Although the public s awareness of infection with the

Transcription

1 Results of a Physician Survey on Ordering Viral Load Testing Opportunity for Laboratory Consultation Louise K. Hofherr, PhD; Diane P. Francis, MPH, MT(ASCP); J. Rex Astles, PhD; William O. Schalla, MS Objective. To profile physicians practices, utilization, and understanding of human immunodeficiency virus type 1 RNA (viral load) testing and the laboratory s role in this testing. Design. Cross sectional study using a 34-item self-report survey mailed to physicians identified as requesting viral load testing, with follow-up mailings to nonresponders. Participants. A sampling of US physicians specializing in infectious diseases, internal medicine, and family practice associated with high, medium, and low human immunodeficiency virus/acquired immunodeficiency syndrome incidence areas. Results. Most respondents using viral load results were infectious diseases specialists practicing in urban areas. The reasons most frequently given for requesting viral load testing were (1) to assist in patient follow-up or monitoring (75.4%), and (2) to initiate/guide therapy (62.5%). Respondents indicated that the interpretation and use of viral load results presented difficulty in the areas of patient treatment and in determining what change from baseline was clinically significant. Few respondents used the testing laboratory pathologist as a resource for interpreting viral load test results. Conclusions. Our study indicates that physicians have questions about (1) the meaning of viral load tests, (2) how often to monitor the viral load, and (3) what change from baseline of the viral load is significant. Few physicians avail themselves of the expertise available in the laboratory for testing viral loads and interpreting such results. (Arch Pathol Lab Med. 23;127:446 45) Although the public s awareness of infection with the human immunodeficiency virus type 1 (HIV-1) infection is not as widespread as in the earlier years of the epidemic, acquired immunodeficiency syndrome (AIDS) remains a serious public health concern. In the United States from July 1999 through June 2, new cases of AIDS were reported, and among the 34 states reporting HIV-1 infection, cases were reported. 1 As of September 2, an estimated persons were living with AIDS in the United States. 2 We currently have a better knowledge of the infectious process and treatment of the disease, including increased information about pathogenesis, viral replication, and viral burden in infected individuals. 3 9 This has resulted in more sophisticated laboratory tests that can enumerate the Accepted for publication November 4, 22. From the Laboratory Assurance Program, Graduate School of Public Health, College of Health and Human Services, San Diego State University, San Diego, Calif (Drs Hofherr and Francis), and the Division of Laboratory Systems, Public Health Practice Program Office, Centers for Disease Control and Prevention, Atlanta, Ga (Dr Astles and Mr Schalla). Poster presentation at the 1999 National HIV Prevention Conference in Atlanta, Ga, August 29 September 1, The opinions expressed are those of the authors and do not necessarily reflect institutional policy. Use of trade names and commercial sources is for identification only and does not imply endorsement by the US Department of Health and Human Services. Reprints: Louise K. Hofherr, PhD, Laboratory Assurance Program, Graduate School of Public Health, 633 Alvarado Ct, #28, San Diego, CA 9212 ( lhofherr@mail.sdsu.edu). viral load in patients and evaluate the efficacy of various treatment modalities Recognizing that the use of HIV-1 viral load testing was increasing, we designed a survey to identify physicians ordering this testing, profile the laboratories performing such tests, clarify the differences in rural, suburban, and urban practices, describe testing methods, and obtain the physician s perception and use of viral load testing. We report on the findings from a survey involving a nationwide sample of primary care physicians whom we believed were actively managing HIV-1 infected patients. METHODS We developed a survey for physicians with the assistance of an expert focus group. This survey was designed to collect demographic information, a history of experience with HIV-1 infection and HIV-1 RNA testing, knowledge about and perceived limitations of this testing, reasons for testing and laboratory selection, knowledge about interpretation of test results, and knowledge about test information resources. We pretested the survey on 3 physicians, incorporated their suggestions, and developed the final version. We used information obtained from previous surveys administered by the San Diego State University Laboratory Assurance Program that was directed to physician specialties caring for the HIV-1 infected patients to increase the number of survey respondents who work with HIV-1 infected individuals. Specialists in infectious diseases, internal medicine, and family practice were chosen because a previous survey by the investigators indicated these physicians were used by HIV-1 infected individuals 43%, 446 Arch Pathol Lab Med Vol 127, April 23 Physician Viral Load Hofherr et al

