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PROFESSIONAL PROFILE Loretta Jemmott, PhD, RN, discusses her life in community outreach. CLINICAL CORNER HIV/AIDS education efforts aimed at PAs and NPs improve patient care.
CLINICAL CORNER Results from the international, Phase 3, double-blind VERxVE trial.
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Combat Compassion Fatigue A few years ago, when his spouse became me ill with leukemia, Joel Wesley Thompson, MHS, PA-C, AAHIVS, DFAAPA, a physician assistant specializing i n H I V/A I DS sin ce the late 1980s, became a 24-hour caregiver. r. Although professionally ly well equipped to provide care, Mr. Thompson mpson soon found himself exhibiting xhibiting characteristics typical al of emotional exhaustion. “It created some burnout in me. But I recognized what was going on because I’d gone through that before, back when HIV was not really treatable and I went to a lot of funerals,” said Mr. Thompson, who also is affiliated with Carolinas Healthcare System in Charlotte, NC. Fortunately, burnout and compassion fatigue can be mitigated by a number of factors that can be identified,
cultivated, and pracculti ticed. Although doctic tors, nurses, and to physician assistants p may feel invincible, m they need to rect ognize that they o are not, and that a in order to care for others, they need to oth care for themselves. The concept of burnout is intertwined with compassion fatigue. Some compassio believe burn burnout is caused by environmental sstressors (eg, the workplace, difficult colleagues), and compassion fatigue is stress caused by the patient care aspect of work and characteristics of the provider that make him/her vulnerable (eg, empathizing too much with the patient, vicarious traumatization).1,2 The distinction, however, may not be so clear-cut. see COMPASSION, page 4
Advanced Practitioners on the Frontline
hroughout the evolution of HIV/ AIDS from an infectious disease outbreak into a chronic disease,1 providers like nurse practitioners (NP) and physician assistants (PA) have played a central role in the HIV/AIDS clinic.2 When HIV/AIDS emerged in the 1980s, there was a natural transition of these advanced practitioners into the field. Their place in the HIV/AIDS clinic was later reinforced by government programs that provided funding to clinics and the recognition of HIV as a chronic disease.3
“NPs and PAs often find themselves where there is great need, among the unserved or the underserved, and that’s really the face of HIV,” said Suzanne Willard, PhD, CRNP, an NP and directorat-large of the Association of Nurses in AIDS Care. At the time HIV emerged, there also was a need to understand what was happening. “One of the things PAs are really well educated in is how to get a good history and physical and see ADVANCED PRACTITIONERS, page 11
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Loretta Jemmott, PhD, RN, Focuses on Outreach teen behavior, such as environment, peers, partners, family, media, and community.” While studying for her master’s degree in child, adolescent, and family psychiatric nursing, Dr. Jemmott learned more about these factors and how to use this knowledge to design interventions. “I opened up our vision on how you do programs, but I still didn’t know whether they were working because I did not know how to evaluate programs.” She learned this crucial step while earning her PhD in education and human sexuality, a program that required her to design and evaluate curricula. During this time, HIV and AIDS started to appear in her community,2 so or those who wish to succeed in the field of patient care or community outreach, Loretta Sweet Jemmott, Dr. Jemmott’s focus shifted from teen pregnancy to HIV PhD, FAAN, RN, advises they practice the “5 P’s”: pasprevention while she wrote her dissertation on the sexual sion (about the work), persistence, perseverance, power behavior of black male teenagers. (belief in your ability), and prayer (Table). Her adher“HIV already was in New York and California, but by the ence to the “5 P’s” is evident to everyone who learns of late 1980s it was coming to Philadelphia,” said Dr. Jemmott. her journey. “By this time we knew HIV was sexually transmitted, and Dr. Jemmott began outreach efforts in her teens when, the same behaviors that would get teens pregnant would as a student in the public schools of west Philadelphia, get them infected with the virus. So I began to focus she saw the crippling effect that teen pregnancy had on HIV risk reduction.” Alongside her research partner, on girls and their likelihood of graduating high school.1 John Jemmott, PhD—who later became her husband—Dr. Jemmott began designing evidence-based programs to “This was the early 1970s, and the kids weren’t getting prevent HIV. Since then, the pair has collaborated to close most of the contraceptives that were available,” said the gaps between clinical knowledge, practical applicaDr. Jemmott. “You’d look around the hallway and the tion, and lasting results. girls were pregnant, and that was “We wrote our first grant in 1988 high school.” Table. Practice the “5 P’s” to design an intervention to reduce Dr. Jemmott’s curiosity about For Effective Outreach sexually related HIV risk behavwhat could be done to reduce teen • Passion (about the work) ior among black male teenagers pregnancy inspired her to become • Persistence in Philly,” Dr. Jemmott said. The a peer educator during high • Perseverance Jemmotts received $50,000 from school, a role that she continued • Power (belief in your ability) the American Foundation for AIDS in college. After graduating from Research to design and evaluate Hampton University, she returned • Prayer a program consisting of 157 black to Philadelphia to continue her Based on a conversation with Loretta Jemmott, PhD, male teenagers.3 “That [program] efforts. Along with a doctor at RN. Spruce Medical Center in west was the first thing published that Philadelphia, she distributed inforshowed interventions influenced mation and conducted workshops sexual behavior in black male teenat local schools, churches, and clinagers, and it put us on the map in ics. These efforts, however, fell short terms of designing evidence-based of the intended goal—girls were programs,” she noted. still having unprotected sex and The curriculum they designed in getting pregnant. that study, called “Be Proud, Be “I needed to be better at what I Responsible,” came to the attention was doing,” said Dr. Jemmott. “I was of the Centers for Disease Control just looking at the person alone as a and Prevention, which selected closed system, but I needed to look it for “Research to Classrooms, at the whole open system to underPrograms that Work!”4,5 Through stand other factors that influence that program, 3 of Dr. Jemmott’s ID Advisor Focus on HIV/AIDS presents our Professional Profile series. In each segment, we interview a prominent thought leader about how he or she got into the field of infectious disease and his or her typical workday. In this issue, Loretta Sweet Jemmott, PhD, FAAN, RN, van Ameringen Professor in Psychiatric Mental Health Nursing at the University of Pennsylvania School of Nursing in Philadelphia, PA, discusses outreach in the HIV/AIDS community.
