Completed Research Studies

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CLOSED RESEARCH STUDIES

COMPLETED RESEARCH STUDIES

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1. Antiretroviral Therapy

CC 006: ddI Database
CC 009/CPCRA 002: A prospective, randomized, open-label comparative trial of dideoxyinosine (ddI) versus dideoxycytidine (ddC) in HIV-infected patients who are intolerant of or have failed zidovudine (AZT) therapy.
CC 013: Phase II randomized study to evaluate the safety and efficacy of combination therapy with AZT and Intron A versus AZT alone in patients with asymptomatic to mildly symptomatic HIV infection
CC 014/CPCRA 007: A phase III, randomized, comparative trial of ZDV versus ZDV plus ddI versus ZDV plus ddC in HIV-infected patients
CC 018: A randomized prospective pilot study of immediate versus deferred antiretroviral therapy in asymptomatic patients with HIV disease (ComPACT 1)

2. Prophylaxis and Treatment of Opportunistic Infections

Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia: The San Francisco community prophylaxis trial
CC 001: A randomized, controlled study of clofazimine to prevent Mycobacterium avium Complex infection in HIV disease
CC 007/CPCRA 001: A randomized, prospective study of pyrimethamine therapy for prevention of Toxoplasmic encephalitis in HIV-infected individuals with serologic evidence of latent T. gondii infection
CC 012/CPCRA 005: Prophylaxis against Tuberculosis in patients with HIV infection and suspected latent tuberculosis infection.
CC 015/CPCRA 010: A randomized, prospective, double-blind study comparing fluconazole with placebo for primary and secondary prophylaxis of mucosal candidiasis in HIV-infected women.
CC 016/CPCRA 006: A randomized, comparative, prospective study of daily trimethoprim/ sulfamethoxazole (TMS) and thrice weekly (TMS) for prophylaxis against PCP in HIV-infected patients
CC 019/CPCRA 023: A randomized, comparative, placebo-controlled trial of the safety and efficacy of oral ganciclovir for prophylaxis of cytomegalovirus (CMV) retinal and gastrointestinal mucosal disease in HIV-infected individuals with severe immunosuppression
CC 020/CPCRA 009/ACTG 196: A prospective, randomized, comparative study of the safety and efficacy of clarithromycin versus rifabutin versus the combination of clarithromycin plus ribabutin for the prevention of Mycobacterium avium Complex (MAC) bacterimia or disseminated MAC disease in HIV-infected patients with CD4 lymphocyte counts less than 100 cells/mm3
CC 023/CPCRA 027: An open-label, randomized trial of four treatment regimens for patients with Disseminated Mycobacterium avium Complex disease and acquired immunodeficiency syndrome (AIDS).
CC 024/CPCRA 034/ACTG 277: A randomized, comparative study of daily dapsone and daily atovaquone for prophylaxis against PCP in HIV-infected patients who are intolerant of trimethoprim and/or sulfonamides.
CC 028/CPCRA 036: The treatment of Mycobacterium tuberculosis in HIV infection.

3. New Diagnostic Technologies

CC 026: A pilot study to determine the impact of initiation or change in antiretroviral therapy on HIV plasma RNA load as measured by bDNA assay.
CC 029/CPCRA 036: A randomized study of the clinical effects of initiating or changing antiretroviral therapy based on plasma HIV RNA quantitation compared with initiating or changing therapy based on current clinical practice alone.
CC 037/CPCRA 046: A pilot study of the short-term effects of antiretroviral management based on plasma genotypic antiretroviral resistance testing (GART) compared with antiretroviral management without plasma GART

4. Complications of HIV

CC 005: Phase III double-blind, randomized, cross-over study of high dose megestrol acetate versus placebo in patients with HIV infection.
CC 010: Interferon-alpha therapy for HIV-related immune thrombocytopenic purpura.
CC 011: Study to determine the efficacy of interferon-alpha in the treatment of severe infection of molluscum contagiosum in HIV-infected patients.
CC 021/CPCRA 022: The efficacy of a standardized acupuncture regimen and amitriptyline compared with placebo as a treatment for pain caused by peripheral neuropathy in HIV-infected patients
CC 027: A pilot study of Chinese herbs in HIV-associated pathogen-negative diarrhea.

5. Complementary and Alternative Therapies

CC 021/CPCRA 022: The efficacy of a standardized acupuncture regimen and amitriptyline compared with placebo as a treatment for pain caused by peripheral neuropathy in HIV-infected patients.
CC 027: A pilot study of Chinese herbs in HIV-associated pathogen-negative diarrhea.

