Several years ago, a patient with HIV arrived at the infectious disease

program at Grady Health System in Atlanta, Georgia, with a bottle of pills covered in soot. A nurse jokingly asked, “Where are you keeping this, the fire-place?” The patient responded, “How did you guess?” Fearing stigma and discrimination, the woman was hiding her pills in order to keep her HIV status a secret.

Today patients are saddled with tough decisions regarding disclosing

their infection status, sexual activity, and parenthood, among others.1 A lack of social support in dealing with these issues can lead to depression that, in turn, can lead to poor adherence to treatment.2 “Patients are much more likely to be noncompliant if they are depressed, and survival is improved by treatment,” said Glenn Treisman, MD, director, AIDS Psychiatry Service at The Johns Hopkins Hospital in Baltimore, Maryland.

The data-reporting requirements for HIV clinics continue to grow. The

specific demands from funding sources, particularly federal money provided through the Ryan White HIV/AIDS Treatment Extension Act of 2009, require an uncommon level of compliance.1 Clinics must imple-ment an automated data report-ing system for electronic health records (EHRs) and generate reports to comply with Ryan White funding requirements.1

“HIV care is complicated because of the growing demand for a broad array of services. Choosing an appropriate EHR system can make things easier, but a limited system can make things more difficult,” said Ann Scheck McAlearney, ScD, associate professor, College of Public Health at The Ohio State University in Columbus. Her research has shown that complex regulatory and reporting requirements, rather than simple tasks like ordering lab results, may be a key challenge

for deriving efficiency from an EHR system.2

Clinics aligned with hospitals already may have adapted to an EHR system, but even comprehensive systems may have serious limitations for HIV care. The information captured in EHR systems that are not specifically designed for HIV may be inadequate. Tasks that involve

EHRs Pose Challenges for HIV Clinics

Psychosocial Issues Impact HIV Care

CLINICAL CORNERThe relationship between providers and patients is crucial for HIV care. 3

CLINICAL CORNERResults from the international, Phase 3, double-blind VERxVE trial. 6

PRACTICE PROFILEWe highlight the exemplary work of the Hopkins HIV/AIDS Care Program. 11

For the latest HIV/AIDS-

related news, please visit

www.theidadvisor.com

Support & information for the next generation of ID/HIV specialists

Brought to you by the publishers of

see EHRs, page 5 �

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VOL. 3, ISSUE 1

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According to Dr. Treisman, the biggest problem for health care workers trying to help depressed patients with HIV is figuring out whether they have major depression or demoralization (sometimes called adjustment disorder). Major depression is caused by a structural or functional brain lesion, whereas demoralization is characterized by a stage of exaggerated grief, persistent sadness, disillusionment, and despondency that arises in response to a difficult event in a person’s life.3

The prevalence of major depression and demoralization among patients with HIV may be as high as 50%, with signifi-cant overlap between the 2 conditions.3 “Major depression clearly responds best to medication. The psychological kind [of depression] doesn’t respond to medication at all,” said Dr. Treisman. Demoralized patients derive the greatest benefit from supportive psychother-apy, encouragement, coaching, and rehabilitation.3 Some patients can have both kinds of depression.3

Anhedonia is a helpful diagnostic tool. Patients with major depression have profound anhedonia, which is the inability to derive pleasure from behaviors such as sleep-ing, eating, having sex, working, engaging in hobbies, and exercising.3 “People with [demoralization] can be dis-tracted from their grief when something good happens to them, but people with major depression cannot,” said Dr. Treisman.

Marcia Holstad, DSN, associate professor of nursing at Emory University in Atlanta, Georgia, and a nurse practi-tioner at Grady Health System, noted that she avoids using the word “depression” and instead asks patients if they are sad. “Destigmatizing the issue of mental health treatment is important,” she said.

Betsy Fife, RN, PhD, a senior research scientist at Indiana University’s School of Nursing in Indianapolis, has imple-mented and evaluated an intervention that promotes coping strategies for people with HIV and their partners.4

Strategies that nurture effective coping between partners include communication and conflict resolution, realistic appraisals of problems, redefining personal goals based on the limitations of one’s illness, and maximizing support within the relationship (Table).4,5

“Many patients feel that they can’t go on because they now have HIV, but they find out that life isn’t that different with HIV except for the pills. People say, ‘Well, I can’t have

unprotected sex now,’ and I say, ‘Neither can I. I don’t have HIV, but that is how you get it,’” said Dr. Treisman.

