New in the Bay Area. . .
Positive Partners

Donald I. Abrams, MD, Editor

Next Meeting

2001! Happy holidays and welcome to the new millennium. A new beginning, a fresh start, unburdened by the fears of last year's Y2K potential disasters - this new year really does feel like a new beginning in many ways. In celebration and in recognition of this time of newness, the Community Consortium is inaugurating an updated program of educational offerings compatible with the new millennium.

Over the past few years we have been involved in strategic planning and taking stock of the successes and shortcomings of the programs that we have been offering. AIDS Clinical Grand Rounds, first inaugurated in September 1987 at Davies Medical Center, has done much to keep HIV care providers in the Bay Area updated on the latest advances and issues concerning treatment of the disease. Originally rotating monthly among different hospitals in the network, the series subsequently resided at the UCSF Mission Center Building and more recently has returned to a stable home at the Davies Campus of California Pacific Medical Center. When AIDS Clinical Grand Rounds was first initiated in 1987, it was pretty much the only act in town. Now there is an AIDS dinner meeting, telephone conference, CME lecture or Internet interactive program available virtually every day. Thus, attendance at AIDS Clinical Grand Rounds has dwindled over the past few years.

Saturday morning half-day CME programs have remained popular with Consortium providers. These more intensive panel presentations on a specific topic go into more depth on a given subject than is possible during the hour long Wednesday night AIDS Clinical Grand Rounds. Generally quite interactive and always "on the cutting edge", the Saturday CME programs have continued to be highly appreciated by those who attend. These programs are underwritten by unrestricted educational grants from generous pharmaceutical sponsors, to whom we are grateful. We also appreciate the industry's support for the highly successful Conference Update dinner meetings, which we have held increasingly over the past few years.

Taking all of these educational offerings into account, the Community Consortium Executive Advisory Board and staff have proposed a revised schedule of educational offerings for the year 2001. AIDS Clinical Grand Rounds will no longer be held on a regular monthly basis, on the third Wednesday of each month at 6:00 pm. at the Davies Campus of the California Pacific Medical Center. Our educational offerings will now consist of a melange of Saturday CME sessions, Conference Update dinner meetings and AIDS Clinical Grand Rounds presentations. We have drafted a tentative schedule for the upcoming months, so grab your Palm Pilot and mark these dates on your e-calendar. Remember that some of the more future dates are still tentative at this time.

To continue to remain in the loop and receive Synopsis and specific invitations to the upcoming educational offerings, please remember to renew your Community Consortium membership today.

The first educational offering of 2001 will be an update on the 8th Conference on Retroviruses and Opportunistic Infection. This dinner meeting at the Palace Hotel will be held on Wednesday, February 21, 2001. Again, just a reminder, to ensure that you receive the final invitation and details regarding this meeting as well as our other upcoming events, please remember to return your completed membership form and nominal Community Consortium dues today.

Educational offerings for the remainder of 2001 will include a Saturday CME program on March 24, from 9:00 am. to 1:00 pm. on Androgens and Anabolic Steroids in HIV. There will be an AIDS Clinical Grand Rounds session on May 23, 2001 at 6:00 pm. at Davies. We are hoping to have an update on the First International AIDS Society Conference on HIV Pathogenesis and Treatment to be held in Buenos Aires, Argentina in early July. The dinner update will likely be scheduled for July 18. Industry sponsors are being sought. The second Saturday CME program of the year will be held on September 8. We would like to hold a dinner meeting to present an update from ICAAC sometime early in October, perhaps October 10. The final educational offering of the upcoming year will likely be a Saturday CME program to be held December 1, 2001, World AIDS Day.

With this change in the AIDS Clinical Grand Rounds schedule, Synopsis will continue to be distributed but on a somewhat reduced publication schedule. Attempts will be made to summarize each of the educational sessions- AIDS Clinical Grand Rounds, dinner update meetings and Saturday CME programs- to the best of the editor's ability. However, remember that nothing is better than actually being there so that you can contribute, ask questions and be interactive! During the year, we will assess whether this experimental redesign of Community Consortium educational offerings is acceptable, to determine whether we continue along the same vein into 2002.

