Jointly Provided by Postgraduate Institute for Medicine and DKBmed, LLC
Supported by an independent educational grant from Gilead Sciences, Inc.

Recent success treating HCV and HIV is threatened by the rise of injection drug use (IDU) and the shifting demographics of people who inject drugs (PWID). As treatments become simpler, more effective, and more readily available, the responsibility to screen at-risk populations and manage patients to prevent and treat these dangerous infections has never been greater.

Join Kathleen Brady, MD, PhD, Alain Litwin, MD, and Sandra Springer, MD in a case based webinar to address ways that you can help fight against the surge in HCV and HIV. Topics include:

  • Identifying high-risk patient populations
  • Screening conversations and mitigating stigma
  • IDU and transmission rates
  • Managing HIV and HCV treatment
  • Pre-exposure prophylactic therapy initiation (PrEP)

Register Now

Recent success treating HCV and HIV is threatened by the rise of injection drug use (IDU) and the shifting demographics of people who inject drugs (PWID). As treatments become simpler, more effective, and more readily available, the responsibility to screen at-risk populations and manage patients to prevent and treat these dangerous infections has never been greater.

Join Kathleen Brady, MD, PhD, Alain Litwin, MD, and Sandra Springer, MD in a case based webinar to address ways that you can help fight against the surge in HCV and HIV. Topics include:

  • Identifying high-risk patient populations
  • Screening conversations and mitigating stigma
  • IDU and transmission rates
  • Managing HIV and HCV treatment
  • Pre-exposure prophylactic therapy initiation (PrEP)

Post-Test

Monograph

Table of Contents

This monograph was adapted from the live webinar HCV/HIV Virtual Roundtable: Treating HCV/HIV in People Who Inject Drugs. The learning objectives for this activity are:

  • Implement the most recent screening and diagnosis guidelines for managing patients at risk of or with HCV.
  • Discuss treatment options when first-line chronic inhaled antibiotics fail.
  • Identify barriers for initiating PrEP therapy for PWID and discuss interventions that could prevent HIV transmission.
  • Evaluate barriers to direct-acting antiviral (DAA) treatment initiation with patients with injection drug use (IDU).

Introduction

Recent success treating hepatitis C (HCV) and HIV is being threatened by the rise of injection drug use (IDU) and the shifting demographics of people who inject drugs. As treatment options improve and access to treatment becomes more readily available, the responsibility to effectively screen at-risk populations and manage patients to prevent new infections has never been greater. Current alcohol abuse and drug use are associated with poorer outcomes and incomplete HIV or HCV treatment. In addition, ongoing drug and alcohol use are associated with poor adherence to antiretroviral therapy for HIV and inability to maintain viral suppression. Therefore, integrated treatment that addresses both the infectious disease and the substance use disorder at the same time is most likely to improve outcomes. However, many providers who treat substance use disorders do not screen for or treat infectious diseases. In addition, many providers who treat infectious diseases do not screen for or treat substance use disorders. Education can help remove some of the barriers to integrated treatment and permit better outcomes for a vulnerable population.

Background


Labels in graph above:
Eg, tramadol and fentanyl
Natural and semisynthetic opioids and methadone

The current opioid crisis is the third in a series of waves that began around 1999.

In the early 2000s, opioid prescriptions increased, as illustrated by the purple line in the chart above. This increase is primarily related to poor education about the use of opioids, poor education about alternative strategies for management of pain, and aggressive marketing by drug companies. As prescriptions increased, so did opioid overdoses.

As this trend became much more broadly known and concern grew about opioid prescribing, some doctors abruptly stopped prescribing opioids. Many people who were taking prescription opioids were unable to obtain them from their doctors; instead, they turned to heroin. The yellow line shows the increase in heroin overdose deaths.

Around 2014 and 2015, synthetic opioids began to overtake prescription drugs and heroin in abuse and overdose. Many of these synthetic opioids (eg, fentanyl and carfentanil) are 10 to 100 times more potent than prescription opioids, with a much lower therapeutic index. Synthetic opioids are much more lethal when overdosed. The black line illustrates the increasingly significant contribution of synthetic opioids to the overdose death toll.

Role of Substance Use Disorder in HIV and HCV

Along with the opioid epidemic, the incidence rates of infectious diseases, such as HIV and HCV, have also increased. HCV has increased 350% between 2010 and 2016, and 80% of new cases are related to injection drug use.1 Injection drug use is responsible for roughly 6% to 8% of HIV transmission rates, and the majority of new HIV cases are occurring in younger populations, roughly in the 20 to 24 age group. This coincides with the demographics of people who inject drugs: those people are increasingly more likely to be younger, female, and in rural areas.

An HIV and HCV outbreak directly related to the prescription opioid outbreak in southeastern Indiana in 2015 is emblematic of this new trend.2 In this particular outbreak, 181 new HIV cases were identified between November 2014 and November 2015; typically, this county would have 10 to 14 new cases per year. Of those new cases, 87.8% involved injection use of extended-release oxymorphone. Almost all of the cases (157 of 159) involving an HIV type 1 pol gene sequence had sequences that were highly related, based on phylogenetic analysis. Transmission of HIV was directly related to sharing injection drug use materials. The majority (92.3%) of persons with HIV were also coinfected with HCV.

Since the 2015 outbreak, several other HIV epidemics related to those who are injecting drugs have struck the United States.


Slide caption: Slide Courtesy of Gregg Gonsalves, PhD, Yale

An outbreak in 2018 in northeastern Massachusetts was primarily related to use of fentanyl. In this outbreak, after years of decline in HIV incidence, five new HIV diagnoses were reported from one community health center in just one month, compared to the typical incidence of <1 case per month from all providers in the area.3 Between January 2015 and June 2019, 129 related cases were identified. Of these, 57% were male, 73% were between 20 and 39 years at diagnosis, 88% reported injection drug use, and 90% had evidence of current or past HCV infection.

Meet Mario

Mario is a college student who was injured in an all-terrain vehicle accident. He sustained three fractured ribs and an open leg fracture, which was surgically repaired. Before the accident, Mario was healthy with no chronic health conditions. Mario was prescribed opioids while recovering from his accident and surgery; however, his primary care doctor stopped prescribing opioids six months after the operation, when Mario requested early refills. In addition, Mario admitted using benzodiazepines that had been prescribed for his girlfriend.