2011 • VOL. 2 , ISSUE 2
adolescent HIV risk-reduction intervention curricula have been disseminated to schools, community agencies, and national and international clinics. Additionally, the curricula have been translated and tailored for use in areas severely affected by HIV.6 Currently, Dr. Jemmott has designed 8 of the 20 HIV, sexually transmitted disease, and pregnancy prevention interventions nationally disseminated by the US Office of Adolescent Health. “We have been blessed,” said Dr. Jemmott. “We have been funded by the NIH [National Institutes of Health] for the past 15 or 20 years and have received more than $100 million in funding to design and evaluate theorybased, culturally sensitive, and developmentally appropriate interventions to reduce HIV risk–associated sexual behavior among various populations.” Over the past decade, Dr. Jemmott and her team have focused their efforts in South Africa, Botswana, and parts of the Caribbean. They spend considerable time immersed in these locales before designing interventions. “We use the first year to meet with the community at all levels, to gain their trust, and build teams so that what we design makes sense for the people we are trying to serve,” Dr. Jemmott said. “If you do these kinds of things, you can design better programs because you have heard their voices and understand their issues. All of that gets integrated into the curriculum.” Dr. Jemmott’s current domestic project is geared toward young black male adults. “How do you reach African American guys [aged] 18 to 25? [You go] where they hang out. We were funded a couple of years ago to do a study in barbershops,” she said. This study is unique not only in its setting, but also in its application of technology. “When the client comes into the barbershop and sits in the waiting room, we give them an iPad with a video and apps on it. That part is educational. Then the app turns into a PowerPoint book for the barber to use as he facilitates discussion with the client while cutting his hair,” Dr. Jemmott explained. The idea for this approach was born partially from the recognition that published journal articles, despite the best of intentions, tend to sit on shelves. “Who reads those articles? Our colleagues do, our students if we make them. But real people in the real world don’t read that stuff,” Dr. Jemmott said. “We do a study, evaluate it, translate it into a curriculum that’s user friendly, and then train people to go back into the community,” she explained. “That’s how we close the gap.”
2. Epidemiology of HIV/AIDS in the United States. http://hivinsite. ucsf.edu/InSite?page=kb-01-03#S1.4X. Accessed October 3, 2011. 3. Jemmott JB, Jemmott LS, Fong GT. Reductions in HIV riskassociated sexual behaviors among black male adolescents: effects of an AIDS prevention intervention. Am J Public Health. 1992;82(3):372-377. 4. Centers for Disease Control and Prevention. Best-Evidence Interventions: Be Proud! Be Responsible. http://www.cdc.gov/ hiv/topics/research/prs/resources/factsheets/Be_Proud.htm. Accessed October 3, 2011. 5. Collins J, Robin L, Wooley S, et al. Programs-that-work: CDC’s guide to effective programs that reduce health risk behavior in youth. J Sch Health. 2002;72(3):93-99. 6. Penn Nursing Science: Loretta Sweet Jemmott, PhD, FAAN, RN. http://www.nursing.upenn.edu/faculty/profile.asp?pid=27. Accessed October 3, 2011.
Editorial Board Maria Eugenia Fernandez-Esquer, PhD Associate Professor of Behavioral Sciences Center for Health Promotion and Disease Prevention Research University of Texas School of Public Health University of Texas Health Sciences Center at Houston Houston, Texas Harry Lampiris, MD Associate Professor of Clinical Medicine Assistant Fellowship Director ID Fellowship Training Program University of California, San Francisco San Francisco, California Glenn Treisman, MD Professor Director, AIDS Psychiatry Service Johns Hopkins University School of Medicine Baltimore, Maryland
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Perper K, Peterson K, Manlove J. Diploma attainment among teen mothers. Child Trends Fact Sheet. http://www.childtrends. org/Files/Child_Trends-2010_01_22_FS_DiplomaAttainment.pdf. Accessed October 3, 2011.
