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Official websites use. Share sensitive information only on official, secure websites. Overwhelming evidence highlights the negative impact of substance use on HIV care and treatment outcomes. Yet, as many countries in SSA expand ART, evidence of the extent of substance use, and its impact in the region, is more limited. Stigma, and the psychoactive effects of substance use, are barriers to seeking HIV treatment and adhering to ART regimens for persons with heavy alcohol use or substance use. As a result, we identified several implementation and operations research priorities and metrics for monitoring the impact of substance use and Treat All. Future research must use existing infrastructure, including large networks of HIV clinics, to enhance our understanding of the implementation and service delivery of substance use screening, referral and treatment. Keywords: injection drug use, non-injection drug use, alcohol, antiretroviral treatment, Africa. While alcohol is the most commonly used substance, injection drug use and non-injection drug use are growing \[5\]. An estimated , to 3 million persons reported injecting drugs in SSA and nearly one-fifth are estimated to be living with HIV \[3,4\]. Non-injection drug use in Africa ranges widely across substances; in an estimated 1. As Africa becomes more integrated within drug trafficking routes, injection and non-injection drug use are expected to expand \[1\]. The intertwining relationships between substance use and HIV are complex in many ways, with each simultaneously hindering optimal physical and mental health, well-being and quality of life. PLWH who use substances, and are not engaged in substance use treatment, may be less likely to achieve optimal engagement into HIV care and treatment when compared to non-substance-using PLWH \[\]. In parallel, those who are engaged in substance use treatment are likely not offered HIV testing and do not receive HIV risk-reduction counselling \[\]. However, to achieve the full benefits, all PLWH must be fully engaged in HIV care and treatment, including those engaging in substance use \[18,19\]. Alcohol continues to be the most predominantly used substance within SSA Figure 1 a \[6,20\]. In many SSA countries, over half of key populations, such as female sex workers FSW and men who have sex with men MSM , supplement sexual encounters with frequent heavy alcohol use, which may ultimately lead to alcohol use disorders \[\]. The association between heavy alcohol use and HIV acquisition and transmission has been well documented \[25\]. Alcohol use can directly affect cognitive ability and judgement \[26,27\] , which can lead to high-risk sexual behaviours, including unprotected, multiple sexual partners, and coercive sex \[\]. Heavy alcohol use is also biologically linked with increased genital viral shedding, increasing the potential for HIV transmission \[36,37\]. Often, due to concerns of potential interactions, ART medication is missed when drinking \[40\] , which can lead to ART resistance \[41\]. Evidence of substance use, including: a Total annual alcohol per capita consumption of those 15 years or older in litres of pure alcohol as stated in each country's profile in the WHO's Global Status Report on Alcohol and Health was used \[6,20\]. All non-injection drug use sources were combined to create Figure 1c. The emergence of injection drug use provides an additional route for HIV transmission. Serial use and sharing of drug injection equipment, preparing drugs for injection, and collectively using shared drug preparations, create risks for acquiring and transmitting HIV \[74\]. Injection drug use, particularly of heroin, is commonly associated with poor ART adherence \[7\]. However, involvement in substance use treatment, such as methadone substitution therapy, significantly improves HIV clinical outcomes, including ART adherence and viral suppression \[9,77,78\]. PWID face persistent social barriers to HIV testing and linkage to care, including stigma and punitive legal systems \[79,80\]. Therefore, the integration or linkage of harm-reduction services with HIV care programmes might constitute a central element to achieve universal access to treatment. However, since , availability of these harm reduction services has expanded, particularly within East Africa \[\]. Non-injection substance use is emerging and is a major concern for several SSA countries Figure 1 c \[4,5,\]. Specifically, smoking or ingesting heroin, methamphetamine and amphetamine-type stimulants has been increasing \[4,8,89\]. Although injection drug use has received much attention for its direct link to HIV transmission, heroin is also commonly smoked, particularly in developing markets. Several countries within Africa have become major international transport corridors for heroin and cocaine trafficking \[1,2,4\]. As a result, cocaine use throughout West Africa and heroin consumption throughout East Africa have been documented \[4,76,90\]. South Africa is also experiencing a severe methamphetamine epidemic, the majority of which is with non-injection routes, particularly among key populations at risk for HIV, including sex workers and men who have sex with men \[89,91\]. Similar to other substances, non-injection substance use can lead to delays in HIV diagnosis, poor linkage to care and treatment, as well as sub-optimal ART adherence for viral suppression \[8,70,92\]. Without adequate surveillance, the impact of these emerging non-injection drug use epidemics on HIV acquisition, transmission and treatment within the context of high HIV prevalence is unknown \[8\]. Furthermore, harm-reduction strategies are often tailored for injection drug use to improve HIV treatment outcomes and need to include strategies for sexual and non-injection drug-related risk reduction \[70\]. Develop, adapt and evaluate valid and reliable screening methods for substance use, including injection and non-injection drug use. Integration of low-cost and reliable point-of-care testing for alcohol use among patients receiving HIV care. Identify barriers and facilitators to the integration of the prevention and treatment of substance use disorders with HIV care. Estimate and characterise availability of evidence-based substance use disorder prevention and treatment services. Assess substance use effects, including time-varying changes in patterns of injection and non-injection substance use, on HIV outcomes e. Evaluate substance use effects, including time-varying changes in patterns of injection and non-injection substance use, on co-occurring infections and non-communicable diseases through longitudinal studies. Substance use screening tools that are culturally appropriate and reliable must be prioritised. Within several areas of SSA, screening for substance use is either non-existent or severely limited \[93\]. Substance use screening can include biomarkers and self-report behavioural surveys, particularly within treatment settings. Biological tests for biomarkers of substance use, such as urinalysis, hair testing and saliva tests, can often be rapid and accurate for detecting recent substance use. However, these tests require proper training, specialised laboratories and adequate resources, which may be challenging in overburdened HIV clinical