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. 2023 May 12;18(5):e0281030. doi: 10.1371/journal.pone.0281030

High risk injection drug use and uptake of HIV prevention and treatment services among people who inject drugs in KwaZulu-Natal, South Africa

Brian C Zanoni 1,2,3,*, Cecilia Milford 4, Kedibone Sithole 4, Nzwakie Mosery 4, Michael Wilson 5,6, Shannon Bosman 7, Jennifer Smit 4
Editor: Benjamin Bearnot8
PMCID: PMC10180682  PMID: 37172026

Abstract

We conducted a mixed-methods study to understand current drug use practices and access to healthcare services for people who use injection drugs in KwaZulu-Natal, South Africa. We used respondent-driven sampling to recruit 45 people who used injection drugs within the past 6 months from KwaZulu-Natal, South Africa. We found high rates of practices that increase HIV/viral hepatitis risk including the use of shared needles (43%) and direct blood injections (bluetoothing) (18%). Despite 35% living with HIV, only 40% accessed antiretroviral therapy within the past year, and one accessed PrEP. None of the participants ever tested for Hepatitis C.

Introduction

South Africa has an estimated 7.7 million individuals living with HIV, and KwaZulu-Natal has the highest HIV prevalence in the country [1]. In South Africa, there are more than 5 million people accessing antiretroviral therapy (ART), making it the largest national antiretroviral program in the world [1]. However, hidden populations remain that are not reached in the HIV prevention and care continuum, and efforts to expand HIV prevention, HIV testing and linkage to care services in sub-Saharan Africa have largely targeted non-injection drug using communities [1,2]. Before a recent increase in people who inject drugs (PWID) in South Africa, it was estimated that 21% of PWID in South Africa were living with HIV [1,3] compared to 14% in the general population [4]. A recent increase in injection drug use, coupled with poor access to addiction services in the forms of needle exchanges or medication assisted therapy (such as methadone or buprenorphine), has led to the increase in a sequestered population that has potential to reverse many of the investments and gains in public health access to HIV prevention and treatment services [5]. The population of PWID in South Africa spans groups of homeless, sex workers, and working-class individuals, bridging multiple social networks contributing to the potential increase in HIV incidence among individuals not targeted in typical HIV continuum interventions [6].

Whoonga, an opiate-based street drug has been present in KwaZulu-Natal for more than 10 years, yet has only recently seen an increase in injection use [7,8]. In the past, Whoonga was a drug that was smoked; however, intravenous and subcutaneous administration has become more prevalent [9]. The recent increase in cases of infective endocarditis (infection of the heart typically from blood stream infections) in South Africa is indicative of an increase in injection drug use [5,7,8]. In addition, the dangerous practice of “bluetoothing” in which blood is withdrawn from one individual who has recently injected a drug and directly injected intravenously into another person, has been reported [10,11]. Called flash-blooding in other African countries, this practice is often performed in settings of poverty and poor access to needles or needle exchange programs [1214]. This practice, in addition to needle sharing, has potential to increase the risk of HIV and viral hepatitis among PWID and spill over into the general population through sexual networks [1518].

Given the limited data on the population of individuals using injection drugs in KwaZulu-Natal, South Africa, we conducted a mixed-methods, respondent-driven study to understand drug use practices and current access to health care in preparation for targeted prevention and treatment interventions.

Methods

We used respondent driven sampling (RDS) to recruit individuals aged 18 years or older, with self-described use of injection drugs within the last 6 months, and currently living in KwaZulu-Natal, South Africa. We excluded individuals who did not speak either English or isiZulu, who were severely or visibly intoxicated, or those with severe mental or physical illness preventing participation in informed consent procedures.

We recruited three initial seed individuals who were attending a harm reduction center in Durban, South Africa. These three seed individuals were encouraged to recruit up to three other PWID from their individual social network. Each additional participant was also asked to recruit up to three different individuals from their own social network, until we reached a total sample of 45 participants in this pilot study. Recruitment and participation in interviews took place from November 1, 2021 to February 8, 2022. After providing written informed consent, participants completed a facilitated questionnaire that collected information on sociodemographics, drug use, sexual behavior and network characteristics, HIV testing practices, and use of HIV prevention or treatment services. Interviewers entered data directly into a REDCap database as questions were answered [19].

