Hepatitis B, Hepatitis C and HIV Prevalence and Related Sexual and Substance Use Risk Practices Among Key Populations Who Access

Scheibe et al. BMC Infectious Diseases (2020) 20:655 https://doi.org/10.1186/s12879-020-05359-y

RESEARCH ARTICLE Open Access Hepatitis B, hepatitis C and HIV prevalence and related sexual and substance use risk practices among key populations who access HIV prevention, treatment and related services in South Africa: findings from a seven-city cross-sectional survey (2017) Andrew Scheibe1,2* , Katherine Young1, Anna Versfeld1,3, C. Wendy Spearman4, Mark W. Sonderup4, Nishi Prabdial-Sing5,6, Adrian Puren5,6 and Harry Hausler1

Abstract Background: People who use drugs including people who inject drugs (PWUD/ID), sex workers (SWs) and men who have sex with men (MSM) are at increased risk of HIV and viral hepatitis infection. Limited epidemiological data on the infections exists in key populations (KPs) in South Africa. We investigated the prevalence of hepatitis B (HBV), hepatitis C (HCV) and HIV and selected risk factors among these KPs to inform effective responses. Methods: We used convenience sampling to recruit a targeted 3500 KPs accessing HIV-related health services across Cape Town (SWs, MSM, PWUD/ID), Durban (SWs, PWUD/ID), Pietermaritzburg (SWs), Mthatha (SWs), Port Elizabeth (SWs), Johannesburg (MSM) and Pretoria (MSM and PWUD/ID) into a cross-sectional survey. An interviewer questionnaire to assess socio-demographic characteristics, drug use and sexual risk practices, was administered. HBV surface antigen (HBsAg); HCV antibody, viral load and genotype, and HIV antibody, was tested. Results: Among the 3439 people included in the study (1528 SWs, 746 MSM, 1165 PWUD/ID) the median age was 29 years, most participants were black African (60%), and 24% reported homelessness. 82% reported substance use in the last month, including alcohol (46%) and heroin (33%). 75% were sexually active in the previous month, with condom use at last sex at 74%. HIV prevalence was 37% (highest among SWs at 47%), HBsAg prevalence 4% (similar across KPs) and HCV prevalence was 16% (highest among PWUD/ID at 46%). (Continued on next page)

* Correspondence: [email protected] 1TB HIV Care, 11 Adderley Street, Cape Town, South Africa 2Department of Family Medicine, University of Pretoria, Pretoria, South Africa Full list of author information is available at the end of the article

© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Scheibe et al. BMC Infectious Diseases (2020) 20:655 Page 2 of 15

(Continued from previous page) Conclusions: HBV, HCV and HIV pose a health burden for KPs in South Africa. While HIV is key for all included KPs, HCV is of particular importance to PWUD/ID. For KPs, HBV vaccination and behavioural change interventions that support consistent condom and lubricant access and use are needed. Coverage of opioid substitution therapy and needle and syringe services, and access to HCV treatment for PWUD/ID need to be expanded. Keywords: Hepatitis B, Hepatitis C, HIV, HBV, HCV, People who use drugs, People who inject drugs, Sex workers, MSM, Key populations, South Africa

Background women (5.0, 95% CI 3.8–6.2%) (p < 0.01) [10]. Despite Viral hepatitis and HIV are significant public health is- being vaccine-preventable, many people remain at risk sues. Globally, annual approximated deaths from viral for HBV infection. The hepatitis B vaccine was intro- hepatitis are 1.34 million superseding the current 1.3 duced into the expanded programme of immunisation in million from HIV/AIDS [1–3]. This burden is concen- April 1995. The country has not implemented a catch- trated in sub-Saharan Africa; 25.7 million people are liv- up vaccination programme. Infants born to highly vir- ing with HIV [2], 60 million people are chronically aemic HBV-infected mothers are particularly at risk. To infected with hepatitis B (HBV) and 10.2 million people date, there has not been an HBV mother-to-child trans- are chronically infected with hepatitis C (HCV) [1]. mission prevention programme - neither maternal These three infections share similar transmission routes, HBsAg screening nor hepatitis B birth dose vaccination particularly exposure to blood and, to a lesser extent, ex- have been provided - but these are now part of National posure to other bodily fluids [4]. Key populations (KPs) Viral Hepatitis Guidelines [11] with implementation an- include groups of people at increased risk for acquiring ticipated 1. Most HBV infections in South Africa are these infections and for their onward transmission, due horizontally acquired before the age of 5 years [12] (un- to a range of structural, social and behavioural risk fac- like in Asia, where most HBV infections occur peri- tors [4]. People who use drugs including people who in- natally [13]), while HCV and HIV are usually acquired ject drugs (PWUD/ID), men who have sex with men in adulthood [14, 15]. (MSM) and sex workers (SW) are some of the KPs iden- HCV seroprevalence in the general population is esti- tified at increased risk for HIV and viral hepatitis [5]. mated to be < 1% [16]. The routine screening of blood and blood products was introduced in South Africa in 1992. Prior to this, most HCV infections were acquired The South African context from contaminated blood/blood products with injecting In 2017, 7.9 million people were living with HIV in drug use contributing a lesser component [17]. In the ’ South Africa [6]. The county s third National Strategic last decade, evidence of injecting drug use and the po- – Plan on HIV, TB and STIs (2017 2022) outlines the tential spread of HCV through the use of contaminated ’ steps to be taken to end AIDS [7]. South Africa sNa- injecting equipment has been identified in South Africa’s tional Hepatitis Guidelines and Action Plan sketch the major cities [18]. With the advent of direct acting antivi- process for the elimination of viral hepatitis as a public rals (DAAs), HCV can, in most cases, be cured with health threat by 2030 [8]. KPs are represented in these short courses of all-oral therapy [19]. At the time of policies, which collectively call for tailored prevention, writing, no DAAs are registered in South Africa, and are testing and linkage to care services. only accessible through a named patient “section 21” A systematic review of 18 studies (136,356 partici- certificate process via the South African Health Products pants) between 1965 and 2013 estimated that South Af- Regulatory Authority. rica had hepatitis B surface antigen (HBsAg) seroprevalence of 6.7% (95% confidence interval (CI) 6.56–6.83) [9]. A recent household survey in KwaZulu- PWUD/ID Natal (a coastal province in the east of South Africa) of People who use drugs are criminalised, many experien- 9791 participants, 15–49 years old, revealed an overall cing stigma and discrimination because of substance use HBsAg prevalence of 4.0% (95% CI 3.4–4.5%): 4.8% (95% [20]. By the end of 2018, access to needle and syringe CI 3.8–5.8%) in men and 3.2% (95% CI 2.5–3.9%) in programmes was limited to five major metropolitan cit- women (p = 0.01) [10]. HBsAg prevalence was 6.4% (95% ies (Cape Town, Durban, Johannesburg, Port Elizabeth CI 5.3–7.5%) among HIV-positive participants compared and Pretoria) [21] and opioid substitution therapy (OST) – to 2.6% (95% CI 1.9 3.2%) among HIV-negative partici- 1 p Personal communication with Dr. Kgomotso Vilakazi Nhlapo, pants ( < 0.01), and was higher among HIV-positive hepatitis lead at the South African National Department of Health on men (8.7, 95% CI 6.3–11.2%) than among HIV-positive 29 April 2020. Scheibe et al. BMC Infectious Diseases (2020) 20:655 Page 3 of 15

