Cumulative Incidence of Cancer Among Persons With HIV in North America: A Cohort Study.

BACKGROUND: Cancer is increasingly common among persons with HIV. OBJECTIVE: To examine calendar trends in cumulative cancer incidence and hazard rate by HIV status. DESIGN: Cohort study. SETTING: North American AIDS Cohort Collaboration on Research and Design during 1996 to 2009. PARTICIPANTS: 86 620 persons with HIV and 196 987 uninfected adults. MEASUREMENTS: Cancer type-specific cumulative incidence by age 75 years and calendar trends in cumulative incidence and hazard rates, each by HIV status. RESULTS: Cumulative incidences of cancer by age 75 years for persons with and without HIV, respectively, were as follows: Kaposi sarcoma, 4.4% and 0.01%; non-Hodgkin lymphoma, 4.5% and 0.7%; lung cancer, 3.4% and 2.8%; anal cancer, 1.5% and 0.05%; colorectal cancer, 1.0% and 1.5%; liver cancer, 1.1% and 0.4%; Hodgkin lymphoma, 0.9% and 0.09%; melanoma, 0.5% and 0.6%; and oral cavity/pharyngeal cancer, 0.8% and 0.8%. Among persons with HIV, calendar trends in cumulative incidence and hazard rate decreased for Kaposi sarcoma and non-Hodgkin lymphoma. For anal, colorectal, and liver cancer, increasing cumulative incidence, but not hazard rate trends, were due to the decreasing mortality rate trend (-9% per year), allowing greater opportunity to be diagnosed. Despite decreasing hazard rate trends for lung cancer, Hodgkin lymphoma, and melanoma, cumulative incidence trends were not seen because of the compensating effect of the declining mortality rate. LIMITATION: Secular trends in screening, smoking, and viral co-infections were not evaluated. CONCLUSION: Cumulative cancer incidence by age 75 years, approximating lifetime risk in persons with HIV, may have clinical utility in this population. The high cumulative incidences by age 75 years for Kaposi sarcoma, non-Hodgkin lymphoma, and lung cancer support early and sustained antiretroviral therapy and smoking cessation.

Effect of early versus deferred antiretroviral therapy for HIV on survival.

BACKGROUND: The optimal time for the initiation of antiretroviral therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection is uncertain. METHODS: We conducted two parallel analyses involving a total of 17,517 asymptomatic patients with HIV infection in the United States and Canada who received medical care during the period from 1996 through 2005. None of the patients had undergone previous antiretroviral therapy. In each group, we stratified the patients according to the CD4+ count (351 to 500 cells per cubic millimeter or >500 cells per cubic millimeter) at the initiation of antiretroviral therapy. In each group, we compared the relative risk of death for patients who initiated therapy when the CD4+ count was above each of the two thresholds of interest (early-therapy group) with that of patients who deferred therapy until the CD4+ count fell below these thresholds (deferred-therapy group). RESULTS: In the first analysis, which involved 8362 patients, 2084 (25%) initiated therapy at a CD4+ count of 351 to 500 cells per cubic millimeter, and 6278 (75%) deferred therapy. After adjustment for calendar year, cohort of patients, and demographic and clinical characteristics, among patients in the deferred-therapy group there was an increase in the risk of death of 69%, as compared with that in the early-therapy group (relative risk in the deferred-therapy group, 1.69; 95% confidence interval [CI], 1.26 to 2.26; P<0.001). In the second analysis involving 9155 patients, 2220 (24%) initiated therapy at a CD4+ count of more than 500 cells per cubic millimeter and 6935 (76%) deferred therapy. Among patients in the deferred-therapy group, there was an increase in the risk of death of 94% (relative risk, 1.94; 95% CI, 1.37 to 2.79; P<0.001). CONCLUSIONS: The early initiation of antiretroviral therapy before the CD4+ count fell below two prespecified thresholds significantly improved survival, as compared with deferred therapy.

Late presentation for human immunodeficiency virus care in the United States and Canada.

