PEPFAR Activities Branch, Division of Pharmacologic Therapies, Center for Substance Abuse Treatment, Substance Abuse and Mental Health Services Administration, SAMHSA, 5600 Parklawn Drive, Rockville, MD 20857, USAUnited States
PEPFAR Activities Branch, Division of Pharmacologic Therapies, Center for Substance Abuse Treatment, SAMHSA, 5600 Parklawn Drive, Rockville, MD 20857, USAUnited States
Division of Pharmacologic Therapies, Center for Substance Abuse Treatment, SAMHSA, 5600 Parklawn Drive, Rockville, MD 20857, USAUnited States
Center for Substance Abuse Treatment, SAMHSA, 5600 Parklawn Drive, Rockville, MD 20857, USAUnited States
Also available as PDF (figures and tables appear in the PDF).
“Test and Start” implements the World Health Organization (WHO) recommendation of “treat all” by providing anti-retroviral treatment to persons newly diagnosed with HIV infection, at the time of their diagnosis. This HIV treatment algorithm is derived from recent international clinical trials and the recent international HIV treatment guidelines by WHO, recommending all people living with HIV be provided anti-retroviral treatment. This “treat all” recommendation removes any and all limitations for receiving anti-retroviral treatment for all people living with HIV, including people who use drugs. However, there are a limited number of “Test and Start” programs that have focused on the barriers to anti-retroviral treatment for people who use drugs. With an increasing number of low and middle income countries developing guidance for “Test and Start” programs, this articles identified four elements that support access to and successful initiation of the early initiation of anti-retroviral treatment for people living with HIV, who use drugs. The elemental services are: outreach with social services, screening for and management of substance use disorders, comprehensive primary care and differentiated care in anti-retroviral treatment. Together these services can provide a supportive foundation for “Test and Start” programs for people living with HIV, who use drugs.
Keywords: ART for all; Drug use; Substance use disorder treatment; HIV infection; Alcohol use; Test and Start
WHEN TO START ANTIRETROVIRAL TREATMENT AND INTERNATIONAL TREATMENT GUIDELINES Clinical trials and studies assessing the efficacy and uptake of antiretroviral treatment have formed the basis for both international and national HIV treatment guidelines on the use of drugs 1-4 for treating and preventing HIV infection.1-4 The most recent international treatment guidelines by the WHO recommend, for the first time, that all people living with HIV be provided anti- retroviral treatment.1 This “treat all” recommendation removes any and all limitations for Copyright receiving anti-retroviral treatment for all people living with HIV, including people who use ©2016 Kresina TF. This is an open drugs. Past treatment guidelines on when to start anti-retroviral treatment, relied on findings access article distributed under the Creative Commons Attribution 4.0 from early clinical trials of treatment naive people living with HIV, by comparing the initiation International License (CC BY 4.0), of anti-retroviral treatment during chronic infection at CD4 levels at or between 200-350 cells/ which permits unrestricted use, 3 4,5 mm . The findings of these studies showed a statistically significant reduction in death when distribution, and reproduction in starting anti-retroviral treatment at higher CD4 counts. There was also a reduction of the risk any medium, provided the original of death and co-morbidities, such as tuberculosis, when starting anti-retroviral treatment at work is properly cited.
14-17 treatment at the initiation of care at higher CD4 counts, rather stimulants. Thus, alcohol, opioid and stimulant-use disorders than deferring to start at a CD4 count of 250 cells/mm3, reduced are important co-morbidities for people living with HIV in the the risk of disease progression. Based on these findings, the era of “treat all” as part of the medical management of HIV 17-22 CD4 threshold to start anti-retroviral treatment in most national infection. However, substance use disorders are not routinely guidelines was raised to 350 cells/mm3 by 2012 and later 500/ screened for in HIV care settings although highly prevalent in 3 4,6,7 mm around 2009-2013.
people who use drugs and seeking care. Opioid use disorders, in particular, are recognized as a significant HIV risk factor for International guidelines have gone further and people who inject drugs and has been shown to be the largest recommended treating all HIV-infected adults regardless of contributor to disability-adjusted life years (DALYs) for people 16,17,23-25 their CD4 count. This most recent step has been justified by living with HIV who use drugs.