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COMPASSION continued from page 1
“Often, it’s a variety of environmental issues and interactions with patients and clients, as well as some of the aspects of ourselves as individuals, that lead us to experience something we may identify as burnout or compassion fatigue,” said Mary L.S. Vachon, PhD, RN, a psychotherapist in private practice, professor in the Department of Psychiatry at Dalla Lana School of Public Health, University of Toronto, and clinical consultant for Wellspring (a community-based support program for people with cancer). For many health care workers, the first sign that there is a problem is irritability toward clients and coworkers. This can spread to the home and social realms, and may manifest as anxiety and/or depression.1 “As Charles Garfield [a noted strategic advisor to business leaders] described it: With compassion fatigue, you still have the ability to care, whereas with burnout, you’re at the point where you don’t have the energy to care anymore,” Dr. Vachon said. To combat or avoid compassion fatigue in the workplace, HIV workers need to be able to discuss intimate topics while still maintaining a professional distance.3 It is essential that HIV workers keep their values to themselves and maintain the boundaries necessary to establish trust with their clients and help them achieve their goals.3 It may also be helpful to be aware of possible triggers. A recent study examined situations that lead to compassion fatigue among nurses at a midwestern hospital (Table).4 “Health care professionals and individuals who volunteer in the field often don’t take care of ourselves because we’re so busy taking care of others,” Dr. Vachon said. When loss occurs, as it inevitably does—clients may revert to risky behaviors, or die—HIV workers need to be able to acknowledge the loss and get on with their lives and careers. Talking things through with a colleague, who has likely experienced similar issues, can be helpful.3 Self-care, of course, varies between individuals. But it starts with attending to the needs of the body, such as
Table. Compassion Fatigue Triggers Among Nurses
proper nutrition, rest, and exercise. Maintaining a social network of family and friends, taking time to pursue personal interests and hobbies, and engaging in meditation or spiritual activities are other self-care tenets to consider.1 “One of the things I think [is] extremely important is to have a life outside of work,” Dr. Vachon said. Regardless of specialty, health care workers and caregivers at all levels need to be able to leave their jobs behind—physically, mentally, and emotionally—when the workday is over.3 In a culture that admires—and theoretically values and rewards—hard workers, the badge of “workaholic” is often worn with a glint of pride. But everyone has a point at which the endless race fails to yield returns. “I had gotten into this habit of logging in when I woke up so that I could do whatever I could before I got to the clinic,” Mr. Thompson said. “I’d work all day, work through lunch, go home and quickly eat; I didn’t even care what I ate. I didn’t watch TV. All I did was work. I became an automaton.” Ultimately, compassion fatigue and burnout lead to tension with coworkers, colleagues, family, and friends. But there is potential for more dire ramifications. “It certainly can cause medical mistakes that can lead to malpractice,” Mr. Thompson said. “It can lead to you losing your job.” As Mr. Thompson’s level of burnout increased, he realized that he was failing to engage in one of the things he needed most to feel whole. “I began to shut out my family and friends, and I am not a loner,” he said. “I recharge my batteries by being around people whom I love and who love me. And that was one of the hardest things to learn— to let people do things for me and take care of me.” Dr. Vachon noted a great example of an HIV nurse who identified her personal needs and made sure they were met. The woman outlined what she needed to do to feel sound and whole, compiled a list, and posted it on her refrigerator. The items on her list ranged from prosaic—eat right, get enough sleep, exercise, to very specific—see a movie every 2 weeks. “On days she was feeling stressed, she would look at her list and see what she was missing and needed to put back into her life,” Dr. Vachon said. That simple list apparently worked. “About 20 years later, I ran into [the HIV nurse] at a meeting. I asked if she still had the list on her refrigerator, and she laughed and said ‘yes,’” Dr. Vachon said.
References Belief that one’s actions “do not make a difference” Institutional problems including high patient census, high acuity, or high patient assignments
Naden RJ. Dousing burnout. http://nurse-practitioners-and-physician-assistants.advanceweb.com/Article/Dousing-Burnout.aspx. Accessed October 19, 2011.
Personal problems including inadequate energy
2. NurseVillage. Compassion fatigue: It’s all the rage, so why are nurses missing out? http://www.nursevillage.com/nv/content/ careerresources/compassion_fatigue.jsp. Accessed October 3, 2011.
Identifying with patients or overlooking serious patient symptoms
3. Little J. Saying no to compassion fatigue. http://www.hiveis.com/ hiv-eis-newsletters.html. Accessed October 3, 2011.
Adapted from reference 4.