What is next for Mario? Clearly, Mario should be screened for substance use disorder and related infectious disease.

Screening for Substance Use Disorder

Screening for substance use disorders is best when completed in the context of a general health screening by asking nonjudgmental, open-ended questions. Screening may be completed by using a single screening question or by using standardized questionnaires. Single screening questions are easy to memorize and can be fit into the flow of a general health interview readily.

Certain single screening questions have been validated in primary care. For example, the question “How many times in the past year have you used an illegal drug or used a prescription medication for nonmedical reasons” is 93% sensitive and 94% specific for any drug use.4 If asked to clarify the meaning of “nonmedical reasons,” the interviewer can add “using the drug for the experience or feeling it caused, not necessarily used as prescribed.” A positive screen on a single question can lead to the more complete standardized questionnaire.

Standardized questionnaire instruments may be more difficult to administer and score; however, they provide more information about severity and consequences. They can be computerized with automatic scoring and can be included in the electronic health record with automatic scoring and prompts to the health care provider when certain thresholds are reached. Examples of standardized screening instruments are shown below.

Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) Up to 6 dozen items, depending on “skip-outs”
Drug Abuse Screening Test (DAST) 10 items, no information about drug of concern
Substance Use Brief Screen (SUBS) 4 items, preliminary testing in primary care
Rapid Opioid Dependence Screen (RODS) 8 items, good sensitivity/specificity
Michigan Alcohol Screening Test (MAST) 10 items, severity measure
Alcohol Use Disorders Identification Test (AUDIT) 10 items, well validated

Because of the comorbidity between opioid use disorder (OUD), HCV, and HIV, screening for infectious disease should be done routinely in substance use treatment settings. Similarly, screening for substance use disorders should be standard in all primary care and infectious disease clinics.

Screening for HIV

Since 2006, the CDC has recommended one-time HIV screening for all individuals between the ages of 13 to 64. Universal screening is required because risk-based screening was not successful in identifying people at risk of HIV. Also, testing is now considered “opt out.” Patients may decline testing, but obtaining official consent and providing prevention counseling are no longer required before testing.

Annual HIV screening is recommended for those at high risk for HIV; however, testing should be done every three months for people who continue to partake in high-risk behaviors, such as injection drug use or having condomless sexual intercourse with unknown-status or HIV-positive partners.

Standard laboratory testing for HIV is an HIV P24 antigen/antibody combination blood test. Typically, results are available in several days, which requires following up with the patient at a later date.

In contrast, the rapid HIV test, through an oral swab or a finger stick, provides results within 10 to 20 minutes after performing the test. These point-of-care testing modalities are recommended by the World Health Organization and are used in multiple settings. Rapid tests require minimal or no equipment and minimal technical skill. They increase access to HIV prevention and intervention; however, if positive, a confirmatory test is recommended.

Screening for HCV

AASLD recommendations:

  • One-time testing for persons born from 1945 through 1965 without prior ascertainment of risk (birth cohort)
  • One-time testing for all persons with behaviors, exposures, and conditions or circumstances associated with increased risk of HCV infection (eg, IDU, intranasal illicit drug use, hemodialysis, incarceration)
  • Annual testing for PWID and for HIV+ men who have unprotected sex with men. Periodic testing should be offered to other persons with ongoing risk factors for HCV exposure

The American Association for the Study of Liver Diseases (AASLD) and Infectious Disease Society of America (IDSA) continuously update their screening guidelines. The current screening recommendations are shown above. Currently, one-time HCV testing is recommended for persons born in the baby boomer birth cohort: those born between the years 1945 and 1965. In addition, screening is recommended for people with other risk exposures or who are part of populations with higher prevalence, such as people who have been incarcerated. Risk behaviors include injection drug use, even if only one time, as well as intranasal drug use. Risk exposures include chronic hemodialysis, receiving a blood transfusion before 1992 or clotting factors before 1987, or being born from an HCV-infected mother.

Annual testing is recommended for two groups: people who inject drugs and HIV-infected men who have unprotected sex with men. For people who have ongoing risk exposure, testing more frequently may be considered.

Source: United States Preventive Services Task Force

In August 2019, the US Preventive Services Task Force published their draft of the revised screening guidelines. The draft recommendation is for universal testing of all adults from 18 years to 79 years of age. The draft recommendations do not define the appropriate interval for those at continued high risk of HCV acquisition.

The recommendation is changing because a number of reports have shown the cost effectiveness of universal HCV screening for all adults 18 and over that have emerged. In addition, the shift in epidemiology from the baby boomer cohort to a more bimodal distribution, with the addition of the younger population, warrants universal testing.

First Step: HCV Antibody

  • If negative, stop if no concern for acute infection or severe immunosuppression
  • If positive, check HCV RNA (viral load)

Second Step: HCV RNA

  • If negative, no current infection
  • If positive, current infection is present

Third Step: Evaluate and treat (or refer for treatment)

Screening for HCV involves two steps. Initially, an HCV antibody test is performed. If negative, no further testing is required. If the antibody test is positive, a viral load must be obtained. Ideally, the viral load test should be a “reflex” test by the laboratory and done automatically if the antibody test is positive. Reflex tests avoid the requirement of bringing the patient back for additional testing and may reduce the risk of losing the patient to follow up before testing is complete.

Point-of-care testing, using a finger stick, for HCV is also available. Results are available in 20 minutes. If the test is positive, a viral load test is required.

If both the antibody and viral load tests are positive, the patient must be evaluated and treated for HCV. AASLD/IDSA guidelines for evaluation and treatment are available.

Mario Continued

Assume that Mario was screened for OUD, HIV, and HCV and was found to have OUD. Fortunately, he does not HIV or HCV.

What are the next steps for Mario? It is important to treat his OUD and to prevent HIV and HCV. To treat OUD, medications are recommended. Three basic classes of medication are available for OUD.

