Synopsis: Winter 2002

Winter 2002

Next Executive Advisory Board Meeting: Wednesday, January 29, 2003

Educational Offerings

Upcoming Conferences

Employment Opportunities

ICAAC Update

Consortium Clinical Trials

Marijuana for Cancer Pain
Marijuana for HIV Neuropathy
SMART
ESPRIT
DHEA
Distant Healing
FIRST
LTM
Observational Cohort Study

Donald I. Abrams, MD, Editor

Next Meeting

The next Community Consortium Executive Advisory Board meeting will be Wednesday, January 29, 2003.

Community Consortium 201 Conference Room, 7:30 a.m.

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Educational Offerings

Post Meeting/Dinner CME Program
Report Back from CROI
Wednesday, February 26, 2003
6:00 - 8:30 p.m.
Davies Campus, CPMC

Saturday CME Program
Resistance
March 22, 2003 - Location to be determined
8:30 a.m. - 1:00 p.m.
Davies Campus, CPMC

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Upcoming Conferences

10th Conference on Retroviruses and Opportunistic Infections (CROI), Hynes Convention Center, Boston
February 10 - 14, 2003
For more info: www.retroconference.org/2003/

2nd IAS Conference on Pathogenesis and Treatment, Paris, France
July 13 -16, 2003. For more information visit: www.ias2003.org

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Employment Opportunities

Community Health Program Manager
The Community Health Program Manager (CHPG), will be responsible for managing, coordinating and evaluating all outreach, recruitment and subject retention activities for the research groups within the UCSF Positive Health Program (PHP). This position will be responsible for supervising other research staff and efforts; coordinating the program-wide human and material resources of PHP and community resources to ensure timely and efficient target accrual goals; and performing other duties as assigned. The PHP is a pioneer in cutting edge research and clinical practices. Interested candidates may fax resumes to Julieann Lewis, MSPH, 415-502-5152.

Assistant or Associate Professor The San Francisco General Hospital Positive Health Program Hematology/Oncology Section of the Department of Medicine of the University of California, San Francisco is seeking applicants at the Assistant or Associate Professor level. The oncology population at SFGH is ethnically and culturally diverse, presenting many challenges as well as opportunities. The applicant should have outstanding clinical and teaching skills for attending in both outpatient and in-patient settings where fellows, house staff and medical students are trained. Board certification in Internal Medicine and Oncology and/or Hematology is required. Please submit current curriculum vitae and three letters of reference to Donald Abrams, M.D., Chair, Search Committee, Ward 84, 995 Potrero Ave, CA 94110. The University is an Equal Opportunity/Affirmative Action Employer. All qualified applicants are encouraged to apply, including minorities and women.

HIV Experienced Physician Sought
To join primary care practice at 45 Castro Street. Associate sought for clinical and hospital practice.
Contact Stephen Knox, M.D. at 415-863-3366

HIV Clinician Medical Writer For HIV InSite (40% -60% Position)
Experienced clinician (M.D., N.P., Pharm.D.) with writing skills sought for keeping up with latest articles and guidelines and synthesizing them for the benefit of other clinicians nationally. On-the-job Web production training provided.
Contact Lawrence Peiperl, M.D. at 415-379-5603

Research Nurse / Part-Time Multicenter AIDS Cohort Study (MACS) Incumbent will conduct physical examinations on research participants with special emphasis on identifying HIV-related signs and symptoms; refer subjects for further medical evaluation as needed; and counsel subjects and answer questions about findings from physical exams, blood test results, their HIV status and safe sex practices. No diagnoses or treatments provided.
REQUIRED SKILLS:
Clinical knowledge and skill sufficient to accurately palpate lymph nodes and abdomen, and recognize abnormalities in skin, oral cavity, rectum, genitalia and fat distribution. Require skill and certification in phlebotomy. Prefer knowledge of the course and treatment of HIV disease.
Contact Max Hechter at 310-825-1073 or email: hechtor@ucla.edu

Physicians & Nurse Practioners - California Dept. of Corrections (Full & Part Time) Fed up with manaaged care hassles? Looking for a 40-hour workweek? Want to practice medicine in a setting where you can truly make a difference? Join a dedicated group providing comprehensive treatment to 550 HIV infected men incarcerated at California Medical facility in Vacaville. On-site hospital, pharmacy, radiology, laboratory, surgery and subspecialist consultative services. Excellent mental health services, transgender program and nationally recognized hospice/palliative care treatment. Competitive salary and superb pension and benefits. Forty-five minutes from the East Bay.
Contact Joseph Bick, M.D., Director, at 707-453-7008.