4. Edmunds MW. Caring too much: Compassion fatigue in nursing. Appl Nurs Res. 2010;23(4):191-197.
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HIV/AIDS Education Aimed at PAs, NPs Helps Patients
“The historical segregation of he HIV/AIDS educational efforts “The fact that clinicians patients with HIV/AIDS into separate for advanced practice clinicians over the past 20 years seem to be have more empathy and clinics for treatment has contributed paying off. The attitudes of nurse better general attitudes to the problem. “When patients go that setting, they can be subpractitioners (NPs), physician assiswill translate to better outside jected to real or perceived stigma,” tants (PAs), and other mid-level care of these patients.” she said. providers toward patients living with Internalized stigma, to some extent, HIV/AIDS slowly have shifted away —Richard D. Muma, PhD, MPH, PA-C depends on a patient’s ethnicity, from stigmatization.1-3 The internal education level, and socioeconomic stigma among patients with HIV/ status. Mental health also plays a AIDS also has decreased in some significant role in perceived stigma. A recent study segments of society; however, this ostracism has negaconducted by Dr. Sayles showed that internal stigma tive consequences and may affect treatment outcomes.4 negatively impacts patients’ self-reported rate of treatSeveral studies on NPs, nurse midwives, and PAs have ment adherence and general access to medical care.4 documented improved attitudes and reduced stigma toward the patients they care for with HIV/AIDS.1,2 “Internalized stigma depends on social norms. In some communities, you can’t admit to having sex with men, so A 2010 study exclusively focused on PAs found that you can feel more isolated and lack social support if you they exhibited supportive and empathetic attitudes develop HIV/AIDS,” said Dr. Sayles. toward patients with HIV/AIDS.3 Several approaches can be used to lessen internal“Previous studies looking at attitudes and stigmatizaized stigma. The health care setting should be safe and tion of people living with HIV/AIDS have combined NPs, accepting, thereby enabling positive patient interacPAs, midwives, and other health care extenders. Our tions. Providers need to approach each patient with study was aimed only at the PA perspective, and we are a culturally sensitive, nonjudgmental attitude so that pleased to report that the majority of those in our sample they can provide support to achieve the desired health have high empathy, low avoidance, and a good general care outcomes, said Dr. Sayles. Providers should try to attitude toward persons living with HIV/AIDS, similar to understand where the patient falls on the spectrum of other studies of nurses and doctors,” said Richard D. internalized stigma so that they can proactively identify Muma, PhD, MPH, PA-C, associate provost and professor barriers, such as disclosure concerns, that may interfere in the Department of Public Health Sciences at Wichita with engagement in treatment or adherence to antiretroState University in Kansas, senior author of the study. viral therapy.4 Dr. Muma believes that these findings demonstrate that HIV/AIDS educational efforts targeted at PAs and “External or internal stigmatization appears to impact other mid-level providers have been successful. “The fact important health behaviors and outcomes, particularly that clinicians have more empathy and better general among communities of color and low socioeconomic staattitudes will translate to better care of these patients,” tus, and thus may further perpetuate health disparities,” he predicted. said Dr. Sayles. Dr. Muma’s study used a random sample of 1,500 PAs References in the United States.3 They were asked to respond to questions about avoidance, empathy, and general atti1. Froman RD, Owen SV. Measuring attitudes toward persons tudes, many of them dealing with controversial issues.3 with AIDS: the AAS-G as an alternative to the AAS. Sch Inq Nurs Pract. 2001;15(2):161-174. The participation rate of PAs in the survey was only 16%,3 which was disappointing, added Dr. Muma. But he spec2. Martin JE, Bedimo AL. Nurse practitioner, nurse midwife, and physician assistant attitudes and care practices related to perulated that the low rate could reflect the fact that the sons with HIV/AIDS. J Am Acad Nurse Pract. 2000;12(2):35-41. stigmatization of HIV/AIDS is not a big issue these days. 3. Talley A, Ritzdorf K, Muma RD. Attitudes of US physician assisBut there still are settings where patients perceive tants toward persons with HIV/AIDS. J Am Acad Physician Assist. a degree of stigma, noted Jennifer Sayles, MD, MPH, 2010;23(12):41-48. medical director, Los Angeles County Department of 4. Sayles JN, Wong MD, Kinsler JJ, Martins D, Cunningham WE. Public Health’s Office of AIDS Programs and Policy, assisThe association of stigma with self-reported access to meditant professor of medicine at the University of California, cal care and antiretroviral therapy adherence in persons living with HIV/AIDS. J Gen Intern Med. 2009;24(10):1101-1108. Los Angeles.
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VIRAMUNE® XR™ (nevirapine) extended-release, 400 mg tablets INDICATIONS AND USAGE VIRAMUNE is indicated for use in combination with other antiretroviral (ARV) agents for the treatment of HIV-1 infection. VIRAMUNE XR is indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults. Important Considerations: • Based on serious and life-threatening hepatotoxicity observed in controlled and uncontrolled studies, nevirapine should not be initiated in adult females with CD4+ cell counts >250 cells/mm3 or in adult males with CD4+ cell counts >400 cells/mm3 unless the benefit outweighs the risk. • The 14-day lead-in period with immediate-release VIRAMUNE 200 mg daily dosing must be strictly followed; it has been demonstrated to reduce the frequency of rash. • If rash persists beyond the 14-day lead-in period with immediate-release VIRAMUNE, do not begin dosing with VIRAMUNE XR. The lead-in dosing with 200 mg once-daily immediate-release VIRAMUNE should not be continued beyond 28 days, at which point an alternative regimen should be sought. • Adult patients already on a regimen of immediate-release VIRAMUNE twice daily can be switched to VIRAMUNE XR 400 mg once daily without the 14-day lead-in period of immediate-release VIRAMUNE. • For patients who interrupt VIRAMUNE XR dosing for more than 7 days restart the recommended lead-in dosing with immediate-release VIRAMUNE, using one 200 mg tablet daily for the first 14 days.