Some women say they are depressed because their diagnosis has quashed their hopes of motherhood. “You can have a baby [even] if you have HIV. The problem is people who have a very unre-alistic view of the world,” Dr. Treisman

said. “They say, ‘I can’t have a baby now.’ I say, ‘Yes you can, but who was going to have the baby with you?’ They say, ‘I don’t know.’ And I say, ‘Maybe you should work on that first.’”

According to Dr. Holstad, care providers can help dis-courage avoidance coping mechanisms, such as drug and alcohol abuse, but recognizing them can be difficult. “People are good at hiding things,” she said. “Phrase ques-tions so they are not threatening. You might say, ‘A lot of our patients have difficulties with drugs such as crack cocaine; have you ever experienced these kinds of difficul-ties?’ instead of asking, ‘Do you use illegal drugs?’”

Motivational interviewing (MI) is a client-centered tool health care workers can use to spur behavior change or maintain healthy behaviors.6 “MI helps patients see that there is a discrepancy between what their goals in life are and the way they are currently behaving,” said Dr. Holstad. She said that MI often is used to treat substance abuse, but it can help patients with HIV understand their medication-taking behaviors6 and also improves self-efficacy, another major predictor of medication adherence.2

Dr. Holstad uses a confidence ruler ranging from 0 (not at all confident) to 10 (completely confident) with her patients. She asks her patients to rate how confident they

are in taking their medications properly. She then asks them to identify their barriers to achieving a higher score. These rulers, she said, can uncover issues such as housing difficulties, a stressful family situation, or substance abuse.

After Dr. Holstad used the confidence ruler with one patient who rated her confidence level as 6, she asked the patient what it would take to increase that score to 8. The woman then admitted to using crack cocaine, which is a barrier to achieving a higher score. “Many times these psychosocial issues are worse than the disease,” she said.

Table. Coping Strategies for Patients With HIV

Maladaptive Coping Effective Coping

Self-distraction Effective communication and conflict resolution among family and friends

Behavioral disengagement

Using realistic appraisals of the situation and prognosis

Substance abuse Setting realistic life goals based on potential disease limitations

Denial or venting Relying on a strong social support system

Adapted from references 4 and 5.

“Patients are much more

likely to be noncompliant

if they are depressed, and

survival is improved by

treatment.”

—Glenn Treisman, MD

Clinical Corner

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Patient–Provider Relationship Is Crucial to SuccessLiving with HIV is a constant challenge, and providers

caring for patients with the disease play a key role in helping their patients meet that challenge. The current guidelines from the US Department of Health and Human Services (DHHS) state, “Patients initiating ART [antiret-roviral therapy] should be willing and able to commit to lifelong treatment and should understand the benefits and risks of therapy and the importance of adherence.”1

This commitment is significant, especially given the psychological and socioeconomic difficulties facing many patients who live with HIV. “A lot of people may lose social support once they get diagnosed as a result of the con-tinuing social stigma associated with an HIV diagnosis,” said Leonard Sowah, MB, ChB, MPH, assistant professor of medicine in the Institute of Human Virology at the University of Maryland School of Medicine in Baltimore. “That makes it so important for the provider to have a relationship that may go beyond what we consider nor-mal patient relationships. Without that relationship, a lot of patients may have difficulties with engaging in care.”

Although the treatments for HIV have improved sig-nificantly over the past few years, many people living with the disease still are not receiving ART and are not engaged in care.2 One study found up to 40% of newly diagnosed patients who were given passive referrals had not initiated HIV care within 6 months of their diagnosis. Alternatively, 78% of patients who received case manage-ment and help finding HIV clinics were in care 6 months after diagnosis.3

“As providers, we have to be able to build trust with [patients], involve them in decisions about their health care, and be really clear about what we expect them to do,” said Mary Catherine Beach, MD, associate pro-fessor in the Division of General Internal Medicine and core faculty at the Berman Institute of Bioethics and the Welch Center for Prevention, Epidemiology, and Clinical Research at Johns Hopkins University in Baltimore. She pointed out that patients with HIV may need to make life-style changes, such as safer sexual practices and changes in substance use habits, as well as medication adherence.