2 35%, and 22% of the time, respectively. The sample of survey recipients selected was weighted using these percentages. We devised a comparison by incidence area using the most recently available HIV/AIDS Surveillance Report (December 1997) 2 for our anticipated August 1998 initial mailing. Metropolitan/geographic areas in the United States were further divided and referred to as areas of high, medium, and low incidence in this study. The cutoffs were made such that high incidence areas included cities with more than 38. cases per 1, medium incidence included cities with 19.8 to 38. cases per 1, and low incidence included cities with fewer than 19.8 cases per 1. By these definitions, the high incidence areas accounted for 37.6% of all US cases of HIV infection, the medium incidence areas accounted for 35.9%, and the low incidence areas accounted for 26.5%. These 2 factors, utilization and incidence, along with a goal of 5 physicians included in the sample, were weighted in the final selection of survey recipients. Accordingly, it was determined that 188 physicians would be surveyed in the high incidence area, 179 in the medium incidence area, and 133 in the low incidence area. Within each area, surveys were sent according to specialty (ie, 43% for infectious diseases, 35% for internal medicine, and 22% for family practice). In the event of mailing errors or returns, backup names and addresses were identified for each of the strata. A total of 15 names and addresses were obtained from a marketing service. These 15 physicians were selected randomly by the marketing service on the basis of the described strata and the following criteria: (1) holding an MD degree, (2) being younger than 65 years, and (3) actively seeing patients. This marketing service also provided the following information: (1) date of birth, (2) gender, (3) preferred professional mailing address, (4) state, (5) county, (6) zip code, (7) office phone number, (8) specialty, and (9) last name (surname) to be used for the greeting. When the electronic list of physicians who met these criteria was received, a spreadsheet software program, Quattro Pro for Windows (version 5., 1993, Borland International Inc, Scotts Valley, Calif), was used to randomly select the 5 who would receive the survey. From these, 215 infectious diseases, 176 internal medicine, and 19 family practice physicians were selected across the area strata. Three mailing waves of surveys were sent to the physicians, with a reminder to return the completed survey sent between wave 1 and wave 2. For surveys returned as undeliverable, the next randomly selected series of physicians in that incidence rate category and specialty were sent a survey. Because of the initial low response rate (7%), the reminders took the form of a 1-page flier bringing attention to the survey and offering the opportunity to complete only the first 5 questions. Physicians who had not treated HIV-infected patients returned the short form and were removed from the mailing list. Again, because of the initial low response rate to the survey and the reminders, a 5% random sample of nonresponders was chosen for a telephone interview. These physicians were contacted and asked about their reasons for nonresponse. Some were also asked to provide demographic information. Changes in the subsequent mailings were made on the basis of this interview, especially in the content of the cover letter. DATA MANAGEMENT AND ANALYSIS The survey data were entered in a database using Paradox (Paradox for Windows, version 5., Borland). The statistical package SPSS for Windows (version 8., 1997, SPSS Inc, Chicago, Ill) was used for all data editing and analysis. Frequencies were calculated for all variables, and stratification was performed for certain variables to determine their impact on the distributions described. In some cases, stratification resulted in numbers too small to be meaningful. RESULTS A total of 147 physicians responded to the survey for a response rate of 29.4%. Only 66 (44.9%) of the 147 physicians responding indicated that they requested HIV- RNA testing. Most of the respondents who requested such testing listed infectious diseases as their specialty (8.3%, 53 of 66). It should be noted that the total number of responses varied because some respondents did not answer all of the questions. The mean number of years for physicians in family practice (n 7) was 12.6 years, with a range of 9 to 2 years. For physicians in infectious diseases (n 48), it was 11.3 years, ranging from 1 to 28 years, and for physicians in internal medicine (n 8), it was 9.8 years, ranging from 6 to 15 years. The distribution of respondents by specialty and the number of years in specialty practice varied. Most respondents worked in a group practice (34.9%) or medical school (19.