BACKGROUND. Initiatives to improve early detection and access to human immunodeficiency virus (HIV) services have increased over time. We assessed the immune status of patients at initial presentation for HIV care from 1997 to 2007 in 13 US and Canadian clinical cohorts. METHODS. We analyzed data from 44,491 HIV-infected patients enrolled in the North American-AIDS Cohort Collaboration on Research and Design. We identified first presentation for HIV care as the time of first CD4(+) T lymphocyte (CD4) count and excluded patients who prior to this date had HIV RNA measurements, evidence of antiretroviral exposure, or a history of AIDS-defining illness. Trends in mean CD4 count (measured as cells/mm(3)) and 95% confidence intervals were determined using linear regression adjusted for age, sex, race/ethnicity, HIV transmission risk, and cohort. RESULTS. Median age at first presentation for HIV care increased over time (range, 40-43 years; P < .01), whereas the percentage of patients with injection drug use HIV transmission risk decreased (from 26% to 14%; P < .01) and heterosexual transmission risk increased (from 16% to 23%; P < .01). Median CD4 count at presentation increased from 256 cells/mm(3) (interquartile range, 96-455 cells/mm(3)) to 317 cells/mm(3) (interquartile range, 135-517 cells/mm(3)) from 1997 to 2007 (P < .01). The percentage of patients with a CD4 count > or = 350 cells/mm(3) at first presentation also increased from 1997 to 2007 (from 38% to 46%; P < .01). The estimated adjusted mean CD4 count increased at a rate of 6 cells/mm(3) per year (95% confidence interval, 5-7 cells/mm(3) per year). CONCLUSION. CD4 count at first presentation for HIV care has increased annually over the past 11 years but has remained <350 cells/mm(3), which suggests the urgent need for earlier HIV diagnosis and treatment.

Trends in multidrug treatment failure and subsequent mortality among antiretroviral therapy-experienced patients with HIV infection in North America.

BACKGROUND: Although combination antiretroviral therapy continues to evolve, with potentially more effective options emerging each year, the ability of therapy to prevent multiple regimen failure and mortality in clinical practice remains poorly defined. METHODS: Sixteen cohorts representing over 60 sites contributed data on all individuals who initiated combination antiretroviral therapy. We identified those individuals who experienced virologic failure (defined as a human immunodeficiency virus [HIV] RNA level >1000 copies/mL), received modified therapy, and subsequently had a second episode of virologic failure. Multivariate Cox regression was used to assess factors associated with time to second regimen failure and the time to death after the onset of second regimen failure. RESULTS: Of the 42,790 individuals who received therapy, 7159 experienced a second virologic failure. The risk of second virologic failure decreased from 1996 (56 cases per 100 person-years) through 2005 (16 cases per 100 person-years; P < .001). The cumulative mortality after onset of second virologic failure was 26% at 5 years and decreased over time. A history of AIDS, a lower CD4(+) T cell count, and a higher plasma HIV RNA level were each independently associated with mortality. Similar trends were observed when analysis was limited to the subset of previously treatment-naive patients CONCLUSIONS: Although the rates of multiple regimen failure have decreased dramatically over the past decade, mortality rates for those who have experienced failure of at least 2 regimens have remained high. Plasma HIV RNA levels, CD4(+) T cell counts at time of treatment failure, and a history of AIDS remain independent risk factors for death, which emphasizes that these factors remain important targets for those in need of more-aggressive therapeutic interventions.

Contributions of traditional and HIV-related risk factors on non-AIDS-defining cancer, myocardial infarction, and end-stage liver and renal diseases in adults with HIV in the USA and Canada: a collaboration of cohort studies.