Introduction

As the New Year approaches, the Community Consortium readies to begin our 18th year of existence as an organization striving to serve Bay Area HIV care providers by providing educational programs, research opportunities and a unified voice to advocate on behalf of us and our patients in the sociopolitical arena. We thank you for your support over the years and hope we can continue to count on it in 2003! Our first offering of the year will be the "Report Back from the 10th Conference on Retroviruses and Opportunistic Infections" dinner meeting to be held Wednesday, February 26, 2003, returning to the Davies Campus of California Pacific Medical Center. Invitations will be sent to all Consortium members so that you may RSVP and let us know that you are coming. Information is also available on our new and improved web page: www.communityconsortium.org. Stephen Follansbee, M.D., Director of HIV Services, Kaiser Permanente San Francisco, and Consortium Vice-Chair, will moderate the program. Included on the panel will be Steven Deeks, M.D., Associate Professor of Medicine at the UCSF Positive Health Program at SFGH, and Meg Newman, M.D., Associate Professor of Medicine at UCSF Positive Health Program at SFGH. Come join us in this first Consortium CME program of the New Year! Attendees will be eligible for 2.0 hours of Category 1 CME credit. California Pacific Medical Center is accredited by the California Medical Association to provide continuing medical education activities to physicians. The CPMC Office of Continuing Medical Education certifies that this continuing medical education activity meets the criteria for 2.0 hours of category 1 of the physicians' recognition award of the AMA and the certification program of the California Medical Association.

Please Rejoin!
As the Community Consortium begins our 18th year of fighting the battle against HIV, we once again seek your support to assist us in the work that we do for HIV care providers in the Bay Area and beyond. We appreciate the fact that there are many competing demands and requests for our ever shrinking resources, but we hope you will continue to be able to renew your Consortium membership to allow us to accomplish our goals and better serve your needs. We need to keep an accurate updated list of individuals interested in learning of Community Consortium activities; following our research endeavors and gleaning whatever gossipy tidbits Synopsis may otherwise have to offer. To this end, we ask for you to send back a membership application with the nominal fee that helps us with the printing and mailing of Synopsis and some of our other educational brochure materials. In addition, we have always claimed that our strength is in our numbers. When the Consortium takes a stance on an issue and, for example, writes a letter to an elected official, it behooves us to say that we are an organization of XXX HIV care providers in the San Francisco Bay Area. Obviously, the larger the number that fills in the blank, the more clout we have. The Community Consortium has much to be proud of. We have served as an ongoing model for community based clinical trials and provider education in the country. We intend to continue our efforts for as long as they are necessary. We do need and appreciate your support! Please take a moment now to fill out and send back the enclosed membership application. In the past we initiated our membership drives in July, but in an effort to get on a calendar year schedule we have postponed this pitch until now! So just think - you've already had six months of free Consortium membership! We know there are more providers out there who would be interested in our programs, so feel free to copy your form and share with colleagues! Thanks again for your continued support!