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Prayer and Distant Healing

The November 2000 AIDS Clinical Grand Rounds session featured a presentation on "Prayer and Distant Healing in HIV/AIDS" by Elisabeth Targ, M.D., Director of the Complementary Medicine Research Institute at California Pacific Medical Center. Dr. Targ, NIH funded through the National Center for Complementary and Alternative Medicine, opened the program by suggesting that she planned to discuss the concept of research in prayer and distant healing. She noted that, to many, this is a bit of an oxymoron. "Some say it cannot be studied; others say it shouldn't be studied." She began by explaining how she became involved in the field. As a psychiatrist, one who knows it is "all in people's heads anyway," her initial involvement was not because she thought it would work. Dr. Targ found herself working in spiritual exploration groups for women with breast cancer. Because she was there, a number of patients asked her if she was therefore interested in energy research and prayer. She, in fact, felt that much of the benefit was placebo effect generated by the patient thinking that other people were thinking of them. Many people told her, however, that it actually worked. She decided that it needed to be studied. A psychologist colleague from the Institute of Noetic Studies approached her six to seven years ago and they began to outline trials that could be undertaken and initiated studies in the field.

Dr. Targ asked parenthetically if anyone was really interested in the topic of distant healing and prayer. She remarked that obviously people are, as the subject has been cover stories of both Time and Newsweek and also featured in The New York Times and The Wall Street Journal. CNN did a survey which demonstrated that 73% of adults believe "praying for someone else can help cure their illness." In this survey of 1,004 Americans conducted in June 1999, 28% said that they believed in "the utility of faith healers to make people well through their faith or personal touch." Although many equate faith healing with charlatanism, obviously a significant minority of individuals do believe in it. One study that was initially conducted on hospitalized inpatients in Alabama found that 50% wanted their physicians to pray with them, not only for them. Dr. Targ said that, coming from Alabama, this might not be such a surprising result, however, the study was replicated in Philadelphia, with the same findings. She mentioned that these desires of patients are not often appreciated by providers, who frequently feel that a patient might feel offended or intruded upon if such topics were raised.

"Distant mental influence on living systems" is the NIH approved definition of the phenomenon that Dr. Targ discussed. Synonyms that are perhaps more user-friendly and well recognized include psychic healing, intentionality healing, therapeutic touch, non-local healing, spiritual healing, prayer, laying on of hands, subtle energy healing, and distant healing. The NIH apparently differentiates distant healing from energy healing because they believe that there is, in fact, a mechanism involved in energy healing. Dr. Targ's definition of distant healing is "a conscious and compassionate act of mentation intended to benefit the physical and/or emotional wellbeing of another person at a distance." She reported that research on distant healing has been going on for a long time. There were 130 studies that were reviewed in 1992. The studies had a variety of target systems, including the effects of distant healing on enzymes, yeast, bacteria, plants, mice, and humans. In two-thirds of the studies, statistically significant findings were reported. She reviewed a study on the impact of distant healing on the rates of hemolysis of human red blood cells. This was an in vitro study, where healers were asked to protect red blood cells from hemolysis (Braude 1990). Thirty-two psychology students were the subjects. Blood was placed in 20 test tubes (10 control, 10 treatment). Subjects were told to protect the red blood cells from hemolysis by distilled water. Nine of 32 subjects showed statistically significant results (P < 0.05). There is also evidence of greater effects when the individuals were trying to protect their own blood cells from hemolysis. Dr. Targ pointed out again that these were psychology students who were not actually trained healers.

She went on to summarize a study of 53 preoperative hernia patients. This was a double blind study. Patients in Group A received distant healing; patients in Group B underwent relaxation techniques; and Group C was the control. The patients in the healer group showed significantly more satisfaction with their care, increased physical well being, improved wound healing, fewer fevers, and better satisfaction with life than either the relaxation group or the controls (Butwich 1994).