services to Cape Town, Durban, Johannesburg and Very little data on HIV prevalence among male or trans- Pretoria [22]. These services were implemented by civil gender SWs exist and data on viral hepatitis among SWs society organisations. Services did not provide other is unavailable. injecting equipment (for example, cookers) necessary for People may relate to more than one KP grouping. For limiting the spread of blood borne infections, or routine example, an earlier study among PWID (n = 450) found HBsAg or HCV screening and further management [20]. that 25% of male participants had ever had sex with an- Reliable estimates of the number of people in South other man and 9% had ever worked as a sex worker [18]. Africa who use non-regulated or illicit drugs do not Between 11 and 53% of MSM in major urban areas have exist. Based on regional data (2018), the United Nations sold sex to other men [31]. In contrast, a bio- Office on Drugs and Crime estimates the annual preva- behavioural survey among female SWs in three cities lence of substance use among adults (15–64 years) to be (2013–2014) highlighted that less than 0.5% of female 1% for amphetamine-type stimulants (which includes SWs had ever injected a drug [39]. methamphetamine), 1% for cocaine and 0,5% for opioids This study was designed to investigate the prevalence [23]. Epidemiological data on blood borne infections of HBV, HCV and HIV and their co-infections and to among PWUD/ID in South Africa has been limited, describe selected risk factors among KPs in seven South mostly focusing on people who inject drugs (PWID). African cities. Local modelling data and expert consensus suggests there to be between 67,000 and 75,000 PWID in the country [24, 25], with evidence pointing towards increas- Methods ing injecting practices [26]. HIV prevalence among The selection of cities, populations of focus and sample size n were based on implementing partners’ service delivery plat- PWID was 14% in 2013 [18]. A small study ( = 271 2 PWID) in 2012 found an HCV seroprevalence of 24% form, available resources and relative size of each city. Pro- and HBsAg seroprevalence of 7% [27]. As we have pub- spectively, we aimed to recruit 3500 participants from 11 lished elsewhere [28] we found an HIV prevalence of sites across the seven cities. This included 1550 SWs (400 21%, HBsAg seroprevalence of 5% and a HCV seropreva- each in Cape Town and Durban, cities with populations lence of 55% among 943 PWID from 3 cities. above 1,5 million based on the latest census (2011) [40]and 250 each in Pietermaritzburg, Port Elizabeth and Mthatha, MSM smaller cities); 750 MSM (250 each from Cape Town, Despite a constitutionally progressive approach to same Pretoria and Johannesburg); and 1200 PWUD/ID (400 each sex practices, the HIV burden among the estimated 1.2 in Cape Town, Durban and Pretoria). There were more million MSM is high [29]. HIV prevalence across the SW sites due to the larger SW HIV and health service main metropolitan areas ranges from 18% in Bloemfon- programme relative to other KP programmes at the time. tein to 48% in Durban [30, 31]. Less data is available on PWUD/ID were recruited from cities that operated harm viral hepatitis among MSM. A small study among MSM reduction services at a PWUD:PWID ratio of 1:4 due to the in Cape Town identified an HCV seroprevalence of 27% increased risk of blood borne infection transmission (n = 41) and HBsAg prevalence of 2%. Among those through injecting practices. Fewer (250) MSM were re- MSM with positive HCV antibody tests, 80% reported cruited in each city, due to the existence of some data for having injected heroin or methamphetamine in the pre- this population and due to the limited resources available. vious 3 months [32]. Another Cape Town metropolitan Consenting participants self-defined as being 18 years or based study among HIV-infected MSM identified HCV older and having met the following criteria, as relevant, in n the past 12 months i) SW: having exchanged sex for seroprevalence of 6% ( =285)[33]. HIV prevention and 3 treatment programmes for MSM are well established in money ; ii) MSM: having been born biologically male and most urban settings [34], however, little focus has been having had penetrative or receptive oral or anal sex with placed on the integration of viral hepatitis services. 2At the time of study implementation TB HIV Care operated HIV prevention services for SWs (in Cape Town, Port Elizabeth, Durban, SWs Pietermaritzburg) and PWUD/ID (in Cape Town and Durban) There are an estimated 150,029 (137,641 female, 6882 through mobile outreach and from community based health centres. male and 5506 transgender) SWs in South Africa [35]. OUT Wellbeing provided HIV prevention and treatment services to PWUD/ID and MSM in Pretoria through mobile outreach and from a Sex work remains illegal and related discrimination in community based health centre. Anova Health Institute provided HIV communities and healthcare facilities limits access to prevention and treatment services to MSM in Cape Town and health services and undermines effective disease preven- Johannesburg from community based health centres. 3 tion and care [36]. HIV prevalence among female SWs is The sites which recruited sex workers routinely provided services to people who accessed services tailored towards people who identify as particularly high ranging from 37% in Cape Town to sex workers, but no specific distinction was made between 75% in Durban [37], and 88% in Pietermaritzburg [38]. transactional sex and sex work. Scheibe et al. BMC Infectious Diseases (2020) 20:655 Page 4 of 15

another male; iii) PWUD: having used heroin, cocaine or conducting the questionnaire. All other study documen- methamphetamine and iv) PWID: having injected a sub- tation, including blood samples, used unique participant stance for non-therapeutic purposes, irrespective of the identification codes. type of drug injected or the mode of injection. For HIV, HBV and HCV point-of-care (POC) testing, Convenience sampling was used with the study blood was drawn. POC HIV testing was done in line conducted as an extension of existing HIV prevention, with national protocols [41]. POC HBsAg testing was sexual health and harm reduction services provided by performed using the Determine™ HBsAg (Alere Inc., non-profit organisations targeting KPs in the respective MA, USA). POC HCV testing was done using OraQuick® cities. Each of the service providers operate dedicated HCV rapid antibody test (Orasure Technologies Inc., teams that provide targeted services to specific KPs they PA, USA). Samples that were HCV POC reactive were already served. In Cape Town, for example, routine sent to the National Institute for Communicable Dis- health services for SWs and PWUD/ID were provided eases (NICD) in Johannesburg for anti-HCV testing by a single service provider out of a single physical loca- (ARCHITECT Anti-HCV assay) on the ARCHITECT tion, but were provided in parallel by different mobile i1000SR system (Abbott Laboratories, Diagnostics Div- teams and were designated as two distinct study sites ision, IL, USA). The COBAS® AmpliPrep/COBAS® Taq- recruiting SW or PWUD/ID respectively. Although there Man® HCV Quantitative Test v2.0 on the COBAS® is alignment of services, each site tended to have separ- Ampliprep Taqman® Analyzer (Roche Molecular Sys- ate clients depending on how the clients themselves best tems, CA, USA) was used for quantitative assessment of identified. Participants recruited through a SW site and HCV antibody positive samples. PCR amplification and who met inclusion criteria would have been counted as HCV genotyping was performed using the Versant LiPA a SW irrespective of substance use behaviour and vice amplification and Versant HCV genotyping 2.0 assays versa for PWUD/ID. Similarly, at MSM sites, people (LiPA, Innogenetics, Ghent, Belgium), respectively. accessing HIV testing and/ or treatment services were Study team members provided participants with ap- informed about the study and invited to participate and propriate counselling, condoms and lubricant, and would have been recruited as MSM. Refreshments were PWID received sterile injecting equipment. Participants offered during the last month of the study’s recruitment who screened positive for HBV or who were diagnosed period to encourage enrolment at PWUD/ID sites to with confirmed HIV or HCV infection were referred to a meet the recruitment targets within the time frame allo- pre-identified health facility for work-up and/or assess- cated for fieldwork. ment for treatment. HBV vaccination was offered to all Data collection took place between August 2016 and clients who were HBsAg POC negative4. October 2017. In all cases, a study team member admin- Anonymised data was imported into STATA 14.0 (Sta- istered a standard, confidential health-screening ques- tacorp LLC, Texas, USA) for data analysis. Data was tionnaire to participants who provided written informed analysed using descriptive statistics (proportions, me- consent. The questionnaire captured data on demo- dians and inter quartile range (IQR)), stratified by KP. graphics (age, sex, race and housing), substance use Age was also categorised based on age groups used by (substances used in the last month and injecting in the the Joint United Nations Programme on HIV/AIDS, last month, including injecting frequency, needle and with a binary cut off value of 25 years [42]. Racial group- syringe reuse and sharing), use of opioid substitution ings were based on those used by Statistics South Africa therapy and sexual risk behaviour (condom use, penile- [43]. POC seroprevalence was calculated for HIV and vaginal intercourse, anal intercourse, transactional sex HBsAg. HBsAg seroprevalence was also calculated for and substance use in the context of sex) and prior health people born before and after the introduction of child- screens and previous HIV testing. hood HBV vaccination in 1995. Anti-HCV prevalence The paper-based questionnaire was completed in was based on laboratory results. The HCV viraemic rate English and administered in private spaces. Where is the number of participants with detectable HCV RNA closed rooms were not possible, questionnaires were with laboratory based anti-HCV antibody confirmation. completed out of earshot of other people and then filed The study was approved by the Human Research Eth- and locked away. The questionnaire captured partici- ics Committee of the University of Cape Town (ref: 004/ pants’ names, surnames, dates of birth and included a 2016), the Research Ethics Committee of the University participant identification code. Participants were not ob- of the Witwatersrand (ref: M160510) as well as the East- ligated to provide identifying information. Service pro- ern Cape (ref: EC_2016RP19_818), Western Cape (ref: viders and study staff were all trained in ethical research practices and signed research confidentiality agreements. 4This decision was made based on the acceptable safety profile and Access to participant names and surnames was restricted tolerance of HBV vaccination and insufficient funds for additional to clinicians providing health services and staff HBV testing. Scheibe et al. BMC Infectious Diseases (2020) 20:655 Page 5 of 15