IMPORTANT SAFETY INFORMATION BOXED WARNING: LIFE-THREATENING (INCLUDING FATAL) HEPATOTOXICITY and SKIN REACTIONS HEPATOTOXICITY: Severe, life-threatening, and in some cases fatal hepatotoxicity, particularly in the first 18 weeks, has been reported in patients treated with nevirapine. In some cases, patients presented with non-specific prodromal signs or symptoms of hepatitis and progressed to hepatic failure. These events are often associated with rash. Female gender and higher CD4+ cell counts at initiation of therapy place patients at increased risk; women with CD4+ cell counts >250 cells/mm3, including pregnant women receiving nevirapine in combination with other antiretrovirals for the treatment of HIV-1 infection, are at the greatest risk.
However, hepatotoxicity associated with nevirapine use can occur in both genders, all CD4+ cell counts and at any time during treatment. Hepatic failure has also been reported in patients without HIV taking nevirapine for post-exposure prophylaxis (PEP). Use of nevirapine for occupational and non-occupational PEP is contraindicated. Patients with signs or symptoms of hepatitis, or with increased transaminases combined with rash or other systemic symptoms, must discontinue nevirapine and seek medical evaluation immediately. SKIN REACTIONS: Severe, life-threatening skin reactions, including fatal cases, have occurred in patients treated with nevirapine. These have included cases of Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity reactions characterized by rash, constitutional findings, and organ dysfunction. Patients developing signs or symptoms of severe skin reactions or hypersensitivity reactions must discontinue nevirapine and seek medical evaluation immediately. Transaminase levels should be checked immediately for all patients who develop a rash in the first 18 weeks of treatment. The 14-day lead-in period with immediaterelease VIRAMUNE 200 mg daily dosing has been observed to decrease the incidence of rash and must be followed. MONITORING: Patients must be monitored intensively during the first 18 weeks of therapy with nevirapine to detect potentially life-threatening hepatotoxicity or skin reactions. Extra vigilance is warranted during the first 6 weeks of therapy, which is the period of greatest risk of these events. Do not restart nevirapine following clinical hepatitis, or transaminase elevations combined with rash or other systemic symptoms, or following severe skin rash or hypersensitivity reactions. In some cases, hepatic injury has progressed despite discontinuation of treatment. CONTRAINDICATIONS: Nevirapine is contraindicated in patients with moderate or severe (Child-Pugh Class B or C, respectively) hepatic impairment or for use in occupational and non-occupational PEP. Patients taking nevirapine should not take St. John’s wort or efavirenz. Please see full Prescribing Information for additional drug to drug interactions. Immune reconstitution syndrome has been reported in patients treated with combination ARV therapy, including nevirapine. Fat redistribution or accumulation of body fat has been reported in patients receiving ARV therapy. The mechanism and long-term consequences of this are unknown. Other less common side effects include nausea, fatigue, fever, headache, vomiting, diarrhea, abdominal pain, and myalgia.
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The International VERxVE Trial Evaluated VIRAMUNE XR versus VIRAMUNE in ARV Treatment–naïve Adult Patients VERxVE: Trial Overview and Design The VERxVE trial is an ongoing, multinational, Phase 3, double-blind, double-dummy, parallel-group, activecontrolled trial with stratified randomization.1 It is being conducted at 175 centers in 20 countries around the world: 305 trial subjects from North America and Australia; 541 from Europe; 112 from Latin America; and 110 from Africa.2 The primary objective of this trial is to evaluate the efficacy of VIRAMUNE XR 400 mg once daily in comparison with VIRAMUNE 200 mg twice daily after 48 weeks of treatment. The patients are antiretroviral treatment-naïve men and women with CD4+ cell counts >50 to <400 cells/mm3 and >50 to <250 cells/mm3, respectively, and an HIV-1 viral load (VL) of ≥1000 copies/mL. The CD4+ cell count criteria for this population were chosen specifically to reduce the risk of hepatotoxicity for men and women with CD4+ cell counts >400 cells/mm3 and >250 cells/mm3, respectively. Stratification was by baseline HIV-1 VL (defined as the maximum of screening VL or Day 0 viral load): ≤100,000 copies/mL or ≥100,000 copies/mL. This was a noninferiority trial in which –10% was defined as the lower boundary of the 95% confidence interval (CI) of the difference in virologic response proportions between the VIRAMUNE and VIRAMUNE XR groups.2 Following genotypic confirmation of susceptible HIV-1 and other eligibility criteria, treatment-naïve adult patients received a lead-in dose of VIRAMUNE 200 mg once daily for 14 days (N=1068). After this open-label lead-in period, patients were randomized in a 1:1 ratio to either VIRAMUNE XR 400 mg once daily or VIRAMUNE 200 mg twice daily; both treatment groups also received Truvada® once daily.1 A double-dummy design was used to maintain blinding if adult patients tolerated the lead-in treatment period.2 The duration of treatment was 48 weeks for the primary endpoint within each stratum,1 with an extension to 144 weeks.2 The extension period began after each adult patient had completed the Week 48 visit for the purpose of collecting long-term safety and efficacy data.1
