2019

Overview

Nine Circles Community Health Centre (Nine Circles) has integrated a registered nurse (RN) within a harm reduction supply distribution room for one hour per day, four days a week. A health educator, known as a community facilitator, distributes requested drug supplies and asks clients if they are interested in testing for sexually transmitted and blood-borne infections (STBBIs). If clients are interested, the community facilitator refers them directly to an RN if one is present or notifies clients of testing hours. The goal of the initiative is to increase testing for STBBIs including HIV, hepatitis C and syphilis, and gonorrhea for people who inject drugs. Testing options include blood and urine samples, rectal and throat swabs and point-of-care tests (i.e., rapid HIV tests). A secondary goal of the program is to connect clients to the primary care services on site if they have no current provider. Nine Circles delivers comprehensive primary care, social support, education and prevention services creating healthier communities for Manitobans.

Why was the program developed?

Nine Circles was part of a project that explored STBBI testing challenges and opportunities in Winnipeg through the Manitoba HIV Collective Impact Network, which is working to transform the landscape of HIV in Manitoba through stigma reduction and prevention, as well as testing and linkage initiatives. The project involved reviewing who is currently using testing services, developing opportunities for collaboration to connect with hard-to-reach populations, and sharing tools and best practices related to completing sexual health assessments. The work also included a client survey, a forum for educators and clinicians who do HIV/STBBI testing, and a final report, which outlined results of this work and made recommendations on next steps.

On the basis of the recommendations of the report, Nine Circles recognized that clients who were accessing their low-threshold harm reduction supply distribution services were not accessing the other health services offered at the community health centre (e.g., primary care, STBBI testing). In response to this identified need, an RN from the health clinic was brought into the harm reduction program four days a week for one hour each day to provide testing and primary care referrals to people who use drugs. This program started on July 3, 2018.

Tammy Reimer, Director of Allied Care and Health Promotion at Nine Circles, explains:

“…we were still trying to find ways for those who were not accessing care to come through our door and fit into our system (e.g., make an appointment and return, wait at the drop in). The challenge was to think about what it would look like for us to walk out the door to the client. What we needed to do was utilize the space/program where staff had already developed a level of trust and to build on this by offering testing and subsequently primary care.”

How does it work?

When a client visits the harm reduction program at Nine Circles they can request drug use supplies from the community facilitator, who is a member of the health education team. The community facilitator, through their interactions with the client, asks if the client is interested in STBBI testing. If this occurs Monday, Tuesday, Thursday or Friday between 1:00 and 2:00 pm the community facilitator directly connects the client with an RN if the client wishes to be tested. If this happens outside these hours the client is encouraged to return during testing hours for their test. 

An RN initially connects with a client in the supply distribution room and testing is completed in an exam room, office space or the supply distribution room, although testing in the supply distribution room is less frequent. The RN shares testing options with clients that include point-of-care tests, swabs, and urine and blood sampling, and clients identify which STBBI testing they are interested in (e.g., chlamydia, gonorrhea, syphilis, HIV, hepatitis C), as well as the type of tests that they would like. The client provides verbal consent and the RN proceeds to collect the specimens for analysis. The role of the RN also includes getting to know clients and building trust.

Clients receive results of point-of-care tests on the spot. For other types of testing, the client can provide a contact number or email and the RN will follow up with them in one or two weeks if any of the test results are positive. If the client does not have contact information, they are encouraged to check back with the community facilitator in one or two weeks for test results or make an appointment at the health centre.

In terms of linking clients to primary care, the nurse asks clients about whether they have a primary care provider, and asks those who do not whether they would like to be connected to one. Depending on where clients are at, they may be interested in being linked to a provider or may prefer to see the sexually transmitted infection (STI) nurse if treatment for an STI is required. Under a directive (allows specific procedures to be delegated to and conducted by another trained health professional), nurses can currently provide treatment for STIs at Nine Circles and in the future they will be able to so independently after completing an advanced prescriber course (probably by 2020).

The RNs have documentation requirements related to this program, which requires up to approximately 30 additional minutes/day. The RN creates a chart for the client (with their permission) and collects data such as whether the client is a first-time tester and the test results and then collects information about any repeat testing that the client receives. The initiative does not require any additional funds to implement.

What has the program accomplished?

An evaluation of the first 12 weeks of the program indicates that a nurse was available in the supply distribution room for a total of 44 hours (i.e., one hour per day for four days a week). In this time, 17 people were open to connecting with a nurse about testing, with 15 of those individuals consenting to testing. Out of the 15 clients who consented to testing:

• 40% (six) were first-time testers (i.e., a person who has not previously been tested for an STBBI)
• 40% (six) tested positive for one or more STBBIs (three people had multiple infections)
• 80% (12) consented to HIV, hepatitis C and syphilis testing
• 33% (five) opted for point-of-care testing for HIV
• 33% (five) completed follow-up by either returning for a booked appointment or following-up with their primary care provider, with four people agreeing to receive a referral to a primary health care provider at Nine Circles
• There were no reactive tests for HIV or hepatitis C

What are the challenges and lessons learned?