“The relationship between patients and their providers is a particularly important factor in HIV care because the

References

1. Bravo P, Edwards A, Rollnick S, Elwyn G. Tough decisions faced by people living with HIV: a literature review of psychosocial problems. AIDS Rev. 2010;12(2)76-88.

2. Dilorio C, McCarty F, DePadilla L, et al. Adherence to antiretro-viral medication regimens: a test of a psychosocial model. AIDS Behav. 2009;13(1):10-22.

3. Treisman G, Angelino A. Interrelation between psychiatric disorders and the prevention and treatment of HIV infection. Clin Infect Dis. 2007;45(suppl 4):S313-S317.

4. Fife BL, Scott LL, Fineberg NS, et al. Promoting adaptivecoping by persons with HIV. J Assoc Nurses AIDS Care. 2008;19(1):75-84.

5. Vosvick M, Koopman C, Gore-Felton C, Thoresen C, Krumboltz J, Spiegel D. Relationship of functional quality of life to strategies for coping with the stress of living with HIV/AIDS. Psychosomatics. 2003;44(1):51-58.

6. Dilorio C, McCarty F, Resnicow K, et al. Using motivationalinterviewing to promote adherence to antiretroviral medications: a randomized controlled study. AIDS Care. 2008;20(3):273-283.

Editorial Board

Maria Eugenia Fernandez-Esquer, PhD

Associate Professor of Behavioral SciencesCenter for Health Promotion and Disease Prevention ResearchUniversity of Texas School of Public Health University of Texas Health Sciences Center at HoustonHouston, Texas

Harry Lampiris, MD

Associate Professor of Clinical Medicine Assistant Fellowship DirectorID Fellowship Training ProgramUniversity of California, San FranciscoSan Francisco, California

Glenn Treisman, MD

ProfessorDirector, AIDS Psychiatry ServiceJohns Hopkins University School of Medicine Baltimore, Maryland

ID Advisor® Focus on HIV/AIDS545 West 45th Street, New York, NY 10036. Printed in the USA. All rights reserved, including the right of reproduction, in whole or in part, in any form. April 2012.

Sponsored by

Copyright © 2012 Publisher of

Clinical Corner

see PATIENT–PROVIDER, page 4 �

� PSYCHOSOCIAL, continued from page 2

4 VO L . 3 , I S S U E 1 • 2 0 1 2

illness is a stigmatized and serious chronic illness,” said Dr. Beach.

Patient-centered care, which is defined as under-standing each patient as a unique person, is the stan-dard for high-quality care.4,5 “From my experience, the patients who really form a relationship with their provider do much better, and they tend to get a lot more engaged in their care,” said Dr.

Sowah. “It doesn’t have to be the physician in the team. It can be the case manager, medical assistant, or nurse. There are times when the team leader has to step back and allow the person who has the better relationship with the patient to lead.”

Patient-centered care has a tangible effect on medi-cal outcomes for people living with HIV. Patients who feel that they are seen and appreciated as individuals are more likely to be fully engaged with receiving and adhering to highly active ART, and are more likely to show undetectable levels of serum HIV RNA.5 It has been shown that one of the most important issues in patient–provider communication is how open providers are to lis-tening to and learning from their patients.6 “Doctors need to be skilled in getting patients to express their opinions and preferences,” said Dr. Beach. “The provider has to understand how the patient views [his or her] illness and be able to negotiate a treatment plan based on that par-ticular patient’s goals and beliefs.”

There are some barriers to creating a good patient–provider relationship, both systemic and personal (Table). “Barrier No. 1 is the reimbursement system,” said Dr. Sowah. He stressed the importance of a strong support system, with social workers, physician assistants, and other team members. He points out that, in the current system, unless a center has Ryan White Comprehensive AIDS Resources Emergency Act funding, it may be dif-ficult to make sure that all these services are fully reim-bursed by insurance.

Racial and ethnic disparity between providers and patients also may be a barrier to mutual trust.7 Dr. Beach pointed out that, in many areas, HIV predominantly

affects racial and sexual minorities.1 “Because minorities are under-repre-sented in medicine,” she said, “there’s often racial and ethnic discordance between patients and providers. Cross-cultural communication can

be challenging.”Also, Dr. Beach said, “Many pro-

viders are very well intentioned, but not necessarily trained in communication techniques.”

