Medication Therapy Management

Role of Medication Therapy Management in Preexposure Prophylaxis Therapy for HIV Prevention

Journal of Pharmacy Practice 2015, Vol. 28(1) 10-12 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0897190014562351 jpp.sagepub.com

Kelli W. Ferrell, RPh, MSc1, Laresa M. Woodard, MMSc, PA-C2, and Todd J. Woodard, PharmD, BCPP, BCPS, CGP3

Abstract Patient medication adherence is a long-standing problem and is one that raises serious issues for patient health, public health, and health care quality. Medication nonadherence costs the US economy an estimated US$290 billion in avoidable medical spending every year. One of the most costly health conditions is HIV disease, which continues to be a serious health issue for parts of the world. About 34 million people are living with HIV around the world. With the emerging preventative treatment against HIV, known as preexposure prophylaxis (PrEP), come concerns surrounding the potential impact of nonadherence to this newly approved medication therapy. Nonadherence to antiretroviral treatments are commonly the root cause for patients not reaching their treatment goals, putting them at risk of progression and worsening of their disease and complications, such as increased risk of opportunistic infections. Therefore, it is essential to improve antiretroviral medication adherence. By identifying members who are nonadherent to their prescribed antiretroviral medications and working collaboratively with patients, physicians, and pharmacists, Medication Therapy Management (MTM) can potentially increase medication adherence by helping patients identify, resolve, and prevent issues that may affect their decision not to take a medication as intended. Keywords medication adherence, preexposure prophylaxis, PrEP, medication therapy management, MTM, HIV, antiretroviral therapy, emtricitabine/tenofovir disoproxil

Medication Adherence Medication adherence usually refers to whether patients take their medications as prescribed (eg, twice daily), as well as whether they continue to take a prescribed medication for the right duration.1 Nonadherence is commonly associated with adverse outcomes and associated with higher health care cost. This has become a major concern for most health care professionals, health systems, and insurance companies. Because the population is aging and taking more medications for chronic conditions, medication nonadherence is expected to increase.1

nonadherence has been linked with virologic, immunologic, and clinical failure.2 By identifying patients who are nonadherent to HAART and working together with patients, physicians, and other health professionals, Medication Therapy Management (MTM) can increase medication adherence. This can be done by a pharmacist helping patients to identify, resolve, and prevent issues that may affect their decision not to take a medication as prescribed by their provider. MTM may include but not be limited to medication therapy reviews, pharmacotherapy consults, medication education/adherence, and many other clinical services. This article will address and introduce the pharmacists’ role in adherence in patients

Antiretroviral Medication Adherence In this day and age, people with HIV/AIDS are living longer due to highly active antiretroviral therapy (HAART). Antiretroviral therapy involves using combinations of medications from different classes such as protease inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, nucleotide reverse transcriptase inhibitors, and fusion inhibitors, much like other chronic health conditions. These medications suppress HIV viral load and increase CD4þ count, which improves the immune system and helps prevent opportunistic infections. Therefore,

1 Department of Utilization Management, Clinical Programs, US Script, Inc, Atlanta, GA, USA 2 Department of Family Medicine, The Family Health Centers of Georgia, Inc, Atlanta, GA, USA 3 Department of Pharmacy, The Family Health Centers of Georgia, Inc, Atlanta, GA, USA

Corresponding Author: Kelli W. Ferrell, US Script, Inc, 5909 Peachtree Dunwoody Rd NE, Suite 300, Atlanta, GA 30328, USA. Email: [email protected]

Downloaded from jpp.sagepub.com at GEORGIAN COURT UNIV on February 24, 2015

Ferrell et al

11

undergoing preexposure prophylaxis (PrEP) intervention of HIV with a focus on emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF).

This medication may be costly, particularly for people without insurance and in areas with limited resources.3

Medication Adherence and PrEP Preexposure Prophylaxis PrEP is defined as the treatment of an uninfected person before having sexual contact with an HIV-infected partner. PrEP therapy ideally helps prevent the spread of HIV to at-risk noninfected individuals. In the United States, there are about 50 000 new HIV infections each year, and around three-fifths of these cases occur in men who have sex with men (MSM).3

