Next Meeting: Happy 2000!

The first meeting of the Community Consortium in the new millennium will be held on Wednesday, January 19, 2000 at 6:00 p.m. at the Davies Campus of the California Pacific Medical Center in the auditorium on B level at Castro and Duboce Streets in San Francisco. Refreshments will be served and free parking is available in the lot.

Following brief announcements, AIDS Clinical Grand Rounds will feature a presentation by Jeffrey Klausner, MD, Director for the San Francisco Department of Public Health STD Prevention and Control. Dr. Klausner will discuss "Yin and Yang of STDs and HIV." There have been recent outbreaks of syphilis in certain San Francisco practices as well as the infamous "chat room cluster." It appears that it may now be time to go back to the future to re-evaluate the interaction between sexually transmitted diseases and HIV infection. This promises to be a most informative and provocative session. Please make every effort to attend and to wish your colleagues the best for the New Year! This program is sponsored by the University of California at San Francisco (UCSF) School of Medicine. UCSF is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing medical education for physicians. The office of CME designates this continuing medical education activity on an hour-for-hour basis in Category I of the Physicians Recognition Award of the American Medical Association and the Certificate Program of the California Medical Association. In addition, nurses may obtain CEU credits but must keep a record of their own attendance. One hour of credit is available for this meeting.

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AIDS Clinical Grand Rounds: Issues of Superinfection

The November 1999 AIDS Clinical Grand Rounds featured a presentation by a panel that included Robert M. Grant, MD, MPH, Director of the Gladstone/UCSF Laboratory of Clinical Virology, Michael P. Busch, MD, PhD, Professor of Laboratory Medicine at UCSF and Vice President for Research and Scientific Affairs at the Blood Centers of the Pacific and Blood Systems, Inc., and Eric Delwart, PhD, Assistant Professor of Medicine at UCSF and also at the Blood Centers of the Pacific. Dr. Grant opened the session by pointing out that the question as to whether superinfection with HIV-1 can or does occur remains open. He defined superinfection as "infection with a second strain of HIV-1 after one strain has already established infection in an individual." This is to distinguish superinfection from co-infection in which two strains establish dual infection following concomitant exposure. He outlined that the goal of his presentation would be to review what information is currently available and what is still lacking.

Dr. Grant asked rhetorically who really wants to know if superinfection can occur? Certainly people living with HIV infection are interested as there is a possibility of being exposed to a virus with a more virulent phenotype, i.e., SI. They may also be exposed to resistent viruses through superinfection. Epidemiologists are also curious about the possibility, as superinfection may lead to increased drug resistance in the community. For clinicians, the question is important as superinfection may provide another avenue by which antiretroviral therapy could fail. On the other side of the coin, Dr. Grant pointed out that there are those who really do not want to know because, in some cases, they already believe that they do know. Some believe that superinfection cannot possibly occur. Others say it occurs frequently.

There are a number of biologic mechanisms that may, in fact, act to inhibit superinfection. First among these is viral interference. This concept suggests that the first virion can interfere with replication of subsequent viruses to which a person might be exposed. Infection with the first virus could deplete permissive target cells. Another factor contributing to viral interference would be the HIV-1 induced down regulation of CD4 on infected cells. CD4 is essential for viral entry. The number of CD4 molecules decreases dramatically following HIV infection. This is mediated by nef, vpu and env gp120 proteins. Viral interference may also be mediated by induction of native immunity such as the production of gamma interferon in the infected individual.

In addition to viral interference, anti-HIV-1 immunity is another biologic mechanism that may prevent a second virus from infecting. Dr. Grant described the cell-associated factor discovered by Jay Levy, cytotoxic T-lymphocyte response, and anti-HIV antibody responses as components of this anti-HIV-1 immunity. He suggested, however, that it remains unclear to what extent these immune responses are actually effective.