The program brings STBBI testing to clients in a low-barrier setting where trust can be established between staff and service users. However, it can be challenging to connect clients to follow-up and treatment services after they receive an STBBI diagnosis, as some clients follow through and others do not.

This program is still in its early stages and currently the nurse is only in the supply distribution room for one hour per day, so it can be difficult to reconnect with clients because of the nurse’s limited availability. As the program continues to operate and learning continues, changes can be made to the approaches used.

The best advice from Kim Witges, Clinical Director at Nine Circles:

“Engage your staff and let them take the lead on what needs to happen; it may fail or succeed, but let it unfold. Be willing to not have all of the answers prior to starting, but be keen to figure it out along the way.”

Contact

Kim Witges, Clinical Director
Nine Circles Community Health Centre
705 Broadway
Winnipeg, MB
R3G 0X2
Email: kwitges@ninecircles.ca

 

New York City, USA
2019

Check Hep C is a community-based program in New York City focused on linkage to care and patient navigation for hepatitis C treatment for high-risk populations, including people who use drugs. This program is based out of community health centres (CHCs) and needle and syringe programs (NSPs). Patient navigators support individuals through the testing, diagnosis and treatment process. This program successfully linked 85% of people diagnosed with a current hepatitis C infection to care in year one. Thirty percent of program participants who were diagnosed with hepatitis C infection were cured in year two of the program.

Program description^1,2

The Check Hep C program was rolled out at CHCs and harm reduction programs located in low-income neighbourhoods with high rates of hepatitis C, serving predominantly minority populations. The CHCs provided onsite hepatitis C care and treatment, harm reduction programs and social services. The core program component was a patient navigator at each site who helped support patients through hepatitis C treatment and care. Navigators assessed patient needs for physical and mental health, substance use and social support.

Individuals were recruited to the program via outreach at the participating CHCs and NSPs and in the community. Upon entering the program, patients received a point-of-care antibody test. The point-of-care test produced screening results within the same appointment. If the test result was positive, blood was drawn during the same appointment for the confirmatory RNA test. Confirmatory RNA test results were typically available within seven days.

If patients were diagnosed with chronic hepatitis C infection, they were referred to a patient navigator located at the CHC or NSP. Participants at CHCs had access to onsite clinical care, whereas patients evaluated at NSPs were connected to external clinical care. A care plan for each participant was created on the basis of their assessment. Patient navigators were trained to provide comprehensive linkage-to-care services, including:

• creating and following a care plan for each patient
• making medical appointments for clients and accompanying them if needed
• case management to address barriers to care
• counselling for treatment readiness and adherence
• health education and linkage to other services
• enrollment into benefits programs and assistance with insurance

Results

A study¹ (2012 to 2013) on year one of the program looked at the Check Hep C program’s ability to perform screening and confirmatory tests, link people to care and initiate treatment (only interferon-based treatment was available at the time of this study). The study was conducted at 12 sites including CHCs and NSPs. A patient was considered linked to care if they attended a minimum of one hepatitis C medical appointment after diagnosis.

• A total of 4,751 individuals were tested for hepatitis C infection, with 512 (11%) having a confirmed, current infection.
• Of those with a current infection, 435 (85%) individuals attended at least one hepatitis C medical appointment.  

The study followed patients who were linked to care onsite at a CHC. Of the 157 patients linked to care in year one:

• 30% were considered treatment candidates
• 9% initiated treatment
• 4% were cured (43% of those who started treatment were cured)

A separate study on year two of the program from 2014 to 2015² followed participants after they had already been diagnosed with a chronic hepatitis C infection. This study was conducted in two CHCs and two NSPs that had participated in year one of the program. Sixty-one percent of participants were born between 1945 and 1965, 73% were male (26% female and 1% transgender), 49% reported being dependent on non-injection drugs in the past year, including opioid substitution therapy, and 28% reported having a mental health condition. Of the 388 participants enrolled in the program:

• 77% completed a hepatitis C medical evaluation (linked to care)
• 61% were eligible for treatment (using direct-acting antivirals [DAAs])
• 33% started treatment
• 30% were cured (91% of those who started treatment were cured)

This 30% cure rate represents a two-fold increase over the estimated 12% to 15% cure rate overall in New York City.³

Participants evaluated onsite at CHCs were significantly more likely to be eligible for treatment (86%) than participants who were referred for offsite services (76%) and were more than twice as likely to initiate treatment (46%) than offsite participants (25%). No significant differences were reported in cure rates between the two groups.

Some participants more likely to start treatment than others

In the 2012 to 2013 study,¹ many participants were not considered to be candidates for treatment because they had other conflicting health conditions, they did not have liver fibrosis, they had ongoing alcohol or drug use issues or they were lost to follow-up. This resulted in low overall treatment numbers. At the time of this study, only interferon-based treatment was available. The authors suggest that many providers were waiting for new, more effective DAA treatments to become available before prescribing treatment. 