WC_2016RP19_818) and KwaZulu-Natal (ref: KZN_ where male SWs were recruited (12%, 47/284). PWUD/ 2016RP59_986) Provincial Department of Health Ethics ID were predominantly male (85%, 999/1175). Almost a Committees. Participants did not receive any remuneration. quarter of participants (23%, 807/3439) were between the ages of 18 and 24 years. Age did not vary particularly Findings between KP sub-groups – with 2 exceptions: in Mthatha, In total, 3509 participants were recruited and enrolled. Sev- 42% (104/248) of SWs were under 25 years of age and in enty participants were excluded from the per protocol ana- Cape Town PWUD/ID were older, with only 8% (28/ lysis. Reasons for exclusion included: ineligibility (did not 367) under 25 years. PWUD/ID disproportionately re- meet criteria for KP) (n = 23), study informed consent form ported homelessness; ranging from 55% (201/367) in could not be located (n = 11), source documents missing Cape Town to 70% (278/398) in Durban. In Cape Town, (n = 4), error in testing procedure for HBV and/or HCV or SWs also reported higher levels of homelessness (17% test not done (n = 32). In a per protocol analysis, 3439 KP (66/384)) than were reported in other SW groups. were included (1528 SWs, 746 MSM, 1165 PWUD/ID). Substance use Socio-demographics Overall, 82% (2818/3439) of participants reported use of Table 1 outlines socio-demographics. Participants’ me- at least one substance in the previous month. Alcohol dian age was 29 (IQR 25–35) years. Most participants was the most commonly reported substance used (46%, were black (60%, 2078/3439). SWs were almost exclu- 1568 / 3439), and use was higher among SWs and MSM sively female, in all locations other than Cape Town, than among PWUD/ID. Heroin (known locally as

Table 1 Participants’ socio-demographic characteristics (n = 3439) SWs (n = 1528) MSM (n = 746) PWUD/ID (n = 1165) TOTAL CT PE Mthatha DBN PMB CT JHB PTA CT DBN PTA N 384 248 248 399 249 250 250 246 367 398 400 3439 Age Median 31 28 26 30 27 31 29 29 31 27 30 29 (IQR) (26–37) (24–35) (23–30) (25–35) (24–31) (26–39) (24–34) (24–37) (28–35) (25–31) (26–34) (25–35) < 25 years 80 78 104 90 78 49 68 65 28 96 71 807 (21%) (31%) (42%) (23%) (31%) (20%) (27%) (26%) (8%) (24%) (18%) (23%) ≥ 25 year 304 170 144 309 171 201 182 181 339 302 329 2632 (79%) (69%) (58%) (77%) (69%) (80%) (73%) (74%) (92%) (76%) (82%) (77%) Sex Female 337 247 248 397 246 0006942 55 1641 (88%) (> 99%) (100%) (> 99%) (99%) (19%) (11%) (14%) (48%) Male 47 1 023 250 250 246 298 356 345 1798 (12%) (< 1%) (< 1%) (1%) (100%) (100%) (100%) (81%) (89%) (86%) (52%) Racea Black 106 182 247 369 249 102 197 118 15 (4%) 218 275 2078 (28%) (73%) (99%) (92%) (100%) (41%) (79%) (48%) (55%) (69%) (60%) Coloured 247 49 0120479 9 274 45 13 705 (64%) (20%) (3%) (19%) (4%) (4%) (75%) (11%) (3%) (21%) White 18 17 0509237 109 71 96 109 554 (5%) (7%) (1%) (37%) (15%) (44%) (19%) (24%) (27%) (16%) Indian/ Asian 1 90 10042 4 1 39 1 62 (< 1%) (3%) (2%) (1%) (2%) (< 1%) (10%) (< 1%) (2%) Other 12 01 3 055 6 6 0240 (3%) (< 1%) (1%) (2%) (2%) (2%) (2%) (1%) (1%) Homeless 66 1 000141 3 201 278 262 826 (17%) (< 1%) (6%) (< 1%) (1%) (55%) (70%) (66%) (24%) General 3,740,026 1,152,115 451,710 3,442,361 618,536 3,740,026 4,434,827 2,921,488 3,740,026 3,442,361 2,921,488 populationb aBased on race categories used by Statistics South Africa. Coloured is a South African term which refers to people of mixed ancestry. The national distribution of race is: Black 80,9%, Coloured 8,8%, White 7,8%, Indian/ Asian 2,5% [43] bPopulation of municipality based on most recent census (2011) CT Cape Town, DBN Durban, JHB Johannesburg, PE Port Elizabeth, PMB Pietermaritzburg, PTA Pretoria Scheibe et al. BMC Infectious Diseases (2020) 20:655 Page 6 of 15