6. Observational Cohort Studies

CC 006: ddI Database
CC 008/CPCRA 003: The Observational Database Project.

7. Public Policy

Off-Label drug use in HIV care: ComPACT 2.
Physicians' Attitudes Toward Assisted Suicide in AIDS: A Five-Year Comparison Study.
Nurses' Attitudes Toward Assisted Suicide
Community Patterns of Care for HIV Disease (1996): ComPACT 3
Community Patterns of Care for HIV Disease (1997): ComPACT 4

Trials Descriptions:

Aerosolized pentamidine for prophylaxis against pneumocystis carinii pneumonia: the san francisco community prophylaxis trial
Purpose: To determine the comparative efficacy of three different dosage regimens of aerosolized pentamidine in preventing Pneumocystis carinii pneumonia recurrence (PCP) in patients who have had previous episodes of PCP or who have Kaposi?s sarcoma or AIDS-related complex (specifically oral thrush and/or hairy leukoplakia).

Findings: Aerosolized pentamidine (300 mg every four weeks) was effective for prophylaxis against PCP in patients infected with HIV, according to the dose and schedule of administration. It and zidovudine were well tolerated together and had independent prophylactic benefits.

1990 Leoung G, Feigal D, Montgomery AB, Corkery K, Wardlaw L, Adams M, Busch D, Gordon S, Jacobson M, Volberding PA, Abrams DI and the San Francisco County Community Consortium. Aersolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia. The San Francisco Community Prophylaxis Trial. NEJM 323:769-775.

1989 Leoung G, Wardlaw L, Montgomery AB, Abrams DI, Feigal DW, and the San Francisco County Community Consortium. Aerosol pentamidine for Pneumocystis carinii pneumonia prophylaxis: A 3-arm randomized trial. 5th International Conference on AIDS, Montreal, p. 196.

1989 Leoung G, Wardlaw L, Montgomery AB, Abrams DI, Feigal DW and the San Francisco County Community Consortium. Pneumothorax in patients receiving aerosol pentamidine for Pneumocystis carinii pneumonia. 5th International Conference on AIDS, Montreal, p. 299.

A randomized, controlled study of clofazimine to prevent Mycobacterium avium Complex infection in HIV disease (CC 001)
Purpose: To evaluate the safety and efficacy of clofazimine as prophylaxis for disseminated Mycobacterium avium complex (MAC) infection in patients with HIV disease.

Findings: Thirteen of the 99 eligible patients developed disseminated MAC infection; seven (13.2%) of the 53 patients randomized to receive clofazimine developed disseminated MAC infection compared with 6 (13%) of the 46 patients randomized to no treatment. Kaplan-Meier estimates comparing the probability of remaining free from MAC-related conditions showed no differences between the treated and untreated patients. Clofazimine at a dose of 50 mg/day is well tolerated by patients with HIV disease. Reduction in CD4 lymphocyte count to <50/mm3 is a significant predictor of the development of disseminated infection.

1993Abrams DI, Mitchell TF, Child CC, et al. Clofazimine as prophylaxis for disseminated Mycobacterium avium complex infection in AIDS. Journal of Infectious Disease 167, June 1993.

1992 Abrams DI, Mitchell TF, Child CC, Shiboski S, Mass, M. A Randomized Controlled Study of Clofazimine to Prevent Mycobacterium Avium Complex (MAC) Infection in AIDS: Results of a Pilot Community-based Clinical Trial. Abstract presented at the 8th International Conference on AIDS, Amsterdam, Netherlands.

Phase III double-blind, randomized, cross-over study of high dose megestrol acetate versus placebo in patients with HIV infection (CC 005)
Purpose: To determine the changes in nutritional, immunological and clinical status induced by an 8 week course of 800 mg/day megestrol acetate in ARC patients with weight loss greater than 5% whether or not patients are on AZT.

Findings:

1990 Viteri FE, Kahn J, Mudie H, Conroy A, Abrams DI, Hellerstein M. Evaluation of the effectiveness of megestrol acetate as inducer of appetite, weight gain and improved nutrition in ARC patients. 6th International Conference on AIDS, San Francisco, Vol 3, p.290.

ddI Database (CC 006)
Purpose: To determine the long-term safety and efficacy of ddI therapy by establishing a prospective, community-based database of patients with HIV infection who are receiving ddI through an industry-sponsored expanded access program.