There have been some animal studies that Dr. Grant went on to review. Most of the animal data are related to infection with attenuated simian immunodeficiency virus (SIV). SIV is related to HIV-2. Monkeys infected with an attenuated SIV are protected against superinfection with more virulent strains. This would sound for all the world like an effective vaccine, however attenuated SIV infection ultimately causes immunodeficiency in infant pigtailed macaques and with time in adults as well. Nevertheless, superinfection with subsequent strains is blocked. Studies in monkeys have suggested that there is, in fact, a window period of superinfection susceptibility. Pigtailed macaques were challenged with genetically distinguishable strains of HIV-2. When the two strains were used to infect concomitantly, two out of two monkeys became dually infected. When strains were given two weeks apart, four of the four animals became dually infected. When the window between infection with the two strains was increased to four weeks, only one of four monkeys became infected with both strains. If infection with the second HIV-1I variant occurred eight to 72 weeks after the initial one, none of eight monkeys could be super-infected. Hence, there appears to be a window within the first two weeks following initial infection after which superinfection is less likely in this animal model. Dr. Grant points out, however, that this is a human-adapted virus that may, in fact, behave differently from a virus in its natural host. Speculating as to why the animals are protected after the four-week window, Dr. Grant postulated that it would be either secondary to viral interference or the development of HIV immunity.

Dr. Grant then discussed the process of viral evolution. In HIV-1 infected subjects, viral evolution occurs at a rate of 1-2 percent per year. The average difference between subjects in a community is 8 percent, for example, as it was in San Francisco in the 1980s. This viral drift increased to 16 percent in the '90s. Such an increase is what would be expected from a genetically drifting viral population. Evidence for the existence of superinfection can be related to recombination. Dr. Grant reports that for a long time, virologists predicted that HIV-1 recombination would not occur. However, clade recombinants do occur. These chimeras have been seen. The presence of such chimeras suggest that recombination occurs. This would then also imply that co-infection occurs. Recombination is most evident in Africa, Asia and Brazil areas where multiple plagues exist simultaneously. Evidence of recombination has also been demonstrated by cell culture experiments where cells are infected with an AZT-resistent strain and a protease-resistent strain. Subsequently, a strain resistant to both AZT and proteases can be isolated. In spite of all this evidence, however, dual sequential infection has not yet been observed.

Effective therapy may, in fact, paradoxically increase susceptibility to superinfection. Treatment might have this effect by decreasing viral interference. If there is less virus and more target cells, the innate viral interference may be down regulated. Treatment may also lead to a decrease in anti-HIV immunity with the production of less antibodies, less CTL and less CAF (per Jay Levy personal communication to Robert Grant). It is known that resistent variants can be transmitted to previously uninfected individuals. Dr. Grant is now questioning whether they can, in fact, be transmitted to those already with a drug-sensitive strain of HIV-1.

In an attempt to answer this important question, a prospective study of sero concordant couples is being developed by Dr. Grant and Ron Stall, PhD, of the UCSF Center for AIDS Prevention Studies. The consortium of investigators will be seeking HIV positive couples under treatment who are practicing unprotected sex. This directly recruits the target population. Exposure is more directly measured. Genital secretions can be obtained. A rate of transmission can be estimated. Two hundred couples are required for a 90 percent power to detect a 2 percent transmission rate.

Dr. Grant next introduced Eric Delwart, PhD, who has newly moved to the Bay Area from New York City, where he worked at the Aaron Diamond Research Center. Dr. Delwart is an Associate Professor of Medicine at UCSF working at the Blood Centers of the Pacific. He began by reviewing a phylogenetic analysis of HIV-1. The outer envelope of the virus evolves the fastest. The envelope gene is sequenced. Sequence variation is analyzed and displayed as a tree. Samples that are closely related to each other end up clustered at the tips of the branches of the tree. This phylogenetic analysis allows one to ascertain whether HIV from two different individuals is similar or not. A superinfecting virus may be present at a very low frequency. Dr. Delwart developed a technique to look at PCR products for genetic linkages. His heteroduplex mobility assay (HMA) can be used as a screening tool to determine if individuals are infected with similar viruses. HMA was used to determine that the virus from the patients infected by the dentist in Florida was, in fact, the same strain as that which infected the dentist. The technique is used to rapidly link up donor-recipient pairs.