nyaope or whoonga) was the most frequently reported il- more MSM last injected methamphetamine than legal/unregulated substance used in the last month (33%, PWUD/ID (18% (4/22) versus 6% (15/243)) and injected 1138/3439) followed by methamphetamine (14%, 486/ at a lower frequency (64% (14/22) injecting less than 4 3439), cannabis (13%, 433/3439), cocaine (6%, 204/3439) times a day, versus 74% (179/243) injecting 4 or more and methcathinone (2%, 68/3439) (Table 2). Almost all times per day, respectively). A similar pattern was seen PWUD/ID had used heroin in the last month, ranging among MSM reporting injecting in the last month in from 82% (300/367) in Cape Town to 99% (394/398) in Pretoria compared to male PWUD/ID counterparts, with Durban. Methamphetamine use in the last month was 75% (6/8) MSM reporting to have last injected metham- highest in Cape Town across all three sub-groups: 80% phetamine while 99% PWUD/ID (268/270) last injected of PWUD/ID (293/367), 28% of SWs (107/384) and 11% heroin. Most Pretoria MSM who injected, reported less of MSM (27/250). PWUD/ID living in Pretoria had the frequent injecting when compared to male PWUD/ID highest reported use of cannabis (30%, 121/400) and co- with 63% (5/8) injecting less than 4 times a day, com- caine (30%, 118/400). This was substantially higher than pared to 73% of PWUD/ID (196/ 270) injecting 4 or that reported for any other KP sub-group or region for more times per day. all three substances. Cannabis use in other KPs was vari- Five percent (54/1138) of all participants who reported able, ranging from zero among SWs in Mthatha to about having used heroin in the last month also reported tak- one-fifth of MSM in Johannesburg. ing some form of OST for the last 30 days or more. In the complete cohort, 28% reported injecting a drug in the last month (952/3439). Among PWUD/ID, close Sexual risk practices to 80% reported injecting a drug in the last month. No Sexual activity in the past month was reported in 75% SWs reported having injected any drug in the last (2589/3439) of all participants - highest among SWs month; in this group the reported heroin use was (98%) (Table 3). MSM reporting sexual activity in the through smoking or inhalation. Injecting in the last last month varied from 69% (169/246) in Pretoria to 79% month among MSM ranged from 3% in Johannesburg (197/250) in Cape Town. Sexual activity was lowest and Pretoria (8/250 and 8/236, respectively) to 9% in among PWUD/ID; ranging from 29% (114/400) in Cape Town (22/250). In Cape Town, proportionately Pretoria to 55% (217/398) in Durban.

Table 2 Substance use practices among participants (n = 3439) SWs (n = 1528) MSM (n = 746) PWUD/ID (n = 1165) TOTAL CT PE Mthatha DBN PMB CT JHB PTA CT DBN PTA N 384 248 248 399 249 250 250 246 367 398 400 3439 Substances used in last month Any substancea 296 216 194 305 160 176 199 119 361 396 396 2818 (77%) (87%) (78%) (76%) (64%) (70%) (80%) (48%) (98%) (99%) (99%) (82%) Alcohol 217 205 194 295 148 152 192 102 29 19 15 1568 (56%) (83%) (78%) (74%) (59%) (61%) (77%) (42%) (8%) (5%) (4%) (46%) Heroinb 32 1 001217 3 1 300 394 378 1138 (8%) (< 1%) (5%) (7%) (1%) (< 1%) (82%) (99%) (95%) (33%) Methamphetamine 107 17 021 27 11 6 293 8 14 486 (28%) (7%) (1%) (< 1%) (11%) (4%) (2%) (80%) (2%) (4%) (14%) Cannabis 55 14 0329 39 43 31 45 44 121 433 (14%) (6%) (8%) (4%) (16%) (17%) (13%) (12%) (11%) (30%) (13%) Cocaine 12 00 314 11 4 2 9 13 118 204 (3%) (8%) (2%) (4%) (2%) (1%) (2%) (3%) (30%) (6%) Methcathinone 4 2 02008 11 10 1 1 11 68 (1%) (1%) (5%) (3%) (4%) (4%) (< 1%) (< 1%) (3%) (2%) Injected a drug in the last 12 00000249 8 292 315 313 961 months (10%) (4%) (3%) (80%) (79%) (79%) (28%) Injected a drug in last month 00000228 8 290 313 311 952 (9%) (3%) (3%) (79%) (79%) (78%) (28%) Currently on OST for ≥ 30 days 0000071 1 12 16 21 58 (3%) (< 1%) (< 1%) (3%) (4%) (5%) (2%) aRefers to any of the substances listed in this table bHeroin is known locally as nyaope and whoonga CT Cape Town, DBN Durban, JHB Johannesburg, PE Port Elizabeth, PMB Pietermaritzburg, PTA Pretoria Scheibe et al. BMC Infectious Diseases (2020) 20:655 Page 7 of 15

Table 3 Sexual risk practices (n = 3439) SWs MSM PWUD/ID Total (n = 1528) (n = 746) (n = 1165) CT PE Mthatha DBN PMB CT JHB PTA CT DBN PTA N 384 248 248 399 249 250 250 246 367 398 400 3439 Sexually active in the last month 376 244 245 396 248 197 189 169 194 217 114 2589 (98%) (98%) (99%) (99%) (> 99%) (79%) (76%) (69%) (53%) (55%) (29%) (75%) Number of people had sex with in last week, if 5 3 2 8 4 1 1 1 1 1 1 2 sexually active (median, IQR) (3–10) (2–6) (1–5) (5–10) (2–6) (1–1) (0–1) (0–1) (1–1) (1–1) (1–1) (1–5) Penile-vaginal sex in last week 361 240 246 397 245 8 9 10 178 208 100 2002 (96%) (97%) (> 99%) (100%) (98%) (3%) (4%) (4%) (49%) (52%) (25%) (59%) Condom used at last penile-vaginal sex among 339 147 81 397 230 6 4 3 95 122 61 1485 those who had penile-vaginal sex in last week (93%) (61%) (34%) (100%) (94%) (75%) (44%) (30%) (53%) (59%) (61%) (74%) Receptive anal intercourse in last week 49 7 9 82 9 91 76 81 4 03 411 (13%) (3%) (4%) (21%) (4%) (36%) (30%) (33%) (1%) (1%) (12%) Condom used at last receptive anal sex among 41 7 0817 53 45 51 2 03 290 those who had receptive anal intercourse in (84%) (100%) (99%) (78%) (58%) (59%) (63%) (50%) (100%) (71%) last week Lubricant used at last receptive anal sex among 30 1 0765 71 67 72 2 01 325 those who had receptive anal intercourse in (61%) (14%) (95%) (56%) (78%) (88%) (90%) (50%) (33%) (80%) last week Drugs/ goods received in exchange for sex in 40 137 204 3 26 10 7 1 17 2 10 457 last month (10%) (55%) (82%) (1%) (10%) (4%) (3%) (< 1%) (5%) (1%) (3%) (13%) Money received in exchange for sex in last 363 212 244 388 240 13 9 3 18 7 16 1513 month (95%) (85%) (98%) (97%) (96%) (5%) (4%) (1%) (5%) (2%) (4%) (44%) Alcohol or substance use at last sex 253 124 133 290 11 65 87 54 129 5 162 1313 (66%) (50%) (54%) (73%) (4%) (26%) (35%) (22%) (35%) (1%) (41%) (38%) CT Cape Town, DBN Durban, JHB Johannesburg, PE Port Elizabeth, PMB Pietermaritzburg, PTA Pretoria

