems and HIV-related illnesses. The researchers investigated the prevalence and correlates of prescription drug diversion, and misuse among PLWH in the eThekwini district, KwaZulu-Natal. Methods A cross-sectional study was conducted among 392 PLWH, conveniently recruited from the public healthcare facilities located in rural, semi-urban and urban areas of the eThekwini district. Participants answered questions about their background, prescription medications, substance use, and prescription drug diversion, and misuse. Descriptive analysis was performed to estimate the prevalence of prescription drug diversion, and misuse. Multivariable logistic regression was used to identify predictors of prescription drug diversion, and misuse. Findings Overall, 13% of the participants reported lifetime prescription drug diversion. The most common type of diversion was using prescription medication not prescribed by a healthcare provider (11%), followed by sharing of prescription medication (9%) and buying prescription medication without a medical script (5%). Twenty-three per cent of the participants reported prescription drug misuse in the past 90 days, with using prescription medication without a healthcare providers’ guidance (9%) and not following the scheduled time periods (8%) being the most common reported types of misuse. Self-medicating was identified as a risk factor for prescription drug misuse. There was no association between ART adherence and prescription drug diversion, and misuse. Conclusion The study findings contribute to improving the limited data available on prescription drug diversion, and misuse among PLWH in South Africa. The prevalence underscores a need for urgent interventions when prescribing medications with potential risks. Addressing the risk of self-medicating is imperative for HIV care outcomes and to avert death.

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suggest that chronic pain the common comorbidity among PLWH correlates with prescription drug misuse (10, 71 11). Literature has also found substance use disorder or dependence as a risk factor for prescription drug diversion

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According to the eThekwini Municipality, the population size of eThekwini district was estimated at 3.7 million 103 in 2016 of which about 1.9 million were PLWH (7). One of the key challenges related to eThekwini district health 104 care service provision is the high prevalence of HIV/AIDS and also abuse of drugs and alcohol (29). However,

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until to date the extent of prescription drug diversion, misuse and abuse in eThekwini district is unknown.

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Sampling method

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We employed a stratified sampling method for sampling public health care clinics as recruitment sites for PLWH.

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We grouped all eThekwini district public health clinics providing HIV care programme into strata based on 110 geographic settings i.e. rural, urban and semi-urban. Overall, eThekwini district has 118 public health care 111 facilities of which 6% of the clinics were in rural areas, 53 % in urban areas and 41% clinics were in semi-urban 112 areas. We applied a stratified randomization of public health clinics in the three strata. We did this to ensure that 113 the obtained proportions of our sample matched those from all three geographical settings. We sought permissions 114 to conduct the survey at each clinic through relevant authorities. We excluded clinics which were unable to give 115 permission to participate in the study. We conveniently approached and invited study participants from the people 116 who were waiting for healthcare workers consultations at the clinics. We employed outreach recruitment approach 117 through Non-Governmental Organisation to reach people who were drug users and living with HIV.

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We obtained written consent from 392 people who verbally confirmed to be living with HIV and aged 18 years 121 and older. Some participants were assisted in their preferred language during consenting and conducting the 122 survey. All participants were in eThekwini district at the time of the survey.

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We adapted the cross-sectional survey tool from the study conducted by Tsuyuki and Surratt (2015)

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Percentage ARV adherence was calculated by taking the total weekly ARV doses taken and dividing this number 192 by the total ARV doses prescribed (and multiplying by 100 to attain a percentage from 0 to 100). Analysis were 193 conducted to assess the association between percentage ARV adherence with prescription drug diversion or misuse 194 or abuse.

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Detailed analysis for prescription drug abuse was not performed since only few people reported prescription drug 197 abuse in our study. All analyses were performed using R studio and Microsoft excel was used to plot graphs and 198 forest plots.

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The demographics of the 392 HIV positive participants were largely females 67% (n=263), average age 36.78 (± 205 10.0) years, African 99% (n=388), single 86% (n=335), and 4% (n=17) reported been homeless in the past 30 206 days (Table 1 and Table 2 in the supplementary material file). In our sample, 82% of the participants were on 207 antiretroviral treatment with an average of 96% of ART adherence in the past 7 days. In our sample, 61% (n=238) 208 of the participants have not completed high school. More than half of the sample were employed, 53% (n=209).

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Overall, 13% (n=51) of the sample reported ever diverting prescription drugs ( Figure 2). Majority, 11% (n=42), 212 9% (n=36) and 5% (n=20) reported using PM not prescribed by a health care provider, sharing PM and to have 213 bought PM from someone else or from a pharmacy without a medical script for their own use in the past 90 days, We determined correlations between characteristics of participants who ever diverted versus and never diverted 221 prescription drugs (Table 1). In the multivariable model A ( Figure 3)  Comparisons were performed to compare characteristics of participants who ever misused versus never misused 259 prescription drugs (Table 1). Participants who used illegal drugs had more than 3-fold higher odds of misusing

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In average, our sample reported ART adherence level greater than 95% which is required in order to obtain 286 successful ART outcome. Although, not found to be statistically significant participants who were diverting PM 287 had lower ART adherence (96%) when compared with participants who never diverted PM (97%) in the past 7 288 days. Similarly, participants who were misusing PM had lower ART adherence (96%) when compared with 289 participants who never misused PM (97%) in the past 7 days. No regression analyses were performed since the 290 ART adherence of all groups were relatively similar.