Pharmacology of Current PrEP Therapy TDF has received a total of two Food and Drug Administration (FDA) approved indications within the last 13 years. It was approved on October 26, 2001, for the treatment of HIV and on August 11, 2008, for the treatment of chronic hepatitis B (HepB) by the FDA. TDF is an oral prodrug of tenofovir, a nucleotide analogue with activity against retroviruses, including HIV-1, HIV-2, and hepadnaviruses.4,5,6 Following absorption, TDF is rapidly converted to tenofovir, which is metabolized to its active tenofovir diphosphate, which is a competitive inhibitor of HIV-1 reverse transcriptase and terminates the growing DNA chain. Tenofovir has a long 17-hour half-life compared to the nucleoside analogues, which allow once-daily dosing.5,6 FTC was approved by the FDA on July 2, 2003. FTC is an analogue of cytidine. This drug works by inhibiting reverse transcriptase, the enzyme that copies HIV RNA into new viral DNA. By interfering with this process, FTC can help to lower the viral load in a patient’s body and can indirectly increase the number of T cells or CD4þ T cells.6 As a result of these combined medications, it is associated with healthier immune systems and decreased likelihood of serious illness. This combination has been most intensively studied as PrEP. FTC/TDF has important qualities that make it an ideal agent for PrEP. These qualities include potent antiretroviral activity against all HIV subtypes, rapid onset of activity after ingestion, early action in HIV’s life cycle, and once-daily dosing with few drug interactions.7 On July 16, 2012, this combination became the first FDA-approved agent to reduce the risk of HIV infection in uninfected individuals who are at high risk of HIV infection and who may engage in sexual activity with HIV-infected partners. Although FTC/TDF is to be used for PrEP, it must be used in combination with safer sex practices to reduce the risk of sexually acquired HIV infection in adults at high risk. The normal dosage is 1 tablet given once daily. PrEP with FTC/TDF is a novel approach in PrEP but it is not a guarantee. This combination is not a replacement for condoms and other safe sex practices. Common adverse reactions in people who take the drug to prevent HIV infection include headache, abdominal pain, and weight loss. Safety concerns include impairment of kidney and liver function and decrease in bone mineral density. The long-term safety of the drug in healthy people is not yet known due to availability of studies.

Strict adherence to antiretroviral therapy is key to sustained HIV suppression.8 The same has been shown to be true for PrEP therapy against HIV. Study results on PrEP use from the PrEP Trial Initiative indicated that participants who took the medication on 90% or more days had a 79% decrease in HIV incidence.9 With the emergence of PrEP therapy have come questions surrounding various methods that will be utilized to increase medication adherence. Improvement in adherence to PrEP therapy will likely require efforts by all members of the health care team—physicians, nurses, pharmacists, other health care professionals, and health care delivery systems. For many years, pharmacists have been a focal point in the management of medication therapies. Pharmacists are often in the frontline and have access to real-time utilization claims to identify gaps in therapy. Pharmacy claims can be used to alert members of the health care team about patients who are late to refill their PrEP therapy. Pharmacists can also assist in counseling patients about the risks of becoming infected with HIV, especially in ‘‘high-risk’’ individuals. High-risk individuals include MSM and injection drug users, those who have unprotected intercourse, have sexual partners who have HIV, are bisexual, or exchange sex for money.10 Pharmacists can use these counseling opportunities to also identify and address barriers to adherence with both PrEP medications and other mechanisms such as structural and behavioral interventions. Pharmacist-led counseling should not replace the ongoing discussions between patients and their physicians. Pharmacists may play an important role in this emerging therapy by providing feedback about medication adherence and assisting with counseling using modalities that are effective for all literacy groups and levels.

Prescribers and PrEP The prescriber’s perspective and role in PrEP is duty-bound with key steps in the process. TDF/FTC PrEP cannot be indiscriminately initiated, as it is for those with continuous, increased probability of sexually acquired HIV transmission. This includes high-risk populations of men who have sex with men (MSM), and heterosexual individuals in serodiscordant (one member is positive for HIV infection, and the other is not) sexual relationships, and other contributing behavioral risk factors.10 The Centers for Disease Control and Prevention has provided guidance for providers, which includes using PrEP for injection drug users.11 Laboratory testing must be done to ensure an HIV-negative status before and during therapy. Counseling must be provided to promote medication adherence along with specific behavioral and structural modifications, including limiting the number of sexual partners and condom use with each sexual encounter. The application of HIV prophylaxis in high-risk

Downloaded from jpp.sagepub.com at GEORGIAN COURT UNIV on February 24, 2015

12

Journal of Pharmacy Practice 28(1)

