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reliability of ELISA for different HIV subtypes
Nov 7, 1996

Dear Dr. Gallant, I am working in an environment with a lot of foreign students and recent immigrants to the US, and we have a few questions for you. Thank you for taking the time to answer them:

What is the difference between HTLV-1 and HIV? Just how many subtypes of HIV-1 and HIV-2 are there? On which basis are distinctions drawn? What is the global distribution of these subtypes? Is the ELISA test the same everywhere in the world? That is, would an ELISA test in the U.S be exactly the same as an ELISA test in France, Brazil, Thailand, Uganda or India? Or would these different countries "fine-tune" their ELISA tests to make them react specifically to the antibodies of the HIV subtype prevalent in their parts of the world? Would "fine-tuning" the ELISA test (if indeed there is such a thing) make it less able to detect antibodies of other HIV subtypes? Would anti-viral therapies currently being developed and used in the U.S be useful for individuals infected by HIV subtypes other than the one prevalent in our country? And my own personal question: Does "acute viral syndrome" accelerate the process of seroconversion (that is, could one say that the more acute the syndrome, the greater or faster the production of antibodies to HIV)? Also, would the presence of another, unrelated infection- such as a throat infection- at the time of HIV infection- hasten seroconversion and lead to a faster production of HIV antibodies? Thank you for your assistance. We look forward to your responses.

Response from Dr. Gallant

HTLV-1 stands for human T-cell leukemia virus type I. Like HIV, it is a retrovirus which can be transmitted sexually, perinatally, or through injection drug use or administration of blood products, but the similarity stops there. Infection with HTLV-I does not cause AIDS; it causes adult T-cell leukemia-lymphoma, and neurologic syndromes referred to as tropical spastic paraparesis (TSP) or HTLV-I associated myelopathy (HAM). There is some evidence that people who are infected with both HIV and HTLV-I will have elevated CD4 counts that will not accurately reflect the true state of their immune system. HTLV-I infection is most common in the Caribbean, Japan, parts of Africa, and some South Pacific Islands.

There are a nine subtypes of HIV-1. The first eight, subtypes A through H, are collectively referred to as major group M. The ninth is subtype O, which is genetically distinct from the subtypes in group M. The predominant subtype in North America and Europe is B. In South America and Asia subtypes B and F predominate, and in Africa subtypes A-H are seen. Routine tests will detect A-H, but will not detect subtype O, which is found primarily in the Cameroon and Gabon in West Africa. HIV-2 is a genetic variant that is found primarily in West Africa, but which is also seen in Portugal, France, Germany, Brazil, and India. HIV-2 is only distantly related to HIV-1. Approximately 80% of patients infected with HIV-2 will have a positive HIV-1 ELISA and a weakly reactive Western Blot; thus, most will either be negative or indeterminate by standard HIV-1 serology. Serologic tests for HIV-2 and for combined HIV-1 and HIV-2 are available. As of June, 1995, there were 62 reported cases of HIV-2 infection in the U.S.; most were immigrants from West Africa.

The HIV-1 ELISA test is fairly standard throughout the world. The Western blot for HIV-1 is also standard, although there is some variation in the criteria for a positive test (which bands are required to call a test positive). The combined ELISA and Western blot tests will detect the vast majority of HIV infections throughout the world. In areas where HIV-2 or HIV-1 subtype O occur, specific tests are required.

The antiretroviral therapies being used in the United States and Europe would be expected to work for HIV infection of any type. However, in the parts of the world where HIV-2 or subtype O infection occur, few patients receive any therapy at all because the cost of such therapies are prohibitive.

As far as we know, there are no real predictors of how fast someone seroconverts. The severity of the acute retroviral syndrome can influence long-term prognosis, but it should not affect the speed at which antibodies develop.



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