Findings: CD4 response to ddI, as measured by a sustained 10% increase in CD4 count, is positively associated with increased survival and increased opportunistic infection free survival. Whether increases in CD4 count translate directly into improved survival or the ability to have a CD4 increase serves as a marker for a less damaged immune system requires further investigation.

1992 Charlebois E, Abrams D, Brosgart C, Owen W, Campbell J, Mitchell T, Townley D. CD4 Response to ddI is associated with increased survival and increased OI free survival. Abstract presented at the 8th International Conference on AIDS, Amsterdam, Netherlands.

A randomized, prospective study of pyrimethamine therapy for prevention of Toxoplasmic encephalitis in HIV-infected individuals with serologic evidence of latent T. gondii infection (CC 007/CPCRA 001)
Purpose: To evaluate pyrimethamine and clindamycin as prophylactic agents against Toxoplasmic Encephalitis in individuals who are co-infected with HIV and latent T. gondii.

Findings: Prophylaxis for TE with these agents should not be routine, because the agents were poorly tolerated and ineffective.

1994 Jacobson MA; Besch CL; Child C; Hafner R; Matts JP; Muth K; Wentworth DN; Neaton JD; Abrams D; Rimland D; et al. Primary prophylaxis with pyrimethamine for toxoplasmic encephalitis in patients with advanced human immunodeficiency virus disease: results of a randomized trial. Terry Beirn Community Programs for Clinical Research on AIDS. J Infect Dis. 1994 Feb;169(2):384-94.

The Observational Database Project (CC 008/CPCRA 003)
Purpose: To systematically compile information on the progression of HIV infection and the incidence of opportunistic diseases in patients being seen by a large number of community physicians in the United States.

Findings: To be determined. Data set has been used for various analyses.

A prospective, randomized, open-label comparative trial of dideoxyinosine (ddI) versus dideoxycytidine (ddC) in HIV-infected patients who are intolerant of or have failed zidovudine (AZT) therapy (CC 009/CPCRA 002)
Purpose: To evaluate and compare the efficacy and toxicity associated with ddI and ddC in patients with HIV infection who are intolerant of or have failed zidovudine (ZDV) therapy.

Findings: Zalcitabine (ddC) was as efficacious as didanosine (ddI) in delaying disease progression, including death, and suggested to clinicians that zalcitabine can be used as an alternative second-line therapy. This was the pivotal study that resulted in FDA approval for ddC.

1994 Abrams DI, Goldman A, Launer C, Korvick J, Neaton JD, Crane L, Grodesky M, Wakefield KM, Kornegay S, Cohn DL, Harris A, Luskin-Hawk R, Markowitz N, Sampson JH, Thompson M, Deyton L, and the Terry Beirn Community Programs for Clinical Research on AIDS, (CPCRA), NIAID, NIH, Washington, DC. Results of a randomized open-label comparison trial of ddI and ddC in HIV-infected patients who are intolerant of or have failed ZDV therapy: CPCRA 002. NEJM, 330:657-62.

Interferon-alpha therapy for HIV-related immune thrombocytopenic purpura: (CC 010)
Purpose: To evaluate the use of continuous low-dose interferon-alpha therapy for treatment of HIV-related Immune Thrombocytopenic Purpura (HIV-ITP).

Findings: Continuous, low-dose interferon-alpha therapy is an effective and tolerable therapy for HIV-ITP.

1993 Northfelt DW, Charlebois ED, Mirda MI, Child C, Kaplan LD, Abrams DI and the Community Consortium. Continuous low-dose interferon-alpha therapy for HIV-related immune thrombocytopenic purpura. JAIDS, 8:45-50.

1992Northfelt D, Charlebois E, Mirda M, Child C, Kaplan L, Abrams DI and the Community Consortium. Continuous low-dose interferon-alpha therapy for HIV-related immune throbocytopenic purpura (HIV-ITP). 8th International Conference on AIDS, Amsterdam. POB 3742, B214.

Study to determine the efficacy of interferon-alpha in the treatment of severe infection of molluscum contagiosum in HIV-infected patients (CC 011)
Purpose: To evaluate the response and toxicity of subcutaneous alpha-interferon for the treatment of severe HIV-associated molluscum contagiosum.

Findings: Alpha-interferon at 5 mu daily is not an effective therapy for extensive HIV-associated molluscum contagiosum in patients with less than 200/mm3 CD4 cells.