Fortunately, both cultural dis-parity and lack of communica-tion skills can be addressed with similar tools. “I think that really understanding where someone is coming from is a critical first step,” she said.

Motivational interviewing, for example, which engages the patient in finding his or her own

motivation for behavior change, is the standard of care for risk reduction, according to the Centers for Disease Control and Prevention.8 Luckily, said Dr. Beach, “These are skills that people can learn, and it’s not rocket science.”

Finally, said Dr. Sowah, “I think that, as human beings, we don’t only live for ourselves. So for some patients, providing them with something outside of themselves to live for helps them to engage better.”

References1. DHHS. Guidelines for the use of antiretroviral agents in HIV-1-

infected adults and adolescents: initiating antiretroviral therapy in treatment-naive patients (updated October 14, 2011). http://www.aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-treatment-guidelines/10/initiating-antiretroviral-therapy-in-treatment-naive-patients Accessed March 21, 2012.

2. Mutchler MG, Wagner G, Cowgill BO, McKay T, Risley B, Bogart LM. Improving HIV/AIDS care through treatment advocacy: going beyond client education to empowerment by facilitating client-provider relationships. AIDS Care. 2011;23(1):79-90.

3. Gardner LI, Metsch LR, Anderson-Mahoney P, et al. Efficacy of a brief case management intervention to link recently diag-nosed HIV-infected persons to care. AIDS. 2005;19(4):423-431.

4. Balint E. The possibilities of patient-centered medicine. J Roy Coll Gen Pract. 1969;17(82):269-276.

5. Beach MC, Keruly J, Moore RD. Is the quality of the patient-provider relationship associated with better adherence and health outcomes for patients with HIV? J Gen Intern Med. 2006;21(6):661-665.

6. Apollo A, Golub SA, Wainberg ML, Indyk D. Patient-provider relationships, HIV, and adherence: requisites for a partnership. Soc Work Health Care. 2006;42(3-4):209-224.

7. Saha S, Sanders DS, Korthuis PT, et al. The role of cultural distance between patient and provider in explaining racial/ethnic disparities in HIV care. Patient Educ Couns. 2011;85(3):e278-284.

8. CDC. Motivational interviewing-based HIV risk reduction. http://www.cdc.gov/hiv/topics/research/prs/resources/fact-sheets/mihrr.htm. Accessed March 21, 2012.

Table. Ways To Enhance the Patient–Provider RelationshipBarriers Solutions

Poor reimbursement Apply for Ryan White CARE Act funding;Create strong support system among health care workers

Racial/ethnic discordance between patient and provider

Engage in provider communication training;Try motivational interviewing

Based on conversations with Mary Catherine Beach, MD, and Leonard Sowah, MB, ChB, MPH.

Clinical Corner

Patient–Providercontinued from page 3 �

2 0 1 2 • VO L . 3 , I S S U E 1 5

decision support tools like documenting HIV resistance mutations or comorbidities affecting treatment decisions are not systematically recorded in off-the-shelf programs.2

The need to gather data required for funding and compliance was identi-fied as a major drain on clinical staff in HIV care by Jeffrey Kwong, DNP, MPH, ANP-BC, clinical assistant professor, College of Nursing, Rutgers University, Newark, New Jersey. “The completion of grant proposals takes up enormous time and resources. Although more HIV clinics are using an EHR system, the effort involved in pulling data out to complete the paper-work is very time-consuming. This is a major source of frus-tration for many centers working in HIV care,” Mr. Kwong said.

There are several issues inherent to current EHR systems. For example, none of them allows patient data to readily be pulled for compliance filings without additonal coding to create this function.2 Moreover, these systems may be difficult even for general use. “Simple things can be prob-lematic. Take gender, for example. Many programs provide 2 fields. Is the patient male or female? The transgender patient who goes by a nickname, or the patient who has no fixed address can both be challenging not just for the intake, but also for the reporting that is required once these patients need to be followed,” said Dr. McAlearney.

