The Body Covers: The 6th Conference on Retroviruses and Opportunistic Infections
Abstract No. 52: Viral and Immunologic Examination of HIV-I-Infected Persistently Seronegative (HIPS) Persons
February 1, 1999
In this study the authors observed that in detecting HIV I infection the modalities used were based on serological testing for antibodies. There are nine commercial licensed EIA type kits and confirmation is usually done using Western blot or IFA. The assumption has always been that HIV antibody response can always be detected in blood except during the "window" period of early infection. In this abstract the authors have looked at a series of patients with a documented history of negative HIV I serology despite known HIV infection, and AIDS associated symptoms.
Through AIDS case surveillance they identified people who were HIV I infected, but who remained persistently seronegative. These patients were shown to be HIV positive as determined by P-24 antigen as well as proviral DNA amplification and viral culture. These patients were discovered when they developed signs or symptoms of disease or presented with events commonly associated with HIV. Possible theoretical explanations for the presence of HIV symptoms in the absence of HIV I associated antibodies included testing during "window period"; immunologic defects, such as hypogammoglobulinemia and B cell defects; and lastly, a seroreversion which they characterize as overwhelming failure of the immune system where there is insufficient T cell help to maintain antibody production. Viral factors that may affect detection of antibody, or lack thereof, included diversity of HIV strains making detection difficult, and possibly seroconversion rates that vary among various subtypes of HIV. Environmental issues that may have an impact include severe immunosuppression, the administration of chemotherapeutic agents, and, lastly, laboratory error. In the population examined, the CD4 count ranged from an absolute number of 15 to 415 with viral loads ranging from 17 to 4,108. Opportunistic infections included pneumocystis pneumonia. Wasting syndrome was also noted as well as other HIV associated infections.
They summarized their data as follows. Analysis of the antibodies for specific HIV structural proteins revealed that three of the six specimens had weak antibodies to P24 only, whereas none revealed antibodies to the envelop glycoprotein. To rule out HIV specific antibodies being masked by immune complexes, they utilized a Western blot analysis after using techniques to allow for basic dissociation of immune complexes. No unmissed antibodies were then detected. Indeed, no HIV I specific IgA antibodies were detectable at all.
The full sequence analysis of the partial genome and examination of cellular tropism of the isolated viruses from these individuals did not demonstrate any unusual characteristics. Indeed, biogenetic analysis of the ENV GP41 immunodominant region showed that the virus of these individuals are HIV sub-type B which is the dominant strain in the United States. Utilizing proliferation studies and reconstitution experiments, they concluded that the lack of detectable antibody response may be a result of immune dysfunction rather than viral factors.
This study clearly has epidemiological significance, and implications for blood bank testing. In addition, one cannot assume that an HIV negative test is complete assurance that one's partner is HIV negative. Safe sex techniques still remain extremely important. While this population was identified using such markers as opportunistic infections or other HIV-associated phenomenon, it would be interesting to know if there is a similar phenomenon occurring in long-term nonprogressors. This type of patient may still be in the general population pool, unaware of their infection. It would be very enlightening to use similar techniques in identifying this subpopulation.
Authored by: D.L. Ellenberger, P.S. Sullivan, J. Dorn, C. Schable, T.J. Spira, T.M. Folks, and R.B. Lal
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