We assessed the frequency, type, and methods of drug use, information on needle procurement, use, and sharing using the National HIV Behavior Surveillance System; [20] and WHO ASSIST [21]. HIV risk assessment including sex work, number of sexual partners, condom use and frequency of condom use within the past 3 months was assessed by the Texas Christian University HIV/Hepatitis Risk Assessment [22]. We also evaluated access to health care by exploring knowledge of HIV status, HIV testing in the past 12 months, access and use of medical services in the past 12 months, knowledge and acceptability of HIV self-testing.

For this descriptive analysis we used standard summary statistics (e.g. counts/percentages; median and interquartile range of continuous measures). Basic descriptive data analyses were performed using REDCap. Results of in-depth interviews are reported separately.

This study was approved by the Institutional review Boards of Emory University and the University of Witwatersrand and the KwaZulu-Natal National Department of Health.

Results

We interviewed 45 individuals in Durban, South Africa who reported recent injection drug use. Participants had a median age of 28.5 years (IQR 26.6–32.3) and were predominantly male (58%), heterosexual (91%), had completed secondary education (87%) and were currently (76%) or recently (92%) homeless as indicated by Table 1. The median reported starting age of injecting drug use was 22 years (IQR 19–26). The majority of participants did not use other (non-injection) drugs (85%) or alcohol (64%). Most participants (93%) reported use of injection drugs within the last month with 91% reporting averaging more than one injection per day. All participants (100%) reported daily use of Whoonga. Opioid overdoses were personally experienced in 22% of participants in the last year, with a median of 3.5 (IQR 2–4.75) individual episodes of overdosing. All participants (100%) reported ever re-using needles or equipment with 42% reporting use of shared needles in the past year and 73% reported sharing other drug preparation or use materials. Bluetoothing was practiced in 18% of individuals. Thirty-five percent of individuals were known to be living with HIV but only six (40%) reported accessing antiretroviral therapy within the past 12 months and one individual was taking pre-exposure prophylaxis (PrEP). None of the participants had ever tested for Hepatitis C.

Table 1. Descriptive statistics of individuals recruited through respondent-driven sampling and self-reporting recent injection drug use in KwaZulu-Natal, South Africa.