MOUD Options

Medication Methadone Buprenorphine Naltrexone
Mechanism Full μ agonist Partial μ agonist, partial κ antagonist Full μ antagonist
Delivery Oral, daily Sublingual, film, implant, injection* (daily, monthly, 6 mo) Injection, monthly
Oral, daily
Setting Licensed facility PC/HIV care setting with waivers (MD: 8-hour training; PA/NP: 24-hr) PC/HIV care setting – no special licensing or certification required
Notes Highly structured (safety concerns)
OD potential
Interacts with some antiretrovirals
Safer than methadone, without major OD potential
Less interactions with antiretrovirals
Improves viral suppression in HIV treatment
Also treats AUD
Adherence advantage
NO overdose or diversion concerns
Improves viral suppression

All three of the approved medications for treating DSM 5 moderate to severe OUD, reduce opioid relapse, reduce opioid overdose, reduce HIV and HCV risk, and reduce other bacterial and fungal infectious disease risk; and buprenorphine and extended-release naltrexone have been shown to improve HIV viral suppression among persons living with HIV when combined with antiretroviral therapy. However, the medications have different prescribing requirements and delivery methods.

Methadone is a full opioid-agonist therapy. Methadone is delivered orally with once daily administration. Methadone must be administered within a licensed facility, and people receiving the medication must go to the facility every day, at least initially, because of methadone’s high overdose potential.

Buprenorphine is a partial agonist and a partial antagonist that is available in several formulations (sublingual, film, implant, injection). Buprenorphine implants deliver medication for six months, while injections are given every month. It may be dispensed in a primary care setting or a buprenorphine clinic, with less structure than is required for methadone maintenance. However, prescribers must obtain a DEA X-waiver. For MDs, the waiver requires an eight-hour training program; PAs and nurse practitioners need 24 hours of training to attain waivers. Buprenorphine has less interaction with antiretrovirals used to treat HIV. It reduces HIV risk behavior and reduces the potential for overdose, and improves viral suppression when used in people living with HIV who are also receiving antiretroviral treatment for HIV.5

Naltrexone is a full mu antagonist; as such, it sits on the opioid receptor and blocks other opioids or opioid-agonist drugs from creating the euphoric effects. Accordingly, there is no abuse potential for naltrexone. Naltrexone is available in a once-daily oral formulation and a monthly injectable formulation. Because of adherence and compliance concerns, the monthly injectable form is recommended for OUD. Naltrexone can be administered in any medical setting without any special licensing or waiver requirements. The monthly injectable extended-release naltrexone also reduces HIV risk behavior and improves viral suppression in persons living with HIV who are also administered antiretroviral HIV treatment.6

HIV Prevention

When HIV testing is negative, people at risk for acquiring HIV should be offered medication to prevent HIV. However, it is important to ask patients when they had any high-risk behaviors (ie, sharing injection drug use equipment or condomless sexual intercourse with an unknown status or HIV-positive status partner) within the last seven to 14 days before the HIV test because the antibody may not have reached detectable levels. Also, the patient should be asked about symptoms of acute retroviral syndrome, which include fever and flu-like symptoms. If the person acknowledges those symptoms or has participated in high-risk behaviors, an HIV viral load test is warranted.

If these tests are negative, they should be considered for pre-exposure prophylaxis (PrEP).7 PrEP has been shown to prevent HIV infection in men who have sex with men, at-risk heterosexual men and women, and people who inject drugs. Providers who are not able or confident to prescribe PrEP should refer the patient to a provider who can do so. PrEP is recommended for everyone who has had any unprotected sexual intercourse with men or women, or who have been injecting or sharing injection drug-using equipment with an unknown status partner or with a known HIV-positive partner.

Guidelines for administering PrEP are available online.

Before prescribing PrEP, it is also important to document the person’s hepatitis B status, because the medications used in PrEP are also used to treat hepatitis B. Therefore, those who have chronic hepatitis B infection and use PrEP must be educated about the importance of adherence. PrEP is not contraindicated in people with hepatitis B, but stopping PrEP in people who have begun treatment may lead to significant harm.

Currently, two different formulations are available for PrEP. Both are single tablets that contain tenofovir and emtricitabine; the original PrEP formulation contains tenofovir disoproxil (TDF), but the new PrEP formulation contains tenofovir alafenamide (TAF). The latter is currently approved for use by men and transgender women but not by cisgender women.

Renal function and use of contraindicated medications should also be determined before beginning PrEP. PrEP should only be offered as a 90-day supply, with HIV testing and monitoring of side effects and renal functioning (BUN and creatinine) before renewals. While tenofovir and emtricitabine are effective in preventing HIV, they are not to be used to treat HIV infection. Finally, a discussion of the importance of daily adherence is also critical.

Despite the success of PrEP and its ability to prevent HIV infections, significant barriers limit its use. Similar to barriers to substance use disorder treatment. In particular, negative stigma reduce discussion of risk behaviors and requests for treatment. Other barriers include lack of knowledge by both patients and caregivers, fear, financial and insurance considerations, and from a provider perspective, the time required to fully discussing PrEP.

HCV Prevention

Behavioral interventions alone have not been effective at reducing the spread of HCV;8 combination interventions that integrate medication for OUD (MOUD) with needle/syringe exchange programs are recommended because they have been shown to result in large reductions of HCV transmission.9,10

Comprehensive harm-reduction programs should involve providing people who inject drugs both medications for OUD treatment and clean drug-injecting equipment.11 This extends beyond the needles and syringes to the cooker, cotton, and rinse water. It is also important to note that the MOUD reduces HCV and HIV risk behaviors and ongoing transmission.

Treatment as prevention is also effective. A recent modeling study based on HCV epidemiologic data obtained primarily from the outbreak in Scott County, Indiana showed with the current use of MOUD and syringe service programs, we need to treat 25% of all people each year to reach the World Health Organization elimination target by 2030.12 On the other hand, if we scale up access to both the medications for OUD and syringe service programs, we would need to treat 14.5% of all people per year.

Mario, who has OUD but not HIV or HCV, would be a good candidate for medication treatment for OUD and PrEP. He should be tested for HCV at least annually; perhaps more frequently depending on how well he does on MOUD. Also, Mario should have access to syringes and sterile equipment, preferably through a syringe service program. In areas where a syringe service program is not available, Mario should be instructed to go to a pharmacy for clean equipment.

Meet Donn

Donn is a 58-year-old man who meets a new primary care doctor after a change in his health insurance. His new doctor asks Donn many questions about his previous health and social history, including the single screening question “how many times in the past year have you used an illegal drug or used a prescription medication for nonmedical reasons.” Further screening and questioning and testing show that Donn has OUD and HCV, but testing for HIV is negative. How should Donn be treated for his OUD and HCV?