ICAAC Update

The Consortium hosted a highly successful "Report Back from ICAAC" on October 16, 2002, updating providers on the latest information presented at the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy that had just been held in San Diego. Emcee of the event was Steve O'Brien, M.D., of the East Bay AIDS Center, who was so witty and charming that reports abound suggesting that he may be asked to host the next Academy Awards gala! Steve was not only a clever, witty moderator, but also filled in at the last moment for an indisposed panelist and provided those in attendance with just the sort of juicy pearls that one hopes to glean from a post-conference update. Joining Steve on the panel was Ian McNicholl, Pharm.D., from the UCSF Positive Health Program at SFGH, and Paul A. Volberding M.D., UCSF Professor and Chief of Medicine at the San Francisco Veterans Affairs Medical Center. Steve opened the session with some discussion of the growing problem of hepatitis coinfection in patients with HIV. Serial data from a Boston cohort reveals an accelerating frequency of liver-related deaths, rising from 11% in 1991 to 14% in 1996 and up to 50% of all deaths in 1998. Coinfection causes a 30% faster rate of progression to cirrhosis than in people not infected with hepatitis C virus. He reviewed the data presented on the study comparing pegylated alpha interferon (PegIF, Pegasys) with ribavirin to alpha interferon/ribavirin, presented by Peronne et al. Ribavirin was dosed at 800 mg daily. Four hundred sixteen coinfected patients were randomized to those two treatment arms. At baseline, median CD4+ cell count was 515/mm3 and 60% of the subjects had undetectable HIV RNA. At the end of the study, 44% of those receiving PegIF/RBV had undetectable HCV levels compared to 27% in the aIF/RBV cohort. The responses to PegIF/RBV were lower (19%) in patients with HCV genotypes 1 and 4 than in genotypes 2 and 3 (57%). Steve summarized by saying PegIF may be better than non-pegylated versions of the drug. He remarked that some patients might benefit from treatment (decreased rates of cirrhosis and liver deaths) even without achieving a complete viral response. He reminded providers not to use ribavirin in patients receiving ddI as this may increase mitochondrial toxicity leading to pancreatitis and steatosis. Finally, he urged all in attendance to remember to vaccinate vulnerable HCV patients against HAV and HBV to minimize further hepatic insult. In response to an audience question, Steve pointed out that although 21% of EBAC patients are coinfected with HCV, he believes only 4 had been treated with IF/RBV. A quick poll of the audience confirmed only scattered use of the combination therapy in coinfected patients to date. Ian McNicholl, Pharm.D., BCPS, provided an update on the T-20 TORO trials presented at ICAAC by San Francisco's own Jay Lalezari, M.D. The Roche/Trimeris drug, T-20 (enfuvirtide) was added to optimal background (OB) therapy and compared to optimal background therapy alone in TORO-1, a study designed for heavily pre-treated individuals who had previously received at least one NRTI, one NNRTI and 2 PIs for at least six months of prior HAART. At entry, viral load had to be > 5000 copies/mL. Over 500 people were evaluated, 92% men, with a median age of 42 years. The median CD4+ cell count at baseline was ~ 80/mm3 with a viral load of 5.2 log10. Fifty percent had HIV RNA levels > 100,000 copies/mL. Optimized background therapy generally consisted of 3-5 antiretroviral drugs. At week 24, the OB group had a -0.76 log decline in HIV RNA compared with a -1.7 log decline in the group receiving T-20. Subgroup analyses revealed no effect of baseline gender, CD4+ cell count or HIV RNA level on response. The most common adverse reactions were injection site reactions, which were common but only led to drug discontinuation in less than 3% of the recipients. Dr. McNicholl then reviewed an analysis of enfurvitide tolerability garnered from a review of three Phase II open-label, non-randomized, uncontrolled trials involving 168 patients. In general, the injection site reactions, although frequent, were mild to moderate and not generally dose-limiting. Other common clinical adverse drug reactions included diarrhea, nausea, fatigue, headache and infection. The infection may have been related to the Grade 3/4 neutropenia that was noted in 11-15%. Elevated GGT was the only other Grade 3/4 laboratory adverse event noted. T-1249, another fusion inhibitor, has a longer half-life (6-13 hours) than T-20 so twice daily dosing is not necessary. It also appears to be effective against T-20 resistant viruses. In the T-1249-101 trial, fusion inhibitor naïve patients with HIV RNA levels between 5000 and 500,000 copies/mL were enrolled. In this dose-ranging trial, heavily pretreated patients (10 prior antiretrovirals) with advanced HIV (median CD4=57/ mm3, viral load 204,000 copies/mL) received 14 days of T-1249 therapy. HIV RNA decreased by an average of -1.25 log in the 100mg group and -1.9 log in the 150 or 200 mg groups. CD4+ cells increased by 20-70 cells/mm3 in patients receiving from 25 to 200 mg of drug. Injection site reactions occurred in 57% of those receiving treatment. Headaches and fever were both reported by 14% and 10% were noted to develop oral candidiasis. There were only three treatment related serious adverse experiences reported: neutropenia, injection site reaction and hypersensitivity. Dr. McNicholl explained that 200mg/day might be the most effective as