By 2014 to 2015, DAA treatments had become available, although strict guidelines set by health insurers prevented many patients from accessing the drugs. Reasons for ineligibility included active drug use, conflicting health conditions and current alcohol use. Participants with more severe fibrosis (F3 or F4 fibrosis score) were twice as likely to begin treatment as those with less severe fibrosis (F1 or F2), and those born between 1945 and 1965 were twice as likely to start treatment as all other age groups. Participants who were homeless, used injection drugs, used alcohol or had a chemical dependence were less likely to start treatment than those who were housed and/or who didn’t use substances.

What does this mean for service providers?

People who use drugs continue to experience significant barriers to treatment such as lack of access to healthcare, and stigma and discrimination associated with substance use. Linkage to care is even more essential because new DAA treatments are highly effective and easy to complete and they can be accessed with few restrictions in Canada. This study shows that high hepatitis C cure rates can be achieved in populations that have not been traditionally well-served by the healthcare system when health navigation is part of their care plan.

Patient navigators played a central role in this program in helping clients navigate the HCV continuum of care, including testing, diagnosis and treatment. There is typically significant patient drop-off at each stage and using a patient navigator helped to mitigate this.

The Check Hep C program model also demonstrates the effectiveness of point-of-care testing followed by immediate blood draws for confirmatory testing. Because this testing can all be done in one appointment (followed by a seven-day wait for RNA results), a hepatitis C diagnosis can be made in a shorter time, reducing the risk of losing a patient to follow-up.

Related resources

Hepatitis C point of care testing: What is its impact on testing and linkage to care?

HepTLC – evidence brief

Patient Navigation – evidence brief

Ontario Hepatitis C Team: The Ottawa Hospital and Regional Hepatitis Program – case study

Practice Guidelines in Peer Health Navigation for People Living with HIV

References

1. Ford MM, Jordan AE, Johnson N et al. Check Hep C: a community-based approach to hepatitis C diagnosis and linkage to care in high-risk populations. Journal of Public Health Management and Practice. 2018:24(1):41–8.
2. Ford M, Johnson N, Desai P et al. From care to cure: demonstrating a model of clinical patient navigation for hepatitis C care and treatment among high-need patients. Clinical Infectious Diseases. 2017:64(5):685–91.
3. Balter S, Stark JH, Kennedy J et al. Estimating the prevalence of hepatitis C infection in New York City using surveillance data. Epidemiology and Infection. 2014 Feb;142(2):262–9.

 

Summary

Isentress HD contains the anti-HIV drug raltegravir. Isentress HD belongs to the class of drugs called integrase inhibitors. Isentress HD is taken once daily with or without food. Overall, Isentress HD was well-tolerated in clinical trials. General side effects were uncommon and included headache and diarrhea; these were usually mild and temporary.

What is Isentress HD?

Isentress HD contains the anti-HIV drug raltegravir. Isentress HD belongs to the class of drugs called integrase inhibitors.

How does Isentress HD work?

Isentress HD works by interfering with an enzyme needed by HIV called integrase. Using Isentress HD greatly reduces HIV’s ability to infect cells and make copies of itself.

How do people with HIV use Isentress HD?

Isentress HD is meant to be used as part of combination therapy for the treatment of HIV. Combinations of anti-HIV drugs are called ART (antiretroviral therapy).

For more information about HIV treatment, see CATIE’s Your Guide to HIV Treatment.

For many people with HIV, the use of ART has increased their CD4+ cell counts and decreased the amount of HIV in their blood (viral load). These beneficial effects help to greatly reduce the risk of developing a life-threatening infection or an AIDS-related cancer. Neither Isentress HD nor any other treatment regimen (ART) is a cure for HIV. It is therefore important that you see your doctor for checkups and lab tests on a regular basis.

Evidence shows that HIV-positive people who are on ART, engaged in care, and have an ongoing undetectable viral load are substantially less likely to transmit HIV to others, be it through sex, when sharing equipment to use drugs or during pregnancy and birth. In fact, the evidence for sexual transmission shows that people on ART who maintain an undetectable viral load do not pass HIV to their sexual partners. For further information see the CATIE fact sheet HIV treatment and an undetectable viral load to prevent HIV transmission. However, it is still a good idea to use condoms because they can reduce your risk for getting and passing on other sexually transmitted infections.

Warnings

Although Isentress HD is generally well-tolerated, side effects can occur.

1. Skin—rash and hypersensitivity

In clinical trials, the most common side effect affecting the skin was rash; this is usually mild or moderate in severity and temporary.

Symptoms of hypersensitivity reactions can include severe rash or rash with a fever, together with lack of energy and painful muscles or joints. In severe cases additional symptoms can include peeling of the skin, blisters on the lips, swollen eyes and face, stomach cramps, and difficulty breathing. The manufacturer advises that Isentress HD (or any other drugs suspected of causing this reaction) should be discontinued immediately if these symptoms occur, otherwise the hypersensitivity reaction can become life threatening. If symptoms suggestive of hypersensitivity occur, see your doctor immediately or go to the emergency room of your nearest hospital or medical centre.

2. Muscles—soreness and/or weakness

Isolated cases of muscle-related weakness and aches have been reported in association with the use of Isentress twice daily. In some cases, affected people also had increased levels of the enzyme creatine kinase in the blood.