VERxVE: Outcome Evaluations Primary Endpoint The primary endpoint of this trial was sustained virologic response at Week 48. A virologic response was defined as 2 consecutive measurements of VL <50 copies/mL, at least 2 weeks apart. A sustained virologic response had no virologic rebound or change of ARV
therapy through Week 48. The time window of Week 48 was defined as 48±4 weeks from Day 0 (the day a patient started treatment).2 A virologic rebound was defined by 2 consecutive VL measurements ≥50 copies/mL, at least 2 weeks apart, after a virologic response. If there was an unconfirmed change of VL status (rebound or response) at Week 48, then another measurement at least 2 weeks later was necessary to confirm whether virologic rebound or response had occurred.2
Key Secondary Endpoints Key secondary efficacy endpoints included mean change in CD4+ cell count at Week 48, treatment-emergent resistance, and time to new AIDS or AIDS-related progression event or death.2 Other key secondary safety endpoints included adverse events and serious adverse events (including AIDS-defining events), occurrence of rashes and hepatic events, occurrence of elevations in laboratory measurements by Division of AIDS (DAIDS) Grade, and occurrence of discontinuations due to adverse events.2
VERxVE: Efficacy Data Virologic Success and CD4+ Cell Count Changes The primary efficacy endpoint was sustained virologic response at Week 48 using LLOQ (lower limit of quantification) = 50 copies/mL.2 Using SNAPSHOT analysis, a virologic success was defined as a patient with a VL <50 copies/mL in the Week 48±4 window (using the last measurement if multiple measurements were taken in the window). Based on the SNAPSHOT analysis, at Week 48, 75% of VIRAMUNE and 80% of VIRAMUNE XR patients were Virologic Successes (Figure 1, page 8).1 The results from all secondary analyses of the primary endpoint show the difference in sustained virologic response proportion between VIRAMUNE XR and VIRAMUNE was 4.9% (95% CI, -0.2%, 10.1%). The baseline HIV-1 viral load ≤100,000 copies/mL stratum had a higher response proportion than the >100,000 copies/ mL stratum and this result was observed for both treatment groups.1,2 There appeared to be no relationship between baseline CD4+ cell count and the response proportion (Table, page 8).1,2 The SNAPSHOT approach also was used to analyze virologic failure. Patients who changed optimized background therapy (OBT) to new class or changed OBT not see VERXVE, page 8
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Figure 1. Virologic Success at Week 481,2
VERxVE Patients With Undetectable Viral Load at Week 48 Virologic Successa,b (HIV-1 RNA <50 copies/mL), %
continued from page 7
60 40 20 0
100,000 Baseline VL
a A patient with a VL<50 copies/mL in the Week 48±4 window (using the last VL measurement if multiple measurements were taken in the window) was defined as a Virologic Success.1,2 b
Adjusted for baseline HIV-1 VL stratum.
Table. Mean CD4+ Cell Count and Changes at Week 481,2 VIRAMUNE Mean CD4+ Count at Baseline (cells/mm 3 ) 3 a
Mean Change in CD4+ Count (cells/mm )
Adjusted for baseline HIV-1 VL stratum.
permitted per protocol or due to lack of efficacy prior to Week 48, patients who discontinued prior to Week 48 for lack or loss of efficacy, and patients with HIV RNA >50 copies/mL in the Week 48 window were considered a virologic failure.2 Using SNAPSHOT analysis, the virologic failure proportion was 13% in the VIRAMUNE group and 11% in the VIRAMUNE XR group (Figure 2).1
VERxVE: Safety Data Selected Adverse Events The safety data include all adult patient visits up to the last patient’s completion of the 48-week primary endpoint in the trial (mean observation period, 61 weeks).1 After the lead-in period, the incidence of any hepatic event was 9% in the VIRAMUNE group and 6% in the VIRAMUNE XR group. The incidence of symptomatic hepatic events (anorexia, jaundice, vomiting) was 3% in the VIRAMUNE group and 2% in the VIRAMUNE XR group. The incidence of Grade 3 or 4 ALT/AST elevations was 7% in the VIRAMUNE group and 6% in the VIRAMUNE XR group (Figure 3).1
Overall, there was a similar incidence of symptomatic hepatic events among men and women enrolled in VERxVE.1
Selected Adverse Reactions Adverse reactions of at least moderate intensity (Grade 2 or above) and considered to be related to treatment by the investigator in at least 2% of treatment-naïve patients receiving either VIRAMUNE or VIRAMUNE XR after randomization were rash and clinical hepatitis. Severe or life-threatening rash considered to be related to nevirapine treatment occurred in 1% of patients during the lead-in phase with VIRAMUNE, and in 1% in each treatment group during the randomization phase. In addition, 5 cases of Stevens-Johnson syndrome were reported in the trial, all of which occurred within the first 30 days of treatment (Figure 4, page 10).1
Pharmacokinetic Data VIRAMUNE XR is absorbed throughout the the gastrointestinal tract. The extended-release 400 mg oncedaily formulation was developed to provide consistent therapeutic drug levels over 24 hours (Figure 5, page 10).
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Figure 2. Virologic Failure Rates1 Patients With Virologic Failure at Week 48 50
SNAPSHOT A nalysisa
Includes patients who changed optimized background therapy (OBT) to new class or changed OBT not permitted per protocol or due to lack of efficacy prior to Week 48, patients who discontinued prior to Week 48 for lack or loss of efficacy, and patients with HIV RNA >50 copies/mL in the Week 48 window.