1992 Tappero J, Gorter R, Fila D, Child C, Mitchell T, Mirda M, Shiboski S, Berger T, Abrams D. Alpha interferon for severe HIV-associated molluscum contagiosum. Abstract presented at the 8th International Conference on AIDS, Amsterdam, Netherlands.

Prophylaxis against Tuberculosis in patients with HIV infection and suspected latent tuberculosis infection (CC 012/CPCRA 005)
Purpose: To evaluate the safety and efficacy of a 6-month course of isoniazid in the prevention of clinical tuberculosis in anergic HIV-infected persons who are at high risk for tuberculosis infection.

Findings: The results of this study do not support the use of isoniazid preventive therapy for HIV-infected, anergic individuals in the United States as had been suggested by the CDC other than in specific high-risk situations, such as individuals who are recent close contacts of active cases of tuberculosis.

Phase II randomized study to evaluate the safety and efficacy of combination therapy with AZT and Intron A versus AZT alone in patients with asymptomatic to mildly symptomatic HIV infection (CC 013)
Purpose: To compare, in a community-based therapeutic setting, the safety, tolerance, and efficacy of combination therapy with recombinant interferon-alpha2b (rIFN-alpha2b) and zidovudine (ZDV) to ZDV monotherapy.

Findings: At the doses and schedule used in this study, the combination of ZDV with rIFN-alpha2b was not therapeutically superior to ZDV alone and was less well tolerated. The addition of rIFN-alpha2b to ZDV did not prevent or delay the development of ZDV resistance.

1999 Krown SE; Aeppli D; Balfour HH Jr. Phase II, randomized, open-label, community-based trial to compare the safety and activity of combination therapy with recombinant interferon-alpha2b and zidovudine versus zidovudine alone in patients with asymptomatic to mildly symptomatic HIV infection. HIV Protocol C91-253 Study Team. J Acquir Immune Defic Syndr Hum Retrovirol. 1999 Mar 1;20(3):245-54.

A phase III, randomized, comparative trial of ZDV versus ZDV plus ddI versus ZDV plus ddC in HIV-infected patients (CC 014/CPCRA 007)
Purpose: To compare ZDV alone with ZDV given as combination therapy with either ddI or ddC with respect to efficacy and safety in HIV-infected individuals with CD4+ cell counts of less than or equal to 200 cells/mm3.

Findings: In patients with advanced HIV infection, combination therapy with zidovudine and either didanosine or zalcitabine was studied and found not to be superior to zidovudine therapy alone. However, these combinations may be more effective than zidovudine monotherapy in patients with little or no previous zidovudine therapy.

1996 Saravolatz LD, Winslow DL, Collins G, Hodges JS, Pettinelli C, Stein DS, Markowitz N, Reves R, Loveless MO, Crane L, Thompson M, Abrams DA. Zidovudine alone or in combination with didanosine or zalcitabine in HIV-infected patients with the acquired immune deficiency syndrome or fewer than 200 CD4 cells per cubic millimeter. N Engl J Med, 335(15):1099-1106.

A randomized, prospective, double-blind study comparing fluconazole with placebo for primary and secondary prophylaxis of mucosal candidiasis in HIV-infected women (CC 015/CPCRA 010)
Purpose: To evaluate the efficacy of fluconazole once weekly vs. placebo for the prevention of Candida esophagitis and vaginal/oropharyngeal candidiasis in HIV-infected women, including a comparison of development of clinical resistance.

Findings: Weekly fluconazole (200 mg) seems to be safe and effective in preventing oropharyngeal and vaginal candidiasis. This regimen has a useful role in the management of HIV-infected women who are at risk for recurrent mucosal candidiasis.

1997 Schuman P, Capps L, Peng G, Vazquez J, El-Sadr W, Goldman AI, Alston B, Besch C, Cobb MN, Vaughn A, Thompson MA, Kerkering T, Sobel JD. Weekly fluconazole for the prevention of mucosal candidiasis in women with HIV infection. A randomized, double-blind, placebo-controlled trial." Ann Intern Med, 126(9):689-696.

A randomized, comparative, prospective study of daily trimethoprim/ sulfamethoxazole (TMS) and thrice weekly (TMS) for prophylaxis against PCP in HIV-infected patients (CC 016/CPCRA 006)
Purpose: To compare the safety and efficacy of two dosage regimens (daily and thrice weekly) of trimethoprim/sulfamethoxazole (TMS) in the prevention of Pneumocystis carinii pneumonia (PCP) in high-risk HIV-infected patients.