Special populations

Pregnant women

Isentress twice daily was the first integrase inhibitor approved in Canada in 2007. Data from more than 500 HIV-positive pregnant women who took Isentress twice daily as part of ART found that there was no overall increase in birth defects compared to births in HIV-negative women. This finding is encouraging. However, if you are pregnant or want to have a baby, talk to your doctor.

Older people

Clinical trials of Isentress HD have not included large numbers of people who are 65 years or older so its effectiveness and safety in this population is not known.

General side effects

In clinical trials, Isentress HD was well tolerated, generally safe and effective. However, as with any treatment, there were side effects but these were usually of mild to moderate intensity and temporary, such as the following:

• nausea
• diarrhea
• headache
• dizziness

Note that the HIV-positive people who are typically enrolled in pivotal clinical trials of HIV treatments, including Isentress HD, are generally young and healthy. Once a drug is approved and more widely available, it gets used by populations who are not usually in pivotal clinical trials. These people may be older and may have other health issues—such as cardiovascular disease, liver injury, kidney injury, type 2 diabetes, anxiety, depression, and substance use—that require medications or that cause symptoms. As a result, their experience of side effects may be different from those reported in pivotal clinical trials.

Uncommon side effects

These side effects occurred in less than 2% of adults in clinical trials:

Anxiety and depression

Although not common in clinical trials, a small proportion of people (less than 2%) who took Isentress-based combination therapy developed one or more of the following: depression, negative thoughts, anxiety and thoughts of suicide that in some cases led to attempted suicide.

Anxiety and depression are relatively common in HIV-positive people (regardless of whether they are on treatment or the type of treatment that they take). If you are taking Isentress HD and think that you may have developed anxiety or depression, speak to your doctor right away. Your doctor can help determine if you have anxiety or depression and if there is any relationship between them and the medicines that you are taking.

There have been reports of rare cases where people developed anxiety and/or depression after initiating treatment with Isentress-based regimens. Symptoms of anxiety and depression can include the following:

• becoming easily upset or angry
• feeling fearful
• excessive worry
• difficulty falling asleep or staying asleep, or waking up prematurely
• unexpected feelings of sadness
• recurrent nightmares
• prolonged feelings of sadness, anger or depression
• feeling hopeless
• loss of pleasure in everyday activities
• unexpectedly feeling tired or experiencing a lack of energy
• strange thoughts

If you experience any of the above, contact your doctor or nurse right away.

If you have thoughts of harming yourself or others, dial 911 right away.

Drug interactions

Some drugs (including prescribed and over-the-counter), herbs and supplements can interfere with the absorption and/or effectiveness of Isentress HD. Such interference is called a drug interaction. Some drugs can reduce the levels of Isentress HD in your blood. This can make Isentress HD less effective and lead to treatment failure, possibly reducing your future treatment options. Other drugs can raise the levels of Isentress HD in your blood, resulting in enhanced side effects or new side effects. Therefore it is important to disclose to your doctor and pharmacist all the supplements, drugs, and herbs you are taking.

In general, Isentress HD does not have many drug interactions.

This factsheet is not comprehensive and only lists some of the potential and actual drug interactions with Isentress HD. Speak to your pharmacist to find out more about drug interactions with Isentress HD.

Acid-reducing agents, laxatives, metal supplements and buffered medicines

Examples of acid-reducing agents (antacids) include the following:

• Alka-Seltzer
• Calcium and/or magnesium liquids and tablets
• Gaviscon (tablets and syrup)
• Maalox (liquid and tablets)
• Milk of Magnesia
• Pepto-Bismol
• Rolaids
• Tums

Some antacids contain calcium while others contain magnesium or aluminum; some contain combinations of these metals. The drug manufacturer, Merck, warns that antacids containing calcium, aluminum or magnesium should not be taken with Isentress HD. If you have issues with excess stomach acid, speak to your pharmacist. Remind your pharmacist that you are taking Isentress HD.

Resistance and cross-resistance

Over time, as new copies of HIV are made in the body, the virus changes its structure. These changes, called mutations, can cause HIV to resist the effects of anti-HIV drugs, which means those drugs will no longer work for you.

To reduce the risk of developing drug resistance, all anti-HIV drugs should be taken every day exactly as prescribed and directed. If doses are delayed, missed or not taken as prescribed, the level of Isentress HD in the blood may fall too low. If this happens, the HIV in your body can become resistant to Isentress HD and possibly other drugs you are taking. If you find you are having problems taking your medications as directed, speak to your doctor, nurse or pharmacist about this. They can find ways to help you.

When HIV becomes resistant to one drug in a class, it sometimes becomes resistant to other drugs in that class. This is called cross-resistance. Feel free to talk with your doctor about your current and future treatment options. To help you decide what these future options might be, at some point your doctor can have a small sample of your blood analyzed to test for resistance.

Dosage

Isentress HD is supplied as yellow tablets. Each tablet contains 600 mg raltegravir. The dose recommended by Merck for adults is 600 mg taken once daily, together with other anti-HIV drugs. Isentress HD can be taken with or without food.

If you forget to take a dose, Merck recommends that “you take it as soon as you remember. If you do not remember until it is time for your next dose, skip the missed dose and go back to your regular schedule.”

