Correspondence

Detection of Acute HIV Infections

N Engl J Med 2005; 353:631-633August 11, 2005

Article

To the Editor:

The recent article by Pilcher et al. (May 5 issue)1 described successful public health methods to control HIV transmission, but the authors' findings may not be generalizable to states that do not have confidential HIV-reporting systems, such as California. In the fall of 2003, we initiated a program of RNA screening, routine patient interviewing, and HIV genotypic-resistance testing at the San Francisco municipal sexually transmitted disease (STD) clinic.

During 2004, we identified 136 of 3789 persons (3.6 percent) as having an HIV infection, among them 11 (0.3 percent) who had an acute infection. HIV RNA screening increased the rate of HIV case detection to 8.8 percent, more than double the overall rate of 3.9 percent reported by Pilcher et al. Eight percent of the viruses detected exhibited drug resistance to one drug class, 4 percent to two drug classes, and none to more than two drug classes. Interviews with patients elicited information about 112 sex partners, 10 of whom were newly identified as having an HIV infection.

The combined data support the real benefit that routine HIV RNA screening, HIV resistance surveillance, and patient interviews can have in the control of HIV. Further efforts should be made to strengthen and expand HIV-control efforts in STD clinics as well as to ensure confidential HIV reporting nationwide.

Jeffrey D. Klausner, M.D., M.P.H.
San Francisco Department of Public Health, San Francisco, CA 94103
jeff.klausner@sfdph.org

Robert M. Grant, M.D., M.P.H.
Gladstone Institute of Virology and Immunology, San Francisco, CA 94141

Charlotte K. Kent, M.P.H.
San Francisco Department of Public Health, San Francisco, CA 94103

1 References

1. 1

   Pilcher CD, Fiscus SA, Nguyen TQ, et al. Detection of acute infections during HIV testing in North Carolina. N Engl J Med 2005;352:1873-1883
   Full Text | Web of Science | Medline

To the Editor:

Pilcher and colleagues added nucleic acid amplification to diagnose HIV infection in a cohort of 109,250 persons. They concluded that “this form of testing should be a standard tool for the prevention and surveillance of HIV infection.” However, HIV experts1,2 and the maker3 of the RNA test used by the authors assert that it “is not to be used as a screening test for blood or blood products for HIV or as a diagnostic test to confirm the presence of HIV infection.” The Centers for Disease Control and Prevention (CDC)4 asserts that “in adults, adolescents, and children infected by other than perinatal exposure, plasma viral RNA nucleic acid tests should not be used in lieu of licensed HIV screening tests.”

The confirmatory Western blot test used by the authors was considered positive according to the revised CDC criteria. However, the criteria for a positive Western blot remain unstandarized. Band patterns considered proof of HIV infection vary among laboratories, institutions, and countries (Table 1Table 1Global Variation in the Criteria for a Positive Western Blot.).5 For example, results that are positive according to the revised CDC criteria are not considered positive by the Food and Drug Administration or by the National Serology Reference Laboratory in Australia. Thus, a situation may arise wherein a person considered seropositive and infected according to one set of criteria may be serologically indeterminate and not infected according to another, and vice versa.

Valendar F. Turner, F.R.A.C.S., F.A.C.E.M.
Department of Health, Western Australia, Perth 6004, Australia
vturner@westnet.com.au

5 References

1. 1

   Rich JD, Merriman NA, Mylonakis E, et al. Misdiagnosis of HIV infection by HIV-1 plasma viral load testing: a case series. Ann Intern Med 1999;130:37-39
   Web of Science | Medline

2. 2

   de Mendoza C, Holguin A, Soriano V. False positives for HIV using commercial viral load quantification assays. AIDS 1998;12:2076-2077
   CrossRef | Web of Science | Medline

3. 3

   Amplicor 1.5 HIV-1 Monitor Test. Branchburg, N.J.: Roche Diagnostic Systems, 1999 (package insert).
   

4. 4

   Guidelines for national human immunodeficiency virus case surveillance, including monitoring for human immunodeficiency virus infection and acquired immunodeficiency syndrome. MMWR Recomm Rep 1999;48:1-27, 29
   

5. 5

   HIV BLOT 2.2 Western Blot Assay. Singapore: Genelabs Diagnostics, 2004 (package insert).
   

