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Contributions to the improvement and understanding of new diagnostics for HIV infection and syphilis

  • Author(s): Bristow, Claire C.
  • Advisor(s): Sorvillo, Frank J
  • et al.
Abstract

Syphilis is a curable disease, yet 10 million persons worldwide are infected each year, of which 1.4 million are pregnant women. Syphilis is an infection caused by the spirochete Treponema pallidum and frequently has atypical presentations that may be difficult to differentiate from other sexually transmitted infections (STIs) making effective diagnostics essential to the identification of infection. Additionally, the manifestations of the disease vary depending on the duration of infection and time of presentation. There are four stages-primary, secondary, latent (early and late), and tertiary.

Syphilis screening and treatment programs that utilize laboratory-based testing have been hampered by limited laboratory access, long turn-around time for results, and loss to follow-up of syphilis infected individuals. When syphilis diagnostic testing involves multiple tests performed off-site, only a proportion of infected individuals receive treatment and continued transmission occurs.

A rapid test is a simple point-of-care test that can be used in a variety of settings and provides a result to guide clinical management during the time of the initial consultation (ideally within 30 minutes or less). The advent of rapid point-of-care tests for syphilis has reduced barriers and allowed for new health systems approaches to syphilis prevention, including same day testing and treatment. Dual rapid tests that have multiple analytes for the detection of antibodies for both HIV and syphilis infections are now available.

Our first study addressed preferences for dual HIV/syphilis tests through a conjoint survey analysis. Conjoint analysis is a method for systematically estimating consumer preferences across discrete attributes. Conjoint analysis has been used extensively in marketing research and measures the value that consumers place on each feature of a product. Conjoint analysis has recently begun to be applied in health research. We recruited 298 men and women 18 years of age and over seeking testing or care at GHESKIO (Haitian Study Group for Kaposi’s sarcoma and Opportunistic Infections) clinics. We created 8 hypothetical dual test profiles varying across six dichotomous attributes: cost (free versus $4), accuracy (no false positive versus false positive), time-to-result (20 minutes versus 1 week), blood draw method (finger prick versus venipuncture), number of draws (1 versus 2), and test type (rapid versus laboratory). Cost (free vs. $4; impact score=27.2, SD=36.6, p<.0001) had the highest impact on likelihood of testing, followed by number of blood draws (1 versus 2; impact score=17.5, SD=29.8, p<.0001), blood draw method (fingerprick versus venipuncture; impact score=9.7, SD=26.5, p<.0001), test type (rapid versus laboratory; impact score= -4.5, SD=21.9 , P=.0005), and time-to-result (20 minutes versus 1 week; impact score=3.6, SD=25.6, p=.0139). This analysis showed that implementation of a low cost dual rapid test in the laboratory for HIV and syphilis could be used to improve screening uptake and accessibility to accelerate time to treatment.

Our second study was a field study of a dual HIV and syphilis rapid test in Port-au-Prince, Haiti. Field studies using whole blood fingerprick specimens are essential to understand how the test will perform in real-world settings. We found that for the HIV test component, sensitivity and specificity were 99.2% (95% CI: 95.8%, 100%) and 97.0% (95% CI: 93.2%, 99.0%), respectively; and for the syphilis component were 96.5% (95% CI: 91.2%, 99.0%) and 90.8% (95% CI: 85.7%, 94.6%), respectively. This test performed well and could be considered for wider use to increase rates of HIV and syphilis screening.

Our final analysis was an epidemiological bias analysis using estimates of potential misclassification by use of an imperfect gold standard test. We used regression calibration methods to assess the effect of reference standard misclassification bias using the syphilis component of the dual HIV and syphilis rapid test as an example. We concluded by making recommendations for reporting diagnostic performance ranges instead of point estimates when using an imperfect reference test.

In conclusion, dual HIV and syphilis testing is a preferred screening modality that can be used to streamline HIV and syphilis prevention and case finding. These tests perform well in both laboratory and point-of-care settings and should be considered for wider implementation. Use of regression calibration methodology can provide accurate information on the potential performance characteristics of these tests when a perfect gold standard test is unavailable.

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