Availability

Isentress HD is licensed in Canada. Your doctor or pharmacist can tell you more about the availability and coverage of Isentress in your region. CATIE’s online module Federal, Provincial and Territorial Drug Access Programs also contains information about Canadian drug coverage.

References

Merck Canada. Isentress HD (raltegravir tablets 600 mg). Product Monograph. 19 September, 2018.

Author(s): Hosein SR

Published: 2019

Summary

Symtuza contains four medicines—darunavir, cobicistat, tenofovir alafenamide (TAF) and FTC. Darunavir belongs to the class of drugs called protease inhibitors. Cobicistat is a booster; it raises and maintains levels of darunavir in the blood. TAF and FTC belong to the class of drugs called nucleoside reverse transcriptase inhibitors (“nukes”). Symtuza is taken at a dose of one pill once daily with food. Overall, Symtuza was well-tolerated in clinical trials. General side effects were uncommon and included diarrhea and nausea; these were usually of mild to moderate intensity, and temporary.

What is Symtuza?

Symtuza contains four medicines—darunavir, cobicistat, TAF and FTC. Darunavir belongs to the class of drugs called protease inhibitors. Cobistat belongs to the class of drugs called boosters; it raises and maintains levels of darunavir so that Symtuza need only be taken once daily. TAF and FTC belong to the class of drugs called nucleoside reverse transcriptase inhibitors (“nukes”). Darunavir was approved in Canada in 2006 and the other drugs were approved several years ago. What is new is that Symtuza combines all of these drugs in one pill.

How does Symtuza work?

The drugs in Symtuza work by interfering with enzymes needed by HIV called protease and reverse transcriptase. Using Symtuza greatly reduces HIV’s ability to infect cells and make copies of itself.

How do people with HIV use Symtuza?

Symtuza is meant as a complete regimen for the treatment of HIV infection in adults and adolescents (aged 12 years and older with body weight at least 40 kg). Symtuza should be taken with food; the type of food does not matter.

For more information about HIV treatment, see CATIE’s Your Guide to HIV Treatment.

For many people with HIV, the use of ART (HIV treatment or antiretroviral therapy) has increased their CD4+ cell counts and decreased the amount of HIV in their blood (viral load). These beneficial effects help to greatly reduce the risk of developing a life-threatening infection or an AIDS-related cancer. Neither Symtuza nor any other treatment regimen is a cure for HIV. It is therefore important that you see your doctor for checkups and lab tests on a regular basis.

Evidence shows that HIV-positive people who are on ART, engaged in care, and have an ongoing undetectable viral load are substantially less likely to transmit HIV to others, be it through sex, when sharing equipment to use drugs or during pregnancy and birth. In fact, the evidence for sexual transmission shows that people on ART who maintain an undetectable viral load do not pass HIV to their sexual partners. For further information see the CATIE fact sheet HIV treatment and an undetectable viral load to prevent HIV transmission. However, it is still a good idea to use condoms because they can reduce your risk for getting and passing on other sexually transmitted infections.

Warnings

Special populations

Pregnant women

A clinical trial has found that levels of darunavir, even when used with the booster cobicistat, are substantially lower in the blood of pregnant HIV-positive women compared with levels in these women after they gave birth. Therefore, the manufacturer of Symtuza, Janssen, recommends “Symtuza should not be initiated in pregnant women. An alternative regimen is recommended for women who become pregnant during therapy with Symtuza.” If you are taking Symtuza and are pregnant or want to have a baby, speak to your doctor right away.

Certain children

Symtuza has not been studied in children who were less than 12 years of age or who weighed less than 40 kg.

Older people

Symtuza has not been studied in large numbers of people aged 65 and older.

Hemophiliacs

HIV-positive people who are hemophiliacs and who use protease inhibitors (including those in Symtuza) may experience more frequent bleeding under the skin and/or in the joints. It is not certain why this may occur. However, Janssen recommends “the frequency of bleeding episodes should be closely monitored in patients on Symtuza.”

Cholesterol and blood sugar

Levels of cholesterol and sugar in your blood may increase when you take Symtuza or other regimens. Janssen suggests regular monitoring of cholesterol and sugar (glucose) levels in the blood.

Lactic acidosis

Lactic acidosis is rare among HIV-positive people in Canada today as the nukes used are generally safer than in the early days of the HIV pandemic. Also, people tend to start HIV treatment when their CD4+ counts are higher and so they are in generally better health than a decade or two ago when lactic acidosis was more common.

In rare cases, levels of lactic acid may accumulate in the blood of some people who use nukes (such as FTC and TAF, which are in Symtuza). Excess lactic acid levels (lactic acidosis) can cause the liver to become enlarged. Excess lactic acid can be detected with a blood test. Early symptoms of excess lactic acid in the blood can include the following:

• tiredness or lack of energy
• nausea
• stomach pain
• unintentional weight loss

If these are persistent, contact your doctor.

If left untreated, lactic acid levels can become very high and cause life-threatening complications, including the following:

• rapid heartbeat when you are at rest
• rapid breathing when you are at rest
• yellowing of the skin (jaundice) and whites of the eyes
• muscle weakness

If you have these symptoms, contact your doctor or go to the Emergency Department of a hospital.