San Francisco General Hospital was the site of a study of intercessory prayer, published by Bird, et al. in the Southern Medical Journal in 1988. Three hundred ninety-three patients hospitalized in the CCU were randomized to receive prayer (N = 192) by Christian prayer groups or were in the control group (N = 201). Patients were not aware to which group they had been randomized. Outcomes were assessed on the basis of a composite severity score based on hospital course. In the prayer group, there were 27 bad outcomes compared to 44 in the control group (P < 0.01). There were 163 good outcomes in the prayer group compared to 147 in the controls. The number of complications including intubations, arrests, CPR, pneumonia and the need for diuretics was significantly reduced in the group receiving the intercessory prayer (P < 0.0001). All of the patients who participated were consented before receiving the intervention. Dr. Targ remarked that 14% of patients approached did not want to be in the Bird study because they were not Christians or felt that the intervention was ridiculous.

The Bird study was recently replicated by a group from the Mid-America Heart Institute (Ferris, et al. Archives of Internal Medicine, 1999). Interestingly, patients were not consented prior to their participation in this trial. Four hundred sixty-six individuals were in the prayer group, with 524 in the controls. There was a small but significant benefit for those receiving the intercessory prayer. The overall effect size was small, with a benefit of 10% seen on the scoring scales used as outcomes.

Over the past six years, Dr. Targ herself has conducted two studies of distant healing in patients with HIV/AIDS. Her effect size was six times larger than that seen in some of the previously reported trials. She attributed some of that success to the fact that the healers that she chose to work with each had a minimum of five years of experience and had worked with at least 10 people with AIDS, so that they were trained and practiced in this area. The first study she conducted was in individuals with advanced AIDS defined as CD4+ cell counts < 200/mm3 with a history of one AIDS-defining infection. Patients were initially stratified on their CD4+ cell counts and their numbers of AIDS-defining infections, and subsequently randomized to usual care versus distant healing for one hour a day daily for 10 weeks by 10 different healers. Outcomes were assessed at the end of 10 weeks and then after six months. In the first small pilot study, there were 10 patients in the treatment group and 10 in the control group. Although no deaths occurred in the group undergoing distant healing, there were four deaths in the control group. She described this as a "startling" finding. On further analysis, it was noted that the mean age in the distant healing cohort was 39.8 years compared to 50.5 years in the control group. The subsequent study was then stratified by age as well.

The healers who participated in Dr. Targ's second HIV/AIDS trial had an average of 17 years of experience. They had worked with a mean of 106 patients each. Seventy percent of the healers were women with a mean age of 47. A number of different modalities of healing were practiced, including energy healing (50%), meditation (25%), devotional (15%), and shamanic (10%). Healers were all given the same instructions "Hold an intention for the health and wellbeing of the patient" every day for a week. Healers were rotated so in case some were not as effective as others, each patient participant would get a chance to be worked on by a good healer. Healers filled out daily diaries describing their work.

Dr. Targ reviewed the results of the second larger confirmatory distant healing trial. Both studies were published in the Western Journal of Medicine in 1998. Forty patients were randomized in the second study. The mean age of both the healer group and the controls was matched at 43 years. The only disparity in baseline characteristics was that 20% of the control participants were minorities compared to none of those who received the active distant healing. The results again confirmed the benefit to the healing intervention. AIDS defining diseases over six months occurred in two patients in the healing group compared to 12 controls (P = 0.04). The illness severity score in the active healing cohort was 16 versus 43 in the controls (P = 0.03). Other outcomes that were significantly affected included decreased outpatient physician visits and decreased numbers and days of hospitalization in the healing cohort compared to the controls. The measures of distress as evaluated in the Profile of Mood States (POMS) were improved in the treatment cohort but not in the controls. Dr. Targ mentioned that all of the participants had a belief in distant healing otherwise they would not have considered joining the trial. Twelve of the 20 patients receiving the active intervention believed that they were in the distant healing group compared to 9 of the 20 controls for a difference that was not statistically significant. Analyzing as to whether thinking they were in the treatment group made the subject do better demonstrated that the only measure where that was found to be the case was in CD4+ cell counts, which certainly would be difficult to attribute to bias or placebo effect.