well as the maximal feasible dose as it requires 4 separate one ml injections daily since the drug concentration is 50mg/ml. Paul Volberding, M.D., then updated the attendees on the status of the Bristol- Myers Squibb protease inhibitor, atazanavir, which is moving along the drug development pathway. The drug is a once-daily azapeptide PI that will be taken as 2 capsules. Phase II efficacy trials in naïve and experienced patients have been completed. The signature mutation of atazanavir is I50Lwhich may be associated with increased in vitro sensitivity to other PIs. Hyperlipidemia has not been seen in treated patients. Results of head-to-head comparisons of atazanavir and nelfinavir were reported in Barcelona. Dr. Volberding reviewed the trial comparing the efficacy of ATV with efavirenz in treatment-naïve patients. The trial was a multicenter, randomized, double-blind, double-dummy study in treatment-naïve patients with HIV RNA > 2000 copies/mL and CD4+ cell counts > 100/mm3. Four hundred four participants received combivir/ATV 400mg qd and EFV placebo while 401 received CMB/EFV 600mg qd and ATV placebo. Only 109 North American subjects were enrolled with many patients coming from resource limited settings. The level of adherence is felt to have been quite variable, especially in Europe, but no data on overall adherence was collected. Paul reviewed some caveats of the trial up front that need to be understood in interpretation of the results. There was a conservative definition of treatment failure, which included rebounding patients who had 2 sequential HIV RNA readings greater than 50 copies/mL or one greater than the level of quantification and then discontinued. Discontinuation of therapy for any reason constituted a treatment failure. No switch or dose reduction in the nucleosides was allowed; hence any intolerance to nucleosides constituted a failure. Overall, one-third of the participants were women, two-thirds were non-white and the average age was 34 years. Median CD4+ cell count was in the 280/mm3 range with an HIV RNA of 4.89 log10. The virologic response, using multiple analyses, was essentially the same for ATV and EFV at 48 weeks. Of note, only about a third of each group achieved HIV RNA levels < 50 copies/mL, a finding that Paul attributes to the strict definition of failure and the inability to adjust the nucleosides. CD4+ cells increased by 176 cells/mm3 in the ATV arm and 160 cells/mm3 in the EFV group. Twenty-five of the 404 ATV treated subjects had a genotypable virus at week 24 or beyond. The signature I50L mutation was only present in 4; the majority failed with nucleoside resistance mutations. Adverse events were reported in ~43% of each group with jaundice (5%) and scleral icterus (1%) being more commonly reported in the ATV group where 33% had increased total bilirubin to Grade 3/4 levels. ATV patients showed none of the hyperlipidemia seen in the EFV cohort. Dr. O'Brien next presented a potpourri of interesting posters. In one study, 197 naïve patients started HAART at either a CD4+ cell count of > 350/mm3 or a count between 200-350/mm3. In the group starting later there were more injection drug users and a higher frequency of HCV coinfection. At one year, 89% of both groups had undetectable HIV RNA levels. Three posters looked at boosted PI regimens. In one study, 58 individuals who had failed NNRTI therapy were randomized open-label to NLF vs. IDV/r (800/100). At 24 weeks 88% of the boosted group had HIV RNA < 50 copies/mL compared with 64% of the NLF group. Another open-label study randomized 306 patients to IDV/r (800/100) or SQV/r (1000/100) for 48 weeks. The regimens were equipotent with only ~19% failing. However, 48% of the IDV/r group changed therapy compared to only 28% of the SQV/r group; 64% of the changes due to adverse events. Finally, in a trial of 152 naïve patients reported by Montaner, 59% of the group randomized to EFV attained < 400 copies/mL at week 48 compared to 73% receiving SQV/r (1600/100) (statistically significant using an intent-to-treat analysis). Steve summarized a tenofovir intensification trial where patients with a median viral load of 2340 copies/mL intensified their regimen with tenofovir. At 48 weeks, 41% had < 400 copies/mL and 18% had < 50 copies/mL. The lower the baseline viral load, the higher the likelihood of becoming undetectable with intensification. The presence of pre-existing TAMs also decreased the chance of success. d4T bid and d4T XR were virologically equivalent at 48 weeks as were 3TC bid or 3TC qd when dosed with AZT/EFV. Ian McNicholl summarized new data on emtricitabine (FTC). A randomized, double-blind, double dummy 24 week trial evaluated enteric ddI/EFV and either d4T bid or FTC (3 pills) in antiviral naïve patients with HIV RNA > 5000 copies/mL. Five hundred seventy-one patients were enrolled at 92 sites. After 42 weeks of follow-up, all efficacy parameters favored the FTC arm. There were fewer diarrheas and less elevation of amylase seen in the FTC arm. He also reported on the NEAT study of the amprenavir pro-drug, GW433,908. In this randomized, Phase 3 48 week trial, 250 antiretroviral naïve subjects with HIV RNA > 5000 copies/mL were randomized to 908 1400 mg bid vs. NLF 1250 mg bid in combination with ABC/3TC. Baseline CD4+ cell count was 213/mm3 and HIV RNA was 4.83 log 10. Overall, 908 was superior to NLF in achieving HIV RNA levels < 400 and < 50, with a marked benefit in the nearly 50% of subjects enrolled with HIV RNA levels > 100,000 copies/mL. No significant