Here are some typical risk factors for lactic acidosis among HIV-positive people:

• being female
• pregnancy
• obesity
• pre-existing liver injury
• low CD4+ cell count (less than 200 cells/mm³)

Liver health

Symtuza has not been tested in people with underlying liver injury.

In rare cases, the liver may become injured in some people who take darunavir (in Symtuza). According to the manufacturer of Symtuza, liver injury among darunavir users has “generally occurred” in patients with one or more of the following:

• advanced HIV infection
• infection with hepatitis B virus or hepatitis C virus
• immune reconstitution inflammatory syndrome

In cases of new or worsening liver dysfunction (including clinically significant elevation of liver enzymes and/or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness and swollen liver), you should contact your doctor right away.

Symtuza contains tenofovir and FTC. Both of these drugs have anti-hepatitis B virus (HBV) activity. People with an HBV infection who take Symtuza and then later stop may experience worsening HBV infection. People who are co-infected with HIV and hepatitis-causing viruses and who take ART are sometimes at increased risk for liver injury. It is important to have regular blood tests so that your doctor can assess the health of your liver.

Pancreatic health

In rare cases, inflammation of the pancreas gland (in the abdomen) has occurred in people who were using darunavir. It is not clear if darunavir caused this problem.

General risk factors for inflammation of the pancreas gland include the following:

• smoking tobacco
• excess intake of alcohol
• elevated levels of a fatty substance in the blood called triglycerides
• having disorders such as inflammatory bowel disease, lupus (SLE) and other diseases whereby the immune system attacks the body

Symptoms of an acute inflamed pancreas gland can include pain that:

• begins slowly or suddenly in your upper abdomen
• sometimes spreads to your back
• can be mild or severe
• may last for several days

Other symptoms may include the following:

• fever
• nausea and vomiting
• fast heartbeat
• swollen or tender abdomen

According to the U.S. National Institute of Diabetes and Digestive and Kidney Diseases, “People with acute pancreatitis usually look and feel seriously ill and need to see a doctor right away.”

Kidney health

Symtuza contains the newer formulation of tenofovir called TAF (tenofovir alafenamide). Although kidney injury from exposure to TAF is unlikely, Janssen states that it cannot be ruled out. Also, Janssen cautions that people who take Symtuza and who have kidney injury and who also take medicines that can injure the kidneys (such as non-steroidal anti-inflammatory drugs) “are at increased risk” for developing kidney-related side effects.

The following drugs and substances have the potential to weaken the health of the kidneys (this list is not exhaustive):

• antibiotics – gentamicin, amikacin, vancomycin, rifampin
• anti-cancer drugs – Cisplatin (cis-platinum), carboplatin, Avastin (bevacizumab), gemcitabine
• anti-fungal drugs – amphotericin B, pentamidine
• anti-viral drugs – foscarnet (Foscavir), cidofovir (Vistide), acyclovir, valacyclovir
• non-steroidal anti-inflammatory drugs (NSAIDs) – Aspirin (acetylsalicylic acid), celecoxib (Celebrex), diclofenac (Voltaren), ibuprofen (Advil, Motrin); indomethacin, naproxen, ketorolac (Acular)
• street drugs – cocaine, heroin

Your doctor, nurse or pharmacist may recommend the temporary use of one of these medicines because they are medically necessary. However, repeated or long-term use of some of these medicines, such as NSAIDS, may increase your risk for kidney injury.

Skin and hypersensitivity reactions

In one analysis, Janssen has reported that out of 3,063 people who used darunavir (in Symtuza), 0.4% developed “severe skin reactions…accompanied by fever and/or elevations of liver enzymes.” Furthermore, Janssen noted that life-threatening skin reactions (called “Stevens-Johnson Syndrome”) were rare, occurring in less than 0.1% of people who used darunavir.

Signs or symptoms of severe skin reactions can include severe rash or rash accompanied by one or more of the following symptoms:

• fever
• generally feeling unwell and in discomfort
• muscle or joint pain/ache
• blisters
• lesions in the mouth and on the lips
• the tissue lining the eyelids and whites of eyes becomes inflamed
• liver inflammation

If these problems occur, contact your doctor right away.

Side effects

General

In clinical trials, Symtuza was generally well-tolerated and effective. However, as with any treatment, there were side effects but these were mostly uncommon and included the following:

• diarrhea
• nausea
• rash
• lack of energy

Note that the HIV-positive people who are typically enrolled in pivotal clinical trials of HIV treatments, including Symtuza, are generally young and healthy. Once a drug is approved and more widely available, it gets used by populations who are not usually in pivotal clinical trials. These people may be older and may have other health issues—such as cardiovascular disease, liver injury, kidney injury, type 2 diabetes, anxiety, depression, and substance use—that require medications or that cause symptoms. As a result, their experience of side effects may be different from those reported in pivotal clinical trials.

The skin

Rash is a common side effect of darunavir-containing medicines such as Symtuza. According to Janssen, such rashes are “mostly mild to moderate, often occurring within the first four weeks of treatment and resolves with continued dosing.”