%) setting. Fewer worked in a nongovernment hospital (14.3%), were in sole practice (11.1%), or worked in a government health system (7.9%). Even fewer of the respondents were affiliated with a health maintenance organization (6.3%), were in research (3.2%), or were affiliated with a community health center (3.2%). Physicians were asked to indicate their specialty and whether they practiced in an urban or a suburban setting. As mentioned earlier, most respondents were infectious diseases practitioners (8.3%), and most respondents indicated that they had an urban practice (68.2%, 45 of 66). When considering the infectious diseases respondents by specialty and geographic setting, most had practices in urban (54.6%) or suburban (24.2%) settings. (Note: There were only 7 respondents in the rural category, none of whom requested this testing.) Of those in internal medicine (% of the total sample), most (83.5%) practiced in an urban setting. Finally, those in general practice (1.6% of this total) were more equally distributed between the urban (57.5%) and suburban (42.4%) settings. Physicians were asked to indicate reasons for using viral load testing and to rank their use in order of frequency. Figure 1 shows the responses to this question. Most respondents used the testing for the follow-up or monitoring of patients (75.4%), with initiation/guidance of therapy being the second most frequent reason (62.5%). In response to whether interpretation and use of viral load results had ever been a problem, only a few physicians (%, 8 of 66) reported frequently occurring problems, and these were reported in the areas of (1) how to treat the patient, and (2) what change from baseline was clinically significant. In the second category, sometimes a problem, the most frequent responses again were for (1) how to treat the patient (65.1%), and (2) what change from baseline is clinically significant (62.1%). Figure 2 displays the results for the possible choices. The resources that physicians use to interpret the results of the viral load test are shown in the Table. Physicians responding to the survey identified other knowledgeable physicians (5%, 36 of 66), medical journals (53.%, 33 of 66), and reference books (27.3%, 18 of 66) as resources consulted often or occasionally. Few physicians used the laboratory pathologist (%, 3 of 66) and test manufacturer (%, 3 of 66) as an often or occasional resource. When asked not about interpretation but about treat- Arch Pathol Lab Med Vol 127, April 23 Physician Viral Load Hofherr et al 447

3 Figure 1. Reasons for requesting viral load testing by ranking for frequency of use (some respondents gave 1 reason for the same ranking). Figure 2. Rating of problem frequency for interpretation and use of viral load results (n 66). Physicians Choices of Resources for Interpretation and Use of Viral Load Results (n 66)* Percentage of Respondents Consulting Source No Response Source Often Occasionally Seldom Never to Question Physicians 4.9 Lab pathologist Lab scientist Test manufacturer 66.7 AIDS hotline Reference book MMWR NIH publications 51.5 Journals Newsletters Internet * AIDS indicates acquired immunodeficiency syndrome; MMWR, Morbidity and Mortality Weekly Report; and NIH, National Institutes of Health. 448 Arch Pathol Lab Med Vol 127, April 23 Physician Viral Load Hofherr et al

4 ment regimen resources, the same 3 responses in the often and occasionally category predominated and were as follows: other physicians (83.3%, 55 of 66), medical journals (8.3%, 53 of 66), and reference books (42.4%, 28 of 66). In addition to these 3, physicians reported the National Institutes of Health publications at 42.4%, 28 of 66 responses in the often and occasionally categories. No physicians indicated they used the laboratory pathologist often or even occasionally. No differences were detected in the reasons for requesting the test between the suburban and urban physicians. The rankings remained the same, with monitoring and follow-up of HIV-1 infection chosen as the primary reason for requesting viral load testing. Apparently, physicians, regardless of practice location, value this test as an important tool when caring for the HIV-1 infected patient. As shown in Figure 1, it appears that viral load testing is used predominantly for follow-up/monitoring, initiation/ guidance of therapy, and, to lesser extent, prognosis. It is rarely used for screening or diagnosis. COMMENT The infectious diseases physician practicing in an urban setting is the most frequent user of viral load testing. This is not surprising since these are the physicians seeing this patient population either as their own patients or through consultation/referral. Much of the literature reflects the use of this testing for establishing the stage of infection or the effectiveness of treatment. In this population, it was not surprising to see that the most