Characteristic Participants n (%)
N = 45
Demographics
Median Age (years)(IQR) 28.5 (26.6–32.3)
Male 26 (58%)
Heterosexual 41 (91%)
Single 17 (39%)
Long term partner but not married and not living together 26 (59%)
Several casual partners 2 (5%)
South African citizen 45 (100%)
Education
Primary education 4 (9%)
Secondary education 39 (87%)
Tertiary level 2 (4%)
Median grade completed (IQR) 10 (10–11)
Employment
Full time employed 1 (2%)
Employed part time 11 (24%)
Unemployed 17 (38%)
Housing
Homeless in the past 12 months 42 (93%)
Currently homeless 32 (76%)
Alcohol Use
No alcohol in the past year 29 (64%)
Binge drinking more than once a month 10 (22%)
Injection drug use
Used injection drugs 45 (100%)
Median age at first use (years) (IQR) 22 (19–26)
Last used injection drugs in the past month 42 (93%)
Injecting more than once a day 41 (91%)
Injecting daily 2 (4%)
Injecting more than once a week 2 (4%)
Using Whoonga/heroin daily or more 45 (100%)
Had an opioid overdose (in last year) 10 (22%)
Median number of opioid overdoses (IQR) (in last year) 3.5 (2–4.75)
Know of others who experienced lethal opioid overdose (in last year) 29 (64%)
Median overdose deaths known about (in last year) 2 (1–3)
Know of others with non-lethal opioid overdose (in last year) 28 (62%)
Most common place acquired needles
 Needle exchange or NGO 29 (64%)
 Friend / acquaintance 4 (11%)
 Pharmacy 1 (4%)
Dispose of needle
 Needle exchange or NGO 25 (56%)
 On the street 8 (8%)
 Trash 7 (16%)
High risk Injection Drug Use
New / unused Needle use in last 12 months
 Always 14 (31%)
 Sometimes 22 (49%)
 Rarely 9 (20%)
 Never 0 (0%)
Median number of people shared needles with in last 12 months (IQR) 0 (0–3)
Median number of people shared other drug-use material with in last 12 months (IQR) 3 (0–5)
Median number of people shared drugs with in the last 12 months (IQR) 3 (1–4)
Used a shared needle in the past 12 months 19 (42%)
Used shared material in last 12 months 33 (73%)
Bluetoothing in the last 12 months 8 (18%)
Re-used needle from someone else at last injection 10 (22%)
Bluetoothing at last injection 2 (4%)
Did not dispose of needle at last injection 29 (64%)
Injected with known HIV+ individual 6 (13%)
Other drug use in last year 24 (53%)
Healthcare Services
Participated in a drug treatment program 27 (60%)
Ever tested for HIV 43 (96%)
Known to be living with HIV 15 (35%)
Accessing ART in the last 12 months 6 (40%)
Median number of HIV tests in last 2 years 3 (1–8.5)
Never tested for Hepatitis C 45 (100%)
Currently taking PrEP 1 (2%)
Interested in PrEP 24 (53%)

Discussion

In this study we found high rates of unsafe injection drug practices that included sharing and re-using needles and drug preparation materials as well as the practice of directly injecting blood from an individual who had recently injected (bluetoothing). These practices coupled with the low uptake of treatment and preventative services described in this study, including HIV testing, PrEP and ART services, could negate some of the efforts made in the HIV prevention and treatment continuum of care in South Africa.

The practice of bluetoothing has previously been described in South Africa [23] and has been termed flashblooding in Tanzania [1214,24]. Although practiced in a minority of injection drug users (10% in Tanzania [24] and 18% in our sample), as an extreme version of needle sharing, this practice amplifies the risk of HIV and/or Hepatitis C acquisition. It has also only been described in areas of poverty and limited access to needle exchanges. However, screening for this practice is uncommon and should be incorporated into routine interviews with PWID to reduce stigma and allow for targeted harm reduction services.

The current and substantial efforts to combat the HIV epidemic in South Africa do not adequately address injection drug use. Although efforts are increasing to routinely screen for alcohol use in HIV care across South Africa [25], screening for drug use (and injection drug use specifically) is not routinely conducted, and drug treatment is rarely integrated with HIV care services. In addition, access to harm reduction services that included access to housing, food, and naloxone nasal spray may improve survival and adherence to medical therapies [12]. Outreach and mobile medical services targeting the homeless and drug using population could assist in introducing this population to medical services; however, evidence-based interventions for low-to-middle income countries (LMIC) are limited [2628].

While the COVID-19 pandemic slowed global access to harm reduction and health services to people who use drugs, parts of South Africa saw a positive shift in care for PWID. Traditionally governmental and policing policies were antagonistic toward individuals with drug use disorder; [29] however, some areas began to support the provision of evidence-based harm reduction practices, especially to low-income and homeless people who use drugs. Nationally, needle exchange programs, harm reduction services, or medication assisted treatment are often difficult to access either due to their high-priced fee-for-service models or limited availability [30]. Although methadone syrup and sublingual buprenorphine are available and on the Department of Health Essential Medicine List for adult hospitals in South Africa, they are only available by prescription from clinicians through drug dependency programs. KwaZulu-Natal’s only needle and syringe exchange program in Durban was reinstated during COVID-19 lockdown, and a harm reduction center was opened to provide daily opiate substitution therapy to more than 200 PWID. The limited resources available for harm reduction services have historically resulted in law enforcement and punishment of substance use as the predominant response to opiate addiction [31]. However after the COVID-19 lockdowns, Durban also saw a dramatic shift in the way that members of law enforcement engaged with people who use drugs, shifting the narrative of police as punitive to one of protectors and advocates of health services for PWID [32,33]. Continued work is needed to reduce ongoing stigma associated with PWID which limits access to HIV prevention services and harm reduction programs [34,35].