Michael Busch, MD, PhD, closed the session by recounting what has been learned in San Francisco by studying transfusion recipients. He described the studies of Ricardo Diaz from the Transfusion Safety Study. Individuals receiving transfusions are exposed to a high dose of intravenous infusion of viruses. The tat HMA is able to document linkages over a longer period of time than the ends HMA as tat is more conserved. Therefore one can use the tat HMA to verify that patients are infected with the same strain because of the same tat sequence shown by heteroduplex analysis. Dr. Diaz noted that in a few hemophiliacs, viruses of multiple different strains could be detected. All of these individuals were repeatedly exposed over a period of years to multiple HIV-1 strains. The analyses were more consistent with the individuals being simultaneously infected at baseline with more than one species as opposed to sequential superinfection.

Another analysis looked at five patients in 1984 who had high risk factors for HIV acquisition prior to their transfusion with HIV+ blood. Transfusion with HIV+ blood usually leads to a 95 percent transmission rate of virus. The investigators looked at tat sequences from the recipients and donor. In four injection drug users, all tat clones in the recipients were related to one another but distinct from the donor. This suggested that the patients had prior infection without any evidence of superinfection. The fifth case was a hemodialysis patient. In this individual, all tat sequences formed heteroduplexes with the donor. This suggested that patient did not have prior HIV infection but acquired it from the donor under study.

The question remains ? if superinfection occurs, does it have clinical relevance? The Transfusion Safety Study looked at three different groups. These included 111 recipients of HIV-infected blood products, 146 HIV-infected donors, and 450 hemophiliacs. These all had highly divergent levels of exposure to multiple strains of viruses. The most rapid rate of progression was seen in the recipient cohort who were also the oldest group. The hemophiliacs, who were the youngest group, had the slowest rate of progression. The HIV+ donors were intermediate in both rate of progression as well as age. Once adjusted for age, there was, in fact, no difference in progression of disease rates.

These fascinating presentations on issues of superinfection were certainly provocative and exposed Consortium providers to important new concepts.

We eagerly await the initiation of the concordant cohort study by Drs. Stall, Grant and collaborators and hope that Consortium providers may be able to enroll participants into this important evaluation.

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Committee Reports

Executive Advisory Board

The next meeting of the Community Consortium Executive Advisory Board will be held on Wednesday, January 26, 2000 at 7:30 a.m. in the Community Consortium conference room. The makeup of the board this year will remain unchanged, with the return of three incumbent members. We are grateful to the continued contributions of Milton Estes, MD, Stephen Follansbee, MD, and Robert Neger, MD, to the Community Consortium Executive Advisory Board.

Tom Mitchell, MPH, Consortium Program Director, described some new and updated publications that the Consortium has been putting together. Probably by now you have appreciated the new format of Synopsis. Thanks to Tom and staff at UC Publications for their work in giving us a new look for the new century. The Community Consortium membership brochure has also been redesigned. Tom has also been working to upgrade the Community Consortium website. The Executive Advisory Board discussed what information Consortium members might want to list to create their own home-pages on the website. We hope to be able to offer this service to all Consortium members sometime early in the new year to help facilitate communications as well as referrals.

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January CME Conference

The next Saturday CME Program, "HIV Into the New Millennium" will take place on Saturday, January 15, 2000 from 8:30 a.m. to 1:00 p.m. at the Davies Campus of California Pacific Medical Center. The program will begin with a discussion of "The Global HIV Epidemic" by Kimberly Page-Shafer, PhD, MPH, Assistant Professor of Medicine at The Center for AIDS Prevention Studies, UCSF. Ronald Stall, PhD, Assistant Professor of Medicine UCSF, will discuss "Challenges Facing HIV Prevention Programs." Susan Buchbinder, MD, Director of the HIV Research Section at the San Francisco Department of Public Health, will describe "Advances in Vaccine Development." "New Diagnostic Technologies" will be discussed by Robert Grant, MD, MPH, of the J. David Gladstone Institute of Virology and Immunology, and William Owen, MD, a highly esteemed Community Consortium practitioner, will describe "New Developments in Antiretroviral Therapies." This promises to be an outstanding program to kick off Consortium educational offerings in the new millennium. We are grateful for generous unrestricted educational grants from Agouron and Smith Kline Beecham, which will assist us in the presentation of the program.