EHR systems promise to solve data management prob-lems in medicine, and they might do so when the systems work well. In her study of urban community health centers, Dr. McAlearney found that some clinical processes, such as lab orders, were simplified and expedited using an EHR system.2 However, other processes, especially compliance with complex regulatory requirements, created workflow inefficiencies as users adjusted to the EHR system.2 “It typi-cally can be assumed that the time required to implement and adjust to a new EHR system will be considerably lon-ger than the time predicted by the vendor,” Dr. McAlearney added.

Several companies market software designed for the unique demands of HIV care. e-MD claims that existing soft-ware can be tailored to meet the needs of HIV care.3 Others, such as the SuccessEHS, AVIGA, and AVIGA REPORTER, are programs specifically designed for application in this setting.4,5 Most emphasize the capability for quality assur-ance reporting, such as that demanded by the Ryan White Comprehensive AIDS Resources Emergency Act.4,5 There also are initiatives to promote EHRs in the United States through a “carrot-and-stick” approach. The Centers for

Medicare & Medicaid Services (CMS) offered incentive pay-ments up to $63,750 for institutions that adopted an EHR by February 2012.6 In 2015, hospitals and providers will be penalized in their Medicare reimbursements if they do not successfully implement an EHR system.6

The demands for EHRs in HIV care are so unique that imposing these sys-tems on top of an existing EHR may make sense. Indeed, this is the problem faced by many clinics affiliated with larger institutions. AVIGA REPORTER, which grew out of an effort to orga-nize lab results and meet the CMS EHR “meaningful use” requirements, is com-

patible with several of the most widely used EHR programs that HIV/AIDS clinics already may be running by default.5

The SuccessEHS system also was designed to provide comprehensive information collection and processing. It uses a dashboard-type concept to allow access to charts, electronic prescribing, managing lab results, and even monitoring workflow.4 However, the potential problem with both of these systems is the learning curve. They may require one or more staff members willing to become an in-house expert.

“Members of the staff who can champion the system are very helpful, but there is a risk of a bottleneck if those individuals are overwhelmed with questions when they are attempting to keep up with their normal workload,” Dr. McAlearney advised. She indicated that there may be no seamless solutions for adapting to new EHR technology, but the goal will be to minimize the pain.

Mr. Kwong, who was unaware of but intrigued by recent developments in EHR systems specific to HIV care that facilitate data collection for grant filing, cautioned that it will be important for such systems to communicate with existing EHR platforms. “An EHR system that helps us com-pile data on HIV care for compliance but speaks to the sys-tem we already have would be a huge advantage,” he said.

References1. 2011 Annual Ryan White HIV/AIDS Program Services Report

(RSR) instruction manual. www.careacttarget.org/library/RSR_Instruction_Manual.pdf. Accessed March 21, 2012.

2. McAlearney AS, Robbins J, Hirsch A, Jorina M, Harropo JP. Perceived efficiency following electronic health record implemen-tation: an exploratory study of an urban community health center network. Int J Med Inform. 2010;79(12):807-816.

3. AIDS care finds success implementing electronic health record [press release]. e-MDs; August 3, 2010. http://www.e-mds.com/news/release_archives/20100803.html. Accessed February 7, 2012.

4. SuccessEHS: Solutions for HIV clinics. http://www.successehs.com/images/stories/downloads/bro-solutions-for-hiv-v2.pdf. Accessed February 7, 2012.

5. AVIGA product comparison. http://www.avigaehr.com/product-comparison. Accessed March 21, 2012.

6. EHR incentive programs. CMS Web site. https://www.cms.gov/EHRIncentivePrograms/01_Overview.asp#TopOfPage. Accessed March 21, 2012.

Guidelines Spotlight

“Choosing an appropriate

EHR system can make

things easier, but a limited

system can make things

more diffi cult.”

—Ann Scheck McAlearney, ScD

EHRscontinued from page 1 �

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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 infec-tion in adults.

Important Considerations:

• Based on serious and life-threatening hepatotoxicity observed in controlled and uncontrolled studies, nevi-rapine 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 fol-lowed; 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

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, hepa-totoxicity associated with nevirapine use can occur in both genders, all CD4+ cell counts and at any time dur-ing 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 reac-tions, 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 treat-ment. The 14-day lead-in period with immediate-release 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 clini-cal 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, includ-ing 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.