Without the availability of widespread interventions, injection drug use has continued to increase in South Africa with a prevalence of 0.6% in a population-based survey in 2012 with 0.2% reporting Whoonga use [36]. More recent studies estimate that up to 15% of South African youth engage in drug use [16,37]. However, small pilot studies have shown high retention rates, opiate reduction, and improvement in mental health in individuals accessing methadone treatment in South Africa [38]. Yet, the lack of hepatitis C testing and access to PrEP indicate significant gaps in service delivery. Integration of harm reduction services into routine healthcare could impact the opiate and HIV epidemics in South Africa.

The major limitations of this study include the small sample size and descriptive nature of this preliminary study. In addition, this study was conducted during COVID-19 when services were interrupted by various lockdown policies. There was also an influx of new people into the city who may not have been familiar with available services, and there were unsafe drug use practices happening as a result of disruption of needle and other supplies during lockdown. However, we are encouraged by the ability to recruit a difficult to reach population through respondent-driven sampling over a short period of time (3 months) and using only 3 initial seed individuals. In addition, since this study was performed with a small sample obtained by respondent-driven sampling from seeds accessing harm reduction services, the results cannot be generalized to all of South Africa or all of KwaZulu-Natal.

Conclusion

The increased prevalence of injection drug use in South Africa along with unsafe injection practices and low uptake of preventative and treatment services, in particular HIV related services, has potential to reverse the significant gains made in HIV prevention services.

Data Availability

The data set has been uploaded to the Open Science Frameworks website and is available at: https://osf.io/6vfbz/.

Funding Statement

This work was supported via Center for AIDS Research at Emory University (P30AI050409); PI: BCZ. The sponsors played no role in the study design, data collection, analysis or decision to publish.

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Decision Letter 0

Benjamin Bearnot

20 Mar 2023

PONE-D-23-01161High risk injection drug use and uptake of HIV prevention and treatment services among people who inject drugs in KwaZulu-Natal, South AfricaPLOS ONE

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Reviewers' comments:

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Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

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Reviewer #1: Yes

Reviewer #2: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: No

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

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Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: PONE-D-23-01161

This is a mixed-methods study (n=45) to understand current drug use practices and access to HIV prevention and treatment services for PWID in KwaZuluNatal, South Africa. The authors used respondent-driven sampling to identify a population at high risk for HIV/viral hepatitis and disconnection from HIV services. The eligible population was individuals who reported injecting opiates within the past 6 months from Durban, KwaZulu-Natal, South Africa. They found high rates of practices that increase HIV/viral hepatitis risk. The author include local unsafe injection practices such as “flashblooding” or “bluetoothing” that could threaten the gains made in HIV prevention and treatment. Of the 35% of participants living with HIV in the sample, only 40% accessed antiretroviral therapy within the past year. There was no prior hepatitis C testing by self report. The importance of this study is access to a high risk population for HIV/hepatitis C, which has been underreported in the literature and has low utilization of HIV and hepatitis C prevention and treatment services. The paper would benefit from a greater emphasis on opportunities for novel program innovation to improve access of HIV/hepatitis prevention and treatment services. I have provided suggestions under major comments for potential avenues for innovation. Please also address how other resource limited countries address high risk injection practices that could be applied to KZN. Overall the paper is well-written and by addressing comments below, should merit publication.

Major comments

Is there any further published literature on bluetoothing / flashblooding or other similar practices in other countries and how the authors’ study findings compare? Please add this to the discussion to set the context of the significance of findings.