Now that she has completed two small trials of 20 and 40 patients that have demonstrated similar outcomes, Dr. Targ's next step is to ascertain whether this is, in fact, a real effect. She states that "remarkable claims require remarkable proofs!" In the study which is being currently launched in collaboration with the Community Consortium, another question being investigated is who exactly is a healer? This three-arm clinical trial will randomize 150 patients. Fifty patients will be in the distant healing group with experienced healers as in the prior two trials. An additional 50 patients will be randomized to receive distant healing intentions from nurses without previous training in distant healing. The goal here is to determine whether or not we may all be surrounded by healers. Fifty additional patients will be randomized to no healing. We are eager to assist Dr. Targ and her group in finding patients who may be interested in participating. Please see below for further details regarding the study or call 415-502-5705 for patient referrals. Dr. Targ's well-received presentation on prayer and distant healing was a most appropriate way to usher in the winter holiday season!

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Committee Reports

Executive Advisory Board

The Community Consortium Executive Advisory Board will meet on Wednesday, January 31, 2001 at 7:30 am. in the Community Consortium conference room. At the November meeting, the EAB was introduced to Mary Ellen Kelly, MPH, the Consortium's new program manager. Ms. Kelly has recently located to San Francisco from New York City, where she was a program administrator for a pediatric HIV unit at Metropolitan Hospital in Harlem. Ms. Kelly, who will oversee all Consortium programmatic activities not directly related to clinical research, is a bright new addition to the Consortium staff, bringing energy and enthusiasm to the job. Please feel free to contact Mary Ellen at 415-476-9554, ext. 25 for any Consortium related issues or just to get acquainted!

Carroll Child, RN, has now assumed the responsibilities of Community Consortium Research Coordinator. Mr. Child will be in charge of providing oversight to all Community Consortium clinical trials, both CPCRA related and those studies conducted outside of the aegis of our CPCRA contract. Carroll has been a vital member of the Community Consortium management team since his arrival on staff 11 years ago. We are delighted that he has accepted increased responsibilities to provide oversight to all of our clinical trial endeavors.

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Scientific Advisory Committee and Community Advisory Board

Leaving nothing untouched in this year of growth and change, the Community Consortium is announcing the termination of our routinely scheduled monthly SAC/CAB meetings. These meetings have also been somewhat of a tradition. Initially inaugurated in 1988, the Community Consortium's Community Advisory Board was the first of its kind in the nation and has served as a model for groups nationwide and, in fact, around the world. As the number of research endeavors in the UCSF Positive Health Program at San Francisco General Hospital requiring community input has increased, the number of community advocates, activists and patients who have the time to spare to attend numerous community advisory board meetings has remained stable. In an effort to consolidate the precious resource, members of PHP related CABS have requested that a single committee be formed to provide oversight to all of the PHP programs. Hence, the Community Consortium's CAB will merge with those serving the ACTG, the Options Project, the PEP Project, etc. We will continue to have our protocols reviewed and our issues deliberated by this combined CAB.

With the impending departure of the CAB representatives from the combined SAC/CAB meeting, the Consortium feels that it would be best to use our Scientific Advisory Committee more on an ad hoc basis than to continue with our routine monthly meetings. We will also suggest that the newly established Positive Health Program Joint CAB include a representative of community physicians. In the meantime, in lieu of coming to a meeting at the Consortium during your lunch hour, please help us by providing us with critical reviews of clinical trials in development as we seek your counsel and input on a prn basis.

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Consortium Clinical Trials

Prayer and Distant Healing

At the November AIDS Clinical Grand Rounds, we heard from Elisabeth Targ, MD, principal investigator of the NIH funded trial to investigate distant healing by nurses and healers as an adjunctive intervention in AIDS. Two preliminary double blind studies conducted by Dr. Targ found significantly improved psychological and medical outcomes in patients with advanced AIDS who had received distant healing attempts by a diverse selection of professional "healers". While provocative, conclusions from these studies are limited by the small study size (N=20 and N=40), by the fact that patients were being treated in a variety of different clinics and by collection of medical data by retrospective chart review. For these reasons, replication is warranted. The purpose of the study which has just been launched is to extend the preliminary work by studying a larger sample, examining additional biological markers of disease progression and following medical and quality of life outcomes for a longer period. In addition, the study will compare distant healing efforts by professional "healers" with distant healing efforts by professional nurses with no previous training.