Clinical Corner

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The International VERxVE Trial Evaluated VIRAMUNE XR versus VIRAMUNE in ARV Treatment–naïve Adult PatientsVERxVE: Trial Overview and Design

The VERxVE trial is an ongoing, multinational, Phase 3, double-blind, double-dummy, parallel-group, active-controlled 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 effi-cacy 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 spe-cifically 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 noninferior-ity 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 EndpointThe primary endpoint of this trial was sustained viro-

logic response at Week 48. A virologic response was defined as 2 consecutive measurements of VL <50 cop-ies/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 con-firm whether virologic rebound or response had occurred.2

Secondary Endpoints

A few of the 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 secondary safety endpoints included adverse events and serious adverse events (including AIDS-defining events), occurrence of rashes and hepatic events, occur-rence of elevations in laboratory measurements by Division of AIDS (DAIDS) Grade, and occurrence of discontinua-tions 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 quanti-fication) = 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 mea-surement if multiple measurements were taken in the win-dow). 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 base-line 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 treat-ment 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 back-ground therapy (OBT) to new class or changed OBT not

Clinical Corner

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8 VO L . 3 , I S S U E 1 • 2 0 1 2

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 viro-logic failure proportion was 13% in the VIRAMUNE group and 11% in the VIRAMUNE XR group (Figure 2).1

VERxVE: Data

Selected Adverse Events

The safety data include all adult patient visits up to the last patient’s completion of the 48-week primary end-point 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 eleva-tions 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 gas-trointestinal tract. The extended-release 400 mg once-daily formulation was developed to provide consistent drug levels over 24 hours (Figure 5, page 10). The

Clinical Corner

VERxVEcontinued from page 7 �

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.

a Adjusted for baseline HIV-1 VL stratum.

Patients With Undetectable Viral Load at Week 48

Total 100,000 100,000

Viro

logi

c S

ucce

ssa,

b

(HIV

-1 R

NA

<50

cop

ies/

mL)

, % 120

100

80

60

40

20

0

75

8280

70 7378

VIRAMUNE VIRAMUNE XR

Baseline VL

Mean CD4+ Count at Baseline (cells/mm3)

Mean Change in CD4+ Count (cells/mm3)a

228

+191

230

+206

VIRAMUNE VIRAMUNE XR

Table. Mean CD4+ Cell Count and Changes at Week 481,2

Figure 1. Virologic Success at Week 481,2

2 0 1 2 • VO L . 3 , I S S U E 1 9

bioavailability of VIRAMUNE and VIRAMUNE XR was tested under fasted and fed conditions with VIRAMUNE showing 100% bioavailability in both settings. The bio-availability of VIRAMUNE XR was 80% under fasted con-ditions and 94% under fed conditions. The difference in the bioavailability of nevirapine when VIRAMUNE XR was dosed under fasted and fed conditions is not considered clinically relevant.1

Dosing and Administration

ARV/VIRAMUNE-naïve Adult Patients

Based on serious and life-threatening hepatotox-icity 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 out-weighs the risk.1

Adult patients must initiate therapy with one 200 mg tablet of VIRAMUNE daily for the first 14 days in combi-nation 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

Clinical Corner

Patie

nts,

%

Total

SNAPSHOT A nalysisa

Patients With Virologic Failure at Week 4850

40

30

20

10

0

1311

VIRAMUNE VIRAMUNE XR

Figure 2. Virologic Failure Rates1

a 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.

Selected Adverse Events During the Randomization (Post Lead-in) Phase

A ny Hepatic Event Symptomatic Hepatic Eventsa

Grade 3 or 4 A LT/ A ST Elevation

Patie

nts,

%

50

40

30

20

10

0

9

26 7 6

3

VIRAMUNE (n=506) VIRAMUNE XR (n=505)

Figure 3. Selected Adverse Events1

a Symptomatic hepatic events included anorexia, jaundice, and vomiting.

see VERXVE, page 10 �

10 VO L . 3 , I S S U E 1 • 2 0 1 1

VIRAMUNE-experienced Adult PatientsAdult 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.1

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 combi-nation with other ARV agents1:

• Without the 14-day lead-in period of once-daily 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) extended-release, 400 mg tablets.

a At steady state, VIRAMUNE XR 400 mg once daily delivered consistent drug plasma levels over 24 hours allowing for once-daily dosing.