The paper could benefit from emphasizing opportunities for high impact novel interventions, in paragraph 2 of the Discussion. For example, the sample noted high rates of homeless and high rates of overdosing. Please address the need and feasibility to address, housing, food security, and Narcan availability, which may improve survival and adherence to harm reduction and HIV/hep C treatment programs? How can HIV/hep C programs be adapted to find this population that has high rates of homelessness.

Furthermore, how do the findings necessitate more locally tailored risk assessments to accurately identify high risk local practices. Are injection drug use risk screening tools adequate to account for practices that include bluetoothing? For example, Dawn K. Smith, Jeffrey H. Herbst et al. doi: 10.1097/ADM.0000000000000123, albeit a U.S. based sample, does not account for local variations in practice. How would more direct solicitation of these practices in one on one interactions reduce stigma and allow consumers of harm reduction services to be more forthcoming of their use?

Please also address how other resource limited countries are addressing high risk injection practices that could be applied to KZN.

Minor comments

Line 24—briefly define endocarditis for the non clinical audience

Results Lines 71 and 72 are a duplication from the methods. Please move the dates of interviews up to the methods Lines 39-41 where the authors report the same information and delete this sentence from the results.

Discussion Line 112-6 -rewrite for better clarity

In addition to the sentence on Line 116, “Nationally, needle exchange programs, harm reduction services, and 117 medication assisted treatment are often difficult to access either due to their high-priced, fee-for118 service models or limited availability. (24)” Can you mention the restrictions on providers to medication assisted treatment /buprenorphine (e.g. are there special restrictions, licenses,/fees required for health care providers to deliver that restricts its implementation?).

Reviewer #2: This is a clearly written, brief report of a mixed methods study of 45 PWIDs in KwaZulu-Natal (KZN). The participants were recruited through respondent driven sampling (RDS) by starting with 3 individuals from a harm reduction center in Durban. It’s commendable that the authors were able to conduct the study during the omicron surge. The quantitative description of characteristics of the 45 individuals, however, resembles the preliminary report of a pilot study that will lay the foundation for a larger project. Of note, the qualitative results are not included in this paper.

The study understandably excluded those who were severely intoxicated or mentally incapacitated because of the need for informed consent but the authors do not provide a consort diagram or other data to indicate how well the 45 participants represent the pool of potential participants. The study surprisingly did not gather information on or otherwise describe the mental health status of the 45 ppts. All of these limitations make it hard to know whether it is reasonable to generalize from these findings to other PWIDs in the KZN region, let along other regions of SA or southern Africa. Perhaps this paper is more suited to a South African scientific journal.

Methods:

There is no justification given for choosing 45 as the size of the study group.

Would be helpful to see a justification for the choice of tools used for the questionnaire; two of the tools have often been used in US settings.

Hard to know to what extent are PWIDs accessing harm reduction programs in KZN when the RDS draws from social networks anchored in a harm reduction program.

Discussion: The main rationale for the study is that injection drug use is on the rise in SA but the citation for this is from ten years ago so is less persuasive ("Without the availability of widespread interventions, injection drug use has continued to increase in South Africa with a prevalence of 0.6% in a population based survey in 2012 with 0.2% reporting Whoonga use. (30)")

**********

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Reviewer #1: No

Reviewer #2: No

**********

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Attachment

Submitted filename: PONE-D-23-01161.docx

PLoS One. 2023 May 12;18(5):e0281030. doi: 10.1371/journal.pone.0281030.r002

Author response to Decision Letter 0


3 Apr 2023

Response to reviewers

RE: High risk injection drug use and uptake of HIV prevention and treatment services among people who inject drugs in KwaZulu-Natal, South Africa– PONE-D-23-01161

April 3, 2023

Dear Journal of PLoS One editorial staff:

We would like to thank the reviewers and editor for their helpful suggestions and comments regarding the manuscripts. We have revised the manuscript and addressed the reviewer concerns as highlighted below and included track changes in the original document. Changes are noted in line numbers from the final clean manuscript. We hope you will find this improved version of the manuscript acceptable for publication in PLoS One. Thank you for your time and consideration.