the results of three clinical trials, HPTN 052, Temprano ANRS 12136 and START. The HPTN 052 study was a Phase III Addressing substance use disorders are fundamental randomized clinical trial at 13 international sites that evaluated components of personal health and well-being as defined by the both whether antiretroviral treatment can prevent the sexual WHO.26 Substance use disorders can be addressed in a health transmission of HIV in serodiscordant couples, as well as, the care setting with interventions, such as screening and brief optimal time to begin anti-retroviral therapy in order to reduce interventions with recovery management to reduce harmful illness and death among people living with HIV. The study use, as well as, by therapies such as cognitive-behavioral showed that that starting anti-retroviral therapy early reduced therapy (CBT)/ Motivational Enhancement Therapy (MET), 8 27-32 HIV transmission by 93% over the course of the entire study. or through pharmacotherapy and medical management. For The TEMPRANOANRS 12136 study showed, with a 2×2 people living with HIV with opioid dependence, treatment with factorial design of four treatment strategies, patients who started Medication Assisted Treatment (MAT) in HIV primary care early anti-retroviral treatment with CD4 counts of ≤800 cells/ improves the HIV-related outcomes of mortality, quality of mm3 in a resource limited setting had a substantially lower risk life, retention in care, and anti-retroviral treatment adherence.33 of death and HIV related disease or co-morbidities, such as WHO notes that substance-use disorders are highly prevalent, tuberculosis.9 The Strategic Timing of Antiretroviral Treatment globally, and burdensome to society; but the gap between (START) study was a global clinical trial in six geographic providing needed treatment and that which is locally available regions that randomized patients with CD4 counts of >500 cells/ to reduce the burden of disease remains very wide.34 WHO mm3 to either immediate or delayed initiation of anti-retroviral guidelines underscore the importance of HIV care settings that treatment. The immediate treatment groups showed a greater can provide the opportunity to screen for and manage common than 50% decrease in death or AIDS related event/co-infection substance-use disorders through a range of care and treatment compared to the delayed treatment group.10 Taken together, these options that include counseling and pharmacotherapy (MAT). hallmark studies recruited over 8,000 patients in 37 countries The guidelines additionally urge that that these services are part and showed a roughly 50% reduction in severe morbidity in the of national HIV/AIDS programs and integrated into primary 23,34 early treatment groups. The trials outcomes were comparable care programs for people living with HIV. Implementation and complementary in demonstrating that earlier initiation of and integration of HIV primary care to address substance-use treatment with anti-retroviral treatment is most beneficial to disorders, including screening, diagnosis and treatment of promote excellent clinical outcomes, i.e. reduced morbidity and substance use disorders, particularly the use of MAT for opioid co-infections, as well as, promoting retention in long term care. dependence, can substantially impact public health and the HIV 35,36 As a result of the latter trial, the “treat all” recommendation epidemic.
is now commonly called “Test and START”, an approach that begins the initiation of anti-retroviral treatment immediately People who use drugs face barriers to accessing anti- after a diagnosis of HIV infection in an effort to improve health retroviral treatment for HIV infection resulting in not only outcomes for people living with HIV.11 less receipt of anti-retroviral treatment but also poorer clinical outcomes when provided anti-retroviral treatment late in 37-39 PEOPLE WHO USE DRUGS, LIVING WITH HIV AND care. For people who inject drugs, access to anti-retroviral ANTI-RETROVIRAL TREATMENT treatment is very low with only one in three reported to receive treatment.38 For those being released from incarceration back People who use drugs are at high risk for HIV infection and into the community, only one in ten may be receiving anti- are frequently disengaged from the healthcare system, thereby retroviral treatment.40 However, the integration of substance limiting their access to HIV services.12 Screening for drug use, abuse treatment and HIV primary care can enhance the access including alcohol consumption, is an important recommendation to anti-retroviral treatment for people who use drugs, as well as, in international guidelines to promote the management of clinical enhance the efficacy of anti-retroviral treatment for people who 13 41,42 issues that are barriers to HIV diagnosis and treatment. Screening inject drugs. Medication assisted treatment has been shown people living with HIV, who use drugs and inject illicit drugs, to increase recruitment in anti-retroviral treatment programs, allows health care providers to address harmful alcohol use and increase treatment coverage, increase retention in care and stimulant use which can enhance the risk of sexual transmission adherence to anti-retroviral treatment regimens and increase of HIV or injection risk of HIV transmission, through injection viral suppression.42 Together, medication assisted treatment opioid use and stimulant injection of amphetamine-type and anti-retroviral treatment have been shown to reduce all cause mortality for people living with HIV who inject drugs.43 should be reduced with community initiated differentiated anti- When integrated into incarceration settings, medicated assisted retroviral treatment at point of HIV testing/diagnostic sites with treatment and anti-retroviral treatment improves HIV treatment patient access to comprehensive care. Thus, people living with outcomes for those being released into the community, can HIV are met with care and treatment based on where they are provide a bridge to community-based services post release, in the course of infection and with a full array of services to and promote better clinical outcomes during the post release meet their needs. The recommendations also support evidence- 44-46 period.