frequent response was use of the test for these reasons. In 1999, a study by Willard et al 21 of California rural primary care physicians concluded that physicians who saw few HIV-1 infected patients (less than 4 patients in this 1- to 2-year study) were less likely to prescribe protease inhibitors and less likely to use viral load tests in their management of patients. We suggest this indicates that physicians with few HIV-1 patients need expanded information resources. In our study, no rural physicians had treated an HIV patient in the previous year. Hechtetal 22 in 1997 said, The management of HIV-1 has become sufficiently complex that primary care physicians cannot be routinely expected to have extensive specialized knowledge in this area. With the requirement for the inclusion of viral load data in the surveillance case definition of the Centers for Disease Control and Prevention for the reporting of HIV-1 infection and AIDS 23 and with the requirement to report HIV-1 case infections in many states for surveillance purposes, these factors, in addition to more new studies indicating the importance of viral load in the prognosis and outcome prediction of such cases, 1,17,24 27 point to the importance of physicians learning more about using viral load tests and interpreting their results. 28 The pathologist and the laboratory are sufficiently knowledgeable to advise clinicians on the availability, use, and interpretation of the newest viral load testing methods. Lau and Pinching 29 have reported that such laboratories provide important information to physicians in their ongoing care and management of HIV-1 infected patients. CONCLUSIONS The results of this survey indicate that physicians do have questions about the meaning of viral load tests, how to treat the patient on the basis of the result, how often to monitor viral load, and what change from baseline is significant. Physicians tend to rely on one another or on current medical journals for information about using or interpreting tests. Few, if any, use the laboratory as a resource for these needs. Laboratorians, especially clinical pathologists, are experts in testing and test interpretation. Viral load testing should be noted as a unique opportunity for greater dialog between treating physicians and the laboratorians, who are best positioned to understand the test methods and provide consultation. Efforts should be made to both increase the awareness and invite the use of this expertise. On the basis of the results obtained in this study, we have identified opportunities for pathology consultation concerning viral load testing. While there may be many approaches and strategies the laboratory pathologist could use to optimize the opportunity for pathology consultation, we suggest some strategies for consideration. A class or seminar on a new technology or methodology could be presented for physicians ordering or considering its use, preferably with continuing education credits offered. Manufacturers may be willing to assist in course development and/or delivery. The test requisition and the laboratory test report could contain the name and telephone number of the laboratory pathologist or the laboratory director for consultation. Laboratory representatives should then be prepared to answer physician questions on the use of the test, the test methods, the test results, and the restrictions in using the test results. The pathologist or laboratory director could also, if appropriate, suggest other test(s) (eg, viral resistance or CD4 T-cell counts) that might provide more information for patient treatment. The laboratory test report could also contain the name and telephone number of a staff infectious diseases specialist who might be able to provide consultation to the requesting physician concerning testing issues and clinical treatment. In the case of physician groups, a hard-copy testing alert could be disseminated throughout the integrated system alerting physicians of potential problems and the most appropriate use of the test. Additionally, commercial laboratories could use this strategy to disseminate information to their client base. In integrated systems, individual hospital complexes or medical organizations could disseminate this information through a Web site. This approach could be used internally for organizations as an Intranet site or as an Internet site for access between external organizations. The laboratory may already be implementing some of these strategies, but maximizing opportunities for additional avenues of consultation could benefit the laboratory s physician clients by providing the added value. This study was funded by the Centers for Disease Control and Prevention through a cooperative agreement with the Association of Schools of Public Health. References 1. Centers for Disease Control and Prevention. U.S. HIV and AIDS cases reported through June 2. HIV/AIDS Surveill Rep. 2;12: Centers for Disease Control and Prevention. Characteristics of persons living with AIDS at the end of HIV/AIDS Surveill Suppl Rep. 21;7:7. 3. Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M. Rapid turn over of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 1995;373: Perelson AS, Neumann AU, Markowitz M, Leonard JM, Ho DD. HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science. 1996;271: Ho DD. Viral counts count in HIV infection. Science. 1996;272: Arch Pathol Lab Med Vol 127, April 23 Physician Viral Load Hofherr et al 449