One hundred fifty subjects with advanced AIDS will be enrolled in the study and randomized to one of three study arms. The study will be completed in ten cohorts of 15 patients. In each cohort, five patients will be randomized to receive DH attempts by professional "healers", five patients will receive DH attempts by nurses, and five patients will receive no special intervention beyond usual medical treatments. The study will be double-blind so that neither patients nor their doctors nor the researchers will know who is receiving the healing treatments. Outcome measures include the clinical course, psychological course, utilization of medications as well as HIV RNA, CD4/CD8, NK cell function, and metabolic measures and antiretroviral therapy toxicity. Inclusion criteria are HIV sero-positive between the ages of 18 and 65 with a history of having had a CD4+ cell count < 200/mm3. Patients who are not English-speaking, unable or unwilling to fill out questionnaires or who have a history of non-HIV related life-threatening disease are excluded. Study procedures will be conducted at the California Pacific Medical Center site. Participants will be required to return after their baseline evaluation to this study site at six months and one year for follow-up questionnaires and blood work. The remainder of the data will be extracted from clinic charts by the research assistant. If you are interested in enrolling eligible patients for the distant healing study, please contact Paul Couey at (415) 502-5705.

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DHEA

We are about to launch a study of dehydroepiandosterone (DHEA) to investigate how it impacts on latent HIV-1 replication and host immunity. DHEA has been touted to have a number of beneficial effects in patients with HIV from antiviral to immunomodulatory as well as being an agent to increase lean body mass and improve quality of life. There is some evidence to suggest that DHEA may have potential benefit in purging the latent pool of HIV in resting cells. To this end, this randomized placebo-controlled trial will be open to patients fully suppressed on an antiretroviral regimen. Eligibility criteria include patients with HIV-1 infection who are 18 years or older on stable antiretroviral regimens for at least eight weeks, with HIV RNA < 50 copies/ml. Women must have a normal PAP smear and mammogram within the past year and men are required to have a normal prostate specific antigen level within the past year. Participants will be randomized in a 1:1 ratio to receive either DHEA (100 mg po twice daily for males, 50 mg po twice daily for females) or placebo for 12 weeks. All study participants will then receive DHEA for an additional 12 weeks, for a total study duration of 24 weeks. Study participants will be seen as outpatients at the General Clinical Research Center. They will have one screening and one baseline visit prior to starting study drugs. At the baseline visit, they will have blood drawn for measurement of HIV RNA, viral DNA, hormone levels, lipid levels, PSA, serum chemistries, and lymphocyte subset analyses for activation antigens and naive and memory T-cell subpopulations. Body weight, height, anthropometric measures as well as body composition measurements by DEXA will be obtained. Quality of life assessments will be completed. Participants will then be randomized to either DHEA or placebo for 12 weeks. Follow-up study visits will occur at weeks 2, 4, 6, and 12. Visits during the ensuing 12 week open label DHEA treatment will occur at weeks 18 and 24. If you have patients who may be interested in participating in this study, please contact Paul Couey at (415) 502-5705.

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Multi-drug Reistant HIV (MDR)

Continued kudos to Michael Jones, RN, Community Consortium Research Nurse, and the providers at Castro Mission Health Center for their continued enthusiasm for the CPCRA MDR trial. To date we have enrolled 12 patients of the 98 accrued nationwide. This study of a structured treatment interruption (STI) in patients with multi-drug resistant (MDR) HIV is a randomized clinical endpoint study to determine whether a prescribed four-month STI will delay clinical disease progression and death compared with a strategy of immediately initiating a new antiretroviral regimen in patients with MDR virus. Subjects will initiate the salvage regimen based on information generated from both genotypic and phenotypic resistance testing that is provided as part of the protocol. As there is little existing information on the optimal amount of time to wait before resuming therapy following an STI, the first 150 participants in the CPCRA trial will have point mutation assays performed. These are more sensitive than routine resistance assays. These initial patients will also undergo more frequent HIV RNA testing, which should enable the investigators to know early in the course of the trial whether four months is too long or too short of an STI.