Treatment for HCV in People with ODU

OUD with HCV is a common situation. Fortunately, in this era of oral, direct-acting antiviral agents, we can and should treat HCV in any setting — primary care, hepatology or infectious disease specialty care, HIV care, substance use treatment setting, and methadone programs.

According to the AASLD/IDSA, treatment is recommended for all patients with chronic HCV, except those with short life expectancies (less than one year) who cannot be remedied by HCV therapy, liver transplantation, or another therapy. Almost all (>95%) of HCV-infected patients are eligible for treatment.

Clinicians should refer to AASLD/IDSA guidelines, which are updated regularly. Choice of specific medications and duration of treatment vary by HCV genotype and whether the patient has cirrhosis, HIV coinfection, or previous treatment experience.

Many new medications are pangenotypic, effective against various HCV genotypes. The regimen is all oral, once daily administration. Most important, the rate of cure is nearly 100%. Cure is defined as sustained virological response (SVR) 12 weeks after treatment completion.

As for PrEP and for OUD, barriers to treatment include patient-driven barriers, such as stigma and lack of knowledge; provider-driven barriers, again including lack of knowledge, time or institutional support; and system barriers, such as lack of insurance coverage and fragmented health care. However, HCV treatment can and should be within the scope of most health care providers, and combined OUD and HCV treatment in a single setting — within infectious disease or substance use treatment centers — is ideal.

The misconception that people who inject drugs should not be treated for HCV because they are not eligible, will not adhere to treatment, or will quickly become reinfected, is also a significant barrier that denies HCV treatment to many people who use injection drugs. Research suggests that such people may effectively be treated for HCV, but the optimal model of care for promoting treatment adherence and SVR had not been evaluated until the recently completed PREVAIL study.13 PREVAIL compared three different models of care delivery for people with HCV and OUD and looked at rates of treatment adherence, treatment completion, SVR, and reinfection.

PREVAIL Study Flow

Source: Akiyama et al. Ann Intern Med. 2019;170(9):594-603. doi:10.7326/M18-1715

Conducted primarily at a methadone clinic in the Bronx in New York City, PREVAIL randomized 150 people with HCV (genotype 1) who were attending the clinic into one of three delivery methods: self-administered individual treatment, group treatment, and directly observed treatment. In the individual arm, study participants self-administered all HCV medications. In the group arm, participants attended a weekly group meeting and received their medications. In the directly observed arm, participants received their daily dose of HCV medication at the window where they also received and were observed taking MOUD.

Characteristics of PREVAIL Participants

Characteristic Individual
(n=51)
Group
(n=48)
DOT
(n=51)
Total
(n=150)
Injection drug use 35 (68.6) 40 (83.3) 38 (74.5) 113 (75.3)
MOUD
Methadone 49 (96.1) 47 (97.9) 51 (100) 147 (98.0)
Buprenorphine 2 (3.9) 1 (2.1) 0 (0) 3 (2.0)
Psychiatric comorbidities
Any 25 (49.0) 22 (45.8) 20 (39.2) 67 (44.7)
Major depressive episode 12 (23.5) 15 (31.2) 11 (21.6) 38 (25.3)
Alcohol to intoxication (last 30 days) 12 (23.5) 11 (22.9) 13 (25.5) 36 (24.0)
Cirrhosis 10 (19.6) 16 (33.3) 15 (29.4) 41 (27.3)
DAA Regimen
SOF/LDV 35 (68.6) 38 (79.2) 31 (60.8) 104 (69.3)
SOF/SMV 4 (7.8) 2 (4.2) 5 (9.8) 11 (7.3)
SOF/RBV 5 (9.8) 3 (6.3) 9 (17.7) 17 (11.3)
SOF/RBV/PEG 7 (13.7) 3 (6.3) 5 (9.8) 15 (10.0)
TVR/RBV/PEG 0 (0) 2 (4.2) 1 (2.0) 3 (2.0)
Combination DAAs 39 (76.5) 40 (83.3) 36 (70.6) 115 (76.7)

Source: Akiyama et al. Ann Intern Med. 2019;170(9):594-603. doi:10.7326/M18-1715 
[SOF, sofosbuvir; LDV, ledipasvir; SMV, simeprevir; RBV, ribavirin; PEG, pegylated interferon; TVR, telaprevir]

The characteristics were similar between the three groups. In total, three-quarters had a history of injection drug use, nearly all were on methadone, nearly half had a psychiatric comorbidity, just about a quarter endorsed drinking alcohol to intoxication, a quarter had cirrhosis, and the majority were on combination direct-acting antiviral regimens.

Adherence was indeed higher in the directly observed therapy arm, with 83% adherence in the directly observed therapy arm versus 78% for group and 74% for individual arms.

Factors Associated with Adherence (<80%)

Source: Akiyama et al. Ann Intern Med. 2019;170(9):594-603. doi:10.7326/M18-1715

Several factors were examined for an association with adherence. Notably, drug use at baseline, during treatment, or six months before treatment were not associated with poor adherence, even though some payers have denied treatment to people who use drugs. About half of the cohort used drugs throughout HCV treatment. However, drinking alcohol to intoxication was found to be associated with poor adherence.

PREVAIL: Overall SVR 12 94% (141/150; P = .24)

Source: Akiyama et al. Ann Intern Med. 2019;170(9):594-603. doi:10.7326/M18-1715

SVR rates were high, similar to those from other reports. Overall, 94% total achieved a cure: 90% in individual arm, 94% in group, and 98% in the directly observed therapy group. The differences were not significant. For the subset of patients who received combination direct-acting antiviral medications, 100% SVR was attained in the directly observed therapy group. Also, an increase in adherence was associated with increased cure: every 10% increase in adherence led to 1.6 greater odds of achieving SVR 12.

Overall, all three models of care were effective.

HCV reinfection has been a concern, but a patient’s continuing to engage in high-risk behaviors should not be a contraindication to treatment. In fact, data support treating active injection drug users who are receiving MOUD. Modeling studies suggest that if we treat enough of those patients — from 8% to 12% per year, reinfection decreases. In addition, reinfection is less frequent than many people expect. A recent meta-analysis examined reinfection rates among different cohorts.14 People who were maintained on MOUD had a reinfection rate of ~3.4 per 100-person year, while those who were recent injectors had a rate of about 5.8 per 100 person years.