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Patient Fact Sheets

During its recent strategic planning process, the Community Consortium received feedback from clinical sites that identified the need for provision of patient-oriented treatment information. Some clinics and practices expressed frustration at the lack of such materials that they were receiving from reputable sources. Others felt inundated with materials from numerous sources, but did not necessarily have the time to sort through the materials, evaluate, and organize them. Recognizing the importance of having printed materials available for patients on key HIV treatment topics, the Consortium has responded by making a binder of patient fact sheets available to Consortium providers. Under the direction of Greg Szekeres, Recruitment and Information Services Coordinator, the fact sheets have been culled from reputable sources, and have been reviewed by a panel convened by the Consortium in order to evaluate them for appropriateness for distribution to patients. Members of the panel included a Consortium physician, clinical research nurse, and professional and volunteer treatment advocates, among others. Members of the review panel included people with HIV.

The fact sheets are grouped by topic, including antiretrovirals (by class), diagnostic tests, complications, and special topics. In general, the target reading level of the fact sheets is low-to-moderate. The Consortium is in the process of working with a local clinic to make their very low-literacy handouts available as well, and will let you know when these become available. Binders will be made available to interested Consortium providers in the near future.

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Consortium Clinical Trials Open for Enrollment

FIRST

The CPCRA Flexible Initial Retroviral Suppressive Therapies (FIRST) trial is the entry point into the CPCRA menu of strategic antiretroviral trials. FIRST is open to patients who are antiretroviral naive. The question being asked is "What constitutes the best initial regimen for patients beginning antiviral therapies?" Patients will be randomized to one of three arms. One arm will include two nucleoside analogs and a protease inhibitor, a second arm will include two nucleoside analogs and a non-nucleoside reverse transcriptase inhibitor (NNRTI), and a third arm will include at least one nucleoside analog plus an NNRTI and a protease inhibitor. Clinicians who so desire will 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, which is still in development. This will allow us to collect further information on clinical status of the patients.

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Metabolic Study

A perplexing question that baffles all 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 has launched the Metabolic Trial as a substudy of FIRST. The trial is designed to capture information from patients as they enroll onto the CPCRA 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 measure- ments (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.

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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. Among the FIRST family of accompanying clinical trials, the CPCRA Adherence Study is now open for enrollment. 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.

Congratulations to Robert Scott, MD and Paula Pell, Consortium Clinical Research Nurse for enrolling our first adherence patient.

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Protease Inhibitor Progression (PIP)

The revised version of the PIP protocol is now open for enrollment. The study is now more clearly presented as four concurrent companion trials under one master protocol. Two strategies are being evaluated. In patients progressing on a FIRST protease inhibitor-containing regimen, who still have adequate nucleoside analog options from which to choose, the strategy question will be one of intervening with immediate versus differed non-nucleoside reverse transcriptase inhibitor (NNRTI) therapy. Patients will be randomized to begin two protease inhibitors or two protease inhibitors and an NNRTI. The specification of the actual drugs to be used, which was found in the initial version of PIP, has now been removed to allow providers to choose among protease inhibitors and NNRTIs. This study is open to patients progressing either on nelfinavir/ amprenavir or indinavir/ritonavir as their initial protease inhibitor treatments. For those patients progressing with limited options of nucleoside reverse transcriptase inhibitors to employ in their next regimen, the strategic question will be whether one or two protease inhibitors in conjunction with an NNRTI is the best salvage regimen. In these studies of PIP, patients progressing on their initial protease inhibitor regimen will be randomized to switch to one or two protease inhibitors and all patients will receive an NNRTI.