Four-hundred-eighty subjects will be randomized in the trial over a 12-month accrual period. This will make this, by far, the largest STI trial conducted to date. Participants will be followed monthly for the first 8 months, and then every 4 months. Should CD4 cell counts drop below threshold levels, prophylaxis for opportunistic infections will be resumed. This study will provide much information on the kinetics or the return of CD4 cells following the reinstatement of an antiviral regimen, as well as much clinical information over its planned two years of follow-up. Entry criteria includes age > 13 years with HIV RNA >10,000 copies/ml.

The potential subject must have demonstrated a multi-drug-resistant HIV strain on genotypic antiviral resistance testing (GART), with evidence of broad PI resistance combined with broad NNRTI and/or broad NRTI resistance. The patient and provider must have the intention of initiating a new regimen and should be able to accept the potential timing of this change as specified in the protocol. Individuals should be on a stable antiretroviral regimen for at least 14 days prior to the qualifying GART test and randomization. Broad PI resistance is defined as having at least two major resistance mutations against PIs. Broad NNRTI resistance would include the 103M mutation or a combination of two other NNRTI mutations. Broad resistance to nucleosides is defined as the presence of 151M/69S mutation or a combination of mutations including the 215Y/S mutation. Any patient previously exposed to three nucleosides, one NNRTI and two PIs, is also eligible for screening and will have GART performed if they meet the remaining entry criteria. If you have any individuals who may be interested in participating in the CPCRA MDR trial, please let your Community Consortium clinical research nurse know!

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FIRST

The CPCRA's Flexible Initial Retroviral Suppressive Therapies (FIRST) trial is the entry point into the CPCRA's menu of strategic antiretroviral trials. FIRST is open to patients who are antiretroviral naive. As of the end of December, the CPCRA has enrolled 917 of the target 1,410 participants. Accrual is expected to close at the end of March 2001. To date, the Consortium has enrolled 37 patients onto the study. The question being asked is "What constitutes the best initial regimen for patients beginning antiviral therapies?" Patients are randomized to one of three arms. One arm includes two nucleoside analogs and a protease inhibitor, a second arm includes two nucleoside analogs and a non-nucleoside reverse transcriptase inhibitor (NNRTI), and a third arm includes at least one nucleoside analog plus an NNRTI and a protease inhibitor. Clinicians who so desire have free reign to choose all of the drugs that the patient begins within the classes to which patients have been randomized. If providers have equipoise among the various protease inhibitors and NNRTIs, patients may undergo a second randomization to specific drugs within the class. With the increasing untoward consequences that are being seen from highly active antiretroviral therapies and the increasing number of agents available in our antiretroviral armamentarium, the FIRST study is poised to answer a very timely and pertinent question. Patients are eligible regardless of their CD4+ cell counts or their HIV RNA levels. In this strategic trial, no drugs are provided; drugs are all currently available by prescription. When a patient is randomized, the provider will write a prescription for the appropriate regimen. The endpoint in the study will be the time to second virologic failure. This endpoint takes into account the fact that it is likely that all of the regimens may be nearly equivalent in their initial ability to suppress HIV RNA. The real differences may appear when switching patients to a second regimen once patients have progressed. Thus, the FIRST trial has a rather unique clinical endpoint. It is hoped that all patients enrolled will also be co-enrolled in the CPCRA long-term monitoring protocol, to allow us to collect further information on clinical status of the patients.

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Metabolic Study

A perplexing question that still baffles HIV care providers is the etiology of the body habitus alterations and metabolic consequences of highly active antiretroviral therapies. Are these changes related to protease inhibitors alone? Are the same consequences seen in patients who being therapy with an NNRTI-containing HAART regimen? To answer this study, the CPCRA designed the Metabolic Trial as a substudy of FIRST. The trial will capture information from patients as they enroll onto the FIRST trial. Patients will undergo serial metabolic evaluations, including laboratory testing and anthropomorphic measurements. By co-enrolling patients from the FIRST trial, we hope to be able to get answers to the question as to whether changes in body habitus alterations and metabolic abnormalities being seen in patients on HAART are related to protease inhibitor therapy or are seen with equal frequency in patients commencing an NNRTI-containing regimen. Patients enrolled in the metabolic study will undergo measurements of glucose, insulin, cholesterol and triglyceride levels.