Reviewer 1:

Major comments:

1. Is there any further published literature on bluetoothing / flashblooding or other similar practices in other countries and how the authors’ study findings compare? Please add this to the discussion to set the context of the significance of findings.

RESPONSE: The published literature on this practice is sparce and why we are eager to publish our findings. We have now included an additional paragraph in the discussion on prior descriptions. Lines 84 – 88.

“The practice of bluetoothing has previously been described in South Africa (1) and has been termed flashblooding in Tanzania.(2, 3, 4, 5) Although practiced in a minority of injection drug users (10% in Tanzania (5) and 18% in our sample), as an extreme version of needle sharing, this practice amplifies the risk of HIV or Hepatitis C acquisition. It has also only been described in areas of poverty and limited access to needle exchanges.”

2. The paper could benefit from emphasizing opportunities for high impact novel interventions, in paragraph 2 of the Discussion. For example, the sample noted high rates of homeless and high rates of overdosing. Please address the need and feasibility to address, housing, food security, and Narcan availability, which may improve survival and adherence to harm reduction and HIV/hep C treatment programs? How can HIV/hep C programs be adapted to find this population that has high rates of homelessness.

RESPONSE: We thank the reviewer for this important point. Unfortunately, there is a lack of evidence-based interventions in LMIC for this population. We included reference for the few interventions in the literature. We have now included this gap in knowledge in our discussion. Lines 94 - 98.

“In addition, access to harm reduction services that included access to housing, food, and naloxone nasal spray may improve survival and adherence to medical therapies.(2) Outreach and mobile medical services targeting the homeless and drug using population could assist in introducing this population to medical services; however, evidence-based interventions for low-to-middle income (LMIC) countries are lacking. (26, 27, 28)”

3. Furthermore, how do the findings necessitate more locally tailored risk assessments to accurately identify high risk local practices. Are injection drug use risk screening tools adequate to account for practices that include bluetoothing? For example, Dawn K. Smith, Jeffrey H. Herbst et al. doi: 10.1097/ADM.0000000000000123, albeit a U.S. based sample, does not account for local variations in practice. How would more direct solicitation of these practices in one on one interactions reduce stigma and allow consumers of harm reduction services to be more forthcoming of their use?

RESPONSE: We agree with the reviewer that elicitation of this practice through typical screening questions is lacking. We have now included this in our discussion. Lines 88 – 89.

“However, screening for this practice is uncommon and should be incorporated into routine interviews with PWID to reduce stigma and allow for targeted harm reduction services.”

4. Please also address how other resource limited countries are addressing high risk injection practices that could be applied to KZN.

RESPONSE: There is very limited data on evidence-based interventions for PWID in LMIC. We highlight a small pilot study done in South Africa (lines 120 - 122); however other evidence is lacking.

“However, small pilot studies have shown high retention rates, opiate reduction, and improvement in mental health in individuals accessing methadone treatment in South Africa.(38)”

And lines: 96 – 98.

“Outreach and mobile medical services targeting the homeless and drug using population could assist in introducing this population to medical services; however, evidence-based interventions for low-to-middle income countries (LMIC) are limited.(26, 27, 28)”

Minor comments

5. Line 24—briefly define endocarditis for the non clinical audience

RESPONSE: We have included a definition of endocarditis: Lines 19 – 21.

“The recent increase in cases of infective endocarditis (infection of the heart typically from blood stream infections) in South Africa is indicative of an increase in injection drug use.(7, 8, 9)”

6. Results Lines 71 and 72 are a duplication from the methods. Please move the dates of interviews up to the methods Lines 39-41 where the authors report the same information and delete this sentence from the results.

RESPONSE: The line was removed from the results section, and we added the dates to the methods section. Lines 41 – 42.

“Recruitment and participation in interviews took place from November 1, 2021 to February 8, 2022.”

7. Discussion Line 112-6 -rewrite for better clarity

RESPONSE: We have rewritten this section. Lines 100 – 104.

