Evaluation of the Mean Duration of Recent Infection (MDRI) and the False Recent Rate (FRR) for the Limiting Antigen Avidity Enzyme Immune Assay (LAg) and Bio-Rad HIV ½ Plus O Avidity Incidence Assay (BRAI)

dc.contributor.advisorHargrove, Johnen_ZA
dc.contributor.advisorNachega, Jeanen_ZA
dc.contributor.advisorVan Zyl, Gerten_ZA
dc.contributor.advisorKilmarx, Peter H.en_ZA
dc.contributor.authorGonese, Elizabethen_ZA
dc.contributor.otherStellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.en_ZA
dc.date.accessioned2017-11-24T13:40:28Z
dc.date.accessioned2017-12-11T11:10:05Z
dc.date.available2017-11-24T13:40:28Z
dc.date.available2017-12-11T11:10:05Z
dc.date.issued2017-12
dc.descriptionThesis (PhD)--Stellenbosch University, 2017.en_ZA
dc.description.abstractENGLISH SUMMARY : Background: The evaluation of laboratory assays in estimating HIV incidence has become a priority because of the complexity of HIV epidemics and the need to measure the impact of public health interventions targeting reduction of HIV incidence. Biomarkers should have test properties that allow the lowest possible False Recent Rate (FRR, or probability of diagnosing a long-term infection as recently infected) over the longest possible period (Mean Duration of Recent Infection or MDRI) during which the case is considered as a recent infection. Methods: We compared the BED Capture Enzyme Immunoassay (BED), Sedia Limiting Antigen (LAg) and Bio-Rad HIV ½ Plus O Avidity Incidence Assay (BRAI) using samples from a prospective cohort trial, the Zimbabwe Vitamin A for Mothers and Babies Project (ZVITAMBO) 1997–2000. We determined MDRI using 591 samples from 184 seroconverting women, and determined FRR by testing 2825 cases known to be HIV- positive for >12 months. We used these results to estimate HIV incidence over the first 12 months postpartum, and during the period prior to childbirth. Results: At recommended cut-offs MDRI values were: BRAI, 135 days (120 – 151) at Avidity Index (AI) 30%; LAg, 104 days (98 - 110) at ODn cut-off 1.5; BED, 188 days (180 -196) at ODn cut-off 0.8. All error bounds in this thesis signify 95% confidence intervals. The coefficients of variation (CV) of the MDRI estimates for BRAI, LAg and BED were 5.9%, 2.9% and 2.1%, respectively. Corresponding FRRs were 1.1% (0.7-1.5) for BRAI, 0.6% (0.3-0.9) for LAg and 4.8% (4.1-5.7) for BED. MDRI and FRR estimates, all derived using postpartum women, were lower than in other published studies. Using original ZVITAMBO HIV diagnoses, adjusted HIV incidence over the first 12 months postpartum was estimated as; BRAI, 2.7% (1.8-3.7); LAg, 3.7% (2.7-4.8); BED, 3.6% (2.4 -4.9). Follow-up incidence was 3.4% (3.0-3.8). When cases with viral load <1000 copies/ml were defined as long-term infections, regardless of serological biomarker level, FRRs were; BRAI, 1.0% (0.7-1.5); LAg, 0.2% (0.2 -0.7); BED 3.8% (3.1-4.6). MDRIs were; BRAI, 133 days (113-154); LAg, 101 days (87-115); BED, 177 days (155 - 199). Corresponding incidences, unadjusted for FRR, were: BRAI, 3.9% (2.9-4.9); LAg, 3.1% (2.1-4.0); BED, 6.2 % (5.0-7.3). Adjusted estimates were 2.7% (1.5-4.0), 2.5% (1.6-3.5) and 2.6% (1.6-3.7) respectively. At baseline, with no follow-up estimate for comparison, adjusted incidence for serological biomarkers used alone were; BRAI, 8.1% (6.6-9.7); LAg, 6.9% (5.7-8.1); BED 6.7% (5.5-7.9). When viral load was also used, the adjusted and unadjusted incidence estimates were; BRAI, 7.3% (5.7-8.8) and 8.4% (6.8-10.0); LAg, 5.1% (3.9-6.3) and 5.7% (4.5-6.9); BED, 5.4% (4.1-6.7) and 8.6% (7.3-10.0). Conclusion: At recommended cut-offs; BRAI FRR was 1.9 times higher than that of LAg. BRAI MDRIs were also 1.3 times higher, but with a relative standard error 2.4 times as high. Postpartum BRAI incidence estimates were consistently lower than follow-up estimates. Adjusted biomarker estimates under-estimated follow-up incidence when we used viral load in combination with either serological test.en_ZA
dc.description.abstractAFRIKAANSE OPSOMMING : Geen opsomming beskikbaar.af_ZA
dc.format.extentxv, 165 pages ; illustrations
dc.identifier.urihttp://hdl.handle.net/10019.1/102902
dc.language.isoen_ZAen_ZA
dc.publisherStellenbosch : Stellenbosch University
dc.rights.holderStellenbosch University
dc.subjectHIV infection -- Epidemiologyen_ZA
dc.subjectMean Duration of Recent Infection (MDRI)en_ZA
dc.subjectFalse Recent Rate (FRR)en_ZA
dc.subjectLimiting Antigen Avidity Enzyme Immune Assay (LAg)en_ZA
dc.subjectBio-Rad HIV ½ Plus O Avidity Incidence Assay (BRAI)en_ZA
dc.subjectHIV infections -- Testingen_ZA
dc.subjectUCTD
dc.titleEvaluation of the Mean Duration of Recent Infection (MDRI) and the False Recent Rate (FRR) for the Limiting Antigen Avidity Enzyme Immune Assay (LAg) and Bio-Rad HIV ½ Plus O Avidity Incidence Assay (BRAI)en_ZA
dc.typeThesisen_ZA
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