Patients must have a viral load >500 copies/ml. All patients will receive baseline genotypic resistance testing and the results will be returned as soon as available to the provider. There is no CD4 cell restriction. The question of how to best manage patients progressing on their first protease inhibitor-containing regimen is still largely unanswered. A survey of the Science Planning Committee of the CPCRA at the recent September meeting revealed that the options available in PIP correlate with the regimens that providers are offering to their patients off protocol. PIP is one of the first randomized trials looking at the question. In this CPCRA strategic trial, no drugs are being offered to the patient. Once the patient is randomized, the drugs will be obtained through provider prescription. We are quite eager to enroll as many of your progressing patients onto this protocol as possible.

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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 trials have intermediate surrogate marker endpoints, co-enrolling patients onto the 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. Our goal is to enroll all patients on the CPCRA core protocols (FIRST and PIP) onto LTM. In this way, even if and when patients reach the endpoint of a clinical trial, they will continue to be followed for disease progression and survival, adding further information to the large CPCRA database. There are no specific laboratory tests. There are no specific laboratory tests required in the LTM trial. Patients are followed at every four-month intervals and CD4 cell and HIV RNA levels that have been drawn as part of their routine clinical care will be collected and reported. Your Consortium clinical research nurse will be making every effort possible to enroll all of your eligible patients onto long-term monitoring.

In addition to patients participating in CPCRA trials, LTM is also open for two other subsets of patients of interest. If you have an antiretroviral naive patient who is offered enrollment onto the CPCRA FIRST trial but who declines to participate in the randomized trial, we are interested in capturing their outcome information by enrolling them onto LTM. Similarly, antiretroviral naive patients who are choosing to remain antiretroviral naive are also being offered enrollment onto the LTM study. In this way, we will be able to amass a significant amount of standardized information on the cohort of patients who remain antiretroviral naive. Enrollment of these patients onto LTM will also facilitate subsequent enrollment onto other CPCRA intervention clinical trials.

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THC

Fifty-two patients have now been enrolled in the Consortium study of the short-term effects of cannabinoids in patients with HIV infection. Due to a few individuals who dropped out of the trial before the 14-day pharmacokinetic evaluation, our target sample size is now up to 66. However we are well on the way to completing this trial and hope that it will be ready for analysis by mid-2000. The goal of the study is to determine whether there is any pharmacokinetic interaction between cannabinoids (oral or smoked) and protease inhibitors, specifically indinavir and nelfinavir. We are hoping to enroll 32 patients on each of these protease inhibitors. We are almost at our target for nelfinavir. Additional indinavir patients are needed. In addition, the majority of patients enrolled to date have been men. It is important for us to be able to investigate these potential interactions in women as well. Therefore if you have any patients on indinavir or any women who may interested in participating in the trial, please have them call the number below for more information.

During the 25-day in-patient evaluation at the GCRC, patients will be randomized to smoke THC three times daily or to oral marinol three times daily or to marinol placebo. Immune parameters, HIV RNA levels, testosterone levels, body composition and pharmacokinetic measure- ments will be obtained. Patients will receive up to $1,000 for completion of the study. They will also be contributing important information that will help to provide some data for the current debate regarding the safety and medical utility of smoked marijuana. Eligibility criteria include prior history of use of marijuana (none in the month prior to randomization), stable viral load and stable antiretroviral regimen (including either indinavir or nelfinavir as the sole PI) for at least eight weeks. Patients who are tobacco smokers, on methadone maintenance, taking anabolic steroids or who are pregnant will be excluded. If you have patients who are interested in participating in the trial and who appear to meet the eligibility criteria, please have them call 415-502-5705 for further information.