Ideally, Donn should be treated for both his OUD and HCV in the same setting. Clinicians can review the AASLD guidelines or use telementoring to learn how to treat; otherwise, Donn should be referred for treatment.

Meet Amanda

Amanda is a 33-year-old woman with OUD who has been in several treatment facilities over the past five years. Currently, Amanda is using injection drugs. After she visited a walk-in clinic for an infection in her arm, she was screened for both HIV and HCV. Testing confirmed that Amanda has both OUD and HIV, but she is HCV negative. How should Amanda be treated for OUD and HIV?

Treatment for HIV in People with OUD

Amanda’s case illustrates another important point: along with increases in HIV and HCV in people who are using drugs, bacterial and fungal infections are also seen. In fact, these infections may be the red herring before HIV and HCV develop. Amanda likely acquired HIV probably through either sharing injection drug use works and/or a combination of both of having unprotected sexual intercourse in the setting of drug use or exchange sex for drugs.

US Department of Health and Human Services guidelines indicate that all individuals living with HIV should be treated with effective antiretroviral therapy. Many antiretroviral therapy regimens are effective in treating HIV. Many are simple, once-a-day, single-tablet regimens that contain a combination of two or three medications.

Example from DHHS Guidelines

Source: US Department of Health and Human Services 
[BIC, bictegravir; TAF, tenofovir alafenamide; FTC, emtricitabine; DTG, dolutegravir; ABC, abacavir; 3TC, lamivudine; RAL, raltegravir. BIC/TAF/FTC, DTG/ABC/3TC, TDF/FTC, and TAF/FTC are available as one pill once daily]

Overwhelming evidence has established that a patient with an undetectable viral load who is taking antiretroviral therapy as prescribed cannot transmit the virus to an uninfected person, even when engaging in high-risk behaviors such as unprotected sex or sharing injection drug use equipment.15 This discovery has led to the treatment-as-prevention public health campaign, known as Undetectable Equals Untransmittable (U=U).

From an individual health perspective, the goals of treatment in a patient living with HIV are to reduce mortality and morbidity, restore and preserve immune function, suppress viral load maximally and durably, and improve quality of life. Viral suppression is usually attained within three to six months of treatment initiation, when used as prescribed.

The clinician treating Amanda for the abscess on her arm has the opportunity to complete a thorough evaluation for her for both infectious diseases and OUD and then either prevent or treat accordingly. Although it is not always possible to initiate treatment for both OUD and HIV at the same time, it is not necessary to stabilize one condition before moving to the next. Critically important is that treatment for OUD helps treat the HIV through maintaining viral suppression, as well as by decreasing the likelihood of continued partaking in high-risk behaviors.

Meet Brian

Brian is a 55-year-old man with OUD who has been on medications for OUD. Screening on entry to a new treatment program shows that he also has both HIV and HCV infection.

Unfortunately, HCV and HIV coinfection is relatively common. Approximately 20% to 30% of people with HIV also have HCV, and among HIV-positive people who inject drugs, 75% to 90% are coinfected with HCV.16

People with both HIV and HCV are more likely to advance to cirrhosis and end-stage liver disease in a shorter time than those who are monoinfected, and they are also more likely to advance to hepatocellular carcinoma.17 All patients with HIV, therefore, should be screened for HCV. If positive for HCV, patients should initiate integrated treatment. With current direct-acting antiviral medications, efficacy and adverse event rates among those who have HIV/HCV coinfection are similar to those for people who have HCV monoinfection. Current HCV medications are less likely than older HCV medications to interact with HIV antiretroviral medications. The HCV guidelines also provide treatment recommendations for coinfected patients and other unique populations.

Initiating treatment for HIV, HCV, and OUD simultaneously may be challenging, so beginning with simultaneous HIV and OUD treatment is a feasible strategy. HCV treatment can be implemented after HIV and OUD treatment adherence has been established, usually within a month or two. However, postponing OUD treatment is not recommended, as MOUD improves infectious disease control.

Referral

Not all clinicians are confident or otherwise able to treat infectious disease in their patients with OUD and vice versa. When the clinician is not confident, patients should be referred to a capable provider. Other reasons for referring patients include psychiatric illness, cirrhosis or high risk for hepatocellular carcinoma, or other significant comorbid illness.

When referring patients to other providers for care, clinicians should not only decrease barriers of access to that provider but also the principles of integrated care by keeping a close connection with the referral source.

While providing integrated care is optimal, engaging the patient in the setting where they are ready to be treated is most important. If the patient is ready to be treated for HCV, try to also engage them in care for OUD and HIV, if appropriate. By being flexible and using patient-centered communication, overcoming at least some of the barriers to treatment is possible. The least desirable action, however, is discharging patients from treatment because they are displaying the behavior that is causing them and society harm.

Additional Resources

CLINICAL CONSULTATION (OUD, HIV, HCV, PrEP)

OUD

HIV

HCV Screening and Treatment

HBV Screening and Treatment

Post-Test

References

1. Viral Hepatitis Surveillance - United States, 2016

2. Peters PJ, Pontones P, Hoover KW, et al. HIV Infection Linked to Injection Use of Oxymorphone in Indiana, 2014-2015. N Engl J Med. 2016;375(3):229-39

3. Cranston K, Alpren C, John B, et al. Notes from the Field: HIV Diagnoses Among Persons Who Inject Drugs — Northeastern Massachusetts, 2015–2018. MMWR Morb Mortal Wkly Rep. 2019;68:253–254.

4. Smith PC, Schmidt SM, Allensworth-davies D, Saitz R. A single-question screening test for drug use in primary care. Arch Intern Med. 2010;170(13):1155-60.

5. Springer SA, Qiu J, Saber-tehrani AS, Altice FL. Retention on buprenorphine is associated with high levels of maximal viral suppression among HIV-infected opioid dependent released prisoners. PLoS ONE. 2012;7(5):e38335.