changes in cholesterol or triglycerides were noted. Diarrhea was reported as an adverse event significantly less often (5%) in the 908 group than the NLF recipients (17%, p=0.003). The pro-drug will markedly reduce the amprenavir pill burden. Paul Volberding felt that one of the more interesting pieces of news emerging from ICAAC was the announcement that Jay Levy's elusive CD8+ antiviral factor (CAF) may have been discovered by David Ho et al. Paul, who worked in Jay Levy's lab during his oncology fellowship, outlined the role of the CD8+ cells in HIV infection. Although CD8+ cells are not infected with HIV since they have little if any CD4, they clearly have a role in the infection. Jay Levy's pioneering work has shown that CD8+ cells secrete a soluble factor that inhibits HIV in CD4+ cells exposed, even across a membrane. If a culture is depleted of the CD8+ cells, viral replication occurs with much higher HIV titers. Beta-chemokines are thought to explain only some of this effect. Jay Levy has been searching for the nature of the CAF for a long time, but has been unable to identify it despite heroic efforts. Paul reported that coincident with ICAAC, David Ho's group from the Aaron Diamond Center in New York published on line their finding that the CAF is alpha-defensins 1,2 and 3. These are proteins that are involved in protecting against bacteria, fungi and enveloped viruses as part of the primitive host defense system. Using a new proteomics machine, the Ho team found the defensins in the CD8+ cells of HIV non-progressors. When the defensins were removed, the CD8+ cells failed to control the HIV replication. Paul reported that Tony Fauci's group at the NIAID suggests a similar role for perforins. Jay Levy, however, says he's looked for both alpha defensins and perforins and finds no role of either in his system. The bottom line is that this story is likely not over yet and there may ultimately be a therapeutic role for defensins and/or perforins once it is all resolved. Steve returned with more clinical pearls to share. With regard to lipoatrophy, one study suggested that switching AZT or ABC for d4T led to improved limb fat at 48 weeks. Moyle from the UK gave 12 patients with lipoatrophy recombinant human growth hormone for 24 weeks and noted a subjective improvement in lipoatrophy and measurable improvement in lean body mass. Patients with prior CD4+ nadirs of less than 50 cells/mm3 are more likely to have significant declines during a treatment interruption. Data from the Kaiser cohort reported by Dan Klein from Hayward finds that appendicitis is 4 times more common in HIV positive men than in HIV negative controls. A French analysis of deaths in the year 2000 among 65,000 HIV patients revealed a total of 975. In the group who died, 70% had CD4+ cells < 50/mm3 and 87% had detectable HIV RNA levels. The single most common cause of death was an OI in 27%. An additional 20% died of other AIDS complications, not OI-related. Fifty-three percent of the deaths were non-AIDS related. One third of the patients coinfected with HIV and HCV died of HCV. Another report enumerated the risk factors for death as being thrombocytopenia, glucose > 120, hemoglobin < 12, VL > 10,000 copies/mL, LDH > 700, HCV positive, CD4+ < 200/mm3 and age > 39. A study from the University of Alabama Birmingham group enumerated costs of caring for patients with HIV in terms of those with CD4+ cells > 200, 50-200 and < 50/mm3. Antiretroviral drugs constituted the main cost in all groups although non-AIDS drugs were more of an expense in the group with the lowest CD4+ cell counts. Hospitalization costs were negligible except at the lowest CD4+ strata. Physicians' fees were hardly a blip on the cost radar screen! Finally, Dr. O'Brien reviewed a vaccine update presentation by Larry Corey, M.D., from Seattle. Vaccines are important because the magnitude of the HIV pandemic has been constantly underestimated. They are difficult to develop because there are no markers of prevention and there are poor economic incentives compared to drugs. He suggested that vaccines to prevent HIV infection are not on the horizon and that the current focus is on modifying viral replication via increased immunity. Ian McNicholl concluded the evening's Report Back with a discussion of virtual phenotype. In a virtual phenotype (VP), the viral genotype is run through a computer which then uses the stored database to predict the phenotype as compared to doing the phenotypic (P) assay on the patient's actual virus. Two hundred seventy-six patients with HIV RNA > 1000 copies/mL on HAART were randomized to receive VP vs.. P. The median CD4+ cell count at baseline was ~347/mm3 with an HIV RNA of approximately 4.0 log10. At 24 weeks, HIV RNA was reduced by -0.92 log when a salvage regimen was devised using the P compared to -1.3 log with the VP (p=0.003). The primary endpoint of the study, however, was the percent with HIV RNA < 400 copies/mL, which was 46% in the P and 56% in the VP (p=0.1). Dr. McNicholl remarked that these results suggest that the two methods are comparable and could be used interchangeably. The VP, however, is cheaper, faster and more widely available. The panel's informative presentation was greatly appreciated by all in attendance. The Community Consortium is grateful to our friends and colleagues at Abbott Laboratories, Agouron, Bristol-Myers Squibb, BTG Pharmaceuticals, GlaxoSmithKline, Gilead, Merck & Co., Serono, and ViroLogic, Inc. for their support of this educational program.