Clinical Corner

VERxVEcontinued from page 9 �

Selected Adverse Reactions of at Least Moderate Intensity (Grade 2 or above) in 2% of Patients 1,a,b

Clinical Hepatitis d

Pati

ents

, %

20

15

10

5

0

3 3 32

VIRAMUNE VIRAMUNE (n=506) (n=505)

Rash c

XR

a Includes adverse drug reactions considered by the investigator to be at least possibly, probably, or definitely related to the drug.

b Mean observation period was 61 weeks.

c Rash includes terms rash, rash maculo-papular, erythema nodosum, rash erythematous, rash pap-ular, skin reaction, Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms (DRESS), and allergic dermatitis.

d Clinical hepatitis includes terms hepatitis, hepatotoxicity, hepatitis acute, liver disorder, hepatitis toxic, hepatic failure, and jaundice.

Figure 4. Selected Adverse Reactions1

Nev

irap

ine

Plas

ma

Con

cent

ratio

ns (μ

g/m

L)

Time (Hours)

200 mg VIRAMUNE (n=25)

400 mg VIRAMUNE XR (n=24)a

Figure 5. VIRAMUNE XR (400 mg) Delivered Consistent Drug Levels Over 24 Hours

2 0 1 2 • VO L . 3 , I S S U E 1 11

Spotlight on Hopkins AIDS Care Program

The Hopkins AIDS Care Program began in January 1984 with the opening of the Moore Clinic for patients with HIV infection. It has since developed into a full-service care network.1 “The AIDS care program was originally estab-lished to meet the need for primary care services for peo-ple who didn’t have medical insurance,” said Jeanne Keruly, MS, CRNP, assistant professor of medicine and director of Ryan White Adult Services in the Division of Infectious Diseases at the Johns Hopkins University School of Medicine in Baltimore. “It has grown over the years to meet the changing needs of the population.” The AIDS Service cur-rently comprises 6 arms: an inpatient unit, a social work program, 3 outpatient clinical programs, several specialty services located in the outpatient clinics, a large clini-cal research program, and a longstanding observational study of patients in care—the HIV Clinical Cohort data-base also known as the Moore Clinic database.

“The 1980s and 1990s were a period of big change for ID [infectious disease] training because with HIV, we had a whole new fund of knowledge. There was a lot of research happening in the course of clinical care,” said Stuart Ray, MD, professor of medicine and oncology, and director of the Infectious Diseases Fellowship training program in the Division of Infectious Diseases at Johns Hopkins University School of Medicine. “HIV was clearly a condition where it wasn’t enough to have a doctor,” said Dr. Ray. “You needed a big multidisciplinary team to man-age all the challenges that HIV presented. We developed a group of staff that became the heart of that service.”

According to Dr. Ray, ID fellows who rotate through the AIDS Service spend their first 3 to 4 months on the general ID consult service, 2 months at the Johns Hopkins Bayview Medical Center on general consult, 2 months on the Transplant ID Consult service, and 2 to 3 months on the inpatient Polk Unit HIV service. Fellows rotate through the ID clinic, and some of these rotations are located in the Moore Clinic for HIV Care. In the second year, fellows also complete a 1-year HIV Continuity Clinic at the Moore Clinic.

The Moore Clinic is the outpa-tient unit supervised by the Hopkins AIDS Service. The clinic currently comprises 7 major spe-cialty services: gastroenterology, neurology, psychiatry, gynecology, obstetrics, ophthalmology, and dermatol-ogy.1 In responding to the needs of their patients, said Ms. Keruly, “We co-located services very early on, and the specialties change over time based on need. There was a group of clinicians/scientists that had an interest in this disease, so we were able to amass a group to take care of very complex patients, under the leadership of John

Bartlett, MD.”Stephen Berry, MD, who graduated from

the fellowship program in 2010 and recent-ly joined the faculty as assistant professor of medicine in the Division of Infectious Diseases, was attracted to the ID fellow-ship in part because of Dr. Bartlett’s repu-tation. Dr. Bartlett was inspiring, Dr. Berry said, because of his combined abilities. “He is one of the world’s foremost infec-tious disease researchers but didn’t forget his connection to the clinical world.”