Among SWs, almost all (96–100%) had engaged in at last receptive anal sex act varied from none in penile-vaginal sex in the last week. Condom use at last Mthatha to 95% (76/82) in Durban. penile-vaginal sex was lowest in Mthatha (34%, 81/248) Overall, 38% (1313/3439) of participants reported and over 90% in Cape Town, Durban and Pietermaritz- substance use at last sex. This was generally highest burg (93%, 339/384; 100%, 397/397 and 94%, 230/249, among SWs (53%, 811 / 1528), who mainly reported respectively). PWUD/ID reports of penile-vaginal sex in using alcohol, with those in Durban reporting the high- the last week was lowest in Pretoria (25%, 100/400) and est prevalence (73%, 290/399). Among PWUD/ID, highest in Durban (52%, 208/398). Among these, re- substance use at last sex ranged from 1% (5/400) in ported condom use at last penile-vaginal sex was 61% Pretoria to 35% (129/398) in Durban. Among MSM, (61/100) and 59% (122/208) in Pretoria and Durban, substance use at last sex was more consistent varying be- respectively. tween 22% (54/246) in Pretoria to 35% (87/250) in Receptive anal intercourse was reported by 12% (411/ Johannesburg. 3439) of participants overall. Very few (< 1%, 7/1165) PWUD/ID reported receptive anal intercourse. One Access to HIV services third (33%, 248/746) of MSM reported receptive anal Overall, for 11% (373/3439) of study participants it was intercourse in the last week. Of these, 60% (149/248) the first time that they had ever had a health screen and reported condom use at last receptive anal sex with 85% been tested for HIV. PWUD/ID had the highest levels of (210/248) reporting the use of lubricant. A total of 156 first health screens and HIV tests, with the majority of SWs reported receptive anal sex in the last week, highest their previous contacts being linked to accessing sterile in Durban (21%, 82/399). Seventeen male SWs reported injecting equipment. A quarter of all participants (25%, anal sex in the last week, all from Cape Town. Condom 867/3439) reported to be HIV-infected at the time of use at last receptive anal sex in SWs was generally high, participation, ranging from 2% among PWUD/ID in between 78% (7/9) in Pietermaritzburg to 99% (81/82) Cape Town and Pretoria (9/367 and 9/400, respectively) and 100% (7/7) in Durban and Port Elizabeth, respect- to 62% (154/249) among SWs in Pietermaritzburg. The ively. None of the nine women engaging in receptive proportion of people living with HIV reporting current anal sex in Mthatha reported condom use. Lubricant use antiretroviral therapy (ART) was highest among MSM Scheibe et al. BMC Infectious Diseases (2020) 20:655 Page 8 of 15

recruited from MSM health clinics (93%, 255/274) and 17) were HIV infected, 6% (1/17) HBV infected, one per- lowest among PWUD/ID recruited largely as part of son had HIV-HBV co-infection and no HCV infections community outreach activities (41%, 21/51) (See were detected. Among 4 male PWUD/ID reporting anal Table 4). intercourse in the last week, half were either HCV or HIV infected with one HIV-HCV co-infected; none were Testing results HBV infected. Details of the testing results are provided in Table 5. Of the 38 participants recruited from MSM sites HIV prevalence was 47% (711/1528) among SWs, 43% reporting injecting drugs in the last month, HCV preva- (320/746) among MSM and 19% (227/1165) among lence was 37% (14/38) [45% (10/22) in Cape Town, 38% PWUD/ID. HIV prevalence was highest among SWs in (3/8) in Johannesburg and 13% (1/8) in Pretoria], HIV Pietermaritzburg at 80% (199/249) and lowest among prevalence was 37% (14/38) [23% (5/22) in Cape Town, PWUD/ID in Cape Town (6%, 22/367). There was con- 63% (5/8) in Johannesburg and 50% (4/8) in Pretoria)] siderable variation in prevalence of HIV between cities and HBV prevalence 3% (1 infection in Cape Town). among SWs and PWUD/ID but it remained fairly similar Median HCV viral load was 5.45 log10 IU/ml (IQR among MSM. 4.81–5.95). PWUD/ID had a higher median viral load HBsAg positivity was 4% (141/3439), ranging from 2% compared to MSM, which was not statistically signifi- (6/246) among MSM in Pretoria to 5% among PWUD/ cant (5.38 versus 5.18 log10IU/ml, p = 0.3). Genotyping ID in Cape Town (20/367) and Pretoria (20/400) and was achieved in 92% (400/435). The most prevalent SWs in Pietermaritzburg (13/249). HBsAg positivity was HCV genotypes were 1a (74%, 296/400) and 3a (14%, 1% (3/307) among people born after 1995 (the year that 56/400). Mixed genotype infections were seen in 11 childhood immunisation was implemented) and 4% PWUD/ID with most from Cape Town (6/11). Genotype (138/3132) among those born before 1995. 4 was found only in MSM. Of note, no genotype 5 was In PWUD/ID, anti-HCV ranged from 28% (113/318) detected (see Table 6). in Durban to 72% (288/400) in Pretoria, with an HCV viraemic rate of 80% (90/113) and 79% (227/288), re- Discussion spectively. Six percent (16/250) of MSM in Cape Town This is the largest and most comprehensive investigation had detectable anti-HCV antibodies, among whom all of HBV, HCV and HIV among KPs in South Africa to but one had detectable HCV RNA. Only one SW was date. The study confirms earlier research highlighting anti-HCV antibody positive but not viraemic. The over- the high HIV burden among these populations [16]. all viraemic rate was 78% (436/558). Most importantly, it documents the alarmingly high Overall, 5% (158/3439) were HCV-HIV co-infected, seroprevalence of HCV infection among PWUD/ID and was highest among PWUD/ID in Pretoria (28%, (46%). 113/400). Thirteen percent (158/1258) of HIV-infected study Demographics participants were HCV co-infected; highest among This study follows South African census distinctions of PWUD/ID in Pretoria (81%, 113/140). race. These remain relevant because education, socio- The overall prevalence of HCV-HBV co-infection was economic status and socio-cultural norms continue to less than 1, and 2% (75/3439) were HIV-HBV co- map onto apartheid-era categories to some extent. In infected. Ten participants were HCV-HBV-HIV triple- 2015, 81% of the population self-defined as Black, 9% as infected, all of whom where PWUD/ID. Coloured, 8% as White and 3% as Indian/Asian. The Among male SWs reporting anal intercourse in the Western Cape has the highest proportion of people clas- last week (all of whom were from Cape Town), 41% (7/ sified as Coloured (50% of the population) [43], partially

Table 4 Health care access (n = 3439) SWs (n = 1528) MSM n = 746) PWUD/ID (n = 1165) Total CT PE Mthatha DBN PMB CT JHB PTA CT DBN PTA N 384 248 248 399 249 250 250 246 367 398 400 3439 First health-screen that includes HIV 19 2 2 0115 2 3 58 86 184 372 testing (5%) (1%) (1%) (< 1%) (6%) (1%) (1%) (16%) (22%) (46%) (11%) Self-reported HIV + ve 18 67 109 194 154 90 110 74 9 33 9 867 (5%) (27%) (44%) (49%) (62%) (36%) (44%) (30%) (2%) (8%) (2%) (25%) Self-reported in care on ART, if self- 8 54 93 168 134 87 97 71 1 12 8 733 reported HIV-infected (44%) (81%) (85%) (87%) (87%) (97%) (88%) (96%) (11%) (34%) (89%) (84%) CT Cape Town, DBN Durban, JHB Johannesburg, PE Port Elizabeth, PMB Pietermaritzburg, PTA Pretoria Scheibe et al. BMC Infectious Diseases (2020) 20:655 Page 9 of 15