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Clinical Trials Update

ESPRIT

The Community Consortium has enrolled only 14 of our target goal of 50 subjects onto ESPRIT, an international 25-nation 4000 patient trial. The Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT) study is now accessible for interested participants at the Positive Health Program Research Clinic at 18th and Folsom. A slight divergence from our overall philosophy of taking our clinical trials to the site where participants receive their primary health care was deemed necessary in order to meet our contracted accrual goal. If you know of individuals who may be interested in this IL-2 trial who are not currently cared for in a Community Consortium clinician investigator's practice, they can now be referred for participation in the trial to the PHP research clinic. Donald Abrams, M.D., and the clinic staff will oversee the patients from the trial perspective. Patients randomized to receive IL-2 will have 24/7 access to the study clinicians in case of questions and/or for management of adverse reactions. In ESPRIT, participants on HAART are randomized to receive either interleukin-2 7.5 MIU subcutaneously twice a day for 5 days every 8 weeks or no interleukin-2. ESPRIT data collection only occurs every 4 months. The study is designed to assess clinical benefit of IL-2 and hence will follow 4000 patients worldwide for disease progression events for a minimum of five years. Participants randomized to the IL-2 arm will repeat cycles of therapy to maintain their CD4+ cell counts at twice baseline or above 1000 cells/mm3. If you have patients who may be interested in ESPRIT, please call David MacLeod, R.N., at 415-476-9554, ext 16.