6. Springer SA, Di paola A, Azar MM, et al. Extended-Release Naltrexone Improves Viral Suppression Among Incarcerated Persons Living With HIV With Opioid Use Disorders Transitioning to the Community: Results of a Double-Blind, Placebo-Controlled Randomized Trial. J Acquir Immune Defic Syndr. 2018;78(1):43-53.

7. US Public Health Service. Preexposure prophylaxis for the prevention of HIV infection in the United States-2017 update. A Clinical Practice Update.

8. Page K, Morris MD, Hahn JA, et al. Injection drug use and hepatitis C virus infection in young adult injectors: using evidence to inform comprehensive prevention. Clin Infect Dis. 2013;57 Suppl 2:S32-8.

9. Turner KM, Hutchinson S, Vickerman P, et al. The impact of needle and syringe provision and opiate substitution therapy on the incidence of hepatitis C virus in injecting drug users: pooling of UK evidence. Addiction. 2011;106(11):1978-88.

10. Martin NK, Hickman M, Hutchinson SJ, et al. Combination interventions to prevent HCV transmission among people who inject drugs: modeling the impact of antiviral treatment, needle and syringe programs, and opiate substitution therapy. Clin Infect Dis. 2013;57 Suppl 2:S39-45.

11. Robaeys G, Grebely J, Mauss S, et al. Recommendations for the management of hepatitis C virus infection among people who inject drugs. Clin Infect Dis. 2013;57 Suppl 2:S129-37.

12. Fraser H, Zibbell J, Hoerger T, et al. Scaling-up HCV prevention and treatment interventions in rural United States-model projections for tackling an increasing epidemic. Addiction. 2018;113(1):173-182.

13. Akiyama MJ, Norton BL, Arnsten JH, et al. Intensive Models of Hepatitis C Care for People Who Inject Drugs Receiving Opioid Agonist Therapy: A Randomized Controlled Trial. Ann Intern Med. 2019;170(9):594-603

14. Hajarizadeh B, Cunninghan E, Veleria H, et al. Hepatitis C virus reinfection following antiviral treatment among people who inject drugs: A systematic review and meta-analysis. Presented at EASL 2019.

15. Cohen MS, Chen YQ, McCauley M, et al. Antiretroviral therapy for the prevention of HIV-1 transmission. N Engl J Med. 2016;375:830-839

16. Scott JA, Chew KW. Treatment optimization for HIV/HCV co-infected patients. Ther Adv Infect Dis. 2017;4(1):18-36.

17. Fierer DS, Dieterich D, Fiel MI, Branch AD, Marks KM, Fusco DN, et al. Rapid progression to decompensated cirrhosis, liver transplant, and death in HIV-infected men after primary hepatitis C virus infection. Clin Infect Dis. 2013;56(7):1038-1043.

Faculty

Kathleen L. Brady, MD, PhD

Distinguished University Professor
Vice President for Research
Director, South Carolina Clinical and Translational Research Institute
Medical University of South Carolina

Dr. Brady is an experienced clinical and translational researcher and has been conducting scientific investigations and clinical work in the field of addictions and psychiatric disorders for over 30 years. Her research focuses on pharmacotherapy of substance use disorders, comorbidity of psychiatric disorders and addictions (e.g., posttraumatic stress disorder and bipolar disorder), gender differences and women’s issues in addictions, and the neurobiologic connections between stress and addictions. She has received numerous federal research grants and has published over 300 peer-reviewed journal articles and co-edited 10 books. She is the Vice President for Research at the Medical University of South Carolina. She is the principal Investigator of MUSC’s Clinical and Translational Science Award (CTSA), Principal Investigator of the Southern Consortium Node of the NIDA-funded Clinical Trials Network and Director of MUSC’s Women’s Research Center. Her dedication to furthering research careers has attracted a number of junior investigators and clinicians. She has served at the President of the Association for Medical Education and Research in Substance Use Disorders (AMERSA), the American Academy of Addiction Psychiatry (AAAP) and is currently the President of the International Society of Addiction Medicine (ISAM).

Alain Litwin, MD

Vice Chair of Academics and Research, Department of Medicine
Professor of Medicine, University of South Carolina School of Medicine Greenville
Professor, Clemson University School of Health Research



Sandra Springer, MD

Associate Professor of Medicine,
Department of Internal Medicine
Section of Infectious Disease
Yale School of Medicine

Dr. Sandra Springer is an associate professor of medicine in the Department of Internal Medicine, Section of Infectious Diseases at the Yale School of Medicine and the Infectious Disease physician at the VA Connecticut Healthcare System. She is triple board-certified in internal medicine, infectious diseases and addiction medicine. She has focused her clinical and research career on integrating substance use disorder and HIV treatment. In particular she has evaluated the use of medications for the treatment of opioid and alcohol use disorders among persons living with HIV involved in the criminal justice system to improve HIV viral suppression as well as reduce opioid and alcohol relapse post-release. She also was a working group member of NASEM’s historic meeting calling for action to integrate OUD and infectious disease treatment and currently appointed as NASEM committee member for ‘Examination of the Integration of Opioid and Infectious Disease Prevention Efforts in Select Programs’; and a current member of ASAM’s National Practice Guideline Expert PaneI for Medication Treatment for OUD; and current member of the IDSA and HIVMA Working Group on Infectious Disease Issues In the Opioid Epidemic. She has presented her work at numerous national and international conferences, and has published over 100 manuscripts, book chapters, and abstracts.

CME/CE

Accreditation Information

Jointly Provided by Postgraduate Institute for Medicine and DKBmed, LLC
This activity is supported by an independent educational grant from Gilead Sciences Inc.

Target Audience
This activity has been designed to meet the educational needs of healthcare professionals who treat patients with HCV, HIV, and injection drug use.

Physician Continuing Medical Education

Joint Accreditation Statement

In support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine and DKBmed, LLC. Postgraduate Institute for Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME).

Credit Designation Statements

The Postgraduate Institute for Medicine designates this enduring activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Release date: 02/01/2020
Expiration date: 01/31/2021

Educational Objectives

After completing this activity, the participant should be better able to:

  • Implement the most recent screening and diagnosis guidelines for managing patients at risk of or with HCV.Discuss treatment options when first-line chronic inhaled antibiotics fail.
  • Identify barriers for initiating PrEP therapy for PWID and discuss interventions that could prevent HIV transmission.
  • Evaluate barriers to direct-acting antiviral (DAA) treatment initiation with patients with injection drug use (IDU).