Table 5 HIV, HBsAg, anti-HCV, HCV PCR prevalence and HCV viraemic rate among participants (n = 3439) SWs (n = 1528) MSM (n = 746) PWUD/ID (n = 1165) TOTAL CT PE Mthatha DBN PMB CT JHB PTA CT DBN PTA N 384 248 248 399 249 250 250 246 367 398 400 3439 HIV + ve 69 90 133 220 199 101 122 97 22 65 140 1258 (18%) (38%) (56%) (55%) (80%) (40%) (49%) (41%) (6%) (16%) (35%) (37%) HBsAg + ve 13 8 10 17 13 9 10 6 20 15 20 141 (3%) (3%) (4%) (4%) (5%) (4%) (4%) (2%) (5%) (4%) (5%) (4%) Anti-HCV + ve ELISA 1 00 00163 1 136 113 288 558 (< 1%) (6%) (1%) (< 1%) (37%) (28%) (72%) (16%) HCV viral load detectable 000 00152 0 102 90 227 436 (6%) (1%) (28%) (23%) (57%) (13%) HCV viraemic rate (among anti_ 0 0 0 0 0 94% 67% 0 75% 80% 79% 78% HCV + ve) Anti-HCV-HIV co-infection 000 0063 1 10 25 113 158 (2%) (1%) (< 1%) (3%) (6%) (28%) (5%) Anti-HCV prevalence among HIV + ve 000 0063 1 10 25 113 158 participants (6%) (2%) (1%) (45%) (38%) (81%) (13%) Anti-HCV-HBV co-infection 000 0010055 17 28 (< 1%) (1%) (1%) (4%) (< 1%) HIV-HBsAg co-infection 5 3 9 13 12 5 7 3 3 6 9 75 (1%) (1%) (4%) (3%) (5%) (2%) (3%) (1%) (1%) (2%) (2%) (2%) HIV-anti-HCV-HBV co-infection 000 00000028 10 (1%) (2%) (< 1%) CT Cape Town, DBN Durban, JHB Johannesburg, PE Port Elizabeth, PMB Pietermaritzburg, PTA Pretoria

explaining the proportionally higher number of Coloured people in Cape Town in each demographic category included in this study. MSM were recruited from existing, specialised fixed site sexual health clinics. These served people from a Table 6 HCV genotype among participants with detectable wide range of socio-economic circumstances, reflected n HCV viral load ( = 400) in the comparatively higher number of white MSM (up SW MSM PWUD/ID Total to 44% in Pretoria) included in the study and the lower Genotype 1 314 rates (1 to 6%) of people who reported homelessness. 1011112SWs were recruited through a combination of fixed 1a 0 12 284 296 sites and mobile services. Nationally, 5% of SWs are estimated to be male, a figure relatively stable across prov- 1b 0 0 6 6 inces [35] but this was not reflected in the study (< 1% Genotype 3 71 SWs male). Low numbers of SWs reporting homeless- 3011112ness may be because income generated from SW pro- 3a 0 0 56 56 vides a means of paying for accommodation. Another 3c 0 0 3 3 explanation may be that current SW services are not Genotype 4 4 reaching homeless SWs. PWUD/ID were largely recruited at locations where 402 2 mobile needle and syringe distribution and collection 4a/4c/4d 0 2 2 services where provided. The higher numbers of men Mixed genotype 11 who use drugs included in this study reflects program- 1a and 3 0 0 1 1 matic data that indicates higher numbers of men (be- 1a and 3a 0 0 8 8 tween 87 and 90%) to be using harm reduction services 1a and 3c 0 0 1 1 [44]. The low proportion of females who use drugs in this and other local studies [17, 44] is likely also reflect- 1b and 3a 0 0 1 1 ive of the gender distribution of PWUD/ID. Female- Total 0 18 382 400 specific barriers to services – including a lack of tailored Scheibe et al. BMC Infectious Diseases (2020) 20:655 Page 10 of 15

services and higher rates of stigma and discrimination among PWID [54, 55]. However genotype 5a (a experienced by women who use drugs [45] – likely also unique and prevalent genotype) was not found. A affected the number of female PWUD/ID in this study. study of blood samples from patients attending spe- The need for gender-appropriate and specific HIV and cialist clinics (n = 941) and blood donors (n = 294) be- HCV services for women who use drugs is increasingly tween 2008 and 2012 identified genotype 5a to be recognised locally [46], regionally [47] and globally [48]. common among specialist clinic patients (36%) and The high levels of homelessness among PWUD/ID likely particularly common (60%) among people over 50 reflects the socio-economic circumstances of PWUD/ID years old in both groups, and among Black African who used the services and/or who were accessible by the people (54%) [56]. The lack of genotype 5a in this study team. PWUD/ID with financial means could ac- study suggests that the modes of transmission of cess prevention commodities and supplies from pharma- identified genotypes among PWUD/ID and other KPs cies and/or through the private healthcare system. differs from older patients attending specialist clinics, some of whom contracted HCV through blood trans- HBV fusions and unsafe medical injections [57], traditional The overall HBsAg prevalence of 4% is similar to the practices such as tribal scarification [58] or unknown general population [9, 45] with a marked difference be- risks. tween those born before and after the introduction of HBV childhood immunisation (4% versus 1%). This find- HIV ing provides additional evidence supporting the benefit Lower levels of self-reported HIV status compared with of the introduction of childhood HBV vaccination in measured prevalence (25 and 37% respectively) has been 1995. However, some people born after this date have documented previously in South African KPs [59]. The acquired HBV infection. The overall coverage of the 3- fact that 25% of participants indicated that this was their dose HBV vaccine schedule in South Africa was esti- first health-screening (including HIV testing) may indi- mated to be 74% in 2016 [49], and the birth dose vaccine cate that a large number of people were genuinely un- to prevent mother-to-child transmission is yet to be aware of their status due to fears of testing or competing implemented. priorities. This discrepancy may also relate to reporting bias and internalised stigma, fear of knowing one’s status HCV prevalence and fears of acknowledging positive status while not on The HCV findings are anticipated yet alarming, despite ART [60]. the study bias towards KPs who access HIV prevention, In Cape Town and Pretoria, HIV prevalence was not- treatment and related services. Globally, HCV is a par- ably higher among the few MSM reporting recent inject- ticular concern among PWID [50], with high prevalence ing compared to their male PWUD/ID counterparts. being documented in Africa, ranging from 30% among The different HIV prevalence may be linked to the re- PWID accessing opioid substitution therapy in Tanzania cruitment of MSM from well-established clinics that [51] to 97% of PWID in Mauritius [52]. Our findings have been providing HIV treatment for MSM for several show PWUD/ID carried the highest HCV burden with years, and the elevated risk among MSM who engage in some marked geographic variations. The extremely high multiple high-risk practices. rates of HCV seroprevalence in PWUD/ID in Pretoria Overall reported use of ART, at 84%, was below the (72%) is possibly due to the relatively longstanding na- 90% target for people living with HIV, but higher ture of this injecting community, with sub-optimal ac- than the national average of 57% [61],likelyaconse- cess to prevention interventions [53]. Viraemic rates at quence of the fact that participants were accessed the upper limit (75–80%) of what would be anticipated through HIV service delivery platforms. The wide may point towards repeated infections [46]. Equally, range across cities and populations (from 11% in HCV seroprevalence in MSM, with high HIV-HCV co- PWUD/IDinCapeTownto96%MSMinPretoria) infection prevalence, is expected given the risks of HCV also likely reflects which services are being primarily infection among MSM, especially in HIV positive MSM accessed at the included organisations by the target and MSM with a history of injecting drug use [32]. The populations. The relatively lower levels of ART cover- almost non-existent HCV seroprevalence among SW is age reported among PWUD/ID (51%) further likely supported by the low rate of injecting drug use and high reflects the numerous barriers affecting ART uptake condom use in this sample. [20]inthispopulation. The circulating prevalence of HCV genotypes 1a and 3a is similar to other countries where HCV infec- Blood borne virus co-infections tion is networked and predominantly spread through A global systematic review and meta-analysis of the the sharing of contaminated injecting equipment prevalence and burden of HCV co-infection in people Scheibe et al. BMC Infectious Diseases (2020) 20:655 Page 11 of 15