Drug interactions

Some drugs (including prescribed and over-the-counter), herbs and supplements can interfere with the absorption and/or effectiveness of Symtuza. Such interference is called a drug interaction. Some drugs can reduce the levels of the medicines in Symtuza in your blood. This can make Symtuza less effective and lead to treatment failure, reducing your future treatment options. Other drugs can raise the levels of medicines in Symtuza in your blood, resulting in enhanced side effects or new side effects. Therefore it is important to disclose to your doctor and pharmacist all the supplements, drugs, and herbs you are taking.

This factsheet is not comprehensive and only lists some of the potential and actual drug interactions with Symtuza. Speak to your pharmacist to find out more about drug interactions with Symtuza.

Not to be used

Janssen recommends that people taking Symtuza should not use the following drugs:

• for prostate problems – alfuzosin (Xatral)
• for treatment of abnormal heart rhythm – amiodarone, dronedarone, lidocaine (injected into the body), quinidine
• for reducing the risk of blood clots – apixaban, rivaroxaban; ticagrelor
• anti-seizure drugs – carbamazepine, phenobarbital, phenytoin
• for the treatment of gout – colchicine
• anti-histamines – astemizole, terfenadine
• antibiotics – rifampin
• for treatment of migraine and severe headaches – dihydroergotamine, ergonovine, ergotamine, methylergonovine
• for treating hepatitis C virus infection – Zepatier (elbasvir + grazoprevir)
• for treating high cholesterol – lovastatin, simvastatin
• for treating asthma and other lung issues – salmeterol (Advair, Advair Diskus, Serevent Diskhaler Disk, Serevent Diskus)
• for treating psychosis – lurasidone (Latuda), pimozide
• for treating pulmonary arterial hypertension – sildenafil (Revatio)
• for treating sleeping problems – midazolam, triazolam

Symtuza does not interfere (or vice versa) with acid-reducing agents, including those containing aluminum, calcium or magnesium.

Resistance and cross-resistance

Over time, as new copies of HIV are made in the body, the virus changes its structure. These changes, called mutations, can cause HIV to resist the effects of anti-HIV drugs, which means those drugs will no longer work for you.

To reduce the risk of developing drug resistance, all anti-HIV drugs should be taken every day exactly as prescribed and directed. If doses are delayed, missed or not taken as prescribed, the level of drugs in Symtuza in the blood may fall too low. If this happens, the HIV in your body can become resistant to the medication. If you find you are having problems taking your medications as directed, speak to your doctor, nurse or pharmacist about this. They can find ways to help you.

When HIV becomes resistant to one drug in a class, it sometimes becomes resistant to other drugs in that class. This is called cross-resistance. Feel free to talk with your doctor about your current and future treatment options. To help you decide what these future options might be, at some point your doctor can have a small sample of your blood analyzed to test for resistance.

Dosage

Symtuza is supplied as yellow to yellowish-brown capsule-shaped tablets. Each tablet contains 800 mg of darunavir, 150 mg of cobicistat, 200 mg of FTC and 10 mg of TAF. The recommended adult dose of Symtuza is one pill taken once daily with food; the type of food does not matter. Janssen advises people to take Symtuza “within 30 minutes of eating. Symtuza must be taken with food so that it is absorbed.”

If you forget to take a dose, here is advice from Janssen:

• If you notice within 12 hours of the time you usually take Symtuza, take the tablet immediately with food. Then take the next dose at your usual time.
• If you notice after 12 hours of the time you usually take Symtuza, do not take the missed dose. Wait to take the next dose with food at your usual time.
• Do not take a double dose (two doses together)
• Call your doctor or pharmacist if you are not sure what to do.

Availability

Symtuza is licensed in Canada. Your doctor or pharmacist can tell you more about the availability and coverage of Symtuza in your region. CATIE’s online module Federal, Provincial and Territorial Drug Access Programs also contains information about Canadian drug coverage.

References

1. Janssen. Symtuza (darunavir/cobicistat/emtricitabine/tenofovir alafenamide). Product Monograph. 3rd October, 2018.
2. Alsunaid SR, Ashraf H, Soubani AO. Tenofovir alafenamide associated fatal lactic acidosis in an autologous hematopoietic stem cell transplant recipient. Transplant Infectious Disease. 2018 Oct;20(5):e12960.
3. Eron JJ, Orkin C, Gallant J, et al. A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients. AIDS. 2018 Jul 17;32(11):1431-1442.
4. Lactic acidosis international study group. Risk factors for lactic acidosis and severe hyperlactataemia in HIV-1-infected adults exposed to antiretroviral therapy. AIDS. 2007 Nov 30;​21(18):2455-64.
5. Orkin C, Molina JM, Negredo E, et al. Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non-inferiority trial. Lancet HIV. 2018 Jan;5(1):e23-e34.
6. U.S. Department of Health and Human Services. HIV and lactic acid. Factsheet. 24 August, 2018. Available at: https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/22/68/hiv-and-lactic-acidosis