based guidelines for rapid start of anti-retroviral treatment for persons with opportunistic infection, tuberculosis and those 54,56 TEST AND START FOR PEOPLE WHO USE DRUGS who are pregnant. Clear approaches and management of co- morbidities and non-communicable diseases, such as substance Test and Start implements the WHO recommendation of “treat use disorders is necessary. In the Uganda program, harmful all’ by providing anti-retroviral treatment to person newly alcohol consumption was perceived to be a barrier to early anti- 55,57 diagnosed with HIV infection, at the time of their diagnosis. HIV retroviral treatment due to poor adherence. In a high resource policy watch reports that globally nine countries recommend the setting, a “Test and Start” program has shown that patients “Test and Start” strategy while a lower number of low and middle who inject drugs are less likely to obtain viral suppression.58 income countries, including Thailand, Malawi and Botswana, In a resource limited setting, barriers to early initiation of anti- have a national policy that recommends anti-retroviral viral retroviral treatment for people living with HIV who inject drugs treatment regardless of CD4 count, including key populations.47 were identified as delays in receiving testing and clinical test Most recently, Tanzania has been added to the growing list.48 results, off-site HIV clinics (non-integrated services and sites), This policy is important for people who use drugs since studies stigma, lack of knowledge of the benefits of early treatment, have shown that key populations, people who inject drugs, sex initiation of treatment only when feeling ill, and dysfunctional workers, men having sex with men, transgendered people and care and treatment setting due to limited staff turnover.59 Thus, prisoners, are at high-risk for use and abuse of illicit drugs and there is a clear need to manage substance use disorders and the alcohol and HIV infection.49 A national policy supportive of barriers to early initiation of anti-retroviral treatment in “Test “Test and Start” is an important first step in the implementation and Treat” programs for people living with HIV, who use drugs. of “Test and Start” national programs. What can then follow are initial projects for feasibility and the development of standard Treatment of substance use disorders, particularly operating procedures. The landmark clinical trials could help opioid use disorders, as part of HIV primary care promotes 50-52 21,22,60 with standard operating procedures. However, a closer look at good clinical outcomes. Medication assisted treatment the clinical protocols show that for the HPTN 052 study a history for opioid dependence increases access to anti-retroviral of drug use was an exclusion criteria; for the TEMPRANO study treatment, anti-retroviral coverage, adherence to anti-retroviral only psychiatric illness, anxiety and depression, were addressed; treatment and retention in care, viral suppression, reduces viral 21,60 and while the START trial included injection drug users, it only transmission and mortality. Screening for and management randomized 64 participants, 1.4% of the study enrollment. This of alcohol use disorders in HIV care or anti-retroviral clinics limited enrollment precluded a sub-analysis of the people who results in an increase medication adherence and retention in care used drugs in this study.10 These study designs show both the and treatment, a reduction of HIV transmission and morbidity challenges to recruiting people who use drugs into HIV clinical and mortality, as well as, enhanced quality of life.22 Thus, trials, as well as, the limited information that can be utilized incorporating screening for and management of substance use from clinical trials in developing standards of practice for people disorders in “Test and Start” programs that target people who use living with HIV, who use drugs.53 drugs would promote the attainment of good clinical outcomes. Screening for and management of substance use disorders in However, the Present’s Emergency Plan for AIDS people who use drugs allows for the development of patient Relief Scientific Advisory Board has provided recommendations stability from which further treatment of comorbidities, such as regarding “Test and Start” and women’s treatment programs have HIV infection, can result with improved clinical outcomes. Thus, 54-56 begun to implement “Test and Start”. The recommendations “Test and Start” for people who use drugs would benefit from support the implementation of “Test and Start” initially in screening and management of drug and alcohol use/dependence high volume clinics in urban areas in concert with clinical as an early step in initiation of services.
