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CRF Literature
Aug 26, 2004

Dear Dr Scherer,

Thanks for your precise and thoughtful responses on this forum.

I refer to your response posted on 24 June 04 on diagnosing CRF's of HIV, and in particular the statement that CRF's may in some cases produce antibodies undetectable by any diagnostic test.

Could you please refer me to any published papers/articles (or guidelines, of course) identifying this issue.

This would be of enormous personal assistance in managing my health in consultation with my professional health advisors, and no doubt of great general interest.

Sincerely, P.

Response from Dr. Sherer

Yes, though I will remind readers that these cases are rare, and primarily a concern for individuals with exposures outside of the United States in regions where non-B clades are more common.

However, we do live in a global village, as evidenced by a report from New York City several years ago noting that 20% of recent infections were non-subtype B, and another report presented in Bangkok from Minneapolis where they also noted a 20% incidence of non-B strains among recent infections.

Most people infected with most strains of HIV, including non-B strains, will have a positive ELISA, followed by a positive Western BLot. Patients with HIV-2 will have a positive ELISA screening test for HIV antibodies and a negative or indeterminate western blot; in such cases, performance of an HIV-2 western blot is appropriate.

Patients with Group O ('O' stands for 'Outlier', and 'M' stands for 'Main') or non-clade B M strains of HIV-1 may have falsely negative ELISA screening tests for HIV. Additional antibody testing can be done via the US CDC (see Jaffe reference below) in the event of a high index of suspicion on clinical or epidemiologic grounds for HIV infection in regions of highly prevalent non-B clades, as in Asia or Africa.

In addition, the third generation viral load tests, such as the Roche Amplicor 1.5, detect plasma viral RNA of a wide variety of clades, including sub-type O and clade M. The use of these assays in the diagnosis of HIV is not established, as false positives do occur. HIV DNA testing can also be utilized to detect group M and group O isolates (see the Respess article below).

Regarding references, a succinct summary of this issue can be found in the 2004 Update of the American Academy of HIV Medicine Study Guide (pgs 12-13, and 15-16). Other references include:

Holodny M and Busch MP. "Establishing the Diagnosis of HIV Infection." in Dolin, Masur, and Saag, HIV Therapy, CHurchill Livingston, 2003, pgs 3-20.

Mylonakis et al. Lab testing for infection with HIV: Established and novel approaches. Amer Jl Med 2000;109:568.

Jaffe et al. Group O HIV Infections. Infect Dis Clin North Amer 1998;12:39-46.

Respess et al. Detection of genectically diverse HIV type 1 group M and O isolates by PCR. J Clin Microbiol 1997;35:1284.


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