Author(s): Hosein SR

Published: 2019

Northwest Territories, Canada
2018

Indigenous peoples in Canada experience social and health disparities due to the ongoing effects of racism, colonization, and intergenerational trauma from forced family separation by the residential school system. HIV is an example of one of these health disparities; HIV in Canada disproportionately affects Indigenous people,¹ and more specifically Indigenous women and youth (15–29 years old).² While these social and health disparities persist, there are also strengths and protective factors among Indigenous peoples, including cultural connectedness and resiliency. Fostering Open eXpression among Youth (FOXY) is an arts-based intervention for the prevention of HIV and sexually transmitted infection (STI) that was designed by and for Northern and Indigenous youth in the Northwest Territories (NWT). The FOXY intervention uses trained facilitators and peer leaders to deliver workshops on sexual health, sexuality, and healthy relationships to young women and girls aged 13-17 years. An observational pilot study funded by the Canadian Institutes of Health Research found that participants’ STI knowledge and safer sex self-efficacy were significantly improved after the intervention.

Program description^3,4

FOXY is an HIV and STI prevention program developed by and for Northern and Indigenous Canadian youth in the NWT to foster more open expression and communication regarding sexuality and sexual health. FOXY was developed over two years with the help of adolescent peer leaders and was focus tested with youth. FOXY integrated local knowledge and local context into its development and uses an arts-based approach (e.g., drama activities to facilitate discussion and learning), which can help participants to develop self-reflection and decision-making skills. Through the use of an arts-based approach, which is associated with increased empowerment, FOXY provides judgment free-education on sexual health, HIV and STIs, sexuality, and healthy relationships.

The intervention includes seven workshops of between one and two hours each, which are conducted over one or two days. Workshops are led by trained facilitators and peer leaders with expertise in sexual health and arts-based education. There are eight to 15 participants per workshop.

Participants in this pilot study were recruited from 17 communities across the NWT from September 2015 to May 2016. Participants self-identified as women or girls, resided in the NWT, and were 13–17 years old.

Results

The study compared pre- and post-intervention scores of participants related to STI knowledge, safer sex self-efficacy (i.e., confidence in using condoms consistently), and resilience using the Child and Youth Resilience Measure.* Information was collected immediately before and after the program was delivered, using three self-reported surveys each time.

The majority (79%) of the 199 participants identified as Indigenous and 21% identified as sexual minorities. In terms of sexual practice, 18% of participants self-reported that they had engaged in vaginal sex, 19% believed that they were at risk for STIs, and 15% believed that they were at risk of HIV. The comparison of pre- and post-intervention scores indicated:

• significantly higher STI knowledge scores (median score of 4 pre- and 9 post-intervention [out of 14]);
• significantly higher safer sex self-efficacy scores; and
• slightly higher resilience scores.³

The current study (published in 2018) does not consider the long-term outcomes of the program, but there are plans to follow program participants for a 12-month period.⁴

What does this mean for service providers?

The FOXY intervention, an educational and arts-based intervention that uses peer leaders and trained facilitators, has produced favourable results. The intervention demonstrates the importance of culturally appropriate health education programming for Northern youth that is developed by Northern youth, while contributing to the evidence base for arts-based HIV and STI prevention programs. Indigenous peoples face social and structural barriers that contribute to the disproportionate effect of HIV in Canada among Indigenous women and youth, and this intervention provides a novel and tailored approach to engage young women. Long-term results will be useful in determining the longevity of the positive outcomes and further utility of the program in HIV prevention efforts.

*The Child and Youth Resilience Measure defines resilience as the ability to navigate resources (e.g., individual, cultural) for well-being.

Related resources

Sexuality…Let’s Talk About It! – Case Study

Sexual Health Information Project (SHIP) – Case Study

The Underwear Project – Case Study

Fostering Open eXpression among Youth (FOXY) – Website

References

1. Public Health Agency of Canada. Summary: Estimates of HIV Incidence, Prevalence and Canada’s Progress on Meeting the 90-90-90 HIV targets, 2016. Ottawa: Public Health Agency of Canada; 2018. Available from: https://www.canada.ca/en/public-health/services/publications/diseases-conditions/summary-estimates-hiv-incidence-prevalence-canadas-progress-90-90-90.html
2. Public Health Agency of Canada. HIV/AIDS Epi Updates, July 2010, Chapter 8: HIV/AIDS Epi updates, July 2010 – HIV/AIDS among Aboriginal people in Canada. Ottawa: Surveillance and Risk Assessment Division, Centre for Communicable Diseases and Infection Control, Public Health Agency of Canada; 2010. Available from: https://www.canada.ca/en/public-health/services/hiv-aids/publications/epi-updates/chapter-8-hiv-aids-among-aboriginal-people-canada.html
3. Lys CL, Logie CH and Okuma M. Pilot testing Fostering Open eXpression among Youth (FOXY), an arts-based HIV/STI prevention approach for adolescents women in the Northwest Territories, Canada. International Journal of STD & AIDS. 2018;29(10):980–6.
4. Lys C, Logie CH, MacNeil N et al. Arts-based HIV and STI prevention intervention with Northern and Indigenous youth in the Northwest Territories: study protocol for a non-randomised cohort pilot study. BMJ Open. 2016;6(10):e012399.