For Dr. Berry, the Moore Clinic database is a big part of the reason he ultimately chose to stay at Johns Hopkins. The database was established in 1989 and collects a wealth of information about resource utilization.1 “For my research interest in the cost-effectiveness of modern HIV care,” said Dr. Berry, “it’s wonderful because it’s one of the most comprehensive databases out there.” Because all patients were asked for consent from the beginning of the database, he noted, “we can study everything about a case; not just CD4 counts or medications, but insurance status and other medical conditions.”

Dr. Berry finds the culture of the AIDS Service inspiring as well, and believes it stems in part from the combina-tion of serious clinical care and research fostered by Dr. Bartlett and his colleagues. “I would say that it’s a unique situation,” said Dr. Berry, “where we are expected to learn from everything we do, clinically. One place where this cul-ture is really evident is in our weekly conference.” During this conference, fellows present the faculty with the most challenging cases of the past week and the faculty are called on to come up with a differential diagnosis. The fellow who presents the case is then expected to give an answer and provide literature on an interesting component of the case.

“This kind of conference is common across all ID fel-lowships, but what’s different is that we put the faculty members on the spot rather than putting fellows on the

ID Advisor: Focus on HIV/AIDS presents the Practice Profile series. In each segment, we spotlight an exemplary HIV/AIDS treatment center or practice. In this issue, we highlight the multidisciplinary Hopkins HIV/AIDS Care Program in Baltimore, Maryland.

Practice Profile

see JOHNS HOPKINS, page 12 �

“[John Bartlett, MD] is

one of the world’s fore-

most infectious disease

researchers but didn’t

forget his connection to

the clinical world.”

—Stephen Berry, MD

12 VO L . 3 , I S S U E 1 • 2 0 1 2

ID Advisor Focus on HIV/AIDSprovides support and

information for the

next generation of

ID/HIV specialists.

spot,” said Dr. Berry. “To me this epitomizes the fact that everybody here is trying to learn from the medical condi-tions and patients we see.” Ms. Keruly also emphasized these weekly conferences as a cornerstone of the fellow-ship program. “The weekly clinical conference is attended by a lot of our faculty and clinical staff,” said Ms. Keruly, “and it’s incredibly useful.”

The Johns Hopkins AIDS Service, said Kelly Gebo, MD, MPH, associate professor of medicine in the Division of Infectious Diseases, associate professor of epidemiology at Johns Hopkins Bloomberg School of Public Health, and director of Undergraduate Public Health Studies at Johns Hopkins University, is “a unique opportunity to deliver HIV care to a very needy group of patients in an ideal set-ting, where you have other support services present.” For example, social workers help educate the fellows about resources that patients may need, and how to access them. “I think that’s particularly important for trainees,” she said. Dr. Gebo finds working as a faculty member satisfying because, she said, “I like seeing providers going from novices at HIV care to completely savvy about it in the end. That’s really rewarding, to feel that we’ve made

progress in teaching them that in a relatively short period of time.”

“HIV has been the model for dealing with issues of complex care and polypharmacy, and we can’t manage that alone,” said Dr. Ray. “The personnel at the clinic don’t come and go the way that the attendings and the fellows do—we have people who have been here for 20 years. It provides continuity and serves as a model for multidisciplinary team interaction and research.”

Besides the clinic time, most of the second- and third-year fellowships are spent conducting research. “Most of our fellows get some kind of formal training in research,” said Dr. Ray. “Some of them spend their time primarily in the lab.” This is facilitated by the division’s funding structure, which funds training for fellows in their second and third years.

Ms. Keruly points out that part of the reason the multi-disciplinary team has worked so well is that the clinician-scientists on the team have an interest in studying the components of the disease. “This is not only clinical care; they have a research interest,” she said. “All the parts—the clinician-scientist, the case manager/social worker—give the fellows a really good picture of what they would be dealing with as doctors in HIV care.”

“Finding where the need and your passion intersect is when you know you’ve found the right place. For a lot of [physicians], HIV provides that,” said Dr. Ray, “and we certainly foster that search.”

Reference

1. The Body: Johns Hopkins AIDS Service. http://www.thebody.com/content/art12096.html. Accessed March 21, 2012.

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Johns Hopkinscontinued from page 11 �

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