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We sought to investigate the prevalence and correlates of prescription drug diversion, misuse and abuse in a cohort 294 of HIV-infected adults in eThekwini district, KwaZulu-Natal province. In this study, the overall prevalence of 295 prescription drug diversion among PLWH was found to be 13% during their lifetime meanwhile 23% of 296 participants reported prescription drug misuse in the past 90 days and only a few participants reported prescription 297 drug abuse. Self-medicating was the only predictor found to be statistically significant for predicting prescription 298 drug misuse among PLWH.

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Although there is limited evidence on prescription drug diversion in resource limited settings, numerous studies

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Though, only a few PLWH reported prescription drug abuse, increases in prescription drug overdose deaths have 327 coincided with an increase rates of drug diversion, drug misuse and prescription drug-related illnesses (49-51).

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Despite that there was no association between ART adherence and prescription drug diversion and misuse in the 329 past 7 days, earlier research in the United States found that prescription opioids misuse was linked with less than 330 90% ART adherence (52). Similarly, a study conducted in 2017 in the United States reported that opioid use was 331 significantly associated with failure to achieve viral load suppression (53).

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We observed that after adjusting for geographical settings, PLWH who were aged 30 years and older, male, had 334 no income and used substances were at increased risk of diverting prescription drugs. Meanwhile, PLWH who 335 used substances, self-medicated themselves and aware of the black market had increased risk of misusing 336 prescription drugs. Similar to our findings, substance use disorder or dependence (8, 10, 12-21), male gender (16, 337 20) and unemployment or no income (25) has been reported as risk factors for prescription drug diversion among 338 PLWH. Moreover, evidence has shown that men access health care services including HIV treatment services 339 later at their illness stage than women (54). Nevertheless, our findings highlight a hidden behaviour of diversion 340 that might be practiced by most men living with HIV when they are in need to medicines. Though literature has 341 reported females as more likely to misuse prescription drugs than males (55). This would mean that females 342 frequently access health care services and get prescribed medicines, but clearly they do not follow the instructions 343 of taking the medicines. It is imperative to design tailor-made interventions specific for males and females for 344 different age groups to mitigate the barriers to optimal health care outcomes and prevent potential risks. Though 345 self-medicating is a commonly practiced behaviour, inappropriate self-medication practices has potential risks but 346 not limited to incorrect manner of drug administration, incorrect dosage consumption, incorrect choice of 347 medicines, drug adverse reactions, risky drug-drug interactions and risk of developing drug dependence and abuse 348 (56). This strongly support the association between misuse and self-medicating. Inappropriate self-medicating 349 might hinder progress to achieve and maintain viral suppression outcome among PLWH. We recommend 350 additional awareness interventions to supplement the medicine information pamphlet that is only read and 351 comprehended by only few consumers. PLWH often presents with known risk factors associated with prescription 352 drug diversion, misuse and abuse of which includes but not limited to substance use, mental health problems and 353 chronic pain. They frequently get prescribed controlled medications to alleviate the experienced health problems, 354 therefore consideration of the correlates of prescription drug diversion, misuse and abuse among PLWH is critical.

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Despite our limitations, this study is among the first to investigate prescription drug diversion, misuse and abuse 358 among PLWH in eThekwini district. Although the study consisted of sensitive questions, our study provides 359 valuable information on prescription drug diversion, misuse and abuse. Behaviour practices related questions were 360 based on self-report and these may be implicated by recall and social desirability bias. The exclusion of metal 361 health variable in the analysis could be a limitation since mental health problems is one on the risk factors. Gaps 362 were identified in the study questionnaire and the questionnaire did not adequately cater for the resource limited 363 setting like eThekwini district since most people had low knowledge and awareness of different types of 364 prescription drugs. Comparisons were limited since the prevalence of prescription drug diversion, misuse and 365 abuse were investigated in different time periods in our study and in literature. Laboratory HIV viral load test 366 results can be used to support the self-reported ART adherence. Our findings are generalizable only to PLWH 367 from resource-limited settings accessing care in public health care facilities, whereas prescription drug diversion, 368 misuse and abuse among PLWH accessing care in private facilities might be different.

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The high prevalence rate of prescription drug diversion and misuse among PLWH underscore the need of 372 integrated surveillance tools at all levels in the health care system. Monitoring the dispensing of medicine and 373 evaluation of medicine usage by health care providers is highly recommended for routine prescriptions and for 374 patients presenting with risk factors. We recommend educational and awareness campaigns directed at increasing 375 patient or public knowledge of the potential risks and promoting a greater awareness among health care providers 376 and to the public. Caution should be taken when prescribing of medicines with potential risks for diversion, misuse 377 and abuse especially when the patient is presenting with risk factors. This study estimated the prevalence of 378 prescription drug diversion, misuse and abuse among PLWH in eThekwini district. Prescription drug diversion, 379 misuse and abuse practice needs urgent attention since there is a risk of transitioning to illegal drug use.