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Knowledge of Genotypic Resistance Mutations Among Providers of Care to Patients with Human Immunodeficiency Virus
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A questionnaire assessed clinician knowledge of genotypic resistance
mutations in human immunodeficiency virus. Only 24% of respondents were
able to identify at least 1 mutation for each of >4 drug groups listed, and 36%
were unable to match any mutations with any of the drug groups. Knowledge
was most deficient among providers caring for <50 patients (P = .001) but
also was poor among the 38 physicians caring for >100 patients (mean patient
load, 211 patients).. 17% of respondents correctly identified at least 1 resistance mutation for each of the 6 drug groups ...Thirty-six (36%) providers were unable to correctly identify resistance mutations for any of the 6 drug groups... Fifteen providers described themselves as experts in interpreting genotypic test results.... Our study demonstrated 2 significant findings. First, knowledge among medical-care providers regarding resistance-associated drug mutations is markedly limited, even among clinicians caring for large numbers of patients.. the majority of providers use laboratory-provided interpretation, and few acknowledged using the guidance of recognized experts in HIV resistance testing... The 100 clinicians who completed our survey were providers of medical care for >12,000 patients with HIV infection in the New York metropolitan area... Our data underscore the need to address the issue of provider knowledge
with regard to genotypic testing and its potential effect on patient care.
Editorial comment from Jules Levin: The study authors recommended that doctors consult experts on resistance in interpreting test results. They also said that a standardized algorithm of genotype interpretation that is continually updated and used by all laboratories that perform genotypic testing would be valuable. Firstly, I'm not convinced that providers are any more effective in using phenotypic testing. Of course, there are some doctors and providers who are well educated about resistance and interpreting test results. Second, studies have reported that resistance experts differ a good deal among themselves on the interpretation of resistance. Therefore, you must be careful in utilizing recommendations from experts as well. Clearly, there are experts in interpreting resistance testing. You must also know who those experts are. It is helpful to seek advise from multiple expert thought leaders in trying to interpret resistance data but it is important to understand the data for yourself & to understand that experts also differ in their opinions. Many primary care doctors and providers need better education to understand what they know & what they don't know about genotypic and phenotypic resistance testing, and they should be better educating about the difficulties in interpreting test results that even experts encounter.
Clinical Infectious Diseases 2003;36:101-104; Jan 2003
Carlos Salama, Maurice Policar, and Christina Cervera
Division of Infectious Diseases and Immunology Clinic, Elmhurst Hospital Center, Elmhurst, and Mount Sinai School of Medicine, New York, New York
Resistance to antiretroviral agents is an important challenge facing providers of care to patients with human immunodeficiency virus. Prospective clinical trials have demonstrated improved short-term virologic outcomes when
the choice of antiretroviral drugs was aided by genotypic testing, with further improvements seen when interpretations were guided by experts. Major guidelines recommend the use of genotypic testing to guide treatment changes and emphasize the importance of expert interpretation [46].
Evaluating genotypic test results is complex, and laboratory-provided interpretations do not follow a universal standard. For proper interpretation, clinicians must have a basic knowledge of relevant resistance-associated
genotypic mutations and must recognize the extent with which they affect susceptibility to specific drugs. The focus of our investigation was to ascertain whether clinicians possess knowledge of relevant genotypic mutations and whether they seek expert assistance with interpretation.
An anonymous questionnaire was randomly distributed to medical-care providers attending an International AIDS SocietyUSA meeting in New York City in 2001. This meeting updates HIV providers on HIV pathogenesis, complications of HIV disease, data from recent academic conferences, emerging treatment strategies, and other important topics related to HIV infection. This particular meeting was titled "An Advanced Course in HIV
Pathogenesis, Antiretrovirals, and Other Selected Issues in HIV Disease Management." A 45-min segment dealt with strategies for antiretroviral therapy, including discussion of cases related to antiretroviral failure and resistance. A postmeeting survey was not performed.
The questionnaire took 510 min to complete and was collected before the meeting. Respondents were asked questions associated with their training, their experience with genotypic testing, and sources used for interpretation, including whether they used experts in resistance testing.