settings. Self-report screening tools are likely more feasible to implement within the current HIV care settings \[94\]. Several tools have been developed and validated within the United States, yet few have been evaluated with regard to their sensitivity and specificity for measuring substance use, misuse and disorders in other cultures \[95\]. For example, studies within Kenya have used generic questions to identify types of substances used as well as a pattern of use, while others have adapted the WHO Model Core Questionnaire among students and prison populations for the same purpose \[\]. Cultural adaptations and validation of standardised screening tools must be undertaken to integrate local nomenclature for the various substances used in the region \[\]. Common modifications have included the addition of contextual items such as factors associated with introduction to substance use and its continued use, as well as potential complications of use. Additionally, contextualisation will often require the inclusion of local names for various substances, information that would otherwise be missed without cultural context. Epidemiological studies require this ongoing ethnographic work to monitor the on-the-ground, and often rapidly changing, drug markets \[\]. As alcohol use remains highly prevalent in SSA, strategies are needed to integrate low-cost and reliable point-of-care testing for alcohol use among patients receiving HIV care. As an example, the assessment of excessive alcohol use presents various challenges in the SSA context. An accurate measure of alcohol intake in a given setting requires a minimum knowledge of types of locally brewed alcoholic beverages regularly consumed as well as conversions into standard alcohol drinks. Reproducibility of alcohol intake measures across various settings and populations is also an issue to enable reliable comparisons. Besides these technical considerations, relying on self-report to diagnose excessive alcohol use is subject to desirability bias. This is particularly sensitive in a context of access to care for chronic and lifelong conditions, such as HIV infection. Indeed, recent research using alcohol biomarkers, such as phosphatidylethanol, has found significant rates of underreported alcohol intake among HIV-infected persons \[,\]. Other factors, such as religion, ethnicity and employment, might also significantly affect self-reported alcohol use. Previous prevalence estimates on alcohol use from SSA, based on self-report, showed a particularly low level of alcohol use in predominantly Muslim countries \[,\]. Whether or not these assessments reflect the true consumption of alcohol in these countries remains to be confirmed. The use of inexpensive and reliable point-of-care testing to complement self-report measurements of alcohol intake might provide more reliability in alcohol-use estimates \[\]. Written guidelines and protocols for substance use disorder treatment and referrals must be developed and implemented by non-specialists within HIV clinics. Until integration can be achieved, timely referral strategies can be employed to address treatment gaps in settings where referral services exist \[\]. Referral strategies for those in need of substance use disorder treatment can be successful through collaboration between the patient, service providers and related treatment organisations. However, it is critical to note that throughout much of SSA, referral services are nonexistent or inaccessible, highlighting the need for development of new and innovated models for substance use care and support \[\]. To facilitate an understanding of the barriers and facilitators to integrating substance use disorder and HIV treatments, we advocate for an implementation science framework approach for generating critical and actionable evidence. In HIV care settings in SSA, a complex set of patient, community, provider, organisational and systemic factors must come together to create integrated substance-use treatment among PLWH. At the patient and community levels, the challenges include the inability to engage and retain HIV-positive substance users in care due to varying levels of motivation, loss to follow-up, stigma associated with substance abuse including from service providers , lack of social support, and co-morbid conditions including psychiatric and mental health disorders, as well as complex socioeconomic and contextual factors that inhibit access to and retention in care \[,\]. Provider and organisational level barriers include lack of knowledgeable and skilled providers, personnel shortages, inadequate diagnostic tools and poor treatment infrastructure, all within an environment that continues to prioritise HIV care over conditions that increases the risk of transmission. Systemic challenges are related to the absence of coherent and comprehensive substance abuse policies and programmes that support an integrated care model \[3,,\]. To further address the barriers to treatment among vulnerable drug-using populations, including MSM and FSW, non-HIV sector approaches that use dedicated substance abuse services and more community-based outreach models should be considered \[\]. This should include highlighting optimal models of care delivery, efficiency, and effects of interventions and policy innovations on HIV treatment \[\]. More specifically, implementation science research should be designed to assess context-specific barriers at individual, community, health provider and structural levels to facilitate increased access to HIV prevention and treatment for substance use among PLWH. Robust estimates of substance use and characterisation of substance use treatment services are lacking, particularly at the country level, within SSA \[,\]. Although substance use and harm-reduction services are expanding across SSA, a number of structural barriers remain, including a lack of trained providers and an absence of policy for expansion \[,\]. Population estimates and identification of evidence-based substance use disorder prevention and treatment services will provide essential data for informing future programme development and research. Longitudinal studies are needed on the time-varying changes in patterns of substance use, as well as the effect of substance use, on HIV outcomes and co-infections. This lack of regularity and standardisation in assessing substance use within clinical cohorts leads to a reliance on small convenience samples for characterising substance use among PLWH \[,\]. While these studies enhance our understanding of the impact of substance use on HIV outcomes and co-infections, the estimates are susceptible to bias, limiting the potential for guiding HIV treatment policies \[\]. As the rollout of ART expands in SSA, substance use will remain an ongoing challenge for achieving universal testing and treatment. Evidence from other settings overwhelmingly emphasises the negative impact of substance use on HIV care and treatment outcomes. Participating clinics within IeDEA can serve as a representative sample of HIV treatment sites and provide critical insights on the implementation and operational management of service delivery for substance use screening, referral and treatment. All other sources are smaller studies within SSA countries. 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