Disclosure of Conflicts of Interest

Postgraduate Institute for Medicine (PIM) requires instructors, planners, managers and other individuals who are in a position to control the content of this activity to disclose any real or apparent conflict of interest (COI) they may have as related to the content of this activity. All identified COI are thoroughly vetted and resolved according to PIM policy. PIM is committed to providing its learners with high quality CME activities and related materials that promote improvements or quality in healthcare and not a specific proprietary business interest of a commercial interest.

The faculty reported the following financial relationships or relationships they or their spouse/life partner have with commercial interests related to the content of this continuing education activity:

Faculty / Presenter Reported Financial Relationship

  • Kathleen Brady, MD, PhD
    • Consulting Fees: Genomind
  • Alain Litwin, MD
    • Consulting Fees: Merck & Co., Gilead Sciences Inc., Abbvie Inc.
    • Contracted Research: Gilead Sciences Inc.
  • Sandra Springer, MD
    • None

The planners and managers reported the following financial relationships or relationships they or their spouse/life partner have with commercial interests related to the content of this continuing education activity:
The PIM planners and managers have nothing to disclose.

The following DKB planners and managers Stan Pogroszewski, Cade Schreger, and Rachel Deerr hereby state that they or their spouse/life partner do not have any financial relationships or relationships to products or devices with any commercial interest related to the content of this activity of any amount during the past 12 months.

Disclosure of Unlabeled Use

This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The planners of this activity do not recommend the use of any agent outside of the labeled indications.

The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the planners. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

Disclaimer

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

How to Receive Credit

Participants wishing to earn credit must:

  • Read the content material in its entirety
  • Relate the content material to the learning objectives
  • Complete the post-test and evaluation form online

The estimated time to complete this activity is 1.0 hours.

Successful completion of the post-test is required to earn credit. Successful completion is defined as a cumulative score of at least 75%.

Type of Media

Internet

Course Viewing Requirements

Internet Explorer 8.0+ for Windows 2000, 2003, XP, Vista, or Windows 7, 8, or 10
Google Chrome 18.0+ for Windows, Mac OS, or Linux
Mozilla Firefox 13.0+ for Windows, Mac OS, or Linux
Safari 4.0+ for Mac OSX 10.5+

Contact Information

To contact Postgraduate Institute for Medicine (PIM) please visit www.pimed.com.
For technical issues, please contact info@dkbmed.com

Copyright © 2019. PIM and HCV/HIV Virtual Roundtable.
Presented by PIM in collaboration with DKBmed

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ONLINE PRIVACY POLICY

DKBmed, LLC (DKBmed) operates a network of continuing health care educational activities and their related websites and apps (Programs). For a list of all the programs within our network, see http://www.DKBmed.com/programs. This is the official privacy policy (Privacy Policy) for all DKBmed Programs, and this Privacy Policy forms a part of your legal agreement with us under the DKBmed Terms of Use.

PLEASE READ THIS PRIVACY POLICY CAREFULLY, AS IT DESCRIBES HOW WE COLLECT AND USE INFORMATION WE COLLECT ABOUT YOU ONLINE AND UNDER WHAT CIRCUMSTANCES WE SHARE INFORMATION ABOUT YOU.

DKBmed is committed to keeping accurate confidential, secure, and private any and all personal information collected of those individuals who visit our websites and use our online facilities and services. Our Privacy Policy has been designed and created to ensure those affiliated with DKBmed, of our realization of and commitment to our obligation not only to meet, but to exceed most existing privacy standards.

THEREFORE, this Privacy Policy shall apply to DKBmed and thus it shall govern any and all data collection and use thereof. By using DKBmed.com and any DKBmed Programs you thereby acknowledge that you are familiar with and you agree to the following data procedures expressed within this agreement.

Collection of Information
When you sign on to our Website or participate in our Programs, we collect the following voluntarily provided information, which may include your name, address, email address, profession, specialty, phone, and information for your membership in the National Association of Boards of Pharmacy and/or the American Board of Internal Medicine. In certain circumstances related to the use of our services we may ask you for your date of birth (month/day) and/or your National Provider Identifier (NPI) and/or ABI identification number. This information may be used when you participate in DKBmed Programs or purchase products and/or services from DKBmed to deliver the services and Programs you have requested. This data is collected on the basis of our need to fulfill the contract you have entered into with DKBmed when you decided to sign on to our Website and use our services and/or Programs. We need this information so we can provide you the services and/or Programs you have requested.

Cookies
Currently the only information about you that we collect through cookies is email address, name, and subscription details. This data is used for the sole purpose of automatically logging in users when they visit the Programs or website. This data is processed based on our legitimate business interest to maintain the proper functioning of our services and to provide you with better user experience.

Third-party cookies
DKBmed uses third-party vendor remarketing tracking cookies, including the Google Adwords tracking cookie. This means we will continue to show ads to you across the internet, specifically on the Google Content Network (GCN). As always we respect your privacy and are not collecting any identifiable information through the use of Google’s or any other third party remarketing services. However, you can find out more about the data that will be collected by Google and how it will be processed here: How Google uses information from sites or apps that use our services

The third-party vendors, including Google, whose services we use, will place cookies on users’ web browsers to serve ads based on past visits to our website. Third party vendors, including Google, use cookies to serve ads based on a user’s prior visits to our website. This allows us to make special offers and continue to market our services to those who have shown interest in our service.

To use as described above the personal data of users or visitors who are based in EU, we will rely on their consent.

Please rest assured that this site shall only collect personal information that you knowingly and willingly provide by way of surveys, completed membership forms, and emails. It is the intent of this site to use personal information only for the purpose for which it was requested and for any additional uses specifically provided on this site.

It is suggested and highly recommended that you review the privacy policies and statements of any website you choose to use or frequent to better understand how other websites garner, use, and share information they collect.

Use of information collected
DKBmed may collect and may use personal information to assist in the operation of our website and to ensure delivery of the services and Programs you need and request. At times, we may find it necessary to use personally identifiable information to keep you informed of other possible products and/or services that may be available to you from DKBmed. DKBmed may also contact you to complete surveys and/or research questionnaires related to your opinion of current or potential future services that may be offered.