BACKGROUND: Adults with HIV have an increased burden of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease. The objective of this study was to estimate the population attributable fractions (PAFs) of preventable or modifiable HIV-related and traditional risk factors for non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes. METHODS: We included participants receiving care in academic and community-based outpatient HIV clinical cohorts in the USA and Canada from Jan 1, 2000, to Dec 31, 2014, who contributed to the North American AIDS Cohort Collaboration on Research and Design and who had validated non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, or end-stage renal disease outcomes. Traditional risk factors were tobacco smoking, hypertension, elevated total cholesterol, type 2 diabetes, renal impairment (stage 4 chronic kidney disease), and hepatitis C virus and hepatitis B virus infections. HIV-related risk factors were low CD4 count (<200 cells per µL), detectable plasma HIV RNA (>400 copies per mL), and history of a clinical AIDS diagnosis. PAFs and 95% CIs were estimated to quantify the proportion of outcomes that could be avoided if the risk factor was prevented. FINDINGS: In each of the study populations for the four outcomes (1405 of 61 500 had non-AIDS-defining cancer, 347 of 29 515 had myocardial infarctions, 387 of 35 044 had end-stage liver disease events, and 255 of 35 620 had end-stage renal disease events), about 17% were older than 50 years at study entry, about 50% were non-white, and about 80% were men. Preventing smoking would avoid 24% (95% CI 13-35) of these cancers and 37% (7-66) of the myocardial infarctions. Preventing elevated total cholesterol and hypertension would avoid the greatest proportion of myocardial infarctions: 44% (30-58) for cholesterol and 42% (28-56) for hypertension. For liver disease, the PAF was greatest for hepatitis C infection (33%; 95% CI 17-48). For renal disease, the PAF was greatest for hypertension (39%; 26-51) followed by elevated total cholesterol (22%; 13-31), detectable HIV RNA (19; 9-31), and low CD4 cell count (13%; 4-21). INTERPRETATION: The substantial proportion of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes that could be prevented with interventions on traditional risk factors elevates the importance of screening for these risk factors, improving the effectiveness of prevention (or modification) of these risk factors, and creating sustainable care models to implement such interventions during the decades of life of adults living with HIV who are receiving care. FUNDING: National Institutes of Health, US Centers for Disease Control and Prevention, the US Agency for Healthcare Research and Quality, the US Health Resources and Services Administration, the Canadian Institutes of Health Research, the Ontario Ministry of Health and Long Term Care, and the Government of Alberta.

One-year outcomes and health care utilization in survivors of severe acute respiratory syndrome.

BACKGROUND: Severe Acute Respiratory Syndrome (SARS) became a global epidemic in 2003. Comprehensive information on 1-year outcomes and health care utilization is lacking. Research conducted during the SARS outbreak may help inform research planning for future public health emergencies. The objective of this study was to evaluate the 1-year outcomes in survivors of SARS and their family caregivers. METHOD: The study was prospective and observational. We evaluated 117 SARS survivors from Toronto, Ontario. Patients were interviewed and underwent physical examination, pulmonary function testing, chest radiography, a 6-minute-walk test, quality-of-life measures, and self-report of health care utilization. At 1 year, informal caregivers were identified for a survey on caregiver burden. RESULTS: The enrolled survivors of SARS were young (median age, 42 years), and most were women (67%) and health care workers (65%). At 1 year after hospital discharge, pulmonary function measures were in the normal range, but 18% of patients had a significant reduction in distance walked in 6 minutes. The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) domains were 0.3 to 1.0 SD below normal at 1 year. Of the patients, 17% had not returned to work by 1 year. Fifty-one patients required 668 visits to psychiatry or psychology practitioners. During the SARS epidemic, informal caregivers reported a decline of 1.6 SD below normal on the mental component score of the SF-36. CONCLUSIONS: Most SARS survivors had good physical recovery from their illness, but some patients and their caregivers reported a significant reduction in mental health 1 year later. Strategies to ameliorate the psychological burden of an epidemic on the patient and family caregiver should be considered as part of future pandemic planning.

Successful discontinuation of therapy for disseminated Mycobacterium avium complex infection after effective antiretroviral therapy.