living with HIV reported a 6% coinfection prevalence in instances with multiple sex partners. This can be contin- MSM and 82% in PWID compared to 2% within the ued for long durations (up to days), and has been identi- general population [62]. In comparison, our findings in- fied as a risk factor for HIV and viral hepatitis in other dicate 3% HCV co-infection prevalence in MSM living countries [66, 67]. with HIV and 65% in PWUD/ID living with HIV. A No SWs recruited reported injecting, however, net- South African study among antenatal attendees living works of SWs who inject drugs have been reached with HIV found HCV prevalence of 0.1% [63]. through more recent harm reduction and sex worker Overall 2% were HIV-HBV co-infected with similar programmes operating in Johannesburg.5 Risks involved prevalence in all 3 KPs. in substance use are exacerbated by the criminalisation The number of participants who were co-infected with of drug use, limited access to harm reduction services, HIV/HBV or HIV/HCV, or HCV-HBV-HIV triple- and discriminatory treatment within healthcare service infected is cause for concern given the extent to which settings [68]. co-infections can accelerate and amplify disease [5]. There is therefore the need for screening for co- Sexual practices infections in KPs especially HIV-infected PWUD/ID. Sexual practices, unsurprisingly, differed considerably Viral hepatitis awareness programmes that emphasise between KP sub-groups. SWs were more likely to re- the risk of co-infections and reinfection and provide pre- port recent sexual activity, multiple partners, transac- vention strategies need to be up-scaled across all cities tional sex and substance use at last sex as well as in South Africa for all KPs. The importance of preventa- having the highest reported condom use, in general. tive HBV vaccination needs to be stressed and routine Local research among female SWs in South Africa access to vaccination at all levels of care is essential. has identified high reported levels of condom use in major metropolitan areas (89% in Cape Town and Risk practices 84% in Durban) [39]. Risks for these blood-borne infections are exacerbated SWs in this study were least likely to report lubricant by a host of social and structural factors including lim- use in relation to receptive anal sex. Little data exists on ited access to opioid substitution therapy and needle and the use of lubricant during anal sex among SWs. Data syringe services for PWID; criminalisation of sex work from a three city bio-behavioural survey among female and drug use and corresponding marginalisation and dif- SWs in Cape Town, Johannesburg and Durban showed ficulty accessing healthcare (for PWUD/ID and SWs) that only a quarter of female SWs were aware of lubri- and homelessness (largely PWUD/ID). cant, with low levels of reported use [39]. The greatest regional variation in sexual practices was Substance use also seen among SWs. Those in the Mthatha region In addition to alcohol, the high reported use of heroin is were more likely to engage in high-risk sex, with lower of concern. Though the majority of heroin used in South condom use and a greater propensity to engage in sex in Africa is smoked [44], it is also the most commonly exchange for goods and commodities. In contrast, those injected drug among PWID [28]. The HIV and viral working in KwaZulu-Natal, reported much higher con- hepatitis risks related to heroin are largely through dom use and almost exclusively received money in ex- injecting, with heroin dependant people injecting on change for sex. This may suggest lower negotiating average four times per day [28]. Methamphetamine use power of sex workers in Mthatha and could explain the is more common in Cape Town than in the other cities. markedly lower rates of condom use at last penile- HIV and viral hepatitis risks relating to methampheta- vaginal sex reported there. Elsewhere, penile-vaginal mine use are either indirect, through sexual risk as a re- condom usage in the general population has been shown sult of increased sexual risk taking, or direct, through to correlate to education and exposure to behaviour injecting [64], which has been documented in Cape change interventions [69]. Mthatha is in a more rural Town and is not uncommon [28]. setting compared to the other included metropoles and A small proportion of MSM across the three cities re- SWs there may have relatively less access to education ported injecting drug use, mostly methamphetamine. and information. There is however, little data on SW The prevalence and patterns of heroin and/or metham- sexual practices outside of large metropolitan areas. phetamine injecting among MSM has not been well doc- MSM were most likely to have engaged in receptive umented in South Africa [32]. The injection of anal sex in the past week, had relatively low reported use methamphetamine in the context of sexual encounters of condoms but high lubricant use and comparatively (Chemsex) has been documented among sub-groups of MSM [65]. Chemsex among MSM can be associated 5Personal communication with Leora Casey, key population with unprotected anal intercourse, and in some programme manager at NACOSA, 19 June 2019. Scheibe et al. BMC Infectious Diseases (2020) 20:655 Page 12 of 15

moderate substance use at last sex. High-risk sexual Categorisation bias may have taken place in relation to practices, particularly low levels of condom use have same sex practices among male SWs and injecting drug been identified among MSM in South Africa [70]. HIV use among MSM. However, no notable differences were prevention services for MSM have been operational in identified among male SWs reporting recent anal sex South Africa for almost a decade in the cities where and the prevalence of HIV and HBV (no SWs had HCV MSM were recruited from, where condoms and lubri- infection) compared to MSM. The higher HIV preva- cant are distributed [70]. Pre-exposure prophylaxis lence among the few MSM with a recent history of (PrEP) for MSM is available from the clinics where injecting is potentially linked to selection bias from MSM were recruited, however, experience of PrEP was MSM HIV and sexual health clinics, and the likelihood not assessed, which may have influenced condom use. of them engaging in different sexual practices. The likely PWUD/ID were least likely to have engaged in sexual lower injection frequency among MSM who inject may activity in the last month and reported relatively high have contributed to the lower prevalence of HBV and condom use at last sex. Surprisingly, substance use at HCV identified among MSM with recent injection his- last sex was moderate and comparable to MSM, how- tory compared to male PWUD/ID. Differences in type of ever, due to the frequency of substance use among drug injected and injecting frequency suggest that view- PWUD/ID with a substance use disorder, under reporting these groups separately is useful. ing may have taken place. While data on sexual practices The study did not comprehensively assess all the risk among PWUD/ID in South Africa is limited, inter- factors for blood borne infections, and did not include national research reflects that sexual practices are influ- an assessment of knowledge or attitudes related to HIV enced by a range of factors, including relationship status and viral hepatitis. [71] and mental health. The use of English for the questionnaire in a context of multiple different first languages (including Afrikaans, Xhosa and Zulu), and potential ad hoc translating by re- Limitations searchers, may have undermined accuracy of answers in This paper is limited to a description of the findings, the questionnaire. without in-depth analysis. Additional analysis around Long-standing relationships between participants and HBV, HCV and HIV infection and risks factors among research implementation organisations is likely to have PWID has been published elsewhere [28]. impacted on reporting accuracy. However, reporting bias Several of the limitations and biases described here are may have resulted in under- or mis-reporting of mea- inherent in research that is implemented in the context sures assessing substance use and sexual activity. This of programmatic service delivery in a way that minimizes may have been especially marked in relation to activities impact on clients and staff. generally associated with the KP the participant was not This study drew on individuals already accessing avail- identifying as (for example, SWs may have been less able HIV and related prevention and treatment services comfortable reporting substance use than people identi- and was also limited to a few of the sites and cities with fying as PWUD/ID). Self-protective behaviours encour- existing targeted health services for KPs 6. aged by implementing organizations (such as the use of The selection bias associated with convenience sam- sterile injecting equipment among PWUD/ID or con- pling limits extrapolation to other members of the in- doms across all KPs) may also have been over-reported, cluded populations. The findings may not be resulting in an under-representation of risk practices, applicable to KPs with less access to health services, and an over-representation of harm reduction practices. KPs who access services in the private healthcare sec- The questionnaire did not assess frequency of use of the tor, KPs with different risk profiles, or to KPs from various substances enquired about thus limiting the in- other cities or regions in the country. Another im- sights into substance use within these populations. portant KP group that was not addressed by this Additional research is needed on the epidemiology of study were prisoners in whom HBV, HCV and HIV these infections among hard to reach PWUD/ID not rou- prevalence in other global settings is known to be tinely accessing mobile health services including those who higher than in the general population [68, 72, 73]. may belong to other KPs or have additional risk factors, such as within the correctional service system. Further un- 6At the time of study implementation HIV prevention, sexual health derstanding of whether, and to what degree, knowledge of and harm reduction services for KPs existed in several other locations these infections and their associated risk factors among KP that were not part of this study. Notably, SW services existed in major affects risk practices and prevalence would be valuable in urban areas like Johannesburg, Ekurhuleni and Bloemfontein. MSM the design of prevention and care services. Greater insights services existed in Durban, Pietermaritzburg, Bloemfontein, Kimberly and Ehlanzeni. PWUD/ID harm reduction services were started in are also needed into factors associated with on-going par- Port Elizabeth and Johannesburg after the study started. enteral risk in the presence of harm reduction services. Scheibe et al. BMC Infectious Diseases (2020) 20:655 Page 13 of 15

