Urine antibody tests: new insights into the dynamics of HIV-1 infection.

BACKGROUND: Noninvasive methodologies provide alternatives to diagnostic blood tests and have high patient acceptance, increased safety, and reduced costs. Such tests may supplement or replace blood diagnostic assays currently in use. METHODS: Using a licensed urine-based test for antibody to HIV-1, we performed 25 991 HIV-1 urine antibody enzyme immunoassay (EIA) screening tests [confirmable by HIV-1 Western blot (WB)] on paired urine and blood specimens obtained from high- and low-risk HIV-1 subjects collected at six sites representative of the US population. RESULTS: Using HIV-1 urine EIA tests confirmed by urine Western blot, a compartmentalized immune response (urine positive/serum negative) occurred in 0.24% of a cohort of 11 896 subjects. In the same cohort, specimens that were urine negative/serum positive occurred in 0.17% of subjects. In a second study of 25 991 subjects that included 859 high-risk individuals, the false-positive urine EIA frequency (urine WB negative or indeterminate) was 1.3%. This false-positive frequency in the high-risk cohort was attributed, in part, to an IgA antibody response. We tabulated urine and serum indeterminate reactivities and examined their possible causes. Data are presented showing that antibodies from a seroindeterminate HIV-1vau group O subject were reactive in urine EIA and urine WB tests. An analysis of the HIV-1vau strain group O env nucleotide sequence disclosed a high frequency of homology with human chromosome 7q31, a fragile site implicated in many human malignancies. CONCLUSIONS: These results demonstrate the utility of urine for alternative HIV-1 antibody testing and provide new insights into the pathogenesis of HIV-1 infection and into potential application of this approach in investigation of other microbial pathogens and toxic compounds.

Increased sensitivity of HIV-1 antibody detection.

Clinical trial results from 11,344 paired urine and serum samples revealed 1,181 HIV-1-positive individuals confirmed by western blot (WB). There were 25 discrepant samples: 10 were urine enzyme immunoassay (EIA) and WB positive, serum non-reactive and serum WB negative or indeterminate, and 15 were serum EIA and WB positive, urine EIA non-reactive or urine WB negative or indeterminate. Serum samples, HIV-1 antibody WB confirmed, revealed a 99.15% sensitivity (1,171 out of 1,181); urine samples, HIV-1 antibody WB confirmed, showed a 98.73% sensitivity (1,166 out of 1,181). This study demonstrated that neither serum nor urine results alone are as sensitive for HIV-1 antibody detection as combined results of both samples.

Urine-based diagnostic technologies.

The worldwide dissemination of infectious agents has created a demand for simple diagnostic tests. Urine-based testing makes use of non-invasive collection of specimens, and there is no need for expensive facilities and equipment, or for highly trained personnel. As urine antibodies retain activity under normal conditions of transport and storage, such tests appear to have widespread application. Urine-based antibody tests have also indicated a compartmentalized antibody response to HIV-1 infection. Urine studies suggest that antibodies to the products of endogenous viral genes may be involved in the pathogenesis of chronic diseases of suspected viral etiology.

HIV-1 antibody serum negativity with urine positivity.

7 individuals who were negative for HIV-1 antibody in a licensed serum enzyme immunoassay (EIA) were positive in a urine EIA and western blot (WB). Follow-up in individuals by use of a cell-mediated immune response showed 1 positive and 1 negative for HIV-1 peptide reactivity. In a second study, 4 out of 5 subjects positive by urine EIA and indeterminate or negative by serum WB were HIV-1 peptide positive in the cell-mediated immune test. Comparison of cell-mediated responses with urine antibody responses may help to resolve discrepant HIV-1 results.

HIV-1 testing: product development strategies.

Strategies for the development of diagnostic products for acquired immune deficiency syndrome (AIDS) are inextricably linked to the status of our knowledge of the human immunodeficiency virus (HIV) and the events associated with the pathogenesis of AIDS. This review traces product development strategies from 1984 to the present day. Product development activities in the HIV-1 antibody screening test market were a response to the need to remove contaminated units from the blood supply. With the successes in screening blood and blood products, there has been a shift towards product development for personal health care and applicant suitability. Identification of markers for disease progression and the need to monitor therapeutic efficacy is now leading to tests for patient disease staging, monitoring and prognosis.

Characterization of the interaction between polymerized human albumin and hepatitis B surface antigen.

The interaction of polymerized human albumin with hepatitis B surface antigen was characterized utilizing a solid-phase radioimmunoassay. The interaction was specific as shown by quantitative inhibition of binding by soluble polymerized human albumin. The interaction was species restricted in that hepatitis B surface antigen did not bind nonhuman polymerized albumins. The albumin polymer size was critical to the binding reaction as was the concentration of hepatitis B surface antigen; the interaction was also temperature, ionic strength, and pH dependent. Hepatitis B e antigen positive sera possessed greater polyalbumin binding reactivity than hepatitis B e antigen negative sera. This interaction was shown to be inhibited by normal human serum which suggested that the polyalbumin receptor on hepatitis B surface antigen may be a host rather than viral component. In view of our previous observation that polymerized human albumin binds human C1q, the interactions between polymerized human albumin, hepatitis B surface antigen, and human C1q may be relevant to hepatitis B virus-host receptor mechanisms.