BACKGROUND: Highly active antiretroviral therapy (HAART) is associated with improvement or resolution of several HIV-associated opportunistic infections. Although prophylaxis against disseminated Mycobacterium avium complex infection may be successfully discontinued after a favorable response to HAART, the 1999 guidelines from the U.S. Public Health Service/Infectious Diseases Society of America recommend continuing therapy for disseminated M. avium complex infection, regardless of the response to HAART. OBJECTIVE: To examine the outcome among patients with disseminated M. avium complex infection whose antimycobacterial therapy was discontinued after a favorable response to HAART. DESIGN: Retrospective chart review between May 2000 and May 2001. SETTING: 13 Canadian HIV clinics. PATIENTS: 52 HIV-infected adults (43 men; mean age, 37.3 years) in whom successful antimycobacterial therapy for disseminated M. avium complex infection was discontinued after a favorable virologic response to HAART. MEASUREMENTS: Survival, survival free of disseminated M. avium complex infection, and CD4(+) cell count responses. RESULTS: At the time of diagnosis of disseminated M. avium complex infection, the median CD4(+) cell count was 0.016 x 10(9) cells/L, and the median plasma HIV RNA level was 90 000 copies/mL (plasma HIV RNA levels were available for only 21 patients). The patients received a median of 32 months of antimycobacterial therapy that included ethambutol plus either clarithromycin or azithromycin. When antimycobacterial therapy was discontinued, the median CD4(+) cell count was 0.23 x 10(9) cells/L and the median plasma HIV RNA level was less than 50 copies/mL. A median of 20 months after discontinuation of antimycobacterial therapy, only 1 patient had developed recurrent M. avium complex disease (37 months after stopping antimycobacterial therapy). This patient had stopped HAART 2 months earlier because of uncontrolled HIV viremia. Twenty months after stopping antimycobacterial therapy, the other 51 patients had a median CD4(+) cell count of 0.288 x 10(9) cells/L; 34 (67%) had undetectable plasma HIV RNA levels, and 8 (15%) had plasma HIV RNA levels of 50 to 1000 copies/mL. CONCLUSIONS: Discontinuation of successful disseminated M. avium complex therapy after a successful response to HAART is safe and reduces patients' pill burdens, potential drug adverse effects, drug interactions, and costs of therapy.

Self-Reported Preconception Care of HIV-Positive Women of Reproductive Potential: A Retrospective Study.

OBJECTIVES: We determined the proportion and correlates of self-reported pregnancy planning discussions (that is preconception counseling) that HIV-positive women reported to their family physicians (FPs), HIV specialists, and obstetrician/gynecologists (OB/Gyns). METHODS: In a cross-sectional substudy, HIV-positive women of reproductive potential were asked whether their care providers discussed pregnancy planning. Logistic regression was used to calculate odds ratios for the correlates of preconception counseling. RESULTS: A total of 431 eligible participants (median age 38, interquartile range = 32-43) reported having discussion with a physician (92% FP, 96% HIV specialists, and 45% OB/Gyns). In all, 34%, 41%, and 38% had their pregnancy planning discussion with FP, HIV specialist, and Ob/Gyns, respectively; 51% overall. In the multivariable model, significant correlates of preconception counseling were age (P = .02), marital status (P < .01), number of years living in Canada (P < .001), and age of youngest child (P < .01). CONCLUSIONS: Preconception care in our cohort was suboptimal. We recommend that counseling on healthy preconception should be part of routine HIV care.

Prediction of health preference values from CD4 counts in individuals with HIV.

BACKGROUND: A common measure of health benefit in technology assessments is the quality-adjusted life year, which incorporates health preference or utility scores. OBJECTIVE: To build and test a predictive model using CD4 counts to derive health preference scores. DESIGN: Predictive modeling. Setting. Ontario HIV Treatment Network Cohort Study. Measurement. The relationship between HUI3-derived health preference score and HIV health status measured by CD4 count was examined by a regression model. Additional independent variables considered included age, time since HIV diagnosis, AIDS-defining condition, sex, and education level. A polynomial regression model was fit to predict health preference scores. The final model was established using automated backwards stepwise variable elimination using the Akaike information criterion. Tenfold cross-validation was used to assess the model. RESULTS: Data from 841 participants were available. Mean age and time since diagnosis were 46.78 and 11.03 years, respectively. CD4 counts ranged from 2 to 995 cells per mm(3) with 267 (31.75%) individuals having less than 350 cells per mm(3). Mean HUI3 utility score was 0.72 and ranged from -0.25 to 1. The final model retained squared terms for CD4 counts, age, and time since HIV diagnosis and eliminated history of AIDS-defining condition and the nonsquared time since HIV diagnosis. Prediction error was assessed in 14 subgroups using the validation set. Two subgroups had mean prediction errors greater than 0.02. Limitations. All statistical models are limited by the data used to develop and test the model. The model estimates health utility scores primarily through CD4 counts. Therefore, the model may be inappropriate if noninfectious diseases are a significant factor. CONCLUSIONS: Results provide a model for predicting health preference values from CD4 counts.

Fertility desires and intentions of HIV-positive women of reproductive age in Ontario, Canada: a cross-sectional study.