Findings: Daily TMS is the preferred dose for PCP prophylaxis especially for patients on secondary prophylaxis.

A randomized prospective pilot study of immediate versus deferred antiretroviral therapy in asymptomatic patients with HIV disease (ComPACT 1): (CC 018)
Purpose: To evaluate the feasibility of using a "large, simple trial" (LST) methodology to help determine when patients (pts) with asymptomatic HIV disease should begin anti-HIV therapy.

Findings: Large, simple trials may be useful for answering some strategic questions in the management of patients with HIV infection. Simple, streamlined enrollment, data collection and follow-up procedures can be developed to facilitate conducting large simple trials in primary care settings. The low enrollment in this study was attributed to the difficulty in finding patients who were uncertain about when to begin anti-HIV therapy. Large simple trial methodology should be considered in designing clinical trials to answer patient management questions that affect the health of large numbers of people with HIV disease.

1994 Mitchell T, Abrams DI, Smith RP, Meier P, Peto R. ComPACT 1: A Randomized, Controlled Trial of Immediate vs. Deferred Antiretroviral Therapy in Asymptomatic HIV Infected Individuals. Abstract presented at the 10th International Conference on AIDS, Yokohama, Japan.

1995 Abrams DI, Mitchell TF, Smith RP, Sahl S, Meier P, Peto R. Results of a Pilot Large, Simple Trial to Help Determine When Patients With Asymptomatic HIV Disease Should Begin Anti-HIV Therapy. Abstract presented at the 2nd National Conference on Human Retroviruses and Related Infections. Washington, D.C., Jan.29-Feb.2, 1995.

A randomized, comparative, placebo-controlled trial of the safety and efficacy of oral ganciclovir for prophylaxis of cytomegalovirus (CMV) retinal and gastrointestinal mucosal disease in HIV-infected individuals with severe immunosuppression (CC 019/CPCRA 023)
Purpose: To evaluate the safety and efficacy of oral ganciclovir for prophylaxis against CMV retinal and gastrointestinal mucosal disease in HIV-infected patients with severe immunosuppression.

Findings: Oral ganciclovir in a dose of 3 grams per day did not prevent clinically relevant CMV retinal and gastrointestinal disease in HIV-infected individuals with severe immunosuppression.

1998 Brosgart, C.; Louis, T.A.; Hillman, D.; Craig, C.; Alston, B.; Fisher, E.; Abrams, D.I.; Luskin-Hawk, R.; Sampson, J.; Ward, D.J.; Thompson, M.A.; Torres, R.A.. A randomized, placebo-controlled trial of the safety and efficacy of oral ganciclovir for prophylaxis of cytomegalovirus disease in HIV-infected individuals. AIDS, 123:269-277.

A prospective, randomized, comparative study of the safety and efficacy of clarithromycin versus rifabutin versus the combination of clarithromycin plus ribabutin for the prevention of Mycobacterium avium Complex (MAC) bacterimia or disseminated MAC disease in HIV-infected patients with CD4 lymphocyte counts less than 100 cells/mm3 (CC 020/CPCRA 009/ACTG 196)
Purpose: To compare the efficacy and safety of clarithromycin alone versus rifabutin alone versus clarithromycin plus rifabutin for the prevention or delay of MAC bacteremia or disseminated MAC disease.

Findings: Clarithromycin (CLA) was more effective than rifabutin (RBT) in decreasing the incidence of and delaying time to DMAC. CLA/RBT was more effective than RBT but not CLA alone, but resulted in more treatment discontinuation due to toxicity. No survival differences were noted among the treatment arms. The use of RBT was not associated with selection of resistance to RBT.

The efficacy of a standardized acupuncture regimen and amitriptyline compared with placebo as a treatment for pain caused by peripheral neuropathy in HIV-infected patients (CC 021/CPCRA 022)
Purpose: To evaluate the separate and combined efficacy of a standardized acupuncture regimen and amitriptyline compared with placebo(s) for the relief of pain due to peripheral neuropathy and on the quality of life of HIV-infected patients.

Findings: This is the largest reported randomized, placebo-controlled clinical trial of symptomatic treatment of HIV-related peripheral neuropathy. Neither this standardized acupuncture regimen nor amitriptyline was effective in relieving pain. Additional clinical trials in HIV-associated neuropathies are needed.