In addition, body composition measurements (e.g., BIA, skinfold measurements and body circumference measurements) will also be obtained. This trial promises to contribute much valuable information on risks and rates for developing metabolic and body habitus alterations after initiating HAART. The CPCRA has enrolled 346 of the 360 patient target onto this protocol as of the year's end.

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Adherence Study

How to ensure that our patients can best adhere to the complicated HAART regimens that we prescribe is a most important question. Unlike most CPCRA studies where the individual patient is randomized to one intervention or another, the adherence study has randomized the entire Community Consortium to an adherence intervention that utilizes the services of "medication managers." Patients co-enrolled onto a CPCRA strategic antiretroviral trial who choose to participant in the adherence substudy will have interactions with our trained medication managers. These Consortium clinical research nurses will do everything per protocol to ensure that patients are reminded to adhere to their prescribed regimens. Two different interventions are being evaluated in a two-by-two factorial design involving CPCRA units randomized to different arms across the national network. The ultimate goal will be to evaluate which intervention produces the best HIV RNA results as well as self-reported adherence. The CPCRA has enrolled 536 of the target 592 patients from FIRST onto the adherence protocol.

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Long Term Monitoring (LTM)

The CPCRA is committed to long-term evaluation of patients enrolled on randomized clinical trials. Where a number of our studies have intermediate surrogate marker endpoints, co-enrolling patients onto the long-term monitoring (LTM) protocol will ensure that we are able to capture long-term disease progression and survival information on patients who may not have already reached a clinical endpoint. Currently, we are working to enroll all patients from CPCRA randomized interventional trials onto LTM. The Consortium has a goal of 100% co-enrollment onto the LTM protocol for eligible patients. To date, 2159 patients are being followed on LTM nationwide, including 96 from our site. Please assist your Community Consortium clinical research nurse in explaining to patients participating on eligible trials why the long-term monitoring protocol is essential.

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Nevirapine Warning

Boehringer Ingelheim/Roxane Laboratories, Inc. have issued a "Dear Healthcare Professional" letter to inform providers of important new safety information added to the product labeling for nevirapine (VIRAMUNE). The existing label warnings for the risk of hepatotoxicity have been strengthened in response to continued reports of severe life threatening and in some cases fatal hepatotoxicity that have been reported from clinical trials and post marketing use with nevirapine. Although clinical presentation varied among patients, frequently occurring features included nonspecific prodromal signs and symptoms of fatigue, malaise, anorexia and nausea with or without abnormal serum transaminase levels. In these reports, symptoms progressed to jaundice, hepatomegaly, elevated LFTs, and hepatic failure over a period of several days. Patients with signs or symptoms of hepatitis must immediately seek medical evaluation, have liver function tests performed and be advised to discontinue nevirapine as soon as possible. Based on the reports being collected to date, the first 12 weeks of nevirapine therapy are critical, during which intensive clinical and laboratory monitoring, including LFTs, is essential to detect potentially life threatening hepatotoxicity and skin reactions. The optimal frequency of monitoring during the first 12 weeks has not been established. Some experts are recommending clinical and laboratory monitoring more often than once a month, and in particular would include monitoring of LFTs at baseline prior to dose escalation and at 2 weeks post-dose escalation. After the initial 12-week period, weekly clinical and laboratory monitoring should continue throughout nevirapine treatment. One third of the cases of the most serious hepatic events have been reported to occur after the first 12 weeks. Increased AST or ALT levels and/or a history of chronic hepatitis (B or C) are associated with a greater risk of hepatic adverse events. Serious hepatotoxicity has also been reported in HIV uninfected individuals receiving multiple doses of nevirapine in the setting of post-exposure prophylaxis, and unapproved use. If hepatotoxicity occurs, nevirapine should be permanently discontinued and not restarted after recovery. Additional medical information about nevirapine can be obtained by calling the Drug Information Unit at Boehringer Ingelheim/Roxane Laboratories, Inc. (800-542-6257, option #4).

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New in the Bay Area . . .

Positive Partners

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