Figure 3. Selected Adverse Events1 Selected Adverse Events During the Randomization (Post Lead-in) Phase 50
VIRAMUNE XR (n=505)
A ny Hepatic Event
Symptomatic Hepatic Eventsa
Grade 3 or 4 A LT/ A ST Elevation
Symptomatic hepatic events included anorexia, jaundice, and vomiting.
The bioavailability of VIRAMUNE and VIRAMUNE XR was tested under fasted and fed conditions with VIRAMUNE showing 100% bioavailability in both settings. The bioavailability of VIRAMUNE XR was 80% under fasted conditions and 94% under fed conditions.
Dosing and Administration ARV/VIRAMUNE-naĂŻve Adult Patients Based on serious and life-threatening hepatotoxicity observed in controlled and uncontrolled studies, VIRAMUNE should not be initiated in adult females with CD4+ cell counts >250 cells/mm3 or in adult males with CD4+ cell counts >400 cells/mm3, unless the benefit outweighs the risk.1
Adult patients must initiate therapy with one 200 mg tablet of VIRAMUNE daily for the first 14 days in combination with other ARV agents, followed by one 400 mg tablet of VIRAMUNE XR once daily in combination with other ARV agents. The 14-day lead-in period with VIRAMUNE 200 mg daily dosing has been demonstrated to reduce the frequency of rash. If rash persists beyond the 14-day lead-in period with VIRAMUNE, do not begin dosing with VIRAMUNE XR. The lead-in dosing with 200 mg once-daily VIRAMUNE should not be continued beyond 28 days, at which point an alternative regimen should be sought. If dosing is interrupted for greater than 7 days, restart the 14-day lead-in dosing.1 see VERXVE, page 10
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VIRAMUNE-experienced Adult Patients
continued from page 9
Figure 4. Selected Adverse Reactions1 Selected Adverse Reactions of at Least Moderate Intensity (Grade 2 or above) in 2% of Patients1,a,b
VIRAMUNE XR (n=505)
R ash c
Includes adverse drug reactions considered by the investigator to be at least possibly, probably, or definitely related to the drug.
Mean observation period was 61 weeks.
Rash includes terms rash, rash maculo-papular, erythema nodosum, rash erythematous, rash papular, skin reaction, Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms (DRESS), and allergic dermatitis.
Clinical hepatitis includes terms hepatitis, hepatotoxicity, hepatitis acute, liver disorder, hepatitis toxic, hepatic failure, and jaundice.
Figure 5. VERxVE Therapeutic Drug Levels Over 24 Hours
Nevirapine Plasma Concentrations (μg/mL)
200 mg VIRAMUNE (n=25) 400 mg VIRAMUNE XR (n=24)
Adult patients already on a regimen of VIRAMUNE 200 mg twice daily in combination with other antiretroviral agents can be switched to VIRAMUNE XR 400 mg once daily in combination with other antiretroviral agents without the 14-day lead-in period of once-daily VIRAMUNE 200 mg and without the CD4+ cell count restrictions.1
VERxVE: Clinical Data Summary1 Among 1,011 patients randomized and treated, the Virologic Success at Week 48 was 75% for VIRAMUNE and 80% for VIRAMUNE XR. The mean CD4+ cell count increase from baseline at Week 48 was 191 cells/mm3 for VIRAMUNE and 206 cells/mm3 for VIRAMUNE XR. Adverse reactions of at least moderate intensity (Grade 2 or above) in ≥2% of patients were: • Rash: 3% for both VIRAMUNE and VIRAMUNE XR • Clinical hepatitis: 3% for VIRAMUNE; 2% for VIRAMUNE XR
VIRAMUNE XR: Overall Summary1,2 In the VERxVE trial, sustained virologic response, based on the SNAPSHOT analysis at Week 48 was 80% for VIRAMUNE XR and 75% for VIRAMUNE.2 Adult patients already on a regimen of VIRAMUNE 200 mg twice daily can be switched to one 400 mg tablet of VIRAMUNE XR once daily in combination with other ARV agents1: • Without the 14-day lead-in period of oncedaily VIRAMUNE 200 mg • Without CD4+ cell count restrictions • VIRAMUNE XR tablets can be taken with or without food1 • VIRAMUNE XR tablets must be swallowed whole and must not be chewed, crushed, or divided1
References 1. Viramune® XR™ (nevirapine) extended-release tablets. Prescribing Information. Boehringer Ingelheim Pharmaceuticals, Inc.; 2011. 2. Data on file. Boehringer Ingelheim Pharmaceuticals, Inc.
Please see Important Safety Information on page 6, and enclosed full Prescribing Information, including Boxed Warning, for VIRAMUNE® XR™ (nevirapine) extendedrelease, 400 mg tablets.