1998 Shlay JC, Chaloner K, Max MB, Flaws B, Reichelderfer P, Wentworth D, Hillman S, Brizz B, Cohn DL Acupuncture and amitriptyline for pain due to HIV-related peripheral neuropathy: A randomized controlled trial." JAMA, 280:1590-1595.

An open-label, randomized trial of four treatment regimens for patients with Disseminated Mycobacterium avium Complex disease and acquired immunodeficiency syndrome (AIDS) (CC 023/CPCRA 027)
Purpose: To compare the safety and efficacy of four regimens used to treat disseminated Mycobacterium avium complex (DMAC) disease in patients with acquired immunodeficiency syndrome (AIDS).

Findings: When used in a three-drug regimen for treatment of MAC disease in AIDS patients, clarithromycin 1,000 mg twice daily was associated with early excess mortality compared with clarithromycin 500 mg twice daily. The reasons for the difference in survival are unknown. In treatment of MAC disease in AIDS patients, clarithromycin should be administered at a maximum dose of 500 mg twice daily.

A randomized, comparative study of daily dapsone and daily atovaquone for prophylaxis against PCP in HIV-infected patients who are intolerant of trimethoprim and/or sulfonamides (CC 024/CPCRA 034/ACTG 277)
Purpose: To compare the safety and efficacy of dapsone and atovaquone in the prevention of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients who are at high risk for PCP and who are intolerant of trimethoprim and/or sulfonamides.

Findings: The rates of PCP, survival and tolerance were similar in the atovaquone and dapsone groups. Results of the study support continuation of dapsone among patients already receiving it. However, among patients not already receiving dapsone, atovaquone was significantly better tolerated and may be the preferred initial choice for PCP prophylaxis.

1998 El-Sadr W, Murphy R, Yurik T, Luskin-Hawk R, Cheung T, Balfour H, Eng R, Hooton T, Kerkering T, Schutz M, van der Horst C, Hafner R. Atovaquone compared with dapsone for the prevention of Pneumocystis carinii pneumonia in patients with HIV infection who cannot tolerate trimethoprim, sulfonamides, or both." N Engl J Med, 339:1889-1895.

A pilot study to determine the impact of initiation or change in antiretroviral therapy on HIV plasma RNA load as measured by bDNA assay (CC 026)
Purpose: (1) To assess the impact of initiation or change in antiretroviral therapy on HIV plasma RNA load as measured by bDNA assay during the first 8 weeks after beginning or changing antiretroviral therapy; and (2) To determine the optimal time to obtain bDNA assays to assess if there has been an effect of antiretroviral therapy on HIV plasma RNA load.

Findings: Of those responding to initiation or change in antiretroviral therapy, significant viral load reduction occurred at week 1. Patients with CD4 <50/mm3, often excluded from antiretroviral trials empirically, experienced similar reductions in HIV copy number to patients with higher CD4 counts following changes in antiretroviral therapy.

1996 Follansbee SE, Mitchell TF, Charlebois E, Child C, Pell P, Chernoff D, Abrams D. The Impact of Initiation or Change in Antiretroviral Therapy on HIV Plasma RNA Load as Measured by bDNA Assay. Abstract presented at the 3rd National Conference on Human Retroviruses and Related Infections. Washington, D.C.

A pilot study of Chinese herbs in HIV-associated pathogen-negative diarrhea (CC 027)
Purpose: To assess the effectiveness and safety of a Chinese herbal formulation (Source Qi) in reducing the number of stools per day related to HIV-associated pathogen-negative diarrhea.

Results: There was a reduction in average number of stools per day in each week of treatment (–0.2 to –0.8), except week 1 (+0.1), with improvements in weeks 2-6 approaching or reaching statistical significance (p=0.11 to p=0.0092).

The treatment of Mycobacterium tuberculosis in HIV infection (CC 028/CPCRA 036)
Purpose: To compare the effectiveness of two durations of intermittent therapy for the treatment of TB in HIV- infected individuals.

Findings: The study results provide strong evidence that a four-drug, largely intermittent induction regimen is highly efficacious in the initial treatment of HIV-related pulmonary TB. Both regimens were comparably well tolerated. There was no added benefit noted with the addition of levofloxacin in this population.

1998 El-Sadr W, Perlman DC, Matts JP, Nelson ET, Cohn DL, Salomon N, Olibrice M, Medard F, Chirgwin KD, Mildvan D, Jones BE, Telzak EE, Hafner R. Evaluation of an intensive intermittent induction regimen and duration of short-course treatment for human immunodeficiency virus-related pulmonary tuberculosis." Clin Infect Dis, 26: 1148-1158.