BACKGROUND: Improvements in life expectancy and quality of life for HIV-positive women coupled with reduced vertical transmission will likely lead numerous HIV-positive women to consider becoming pregnant. In order to clarify the demand, and aid with appropriate health services planning for this population, our study aims to assess the fertility desires and intentions of HIV-positive women of reproductive age living in Ontario, Canada. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional study with recruitment stratified to match the geographic distribution of HIV-positive women of reproductive age (18-52) living in Ontario was carried out. Women were recruited from 38 sites between October 2007 and April 2009 and invited to complete a 189-item self-administered survey entitled "The HIV Pregnancy Planning Questionnaire" designed to assess fertility desires, intentions and actions. Logistic regression models were fit to calculate unadjusted and adjusted odds ratios of significant predictors of fertility intentions. The median age of the 490 participating HIV-positive women was 38 (IQR, 32-43) and 61%, 52%, 47% and 74% were born outside of Canada, living in Toronto, of African ethnicity and currently on antiretroviral therapy, respectively. Of total respondents, 69% (95% CI, 64%-73%) desired to give birth and 57% (95% CI, 53%-62%) intended to give birth in the future. In the multivariable model, the significant predictors of fertility intentions were: younger age (age<40) (p<0.0001), African ethnicity (p<0.0001), living in Toronto (p = 0.002), and a lower number of lifetime births (p = 0.02). CONCLUSIONS/SIGNIFICANCE: The proportions of HIV-positive women of reproductive age living in Ontario desiring and intending pregnancy were higher than reported in earlier North American studies. Proportions were more similar to those reported from African populations. Healthcare providers and policy makers need to consider increasing services and support for pregnancy planning for HIV-positive women. This may be particularly significant in jurisdictions with high levels of African immigration.

A cryptic cause of cryptococcal meningitis.

Cryptococcus neoformans commonly causes opportunistic infection in immunocompromised patients, especially in patients with AIDS. The CD4+ T-lymphocyte count is measured in patients with HIV infection, because it signals an increased risk of opportunistic infection and a decline in immunological function. We report a case of cryptococcal meningitis in a patient with persistently low CD4+ cell counts without evidence of HIV infection. The patient's underlying immunocompromised state was attributed to idiopathic CD4+ T-lymphocytopenia (ICL), a recently described syndrome characterized by depletions in the CD4+ T-cell subsets without evidence of HIV infection. Immunodeficiency can exist in the absence of laboratory evidence of HIV infection, highlighting the importance of evaluating T-cell subsets in patients who present with unusual infections.

Monitoring adverse drug reactions to sulfonamide antibiotics in human immunodeficiency virus-infected individuals.

Patients infected with the human immunodeficiency virus (HIV) are at higher risk for adverse drug reactions from trimethoprim-sulfamethoxazole (TMP-SMX) than the HIV-negative population. Studying the HIV-positive population the authors aimed to validate the predictive and diagnostic value of the lymphocyte toxicity assay (LTA) for adverse drug reactions. Patient lymphocytes were analyzed for toxicity to SMX and TMP. Of 35 enrolled HIV patients, 18 had TMP-SMX hypersensitivity syndrome reaction (HSR); 10 tolerated the drug; and 5 had never received the drug. When cases with HSR were compared with controls that tolerated the drugs, cytotoxicity was higher for cases: 29.5% +/- 10.1% versus 19.3% +/- 11.2% for SMX (P < 0.022) and 25.0% +/- 11.9% versus 16.3% +/- 11.0% for TMP (P < 0.04). The authors' proposed threshold value for assigning positive results for TMP and SMX hypersensitivities was 22.5%. The LTA has a strong potential for use as a diagnostic tool to assess TMP-SMX hypersensitivity in HIV-infected individuals. Larger patient populations, as well as in vitro studies are needed to further address the reasons for elevated results in immunocompromised patients and to validate the usefulness of the test.

Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area.

