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The HIV Genomic Incidence Assay Meets False Recency Rate and Mean Duration of Recency Infection Performance Standards.

ABSTRACT: HIV incidence is a primary metric for epidemic surveillance and prevention efficacy assessment. HIV incidence assay performance is evaluated via false recency rate (FRR) and mean duration of recent infection (MDRI). We conducted a meta-analysis of 438 incident and 305 chronic specimens' HIV envelope genes from a diverse global cohort. The genome similarity index (GSI) accurately characterized infection stage across diverse host and viral factors. All except one chronic specimen had GSIs below 0.67, yielding a FRR of 0.33 [0-0.98] %. We modeled the incidence assay biomarker dynamics with a logistic link function assuming individual variabilities in a Beta distribution. The GSI probability density function peaked close to 1 in early infection and 0 around two years post infection, yielding MDRI of 420 [361, 467] days. We tested the assay by newly sequencing 744 envelope genes from 59 specimens of 21 subjects who followed from HIV negative status. Both standardized residuals and Anderson-Darling tests showed that the test dataset was statistically consistent with the model biomarker dynamics. This is the first reported incidence assay meeting the optimal FRR and MDRI performance standards. Signatures of HIV gene diversification can allow precise cross-sectional surveillance with a desirable temporal range of incidence detection.

SUBMITTER: Park SY

PROVIDER: S-EPMC5547093 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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The HIV Genomic Incidence Assay Meets False Recency Rate and Mean Duration of Recency Infection Performance Standards.

Park Sung Yong SY Love Tanzy M T TMT Reynell Lucy L Yu Carl C Kang Tina Manzhu TM Anastos Kathryn K DeHovitz Jack J DeHovitz Jack J Liu Chenglong C Kober Kord M KM Cohen Mardge M Mack Wendy J WJ Lee Ha Youn HY

Scientific reports 20170807 1

HIV incidence is a primary metric for epidemic surveillance and prevention efficacy assessment. HIV incidence assay performance is evaluated via false recency rate (FRR) and mean duration of recent infection (MDRI). We conducted a meta-analysis of 438 incident and 305 chronic specimens' HIV envelope genes from a diverse global cohort. The genome similarity index (GSI) accurately characterized infection stage across diverse host and viral factors. All except one chronic specimen had GSIs below 0. ...[more]

PMID: 28785052

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Project description:IntroductionHIV incidence estimates are important to characterize the status of an epidemic, identify locations and populations at high risk and to guide and evaluate HIV prevention interventions. We used the limiting antigen avidity assay (LAg) as part of a recent infection testing algorithm to estimate HIV incidence in the Akwa Ibom AIDS Indicator Survey (AKAIS), Nigeria.MethodsIn 2017, AKAIS, a cross-sectional population-based study was conducted at the household (HH) level in 31 local government areas (LGAs) of Akwa Ibom state. Of the 8963 participants aged ≥15 years who were administered questionnaires for demographic and behavioural data, 8306 consented to HIV rapid testing. Whole-blood specimens were collected from 394 preliminary HIV-seropositive individuals for CD4+ cell count determination and plasma storage. Samples were shipped to a central quality laboratory for HIV confirmatory testing and viral load determination. A total of 370 HIV-positive specimens were tested for the recent HIV infection using the LAg assay.ResultsOf the 8306 consenting adults, the HIV prevalence was 4.8%. Of the 370 HIV-positive samples tested for HIV recency, the median age was 35 years, 48.8% had CD4+ cell count >500/mm3 and 81.3% was not virally suppressed. Viral suppression was greater among females (21%) than for males (13%). A total of 11 specimens were classified as recent based on the LAg assay and HIV viral load ≥1000 copies/mL. The weighted, adjusted HIV-1 incidence was 0.41/100 person-years (95% CI 0.16 to 0.66); translating to 13,000 new cases of HIV infections annually in Akwa Ibom, a state with a population of 5.5 million. The HIV incidence rate was similar in females and males (0.41% and 0.42% respectively). The incidence rate was the highest among participants aged 15 to 49 years (0.44%, 95% CI 0.15 to 0.74) translating to 11,000 new infections annually, about 85% of all new infections in the state.ConclusionsThe finding of the high HIV incidence among the 15 to 49-year age group calls for renewed and innovative efforts to prevent HIV infection among young adults in Akwa Ibom state.

Project description:HIV incidence is a key measure for tracking disease spread and identifying populations and geographic regions where new infections are most concentrated. The HIV sequence population provides a robust signal for the stage of infection. Large-scale and high-precision HIV sequencing is crucial for effective genomic incidence surveillance. We produced 1,034 full-length envelope gene sequences from a seroconversion cohort by conducting HIV microdrop sequencing and measuring the genomic incidence assay's genome similarity index (GSI) dynamics. The measured dynamics of 9 of 12 individuals aligned with the GSI distribution estimated independently using 417 publicly available incident samples. We enhanced the capacity to identify individuals with recent infections, achieving predicted detection accuracies of 92% (89%-94%) for cases within 6 months and 81% (74%-87%) for cases within 9 months. These accuracy levels agreed with the observed detection accuracy intervals of an independent validation data set. Additionally, we produced 131 full-length envelope gene sequences from eight individuals with chronic HIV infection. This analysis confirmed a false recency rate (FRR) of 0%, which was consistent with 162 publicly available chronic samples. The mean duration of recent infection (MDRI) was 238 (209-267) days, indicating an 83% improvement in performance compared to current recent infection testing algorithms. The shifted Poisson mixture model was then used to estimate the time since infection, and the model estimates showed an 88% consistency with the days post infection derived from HIV RNA test dates and/or seroconversion dates. HIV microdrop sequencing provides unique prospects for large-scale incidence surveillance using high-throughput sequencing. IMPORTANCE Accurate identification of recently infected individuals is vital for prioritizing specific populations for interventions, reducing onward transmission risks, and optimizing public health services. However, current HIV-specific antibody-based methods have not been satisfactory in accurately identifying incident cases, hindering the use of HIV recency testing for prevention efforts and partner protection. Genomic incidence assays offer a promising alternative for identifying recent infections. In our study, we used microdroplet technologies to produce a large number of complete HIV envelope gene sequences, enabling the accurate detection of early infection signs. We assessed the dynamics of the incidence assay's metrics and compared them with statistical models. Our approach demonstrated high accuracy in identifying individuals with recent infections, achieving predicted detection rates exceeding 90% within 6 months and over 80% within 9 months of infection. This high-resolution method holds significant potential for enhancing the effectiveness of HIV incidence screening for case-based surveillance in public health initiatives.

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The HIV Genomic Incidence Assay Meets False Recency Rate and Mean Duration of Recency Infection Performance Standards.

Publications

The HIV Genomic Incidence Assay Meets False Recency Rate and Mean Duration of Recency Infection Performance Standards.

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