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DHEA

We have now enrolled 31 of the target 40 patients onto the study of dehydroepiandrosterone (DHEA) to investigate how it impacts on latent HIV 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 seeks 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 are 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 receive DHEA for an additional 12 weeks, for a total study duration of 24 weeks. Study participants are seen as outpatients at the General Clinical Research Center. They have one screening and one baseline visit prior to starting study drugs. At the baseline visit, they 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 are obtained, and quality of life assessments are completed. Participants are randomized to either DHEA or placebo for 12 weeks. Follow-up study visits occur at weeks 2, 4, 6, and 12. Visits during the ensuing 12-week open label DHEA treatment 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) 476-9554, ext. 15.

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Distant Healing

The Consortium is continuing to assist our collaborators at CPMC to complete enrollment of the study of distant healing in HIV. The study is enrolled in cohorts of 15 patients. In each cohort, five patients are randomized to receive DH attempts by professional "healers", five patients receive DH attempts by nurses, and five patients receive no special intervention beyond usual medical treatments. The study is double-blind so that neither patients nor their doctors nor the researchers 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. Eligible individuals must be 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 are conducted at the California Pacific Medical Center site. Participants return after their baseline evaluation to this study site at six months and one year for follow-up questionnaires and blood work. The research assistant will extract the remainder of the data from clinic charts. We are especially eager to complete enrollment of the remaining participants in this trial in memory of the late principal investigator, Elisabeth Targ, M.D.. Please direct any questions regarding this study to Paul Couey at (415) 476-9554 x 15.

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FIRST

The CPCRA's Flexible Initial Retroviral Suppressive Therapies (FIRST) trial, the entry point into the CPCRA's menu of strategic antiretroviral studies for naïve patients, closed to further enrollment on January 13, 2002. The study surpassed its target enrollment and will now continue to follow subjects already accrued. Stay tuned for further information to be made available as the study matures.

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Marijuana for Cancer Pain

Venturing for the first time into non-HIV territory, the Community Consortium has launched a new study investigating the effects of smoked marijauna in patients with cancer pain secondary to bone metastases from breast or prostate cancer. The study, supported by funding from the University of California San Diego Center for Medicinal Cannabis Research (www.cmcr.ucsd.edu) investigates the interaction of smoked marijuana and oral morphine sulfate. Eligible patients must have persistent cancer pain despite an MS-Contin containing regimen. The study will evaluate the potential synergistic analgesic affect of the cannabis and opioids, whether cannabis decreases opioid side effects and the pharmacokinetic interaction between smoked marijuana and oral morphine sulfate. Initially we will conduct a 16 patient pilot followed by a randomized controlled study. If you know of patients who may be interested in participating in this trial, please have them contact Hector Vizoso, R.N., at 415-476-9554, ext. 21.

Marijuana for HIV Neuropathy

Our pilot trial of smoked marijuana in patients with HIV-related peripheral neuropathy has now enrolled fifteen of its 16 target subjects. The 9-day in-patient study is conducted in the General Clinical Research Unit at San Francisco General Hospital. Eligible subjects must have neuropathy with persistent measurable pain confirmed by Cheryl Jay, M.D., our neurologist co-investigator. Subjects also undergo an experimental pain model using heat and capsaicin that will hopefully provide increased information on the mechanism of cannabinoid-induced anesthesia. It is expected that the results of this small pilot will allow us to calculate the sample size for a follow-up randomized placebo-controlled trial. Participants must have smoked marijuana at least six times previously in their life and need to discontinue marijuana smoking for at least 30 days prior to enrollment. If you have patients with neuropathy who may be interested in participating in the upcoming placebo-controlled trial, please contact Hector Vizoso, R.N., at 415-476-9554, ext. 21.

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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, 3,180 patients are being followed on the LTM nationwide, including 153 from our site.