CONTEXT: Severe acute respiratory syndrome (SARS) is an emerging infectious disease that first manifested in humans in China in November 2002 and has subsequently spread worldwide. OBJECTIVES: To describe the clinical characteristics and short-term outcomes of SARS in the first large group of patients in North America; to describe how these patients were treated and the variables associated with poor outcome. DESIGN, SETTING, AND PATIENTS: Retrospective case series involving 144 adult patients admitted to 10 academic and community hospitals in the greater Toronto, Ontario, area between March 7 and April 10, 2003, with a diagnosis of suspected or probable SARS. Patients were included if they had fever, a known exposure to SARS, and respiratory symptoms or infiltrates observed on chest radiograph. Patients were excluded if an alternative diagnosis was determined. MAIN OUTCOME MEASURES: Location of exposure to SARS; features of the history, physical examination, and laboratory tests at admission to the hospital; and 21-day outcomes such as death or intensive care unit (ICU) admission with or without mechanical ventilation. RESULTS: Of the 144 patients, 111 (77%) were exposed to SARS in the hospital setting. Features of the clinical examination most commonly found in these patients at admission were self-reported fever (99%), documented elevated temperature (85%), nonproductive cough (69%), myalgia (49%), and dyspnea (42%). Common laboratory features included elevated lactate dehydrogenase (87%), hypocalcemia (60%), and lymphopenia (54%). Only 2% of patients had rhinorrhea. A total of 126 patients (88%) were treated with ribavirin, although its use was associated with significant toxicity, including hemolysis (in 76%) and decrease in hemoglobin of 2 g/dL (in 49%). Twenty-nine patients (20%) were admitted to the ICU with or without mechanical ventilation, and 8 patients died (21-day mortality, 6.5%; 95% confidence interval [CI], 1.9%-11.8%). Multivariable analysis showed that the presence of diabetes (relative risk [RR], 3.1; 95% CI, 1.4-7.2; P =.01) or other comorbid conditions (RR, 2.5; 95% CI, 1.1-5.8; P =.03) were independently associated with poor outcome (death, ICU admission, or mechanical ventilation). CONCLUSIONS: The majority of cases in the SARS outbreak in the greater Toronto area were related to hospital exposure. In the event that contact history becomes unreliable, several features of the clinical presentation will be useful in raising the suspicion of SARS. Although SARS is associated with significant morbidity and mortality, especially in patients with diabetes or other comorbid conditions, the vast majority (93.5%) of patients in our cohort survived.

Interpretation of diagnostic laboratory tests for severe acute respiratory syndrome: the Toronto experience.

BACKGROUND: An outbreak of severe acute respiratory syndrome (SARS) began in Canada in February 2003. The initial diagnosis of SARS was based on clinical and epidemiological criteria. During the outbreak, molecular and serologic tests for the SARS-associated coronavirus (SARS-CoV) became available. However, without a "gold standard," it was impossible to determine the usefulness of these tests. We describe how these tests were used during the first phase of the SARS outbreak in Toronto and offer some recommendations that may be useful if SARS returns. METHODS: We examined the results of all diagnostic laboratory tests used in 117 patients admitted to hospitals in Toronto who met the Health Canada criteria for suspect or probable SARS. Focusing on tests for SARS-CoV, we attempted to determine the optimal specimen types and timing of specimen collection. RESULTS: Diagnostic test results for SARS-CoV were available for 110 of the 117 patients. SARS-CoV was detected by means of reverse-transcriptase polymerase chain reaction (RT-PCR) in at least one specimen in 59 (54.1%) of 109 patients. Serologic test results of convalescent samples were positive in 50 (96.2%) of 52 patients for whom paired serum samples were collected during the acute and convalescent phases of the illness. Of the 110 patients, 78 (70.9%) had specimens that tested positive by means of RT-PCR, serologic testing or both methods. The proportion of RT-PCR test results that were positive was similar between patients who met the criteria for suspect SARS (50.8%, 95% confidence interval [CI] 38.4%-63.2%) and those who met the criteria for probable SARS (58.0%, 95% CI 44.2%-70.7%). SARS-CoV was detected in nasopharyngeal swabs in 33 (32.4%) of 102 patients, in stool specimens in 19 (63.3%) of 30 patients, and in specimens from the lower respiratory tract in 10 (58.8%) of 17 patients. INTERPRETATION: These findings suggest that the rapid diagnostic tests in use at the time of the initial outbreak lack sufficient sensitivity to be used clinically to rule out SARS. As tests for SARS-CoV continue to be optimized, evaluation of the clinical presentation and elucidation of a contact history must remain the cornerstone of SARS diagnosis. In patients with SARS, specimens taken from the lower respiratory tract and stool samples test positive by means of RT-PCR more often than do samples taken from other areas.