individuals necessitates continual health involvement, which also includes monitoring for adverse outcomes and development of resistance.12 Factors involved in assessment of suitability for treatment are recording confirmation of an HIV-negative test just prior to PrEP initiation.3 If the patient is symptomatic of acute HIV infection, the provider should test for this, and if the candidate has engaged in sex with a known HIV-infected person in the last month, they should be tested for acute infection. It is important to screen/test for pregnancy, and assess whether women are planning to become pregnant, and if any are breastfeeding. To qualify, candidates have to be identified as having a continuing great probability for HIV transmission. Their creatinine clearance must be estimated as greater than or equal to 60 mL/ min. Known sexual mates with HIVpositive status should be on antiretroviral treatment and care or be assisted with obtaining this treatment. It is advised to screen for and treat sexually transmitted infections (STIs) including HepB, for which immunization should be given if not previously received or detected. Female candidates should be informed that although no harmful effects to infants with exposure during gestation have been found, there is still little research on the safety of this. It is not recommended to treat breastfeeding women with PrEP.13 When starting PrEP therapy, TDF/FTC is typically not prescribed beyond a 90-day supply. It contains 200 mg FTC (brand name Emtriva) and 300 mg TDF (brand name Viread). Refills should be contingent upon negative testing for HIV infection and pregnancy in women, or after appropriate education in the event the women want to continue while pregnant. Counseling for safer sex practices should be performed and condoms provided. The TDF/FTC combination may be used to treat acute HepB infection, if detected, while continuing to provide PrEP therapy. Maintenance guidelines while on a PrEP medication regimen call for testing and recording of a nonpositive HIV antibody result every 2 to 3 months. The prescriber should document results of pregnancy testing for women and confer with the patient and obstetrician if continuing therapy through pregnancy. At a minimum of every visit, a patient assessment and assistance with medication dosing regimen should be performed to promote adherence. Also, a key is risk evaluation and mentorship to decrease the likelihood of practices leading to infection, while providing the barrier option of condoms at these 2- to 3-month intervals. Regular follow-ups should screen for general STI indicators with the appropriate testing and treatment. Providers should test for bacterial STIs at 6-month intervals whether symptoms are present or not. Kidney function should be monitored by calculating creatinine clearance and measuring serum creatinine level 3 months after the start of therapy, then every 6 months during treatment. Should PrEP therapy be stopped, HIV testing must be done to determine whether infection has been transmitted. A positive result necessitates testing for resistant strains and connection with HIV care. If the patient desires to stop PrEP with an HIV-negative test, risk evaluation and mentorship services may still be appropriate.13

Discussion By identifying patients who are nonadherent to their prescribed antiretroviral medications and working collaboratively with patients, physicians, and other health professionals, pharmacist, MTM can potentially increase medication adherence by helping patients identify, resolve, and prevent issues that may affect their decision not to take a medication as intended. MTM may consist of medication therapy reviews, pharmacotherapy consults, medication education/adherence, and many other clinical services. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.

References 1. Ho PM, Bryson C, Rumsfeld J. Medication adherence its importance in cardiovascular outcomes. Circulation. 2009;119(23):3028-3035. 2. Castro A. Adherence to antiretroviral therapy: merging the clinical and social course of AIDS. PLoS Med. 2005;2(12):e338. 3. Steinbrook R. Preexposure Prophylaxis for HIV Infection. JAMA. 2012;308(9):865-866. 4. Gallant JE, Deresinski S. Tenofovir disoproxil fumarate. Clin Infect Dis. 2003;37(7):944-950. 5. Kearney BP, Flaherty JF, Shah J. Tenofovir disoproxil fumarate: clinical pharmacology and pharmacokinetics. Clin Pharmacokinet. 2004;43(9):595-612. 6. Gilead Sciences, Inc. Truvada: Highlights of Prescribing Information. Foster City, CA: Gilead Sciences, Inc; 2007. 7. Baeten J, Celum C. Oral antiretroviral chemoprophylaxis: current status. Curr Opin HIV AIDS. 2012;7(6):514-519. 8. AIDS Info. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents [Internet]. Web site. http://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arvguidelines/37/whats-new-in-the-guidelines-. Published February 12, 2013. Updated May 1, 2014. Accessed May 10, 2014. 9. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363(27):2587-2599. doi:10.1056/NEJMoa1011205. 10. Moyer VA, on behalf of the U.S. Preventive Services Task Force*. Screening for HIV: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2013;159:51-60. doi:10.7326/0003-4819-159-1-201307020-00645. 11. Update to Interim Guidance for Preexposure Prophylaxis (PrEP) for the Prevention of HIV Infection: PrEP for Injecting Drug Users. MMWR Morb Mortal Wkly Rep. 2013;62(23):463-465. 12. Leibowitz AA, Parker KB, Rotheram-Borus MJ. A US policy perspective on oral preexposure prophylaxis for HIV. Am J Public Health. 2011;101(6):982-985. 13. Interim guidance for clinicians considering the use of preexposure prophylaxis for the prevention of HIV infection in heterosexually active adults. MMWR Morb Mortal Wkly Rep. 2012;61(31):586-589.

Downloaded from jpp.sagepub.com at GEORGIAN COURT UNIV on February 24, 2015

Role of medication therapy management in preexposure prophylaxis therapy for HIV prevention.

Patient medication adherence is a long-standing problem and is one that raises serious issues for patient health, public health, and health care quali...
95KB Sizes 0 Downloads 4 Views