A randomized study of the clinical effects of initiating or changing antiretroviral therapy based on plasma HIV RNA quantitation compared with initiating or changing therapy based on current clinical practice alone (CC 029/CPCRA 036)
Purpose: To determine whether using plasma HIV RNA quantitation, in addition to current clinical practice, in deciding when to initiate or change antiretroviral therapy confers clinical benefit or harm when compared with initiating or changing antiretroviral therapy based on current clinical practice alone.

Findings: Baseline CD4+ was a stronger predictor of disease progression or death than baseline HIV RNA in this population. Both baseline and changes in HIV RNA after 4 months were strong predictors of progression. Additional data is anticipated.

A pilot study of the short-term effects of antiretroviral management based on plasma genotypic antiretroviral resistance testing (GART) compared with antiretroviral management without plasma GART (CC 037/CPCRA 046)
Purpose: To determine the short-term effects of using plasma genotypic antiretroviral resistance testing (GART) in the management of antiretroviral-experienced patients failing on a triple drug regimen that includes a single protease inhibitor (indinavir, saquinavir, ritonavir, or nelfinavir) and two licensed nucleoside reverse transcriptor inhibitors.

Findings: GART with expert interpretation in patients failing triple drug therapy was superior to No-GART as measured by short-term viral load responses. The impact of GART was similar for patients failing their first protease inhibitor and for those who had received multiple protease inhibitors.

Off-Label drug use in HIV care: ComPACT 2
Purpose: (1) To determine the extent to which drugs used to treat HIV disease and its clinical manifestations are prescribed for ?off-label? indications (ie, using drugs to treat conditions other than those listed on the U.S. Food and Drug Administration?s approved drug label; (2) How such off-label use varies by patient characteristics and type of HIV-related medical condition; and (3) the extent to which physicians alter the way they treat HIV-related conditions because of reimbursement problems associated with off-label drug use.

Findings: Off-label drug use in HIV care is common and frequently reflects the community standard of care for many HIV-related medical conditions. The majority (81%) of patients received at least one drug off-label, and almost half (40%) of all reported drug therapy was off-label. Reported denials of reimbursement for off-label drug use are also common, sometimes causing physicians to alter their preferred treatments, though such denials frequently are limited to more costly drugs. Reliance on drug compendia for support for off-label drug use is likely to account for the majority of such uses, though many legitimate off-label uses may not be included in a timely fashion. The development of newer and more costly drugs for treatment of HIV and its medical complications argues for the articulation of an explicit national reimbursement policy for off-label uses of prescription drugs.

1996 Brosgart CL, Mitchell T, Charlebois E, Coleman R, Mehalko S, and Abrams DI. Off-label drug use in HIV disease. JAIDS, 12:56-62.

1994 Brosgart CL, Mitchell T, Charlebois ED, Coleman R, Mandel N, Mehalko S, Abrams DI, Gender differences in off-label drug use in HIV disease. HIV Infection in Women: Setting a new agenda. Washington, DC.

1995 Brosgart C, Mitchell TF, Charlebois E, Coleman R, Mandel N, Mehalko S, Abrams DI. Off-label drug use in HIV disease. 34th International Conference on Antimicrobial Agents in Chemotherapy (ICAAC). Orlando, FL, p.116, #1139.

1994 Brosgart C, Mitchell T, Charlebois E, Coleman R, Mandel N, Mehalko S, Abrams D. Off-label Drug Use in HIV Disease: The Impact of Insurance Reimbursement Practices on Patients' Access to Optimal Therapies. Abstract presented at the American Public Health Association Annual Meeting, Orlando, Florida.

Physicians' Attitudes Toward Assisted Suicide in AIDS: A Five-Year Comparison Study
Purpose: (1) To identify ways in which attitudes and practices towards physician-assisted suicide among physicians working with AIDS patients are changing over time; (2) To determine how frequently physicians are faced with requests, and how frequently they are granting requests, from patients to assist in suicides; and (3) To determine predictors of a physician ever having assisted in an HIV-related suicide.

Findings: A majority (53%) of the physicians sampled have assisted in at least one HIV-related suicide. Passive acceptance of assisted suicide is increasing over time. Inhibitions to assisting in suicides may be lessening; however, there is no policy in place to guide physician actions.