5 6. Pantaleo G, Graziosi C, Demarest JF, et al. HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature. 1993;362: Wei X, Ghosh SK, Taylor ME, et al. Viral dynamics in human immunodeficiency virus type 1 infection. Nature. 1995;373: O Brien WA, Hartigan PM, Martin D, et al. Changes in plasma HIV-1 RNA and CD4 lymphocyte counts and the risk of progression to AIDS. N Engl J Med. 1996;334: Piatak M Jr, Saag MS, Yang LC, et al. High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR. Science. 1993;259: Mellors JW, Kingsley LA, Rinaldo CR Jr, Todd JA. Quantitation of HIV-1 RNA in plasma predicts outcome after seroconversion. Ann Intern Med. 1995; 122: Saag MS, Holodniy M, Kuritzkes DR, et al. HIV viral load markers in clinical practice. Nat Med. 1996;2: Harrigan R Measuring viral load in the clinical setting. J Acquir Immune Defic Syndr Hum Retrovirol. 1995;1(suppl 1):S34 S Nolte FS, Boysza J, Thurmond C, Clark WS, Lennox JL. Clinical comparison of an enhanced-sensitivity branched-dna assay and reverse transcription-pcr for quantitation of human immunodeficiency virus type 1 RNA in plasma. J Clin Microbiol. 1998;36: Revets H, Marissens D, De Wit S, et al. Comparative evaluation of NASBA HIV-1 RNA QT, AMPLICOR-HIV Monitor, and QUANTIPLEX HIV RNA Assay, three methods for quantification of human immunodeficiency virus type 1 RNA in plasma. J Clin Microbiol. 1996;34: Schuurman R, Descamps D, Weverling GJ, et al. Multicenter comparison of three commercial methods for quantification of human immunodeficiency virus type 1 RNA in plasma. J Clin Microbiol. 1996;34: Dewar RL, Highbarger HC, Sarmiento MD, et al. Application of branched DNA signal amplification to monitor human immunodeficiency virus type 1 burden in human plasma. J Infect Dis. 1994;17: Mellors JW, Rinaldo CR Jr, Gupta P, White RM, Todd JA, Kingsley LA. Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science. 1996;272: Hughes MD, Johnson VA, Hirsch MS, et al. Monitoring plasma HIV-1 RNA levels in addition to CD4 lymphocyte count improves assessment of antiretroviral therapeutic response. Ann Intern Med. 1997;126: O Brien WA, Hartigan PM, Daar ES, Simberkoff MS, Hamilton JD, VA Cooperative Study Group on AIDS. Changes in plasma HIV RNA levels and CD4 lymphocyte counts predict both response to antiretroviral therapy and therapeutic failure. Ann Intern Med. 1997;126: Centers for Disease Control and Prevention. U.S. HIV and AIDS cases reported through December HIV/AIDS Surveill Rep. 1997;9: Willard CL, Liljestrand P, Goldschmidt RH, Grumbach K. Is experience with human immunodeficiency virus disease related to clinical practice? A survey of rural primary care physicians. Arch Fam Med. 1999;8: Hecht FM, Wilson IB, Wu AW, Cook RL, Turner BJ. Optimizing care for persons with HIV infection. Arch Pathol Lab Med. 1997;121: Centers for Disease Control and Prevention. Guidelines for national human immunodeficiency virus case surveillance, including monitoring for human immunodeficiency virus infection and acquired immunodeficiency syndrome. MMWR. 1999;48(no. RR-13): Demeter LM, Hughes MD, Coombs RW, et al. Predictors of virologic and clinical outcomes in HIV-1-infected patients receiving concurrent treatment with indinavir, zidovudine, and lamivudine. Ann Intern Med. 21;1135: Kempf DJ, Rode RA, Xu Y, et al. The duration of viral suppression during protease inhibitor therapy for HIV-1 infection is predicted by plasma HIV-1 RNA at the nadir. AIDS. 1998;12:F9 F Coombs RW, Welles SL, Hooper C, et al, for the AIDS Clinical Trials Group (ACTG) 116B/117 Study Team and the ACTG Virology Committee Resistance and HIV-1 RNA Working Groups. Association of plasma human immunodeficiency virus type 1 RNA level with risk of clinical progression in patients with advanced infection. J Infect Dis. 1996;174: O Brien WA, Hartigan PM, Daar ES, Simberkoff MS, Hamilton JD, for the VA Cooperative Study Group on AIDS. Changes in plasma HIV RNA levels and CD4 lymphocyte counts predict both response to antiretroviral therapy and therapeutic failure. Ann Intern Med. 1997;126: Centers for Disease Control and Prevention. Guidelines for laboratory test result reporting of human immunodeficiency virus type ribonucleic acid determination: recommendations from a CDC working group. MMWR. 21;5(no. RR-2): Lau RK, Pinching AJ. Analyzing the workload from HIV inpatients: a 1- month retrospective study. Int J STD AIDS. 1991;2: Arch Pathol Lab Med Vol 127, April 23 Physician Viral Load Hofherr et al