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Just Opened in the Bay Area

Antiretroviral Therapy: Nelfinavir, Hydroxyurea

This study will look to see if increasing the dose of nelfinavir or if adding hydroxyurea to a current nelfinavir-containing combination is more effective in lowering the amount of HIV in the blood to an undetectable level. Patients are assigned by chance to increase their dose of nelfinavir or to add hydroxyurea to their nelfinavir plus d4T or ddI-containing combinations. Patients will know which group they are in. There are six study visits for those patients assigned to increase their dose of nelfinavir and eight study visits for those assigned to add hydroxyurea. Study visits include physical exams and blood tests. HIV viral load tests will be paid for by the study but patients and/or insurance carriers will be responsible for other blood tests. The study lasts 24 weeks. There is no CD4 cell requirement but patients must have an HIV RNA viral load between 50 and 400 copies/mL. Patients must have been taking a combination which includes nelfinavir and d4T or ddI for at least 16 weeks prior to study entry. Active infections, pregnancy and use of hydroxyurea within 16 weeks of study entry is not allowed. Please call Amy Sullivan of the Pacific Horizon Medical Group at (415) 292-5480. (1045)

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Abacavir, Efavirenz, ddI, Hydroxyurea

This study is looking to compare abacavir plus efavirenz plus ddI with or without hydroxyurea for safety, tolerability and effectiveness in lowering the amount of HIV in the blood of patients who have failed their first drug combination. All patients will take abacavir, efavirenz , ddI and are randomized to take hydroxyurea in addition. Those patients assigned to take hydroxyurea are further randomized to start taking hydroxyurea at the beginning of the study or to wait until Week 8 to begin taking hydroxyurea. Study visits are every other month and the study lasts about one year. Patients must have at least 100 CD4 cells and between 400 and 50,000 copies of HIV RNA/mL. Patients must have failed their first drug combination which includes a protease inhibitor, 3TC and d4T or ddI. Failure is defined as the inability to achieve a viral load of less than 400 copies/ml within 16 weeks or to maintain a viral load of less than 400 copies/mL after 16 weeks. Pregnancy or any prior use of abacavir, ddI or any NNRTI is not allowed. Contact Cindy Hopewell, PA-C at the East Bay AIDS Center in Berkeley (510) 204-4109 or Amy Sullivan at Pacific Horizons Medical Group (415) 292-5480. (NZTA4008)

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Thought you'd like to know . . .

ddI Safety Information

On November 11, Bristol-Myers Squibb sent a letter to physicians nationwide which included a revised warning regarding the incidence of fatal and non-fatal pancreatitis in the labeling for Videx®. The Videx® drug label has carried a warning about fatal and non-fatal pancreatitis since the drug was approved in 1991. It was felt that a revised warning was deemed necessary because of deaths due to pancreatitis that have been reported from clinical trials studying the combination of ddI plus d4T (Stavudine, Zerit®) with or without hydroxyurea (DroxiaTM). The deaths occurred in patients who were treatment naive as well as treatment experienced without significant immunosuppression and at the recommended dosages of the antiretrovirals.

The Consortium would like to reiterate the updated information from the warning letter as well as the package insert. ddI should be used with extreme caution and only if clinically indicated in patients with known risk factors including but not limited to: ongoing alcohol abuse, morbid obesity, hypertriphusrhydemia, cholelithiasis, patients undergoing ERCP, patients on other medications known to cause pancreatitis (eg., pentamidine) and medications known or thought to increase exposure to ddI (eg., hydroxyurea, allopurinol). An amylase >1.5 x ULN, lipase >1.5 x ULN, fasting triglyceride >1000 mg/dl and a history of pancreatitis would all be contra-indications to the use of ddI. Serum amylase and lipase levels should be performed at baseline and during use of the drug. It is now important to recognize that in patients who develop clinical pancreatitis, clinicians may want to consider discontinuing both ddI as well as hydroxyurea.

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AIDS Doc Memoir

Congratulations Kate Scannell, MD, of Oakland on the publication of her book, Death of the Good Doctor: Lessons from the Heart of the AIDS Epidemic. Dr. Scannell, a Community Consortium member, was the clinical director of HIV/AIDS services at Fairmount Hospital in San Leandro from 1985-1990.

Structured around the stories of 11 of her most memorable patients, her narrative focuses on the individual and the small acts of kindness that make a difference to the terminally ill. Kate herself is currently battling ovarian cancer, which makes her book all the more poignant. Death of the Good Doctor is published Cleis Press.

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