2011 • VOL. 2 , ISSUE 2
At Temple’s HIV program, Dr. Tedaldi said a specialist may only see a stable HIV patient once per year, with continued from page 1 NPs handling everything from initial intakes to interim visits, and triaging emergency patients as necessary. The program also has trained NPs in specialized areas, then document it very well, and in 1987 that was exactly such as performing colposcopy for gynecologic care, or what people doing HIV research needed,” said Susan providing perinatal management of HIV-positive pregLeLacheur, DrPH, PA-C, assistant professor of health care nant women. sciences and director of academic curriculum at George Provided that NPs and PAs have experience with HIV Washington University in Washington, DC. and access to a specialist physician, studies have As HIV has become recognized as a chronic shown that advanced practitioners can prodisease,1 the skills offered by PAs and NPs vide HIV/AIDS care at the same level have become a centerpiece of many HIV/ as that of physician HIV experts and AIDS clinics.4 generally better than physician non“HIV care often is provided by HIV experts.2 NPs and PAs because the reality is that is how it’s evolved,” said The collaborative approach is Ellen Tedaldi, MD, professor of key, says Dr. Tedaldi. Although medicine and director of the HIV NPs and PAs generally do not program at Temple University in overstep the limits of their experPhiladelphia. “The chronic disease tise, developing specific protocols model fits perfectly with having and guidelines for the interaction integrated, collaborative practices.” of NPs and PAs with patients and The role of advanced practitioners physicians helps ensure successful was solidified with the passage of integration into a practice. the Ryan White Act in 1990, the largUnlike some other specialties, in est source of federal funding for HIV/AIDS most HIV/AIDS clinics, the role of NPs clinics.5 and PAs often is not incredibly dif“NPs and PAs often fi nd ferent. When the day-to-day respon“Certainly as we introduced programs like Ryan White, which funded comthemselves where there sibilities of NPs and PAs differ, it is typically the result of state regulation. prehensive centers for practices with NPs and PAs as part of the team, they is great need, among the Both professions are regulated either unserved or the under- by state medical or nursing boards ended up having to become much more can involved,” said Dr. Tedaldi. served, and that’s really and the scope of practice for each vary widely from state to state.6 Now 20 years later, advanced practithe face of HIV.” tioners manage patients all the way from “It’s the state regulations that can diagnosing HIV disease to issuing medi- —Suzanne Willard, PhD, CRNP impede practice,” says Dr. Willard. cation orders.6 These regulations often add a layer of bureaucracy that can affect the day“Many physicians are very good at this to-day efficiency of an HIV/AIDS clinic. too, but we are really good at preventaFor example, until recently, NPs in Pennsylvania could tive medicine issues and I think we add that holistic care write but not formally sign prescriptions, meaning they that some of the infectious diseases doctors are maybe wouldn’t be honored at pharmacies, she said. not as focused on,” said Dr. LeLacheur. In some cases, these regulations can have an outsized Practically speaking, a stable HIV/AIDS patient may effect on clinics in underserved areas, where advanced only see an infectious disease or HIV specialist a couple practitioners play an even greater role.2 “My charts have of times per year, with the rest of the office visits handled by an NP or a PA on staff.2 Typically, the advanced to be reviewed by a physician within a certain time period, to sign off, and for a community clinic that’s been a real practitioner is paired with a staff physician and when problem,” said Dr. LeLacheur. the need arises—a patient’s disease becomes unstable or Dr. Tedaldi noted that insurance companies can add there are questions about adding or subtracting medicatheir own rules regarding billing and reimbursement and tions—the physician will be consulted.2 clinics looking to add advanced practitioners should be “We can do much of a patient’s care, but you have to aware of the position of payers in this area. have a team approach. No physician, PA, or NP should be independent,” said Dr. Willard. see ADVANCED PRACTITIONERS, page 12
ID Advisor Focus on HIV/AIDS provides support and information for the next generation of ID/HIV specialists.
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To obtain more educational information Regardless of any legal or insurance barriers, however, advanced practitioners have moved to the forefront of HIV/AIDS patient care.2 “Physicians may make decisions on the drugs or resistance pattern but certainly in many of the academic centers, [advanced practitioners] do a lot of the chronic care of HIV patients,” Dr. Tedaldi said. “They provide a great deal of capacity that you may not necessarily have if it were just physicians in a practice.”
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Cohen MS, Hellmann N, Levy JA, DeCock K, Lange J. The spread, treatment and prevention of HIV-1: evolution of a global epidemic. J Clin Invest. 2008;118(4):1244-1254.
2. Wilson IB, Landon BE, Hirschhorn LR, et al. Quality of HIV care provided by nurse practitioners, physician assistants, and physicians. Ann Intern Med. 2005;143(10):729-736. 3. U.S. Department of Health and Human Services Health Resources and Services Administration. Part B: AIDS Drug Assistance Program. http://hab.hrsa.gov/abouthab/partbdrug.html. Accessed October 3, 2011. 4. Yehia BR, Gebo KA, Hicks PB, et al. Structures of care in clinics of the HIV Research Network. AIDS Patient CARE STDs. 2008; 22(12):1007-1013. 5. U.S. Department of Health and Human Services Health Resources and Services Administration. Legislation. http://hab.hrsa.gov/ abouthab/legislation.html. Accessed October 3, 2011. 6. American Academy of Physician Assistants. Are NPs and PAs right for your practice? Society of Hospital Medicine Roundtable slides. January 14, 2010.
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Published on Dec 9, 2011