Utility of an HIV-1 RNA Assay
Utility of an HIV-1 RNA Assay
Highly active antiretroviral therapy (HAART) begun during primary infection with human immunodeficiency virus type 1 (HIV-1) can preserve immune function and may alter the long-term clinical course of HIV-1 infection. To diagnose primary HIV-1 infection (PHI) early, when screening serologies may yield negative or indeterminate results, the Department of Health and Human Services recommends the use of an HIV-1 RNA assay for at-risk patients suspected of having acute retroviral syndrome (ARS). Because of the RNA assay's 1.9% to 3.0% false-positive rate, results must be carefully interpreted and compared to HIV-1 viral load levels seen during proven HIV-1 seroconversion. We report the case of a sexually active woman with symptoms suggestive of ARS who had a false-positive HIV-1 RNA assay result. We discuss use and interpretation of the HIV-1 RNA assay in diagnosing PHI.
Current guidelines of the Department of Health and Human Services (DHHS) on initiation of antiretroviral therapy strongly support the use of antiretroviral therapy during the primary infection with human immunodeficiency virus type 1 (HIV-1). Early treatment during HIV-1 seroconversion can lead to preservation of immune function and can lower the HIV-1 viral load set-point. A lower HIV-1 viral load early in the course of infection is predictive of delayed progression to acquired immunodeficiency syndrome (AIDS) and death. Because results of the HIV-1 enzyme-linked immunosorbent assay (ELISA) and Western blot serologies can be negative in primary HIV-1 infection (PHI), the current DHHS guidelines support the use of HIV-1 RNA testing for early diagnosis. These guidelines recommend the use of HIV-1 RNA testing in individuals who report high-risk behavior and have signs and symptoms suggestive of PHI. The guidelines recognize that p24 antigen testing is available but that results may be negative during the initial weeks of PHI.
While the reverse transcription polymerase chain reaction (RT-PCR) viral load assay is sensitive for HIV-1 viral load measurement, it has reported false-positive and false-negative rates that range from 1.9% to 3.0%. Despite its widespread use for early diagnosis of HIV-1, this test was developed for and approved by the Food and Drug Administration only as a method for measuring HIV-1 viral load as a predictor of disease progression. Thus, current DHHS guidelines recommend confirmation of RT-PCR results with Western blot serologies in 2 to 4 months.
As the HIV-1 epidemic evolves, heterosexual exposure has become a more common mode of transmission, and women now represent an increasing proportion of newly diagnosed cases. Thus, clinicians are challenged with attempting to make an early diagnosis of HIV-1 infection in a high-risk group that now includes sexually active women. Since the symptoms of PHI can be similar to those of other viral illnesses, such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), and the viral hepatitides, the clinician is likely to encounter many patients in whom PHI should be considered in the differential diagnosis. The use of the RT-PCR assay as a diagnostic tool may lead to a significant number of false-positive results in this large patient population.
To date, four cases of false-positive RT-PCR viral load results have been reported. Three cases consisted of patients who had potential exposure to HIV-1 and were asymptomatic. The other involved a patient who had participated in an HIV-1 vaccine trial and who had symptoms consistent with acute retroviral syndrome (ARS). We report the first case of a sexually active, young woman with symptoms suggestive of ARS in whom RT-PCR for HIV-1 was falsely positive. We discuss the diagnostic issues that arise in what is likely to become a common clinical scenario.
Highly active antiretroviral therapy (HAART) begun during primary infection with human immunodeficiency virus type 1 (HIV-1) can preserve immune function and may alter the long-term clinical course of HIV-1 infection. To diagnose primary HIV-1 infection (PHI) early, when screening serologies may yield negative or indeterminate results, the Department of Health and Human Services recommends the use of an HIV-1 RNA assay for at-risk patients suspected of having acute retroviral syndrome (ARS). Because of the RNA assay's 1.9% to 3.0% false-positive rate, results must be carefully interpreted and compared to HIV-1 viral load levels seen during proven HIV-1 seroconversion. We report the case of a sexually active woman with symptoms suggestive of ARS who had a false-positive HIV-1 RNA assay result. We discuss use and interpretation of the HIV-1 RNA assay in diagnosing PHI.
Current guidelines of the Department of Health and Human Services (DHHS) on initiation of antiretroviral therapy strongly support the use of antiretroviral therapy during the primary infection with human immunodeficiency virus type 1 (HIV-1). Early treatment during HIV-1 seroconversion can lead to preservation of immune function and can lower the HIV-1 viral load set-point. A lower HIV-1 viral load early in the course of infection is predictive of delayed progression to acquired immunodeficiency syndrome (AIDS) and death. Because results of the HIV-1 enzyme-linked immunosorbent assay (ELISA) and Western blot serologies can be negative in primary HIV-1 infection (PHI), the current DHHS guidelines support the use of HIV-1 RNA testing for early diagnosis. These guidelines recommend the use of HIV-1 RNA testing in individuals who report high-risk behavior and have signs and symptoms suggestive of PHI. The guidelines recognize that p24 antigen testing is available but that results may be negative during the initial weeks of PHI.
While the reverse transcription polymerase chain reaction (RT-PCR) viral load assay is sensitive for HIV-1 viral load measurement, it has reported false-positive and false-negative rates that range from 1.9% to 3.0%. Despite its widespread use for early diagnosis of HIV-1, this test was developed for and approved by the Food and Drug Administration only as a method for measuring HIV-1 viral load as a predictor of disease progression. Thus, current DHHS guidelines recommend confirmation of RT-PCR results with Western blot serologies in 2 to 4 months.
As the HIV-1 epidemic evolves, heterosexual exposure has become a more common mode of transmission, and women now represent an increasing proportion of newly diagnosed cases. Thus, clinicians are challenged with attempting to make an early diagnosis of HIV-1 infection in a high-risk group that now includes sexually active women. Since the symptoms of PHI can be similar to those of other viral illnesses, such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), and the viral hepatitides, the clinician is likely to encounter many patients in whom PHI should be considered in the differential diagnosis. The use of the RT-PCR assay as a diagnostic tool may lead to a significant number of false-positive results in this large patient population.
To date, four cases of false-positive RT-PCR viral load results have been reported. Three cases consisted of patients who had potential exposure to HIV-1 and were asymptomatic. The other involved a patient who had participated in an HIV-1 vaccine trial and who had symptoms consistent with acute retroviral syndrome (ARS). We report the first case of a sexually active, young woman with symptoms suggestive of ARS in whom RT-PCR for HIV-1 was falsely positive. We discuss the diagnostic issues that arise in what is likely to become a common clinical scenario.
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