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Observational Cohort Study

The Consortium continues to follow nearly 900 subjects enrolled on the Observational Cohort Study. Funded by the Universitywide AIDS Research Program (UARP), the OCS has focused on an analysis of how Bay Area patients with HIV are treated compared to the DHHS published treatment guidelines. The OCS has recently pooled data with the SCOPE cohort of Steven Deeks, M.D., at San Francisco General Hospital, leading to increased power to make observations. We are delighted to report that we have successfully competed for continued funding to support the analyses of the Observational Cohort Study and are thankful to the University wide AIDS Research Program (UARP) for their continued support.

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SMART

A special thank you to Harry Lampiris, M.D., VAMC, and Pierre Crouch, R.N., for helping us reach our first year target of 50 patients onto the Strategies for Management of Antiretroviral Therapy (SMART) study. Patient # 50 was randomized on December 3, 2002. The trial is open to subjects with CD4+ cell counts greater than 350/mm3 currently on or naïve to antiretroviral therapy. There are two strategies to which patients are randomized to in the study. In the Viral Suppression (VS) arm the goal is to use antiretroviral therapy to maintain viral load as low as possible throughout the anticipated six to nine years of study follow-up. In the Drug Conservation (DC) strategy arm, antiretroviral therapy is stopped (or deferred) until the CD4+ cell count drops to less than 250/mm3 at which time episodic antiretroviral therapy is initiated to increase the CD4+ cell count to greater than 350/mm3. Three thousand participants are required per arm for a total target sample size of 6000. A participant randomized to the VS group who is already receiving antiretroviral therapy will, if fully suppressed, just continue their current regimen. If there is a detectable HIV RNA level, the regimen should be modified to achieve viral suppression. Naïve individuals not on therapy at the time of randomization to the VS arm will begin HIV therapy - again with the goal of maintaining the HIV RNA level as low as possible for as long as possible. For participants randomized to the DC arm who are on HAART at the time of randomization, antiretroviral therapy will be stopped until the CD4+ cell count drops under 250/mm3, verified on repeat testing. Once that threshold is reached, the provider is instructed to "hit hard" to restore the CD4+ cell count to greater than 350/mm3. For naïve patients randomized to the DC arm, HAART is deferred until the CD4+ cell count drops to less than 250/mm3. The goal of the DC arm is to conserve anti-HIV agents until the risk of HIV disease increases. Clinical judgment prevails over the protocol guidelines throughout, such that if a patient becomes symptomatic or if the provider prefers to use, for example, a cutoff of less than 15% CD4+ cells, therapy can be initiated. Once treatment restores CD4+ cell counts back to greater than 350/mm3 (verified on at least two measurements), it is then discontinued again until the 250/mm3 CD4+ cell threshold is reached. Hence individuals randomized into the DC arm will oscillate with CD4+ cell counts held roughly between 250-350/mm3, a zone with very low risk of HIV disease progression during the course of the entire study. Once a subject is enrolled on the SMART study, follow-up visits will be scheduled at months one and two, and then every two months in the first year. Subsequent visits are every four months until the end of the trial. It is anticipated that the VS group will have a CD4+ cell advantage for the first few years of the study. Whether that advantage persists over the ensuing years and which strategy provides a clinical benefit are the questions being asked in the trial. With a multi-year 6000 participant trial, it would be silly not to ask additional questions. Hence a number of substudies are being conducted as part of SMART. The Community Consortium is participating in a quality of life/healthcare utilization substudy where the VS and DC groups are compared for QOL and symptom severity as well as healthcare utilization and resulting costs. In addition, Consortium participants may participate in an HIV transmission risk behavior substudy. Here subjects complete a confidential risk behavior self-report describing condom use and needle-sharing behavior. In addition, biological testing for subjects in the substudy include syphilis serology and urine testing for Neisseria gonorrhea and Chlamydia trachomatis. If you or your patients might be interested in participating in the SMART study, please contact Pierre Crouch, R.N., at (415) 476-9554, ext. 23, for further information.

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UCSF | Positive Health Program

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tel (415) 476-9554 | fax (415) 476-6948