“While the COVID-19 pandemic slowed global access to harm reduction and health services to people who use drugs, parts of South Africa saw a positive shift in care for PWID. Traditionally governmental and policing policies were antagonistic toward individuals with drug use disorder; however, some areas began to support the provision of evidence-based harm reduction practices, especially to low-income and homeless people who use drugs.”

8. In addition to the sentence on Line 116, “Nationally, needle exchange programs, harm reduction services, and 117 medication assisted treatment are often difficult to access either due to their high-priced, fee-for118 service models or limited availability. (24)” Can you mention the restrictions on providers to medication assisted treatment /buprenorphine (e.g. are there special restrictions, licenses,/fees required for health care providers to deliver that restricts its implementation?).

RESPONSE: We have included the availability of methadone and buprenorphine in South Africa in lines: 106 – 108.

“Although methadone syrup and sublingual buprenorphine are available and on the Department of Health Essential Medicine List for adult hospitals in South Africa, they are only available by prescription from clinicians through drug dependency programs.”

Reviewer 2:

9. There is no justification given for choosing 45 as the size of the study group.

RESPONSE: This was a pilot study with limited funding which capped our enrollment at 45 participants. This is included in lines 39 – 41.

“These three seed individuals were encouraged to recruit up to three other PWID from their individual social network. Each additional participant was also asked to recruit up to three different individuals from their own social network, until we reached a total sample of 45 participants in this pilot study.”

10. Would be helpful to see a justification for the choice of tools used for the questionnaire; two of the tools have often been used in US settings.

RESPONSE: We use the National HIV Behavior Surveillance System, WHO ASSIST and TCU HIV/Hepatitis Risk Assessment which are all validated tools assessing HIV risk and drug and alcohol use. The WHO ASSIST has been validated in South Africa. There are limited tools on injection drug use that have been validated in South Africa; therefore, we chose instruments that were validated in other settings for similar populations.

11. Hard to know to what extent are PWIDs accessing harm reduction programs in KZN when the RDS draws from social networks anchored in a harm reduction program.

RESPONSE: We acknowledge this limitation and have added it to our limitations section. See lines 132 – 134.

“In addition, since this study was performed with a small sample obtained by respondent-driven sampling from seeds accessing harm reduction services, the results cannot be generalized to all of South Africa or all of KwaZulu-Natal.

12. Discussion: The main rationale for the study is that injection drug use is on the rise in SA but the citation for this is from ten years ago so is less persuasive ("Without the availability of widespread interventions, injection drug use has continued to increase in South Africa with a prevalence of 0.6% in a population based survey in 2012 with 0.2% reporting Whoonga use. (30)")

RESPONSE: Published data on injection drug use is in South Africa is very limited. We have included an additional statement and included more recent references. Lines 120 – 122.

“More recent studies estimate that up to 15% of South African youth engage in drug use.(16, 37)”

Decision Letter 1

Benjamin Bearnot

13 Apr 2023

High risk injection drug use and uptake of HIV prevention and treatment services among people who inject drugs in KwaZulu-Natal, South Africa

PONE-D-23-01161R1

Dear Dr. Zanoni,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Benjamin Bearnot, M.D., M.P.H.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Thank you for your careful attention to the reviewers' comments. Congratulations on the acceptance on this manuscript, and good luck continuing this important line of investigation!

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The reviewer appreciates the receptivity of the authors to feedback and the authors have adequately addressed concerns in the response and in the manuscript. I have no further comments.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

**********

Acceptance letter

Benjamin Bearnot

5 May 2023

PONE-D-23-01161R1

High risk injection drug use and uptake of HIV prevention and treatment services among people who inject drugs in KwaZulu-Natal, South Africa

Dear Dr. Zanoni:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Benjamin Bearnot

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    Attachment

    Submitted filename: PONE-D-23-01161.docx

    Data Availability Statement

    The data set has been uploaded to the Open Science Frameworks website and is available at: https://osf.io/6vfbz/.


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