Practitioners were provided with 6 drug groups and a list of 16 resistance-associated point mutations. Respondents were asked to write in next to each drug group the point mutations associated with resistance to that drug. The drug groups and corresponding amino acid sites listed in the questionnaire included the following: zidovudine-stavudine (41,
67, 70, 75, 210, 215, and 219), lamivudine (184), abacavir (184, 65, 74, 41, 67, 70, 210, 215, and 219), nonnucleoside reverse-transcriptase inhibitors (NNRTIs; 103, 106, and 181), nelfinavir (30 and 90), and pannucleoside resistance (151). Although the 69-insertion mutation was not listed on the questionnaire, it was accepted as a correct answer for pannucleoside resistance.
The conference was attended by 421 medical-care providers: 328 physicians (including 22 fellows and 6 residents in training), 59 nurse practitioners, and 34 physician's assistants. The questionnaire was distributed to 128 (30%) of these individuals. One hundred thirteen (88%) questionnaires were returned; 13 were excluded because genotypic testing had not been used. The 100 providers who used genotypic testing included 23 nurse practitioners and
physician's assistants and 77 physicians (38 primary care and 39 infectious diseases physicians). Our sample breakdown was, in general, representative of the conference attendees. The mean patient load for these providers was
123 patients (median, 100 patients).
The conference was attended by 421 medical-care providers: 328 physicians (including 22 fellows and 6 residents in training), 59 nurse practitioners, and 34 physician's assistants. The questionnaire was distributed to 128 (30%) of these individuals. One hundred thirteen (88%) questionnaires were returned; 13 were excluded because genotypic testing had not been used. The 100 providers who used genotypic testing included 23 nurse practitioners and
physician's assistants and 77 physicians (38 primary care and 39 infectious diseases physicians). Our sample breakdown was, in general, representative of the conference attendees. The mean patient load for these providers was
123 patients (median, 100 patients).
Seventeen percent of respondents correctly identified at least 1 resistance
mutation for each of the 6 drug groups, whereas 3%, 4%, 10%, 16%, and 14% correctly identified resistance mutations for 5, 4, 3, 2, and 1 drug group, respectively (table 1). Thirty-six (36%) providers were unable to correctly
identify resistance mutations for any of the 6 drug groups. The average number of drug groups for which providers correctly identified resistance mutations was 2. Fifteen providers described themselves as experts in interpreting genotypic test results.
We independently analyzed the knowledge of all 38 physicians (21 infectious diseases and 17 internal medicine physicians) caring for 100 patients (mean patient load, 211 patients). Twelve (32%) providers could identify resistance mutations for 4 drug groups, and 8 (21%) were unable to correctly identify resistance mutations for any of the drug groups.
Laboratory-provided genotypic interpretations are inherently more accurate for drugs such as lamivudine, nelfinavir, and NNRTIs, to which single-signature mutations cause high-level resistance. For other antiretroviral drugs
(zidovudine and abacavir), resistance develops in a stepwise fashion. When multiple mutations are necessary to significantly affect resistance, interpretations provided by laboratories may be less reliable, and clinician knowledge becomes more important for adequate interpretation of results. Unless significant clinician knowledge exists or until laboratories incorporate a universally accepted and standardized interpretation algorithm, it is prudent for clinicians to consult with recognized expert sources for assistance in genotype test interpretation.
Prospective studies have demonstrated the important contribution of expert interpretation for the success of regimen changes that are based on genotypic testing results. In the Havana trial, a panel of experts consisting of 4 clinicians and 2 virologists with extensive experience in care of patients with HIV infection had a significant effect on virologic outcomes. This kind of expert panel is not readily available for the majority of practicing physicians. In our study, only 10 (10%) clinicians reported consulting with a regional or nationally recognized expert in genotypic testing. Whether this low number was the result of a lack of access to such an expert is not clear from our data. Fifty other providers claimed to use "colleagues with expertise" as sources of interpretation. Although it is encouraging that providers who described themselves as experts in genotypic interpretation scored somewhat better in the knowledge assessment portion of the questionnaire (53% were able to identify resistance mutations for 4 drug groups), the term
"expert" is often subjective and should be defined in a more standardized manner for the general treating community.
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