1996 Slome L, Mitchell TF, Moulton Benevedes J, Charlebois E, Mandel N, Townley D, Abrams DI. Physicians' Attitudes Toward Assisted Suicide in AIDS: A Five Year Comparison Study. Abstract presented at the 11th International Conference on AIDS, Vancouver, Canada.

1997 Slome LR, Mitchell TF, Charlebois E, Benevedes JM, Abrams DI. Physician-assisted suicide and patients with human immunodeficiency virus disease. NEJM, 336:417-421.

Nurses' Attitudes Toward Assisted Suicide
Purpose: To provide information about nurses' attitudes toward assisted suicide in AIDS; to determine how frequently nurses are faced with requests from patients to assist them in committing suicide; and to determine predictors of nurses' willingness to assist in an HIV-related suicide.

Findings: A majority of nurses working with AIDS expressed a willingness to assist in a patient's plan to commit suicide by providing information assisting in obtaining medications (if it were legal) or being at the patient's bedside after a lethal dose was self-administered.

1998 Leiser RJ, Mitchell TF, Hahn JA, Slome LR, Abrams DI. Nurses' attitudes and beliefs towards assisted suicide in AIDS. JANAC, 9:26-33.

1998 Leiser R, Mitchell TF, Abrams DI. The Role of Critical Care Nurses in Euthanasia and Assisted Suicide [Letter to the editor] N Engl J Med 1996;335:972-3.

1996 Leiser R, Mitchell TF, Hahn J, Mandel N, Slome L, Townley D, Abrams D. Nurses' Attitudes Toward Assisted Suicide in AIDS. Abstract presented at the 11th International Conference on AIDS, Vancouver, Canada.

Community Patterns of Care for HIV Disease (1996): ComPACT 3
Purpose: To determine if providers experienced in the management of HIV disease preferred different treatment regimens than providers with less experience.

Findings: We found a statistically significant association between the number of HIV-infected patients cared for by the provider and the likelihood that the provider would report prescribing highly active antiretroviral therapy and multidrug combinations for treatment of opportunistic infections. Providers with few HIV-infected patients were substantially less likely to report using new therapeutic regimens or new diagnostic tools. We concluded that the preferred regimens of experienced providers are more likely to be consistent with the latest information on treatment for HIV disease than are those of less experienced providers.

1999 Brosgart CL, Mitchell TF, Coleman RL, Dyner T, Stephenson KE, Abrams DI. Clinical Experience and choice of drug therapy in HIV disease. Clinical Infectious Diseases 1999;28 (January).

1999 Coleman RL, Brosgart CL, Mitchell TF, Dyner T, Gee L, Abrams DI and the Community Consortium. Antiretroviral prescribing patterns following introduction of protease inhibitors. 4th Conference on Retroviruses and Opportunistic Infections, Washington, DC. Abstract 258, p.112.

1997 Mitchell TF, Brosgart CL, Dyner T, Coleman RL, Gee L, Abrams DI and the Community Consortium. Community patterns of care for HIV disease: Does clinical experience make a difference? Abstract presented at the 4th Conference on Retroviruses and Opportunistic Infections, January 22-26, 1997, Washington, DC.

Community Patterns of Care for HIV Disease (1997): ComPACT 4
Purpose: To determine if preferred regimens of drug therapy by physicians experienced in treating HIV disease are more likely to be consistent with 1997 US federal guidelines for prevention of opportunistic infections and use of antiretroviral therapy than regimens used by less experienced physicians

Findings: Experienced physicians and specialists were significantly more likely to recommend care consistent with 1997 US federal guidelines for prevention of opportunistic infections and use of antiretroviral therapy in patients with HIV infection.

1998 Brosgart C, Mitchell TF, Coleman RL, Cotton D, Dyner T, Jones J, Kaplan J, Smith M, Stephenson K, Reingold A, Volberding PA, Bacchetti P, Abrams DI. Community patterns of care for HIV disease: experience makes a difference. Abstract (60779, p. 1143) presented at the 12th World AIDS Conference, Geneva, Switzerland, July 28-July 3, 1998.

1998 Brosgart CL, Mitchell TF, Bacchetti P, Jones J, Kaplan J, Stephenson KE, Coleman RL, Dyner T, Volberding PA, Abrams DI. Community Patterns of Care for HIV Disease: Clinical experience and medical specialty training make a difference. Abstract 0406, presented at the 36th Annual Meeting of the Infectious Disease Society of America, Denver, CO, November 12-15, 1998.

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