Pilot projects that explore innovative ways to provide Acknowledgements integrated HBV-HCV-HIV and other holistic services to Special thanks goes to the study participants. We would also like to acknowledge the input and participation from: Lorraine Moses, Andrea KPs in the South African context are needed to inform Schneider, Kalvanya Padayachee, Dawie Nel, Nelson Medeiros, Angela the granular detail and implementation experience that McBride, Kevin Rebe, Ruth Motlafi, Penelope Daki, Yolaan Andrews, Andrew will be necessary for an effective integrated HBV/HCV/ Lambert, Rudolph Basson, Wendy Joyce, Joezette MacKay, Angelina Satira, Mfezi Mcingana, Lesedi Mohlalal, Zara von Hofmeyer, Laurene Booyens, HIV response. Future research is needed to understand Jayendrie Thaver, Lucinda Gaelejwe, Jack Manamela, Susan Malfeld, Lillian health care providers’ knowledge around viral hepatitis Makhathini, Angella Musisi and the teams that implemented the study and and HIV among at risk KPs to complement the existing supported laboratory procedures. Implementation at sites operated by TB HIV Care was additional to HIV services supported by the United States epidemiological data. President’s Emergency Plan for AIDS Relief and the United States Centers for Disease Control and Prevention and the Global Fund.

Conclusions Authors’ contributions AS led protocol development, was involved in oversight of implementation, HBV, HCV and HIV pose major health threats for KPs in data analysis, development of drafts and incorporation of co-author inputs. South Africa. Current HCV prevalence in PWUD/ID will KY was involved in oversight of implementation, interpretation of data, input increase in the absence of comprehensive HCV prevention into drafts. AV was involved in oversight and approval of final manuscript. CWS was involved in oversight of implementation and provided input into services that include opioid substitution therapy and nee- the manuscript. MS was involved in oversight of implementation and pro- dle syringe services and a rapid, targeted and acceptable vided input into the manuscript. NPS was involved in oversight of the labora- treatment programme. Similarly, the risk of HCV and tory implementation, data quality control and analysis and input into the manuscript. AJP was involved protocol development for diagnostics, diag- HIV transmission needs to be addressed among MSM. nostic data review and provided inputs into the manuscript. HH contributed HIV prevalence remains high across all KPs. The fact to the design of the work, interpretation of data and provided input into the that almost a fifth of HIV infected SWs are not on treat- manuscript. All authors reviewed and approved the final manuscript. ment indicates the need for tailored care provision based Funding on an assessment of care access barriers as well as active Funding for the study was received from the Bristol-Myers Squibb Founda- education around transmission of blood borne viruses. tion. The funder was not involved in the design of the study, or the collec- Eliminating viral hepatitis as a public health threat in tion, analysis or interpretation of data. South Africa by 2030 will only be an attainable reality Availability of data and materials once viral hepatitis prevention, testing and treatment ser- The datasets used and/or analysed during the current study are available vices are provided to all high-risk KPs. Similar to dedi- from the corresponding author on reasonable request. cated MSM sexual health clinics, we need to provide appropriate healthcare services for SWs and PWUD/ID, Ethics approval and consent to participate Ethics approval was obtained from the Human Research Ethics Committee of ensuring access to sterile injecting equipment and opioid the University of Cape Town (ref: 004/2016), the Research Ethics Committee substitution therapy as needed. HBV, HCV and HIV of the University of the Witwatersrand (ref: M160510) and the Western Cape screening, preferably with easily accessible and affordable (ref: WC_2016RP19_818) and KwaZulu-Natal (ref: KZN_2016RP59_986) Provin- cial Department of Health Ethics Committees. All participants provided writ- POC diagnostics and seamless initiation of antiviral ther- ten informed consent. apy should be standard of care. Like many other countries, South Africa has developed national guidelines for the Consent for publication management of viral hepatitis and even has a costed na- Not applicable. tional action plan to address this issue, but political sup- Competing interests port, appropriate resource allocation and dedicated and AS: is a faculty member of the Bristol-Myers Squibb Foundation and has re- passionate people, that include KPs, will be required to ceived an honorarium from Gilead Pharmaceuticals to present hepatitis prevalence data at a South African conference for HIV clinicians. support implementation to achieve this ambitious goal. KY: No competing interests. AV: No competing interests. CWS: No competing interests. Abbreviations MS: No competing interests. AIDS: Acquired Immunodeficiency Syndrome; ATS: Amphetamine-type NPS: No competing interests. stimulants; CPT: Cape Town; CI: Confidence Interval; CT: Cape Town; AJP: No competing interests. DAA: Direct Acting Antiviral; DBN: Durban; ELISA: Enzyme-linked HH: No competing interests. Immunosorbent Assay; HBsAg: HBV Surface Antigen; HBV: Hepatitis B Virus; HCV: Hepatitis C Virus; HIV: Human Immunodeficiency Virus; IQR: Inter Author details quartile range; JHB: Johannesburg; KP: Key Population; MSM: Men who have 1TB HIV Care, 11 Adderley Street, Cape Town, South Africa. 2Department of sex with men; NICD: National Institute for Communicable Diseases; Family Medicine, University of Pretoria, Pretoria, South Africa. 3University of OST: Opioid Substitution Therapy; PE: Port Elizabeth; POC: Point-of-care; Cape Town, Anthropology Section, School of African and Gender studies, PCR: Polymerase chain reaction; PMB: Pietermaritzburg; PTA: Pretoria; PWUD/ Anthropology and Linguistics, Cape Town, South Africa. 4Division of ID: People who use drugs, including people who inject drugs; PWID: People Hepatology, Department of Medicine, Faculty of Health Sciences, University who inject drugs; RNA: Ribonucleic acid; SW: Sex worker; NDOH: South of Cape Town and Groote Schuur Hospital, Observatory, Cape Town, South African National Department of Health; UI: Uncertainty interval; WHO: World Africa. 5National Institute for Communicable Diseases, 1 Modderfontein Road, Health Organization Sandringham, Johannesburg, South Africa. 6Division of Virology, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa. Scheibe et al. BMC Infectious Diseases (2020) 20:655 Page 14 of 15

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