DKBmed does not now, and in no circumstance will in the future, sell, rent, or lease any of our customer lists and/or names to any third parties.

We do not use automated decision-making, including profiling.

Sharing your personal data
We do not share your personal information with others except as indicated within this policy.

We may share your information in the following ways:

With third-party service providers, agents, or contractors who are performing or may perform services on our behalf or to assist us with providing services to you. For example, we may engage third-party providers for hosting and IT services. These service providers may have access to your personal or other information as they provide these functions.

DKBmed may find it beneficial to share specific data with our trusted partners in an effort to conduct statistical analysis, provide you with email and/or postal mail, deliver support, and/or arrange for deliveries to be made. Those third parties shall be strictly prohibited from making use of your personal information, other than to deliver the services you requested, and thus they are required to maintain the strictest confidentiality with regard to all your information.

DKBmed may share your data with accredited providers of content or certification bodies when needed to complete certain certifications. This sharing makes the provider of the certification aware of persons who have completed the activity and process the certification to ensure the user receives proper certification.

DKBmed may disclose your personal information, without prior notice to you, only if required to do so in accordance with applicable laws and/or in a good faith belief that such action is deemed necessary or is required to:

  • Remain in conformance with any decrees, laws, and/or statutes or to comply with any process that may be served on DKBmed, and/or our website;
  • Maintain, safeguard, and/or preserve all the rights and/or property of DKBmed;
  • Perform under demanding conditions in an emergency to safeguard the personal safety of users of DKBmed.com and/or their Programs and/or the general public.

Children under the age of 13
DKBmed does not knowingly collect personally identifiable information from children under age thirteen (13) years without verifiable parental consent. If it is determined that such information has been inadvertently collected on anyone under age thirteen (13), we shall immediately take the necessary steps to ensure that such information is deleted from our system's database. Anyone under age thirteen (13) must seek and obtain a parent’s or guardian’s permission to use this website.

Unsubscribe or opt out
Users and/or visitors to our website have the option to discontinue receiving communication from us for any reason and have the right to discontinue receiving communications by email or newsletters. To discontinue or unsubscribe to our website and/or Programs, please send an email to [email protected] indicating that you want to unsubscribe. If you want to unsubscribe or opt out from any third-party websites linked on DKBmed.com, you must go to the specific websites to unsubscribe and/or opt out.

Links to other web sites
Our website contains links to affiliate and other websites. DKBmed neither claims nor accepts responsibility for any privacy policies, practices, and/or procedures of other such websites. Therefore, we encourage all users and visitors to be aware when they leave our website and to read the privacy statements of every website that collects personally identifiable information. The aforementioned Privacy Policy Agreement applies only to the information collected by our website.

Security
DKBmed shall endeavor and shall take every precaution to maintain adequate physical, procedural, and technical security with respect to our offices and information storage facilities to prevent any loss, misuse, unauthorized access, disclosure, or modification of the user's personal information under our control.

Transfer of data
Your information may be transferred to and processed by DKBmed in the United States or countries other than your own. If you are a data subject in the European Union and the rules of the General Data Protection Regulation (GDPR) apply, we will make sure that any recipients of your data in countries that do not provide the same standard of protection of your personal data as in the EU and where you may not be able to exercise your rights as data subject, have signed special contracts, such as Standard Contractual Clauses, to make sure your confidentiality is respected.

Email marketing
If you are our subscriber/user, we may use your email address to send you offers for educational courses, educational materials, or promotions that we think might be of interest to you, where these are related or similar to DKBmed services and/or Programs that you are using. Each time we send you such marketing or promotional communication, we will provide you the option to refuse future such emails from DKBmed.

How long we will store your personal data
For the various types of personal data we collect, different retention periods may apply. Generally speaking, we store your data for the period for which you use our services and after for the applicable limitation period for related claims.

Your rights under the EU privacy law, the General Data Protection Regulation (GDPR)
If you are a data subject who is in the European Union and the rules of the GDPR are applicable, you will be entitled to the following rights:

  • Right of access – you have the right to request a copy of the information we hold about you.
  • Right of rectification – you have a right to correct data we hold about you that is inaccurate or incomplete.
  • Right to be forgotten – in certain circumstances you can ask that the data we hold about you be erased from our records.
  • Right to restriction of processing – where certain conditions apply you have a right to restrict processing of your personal data.
  • Right of portability – you have the right to have the data we hold about you transferred to another organization when certain circumstances are met.
  • Right to object – you have the right to object to certain types of processing such as direct marketing.
  • Right to object to automated processing, including profiling – you also have the right not to be subject to the legal effects of automated processing or profiling.
  • You have the right to withdraw your consent for processing of your data where such was given without affecting the lawfulness of processing based on consent before its withdrawal.
  • You have the right to lodge a complaint related to collection or the processing of your personal data with the relevant supervisory authority.

If you want to exercise the above-listed rights (except the right to lodge a complaint before a supervisory authority), or to obtain a copy of the Standard Contractual Clauses, please submit a request to [email protected].

Changes to Privacy Policy
DKBmed reserves the right to update and/or change the terms of our Privacy Policy, and we will post those changes to our website privacy page at DKBmed.com and our Program’s Privacy Policy page, so our users and/or visitors are always aware of the type of information we collect, how it will be used, and under what circumstances, if any, we may disclose such information. If at any time DKBmed decides to use any personally identifiable information on file in a manner other than that which was stated when this information was initially collected, the user or users shall be promptly notified by email. Users at that time shall have the option whether or not to permit the use of their information in this separate manner.

Acceptance of terms
Through using this website, you hereby accept the terms and conditions stipulated within the aforementioned Privacy Policy. If you do not agree with our terms and conditions, you should refrain from further use of our sites. In addition, your continued use of our websites following the posting of any updates or changes to our terms and conditions shall mean that you agree with and accept such changes.

How to contact us
If you have any questions or concerns regarding the Privacy Policy related to our website, please feel free to contact us at the following email, telephone number, or mailing addresses:

Email:
[email protected]

Telephone:
646-336-6495

Mailing address:
DKBmed, LLC
122 W. 26th St., Suite 1100
New York, New York 10001

We want to inform you that we have appointed EU GDPR Privacy Officers Ltd. with email [email protected], as our data protection representative based in the European Union in order to comply with the requirements of the GDPR.