Author/Editor Response

Dr. Turner notes correctly that HIV nucleic acid amplification tests are not marketed for clinical diagnostic use. Generally, this is understandable: the specificity of nucleic acid amplification tests can be as low as 97 percent — inadequate for HIV screening, except in clinical circumstances in which the pretest probability of infection is extremely high (for instance, in the evaluation of suspected acute retroviral syndromes). However, group-testing algorithms in our study drastically cut the number of individual samples tested by nucleic acid amplification, resulting in excellent specificity (>99.99 percent) for the combined antibody and nucleic acid amplification approach. The positive predictive value for positive results on nucleic acid amplification testing among antibody-negative clients was remarkably high (90 percent), considering the low prevalence of the disease. It is interesting to note that nucleic acid amplification tests are both licensed and marketed for diagnostic testing of blood donors, for which the group-testing strategy is preferred. Still, even when pooled, nucleic acid amplification tests must be considered screening tests that, if positive, warrant additional testing to confirm or rule out seroconversion. With regard to our study's criteria for HIV-antibody positivity on confirmatory testing, varying Western blot criteria made no difference in the results. Moreover, the various Western blot criteria have very little or no effect on the sensitivity of antibody screening (the problem with current antibody testing that the addition of nucleic acid amplification testing aims to improve).

Dr. Klausner and colleagues point to the fact that the public health infrastructure in North Carolina favored the state's success in implementing testing procedures for acute HIV infection. In addition to confidential testing, the state also has invested in the systems necessary for partner counseling and referral, with staffing by specialists experienced in HIV and STD intervention, and continues to favor the use of venipuncture (as opposed to oral-fluid or finger-prick–blood collection) at most HIV-testing sites. Particularly in areas with a high burden of HIV disease, such as California, the potential benefit of programs designed for the prevention of acute HIV infection may merit reconsideration of these issues.

Christopher D. Pilcher, M.D.
Peter A. Leone, M.D.
University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7215
cpilcher@med.unc.edu

Citing Articles (9)

Citing Articles

1. 1

   G. U. van Zyl, W. Preiser, S. Potschka, A. T. Lundershausen, R. Haubrich, D. Smith. (2011) Pooling Strategies to Reduce the Cost of HIV-1 RNA Load Monitoring in a Resource-Limited Setting. Clinical Infectious Diseases 52:2, 264-270
   CrossRef

2. 2

   Davey M Smith, Susanne J May, Josué Pérez-Santiago, Matthew C Strain, Caroline C Ignacio, Richard H Haubrich, Douglas D Richman, Constance A Benson, Susan J Little. (2009) The use of pooled viral load testing to identify antiretroviral treatment failure. AIDS 23:16, 2151-2158
   CrossRef

3. 3

   Victor DeGruttola, Susan Little, Robert Schooley. (2008) Controlling the HIV epidemic, without a vaccine!. AIDS 22:18, 2554-2555
   CrossRef

4. 4

   Rachel Smith, Nicola M Zetola, Jeffrey D Klausner. (2007) Beyond the end of exceptionalism: integrating HIV testing into routine medical care and HIV prevention. Expert Review of Anti-infective Therapy 5:4, 581-589
   CrossRef

5. 5

   Nicola M. Zetola, Christopher D. Pilcher. (2007) Diagnosis and Management of Acute HIV Infection. Infectious Disease Clinics of North America 21:1, 19-48
   CrossRef

6. 6

   Frances H Priddy, Christopher D Pilcher, Renee H Moore, Pradnya Tambe, Mahin N Park, Susan A Fiscus, Mark B Feinberg, Carlos del Rio. (2007) Detection of Acute HIV Infections in an Urban HIV Counseling and Testing Population in the United States. JAIDS Journal of Acquired Immune Deficiency Syndromes 44:2, 196-202
   CrossRef

7. 7

   Sandra Schwarcz, Hillard Weinstock, Brian Louie, Timothy Kellogg, John Douglas, Marlene LaLota, Gordon Dickinson, Lucia Torian, Deborah Wendell, Sindy Paul, Garald Goza, Juan Ruiz, Brian Boyett, Lyle McCormick, Diane Bennett. (2007) Characteristics of Persons With Recently Acquired HIV Infection. JAIDS Journal of Acquired Immune Deficiency Syndromes 44:1, 112-115
   CrossRef

8. 8

   Christopher D. Pilcher, Lisa Eaton, Seth Kalichman, Cláudia Bisol, Ricardo da Silva Souza. (2006) Approaching "HIV elimination": Interventions for acute HIV infection. Current HIV/AIDS Reports 3:4, 160-168
   CrossRef

9. 9

   Joanne Stekler, Ann C. Collier, King K. Holmes, Matthew R. Golden. (2006) Primary HIV Infection Education. JAIDS Journal of Acquired Immune Deficiency Syndromes 42:1, 123-126
   CrossRef