protocols that prioritize the sickest patients, as well as, provide continued access and retention for those receiving anti-retroviral For people living with HIV, who use drugs, a “Test and treatment. Other recommendations include the importance of Start” program with the following services support the needs of health care worker training and education and a public health people who use drugs: outreach with social services, screening education program for people living with HIV, peer educators, for and management of substance use disorders, comprehensive community health workers and differentiated care as part of anti- primary care and differentiated care in anti-retroviral treatment retroviral treatment.54 Patient education about the health benefits (Table 1). Peer based outreach is critical to meet people who use 61-63 of early initiation of anti-retroviral treatment is important, drugs where they are in the community. These peer groups with a pilot “Test and Start” program in Uganda showing that can comprise community counselling teams, who are people who asymptomatic patients questioning the need for medication.55 use drugs in recovery, family members affected by drug use and Health service barriers to receiving anti-retroviral treatment health care staff. These groups have drug scene credibility, local Element Activities that “Support Test and Start” peer education of people who use drugs, provision of HIV prevention interven- Outreach with Social Services tions, social support; screening for drug use and brief interventions, point of care for HIV rapid testing; prevention of overdose mortality screening for and management of substance use disorders, medication assisted Substance Use Disorder Treatment treatment for opioid dependence and alcohol dependence, point of care for HIV rapid testing; recovery support Patient centered screening and management of co-infections and co-morbidities, Comprehensive Primary Care confirmatory HIV testing Differentiated care and tailored anti-retroviral treatment that allows for an en- Anti-Retroviral Treatment abling environment for people who use drugs
knowledge and connectivity, and a level of medical competence 3. Plazy M, Dabis F, Naidu K, Orne-Gliemann J, Barnighausen to perform screening and brief interventions to reduce harmful T, Dray-Spira R. Change of treatment guidelines and evolution substance use. With basic training in addiction counselling these of ART initiation in rural South Africa: data of a large HIV care groups can organize self-help groups, recovery communities and and treatment programme. BMC Infect Dis. 2015; 15: 452. doi: provide an alternative to law enforcement.62 These individuals 10.1186/s12879-015-1207-2 can also act as peer navigators promoting access to screening for substance use disorders and entry into treatment for 4. Federal Ministry of Health, Nigeria. National guidelines for substance use disorders and primary care.64 An enabling, non- hiv and aids treatment and care in adolescents and adults. 2010. discriminatory environment in primary care for people who Web site. http://www.who.int/hiv/pub/guidelines/nigeria_art. use drugs can be enhanced utilizing peer and community-based pdf. Accessed August 29, 2016 health care workers.65 Community based care delivery models that are patient-centered models of care can facilitate people 5. Siegfried N, Uthman OA, Rutherford GW. Optimal time living with HIV, who use drugs to access and be retained on for initiation of antiretroviral therapy in asymptomatic, HIV- anti-retroviral treatment, promote adherence to medications and infected, treatment-naive adults. Cochrane Database Syst Rev. 66,67 improve survival rates. Differentiated care in anti-retroviral 2010; (3): CD008272. doi: 10.1002/14651858.CD008272.pub2 treatment provides tailored care so that people who use drugs with suppressed viral load visit the HIV clinic less frequently 6. Ministry of Health, Government of Botswana. 2012 Botswana and focus on their treatment for substance use disorders; HIV National HIV & AIDS treatment Guidelines. Web Site. http:// clinic staff then focus attention on people who use drugs with www.emtct-iatt.org/wp-content/uploads/2013/04/Botswana_ unsuppressed viral load and the barriers these individuals face to National-HIV-AIDS-Guidelines_2012.pdf. Accessed August achieve adherence and good clinical HIV outcomes.68 Together 29, 2016 outreach with social services, screening for and management of substance use disorders, comprehensive primary differentiated 7. World Health Organization. WHO issues new HIV care and anti-retroviral treatment comprise a package of services recommendations calling for earlier treatment. Web Site. http:// that can comprise a “Test and Start” program for people living www.who.int/mediacentre/news/releases/2013/new_hiv_ with HIV, who use drugs.
recommendations_20130630/en/. Accessed August 29, 2016 CONFLICTS OF INTEREST 8. Myron S, Cohen MD, Ying Q, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011; 365: 493-505. doi: 10.1056/NEJMoa1105243 The authors declare that they have no conflicts of interest. 9. Danel C, Moh R, Gabillard D, et al.A trial of early antiretroviral