The Effect of Viral Suppression on Cross-Sectional Incidence Testing in the Johns Hopkins Hospital Emergency Department

Laeyendecker, Oliver; Rothman, Richard E.; Henson, Charlamaine; Horne, Bobbi Jo; Ketlogetswe, Kerunne; Kraus, Chadd K.; Shahan, Judy B.; Kelen, Gabor D.; Quinn, Thomas C.

doi:10.1097/qai.0b013e3181743980

Cited by 60 publications

(72 citation statements)

References 21 publications

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“…This finding could be due to the observation of significantly higher EndoCAb levels in the African subjects before seroconversion, most likely related to differences in sanitation between the U.S. and African environments, and the endemic parasitic and bacterial disease load in the African population. It also is possible that genetic differences between the 2 uninfected populations affected the differences observed; however, the U.S. comparison group was predominantly African-American, which should limit this effect (23). EndoCAb levels in the African subjects remained consistently high throughout infection regardless of progression status, which may explain in part why circulating LPS levels did not increase in the African subjects.…”

Section: Discussionmentioning

confidence: 85%

Microbial translocation, the innate cytokine response, and HIV-1 disease progression in Africa

Redd

Dabitao²,

Bream³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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111

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Reports from the United States have demonstrated that elevated markers of microbial translocation from the gut may be found in chronic and advanced HIV-1 infection and are associated with an increase in immune activation. However, this phenomenon's role in HIV-1 disease in Africa is unknown. This study examined the longitudinal relationship between microbial translocation and circulating inflammatory cytokine responses in a cohort of people with varying rates of HIV-1 disease progression in Rakai, Uganda. Multiple markers for microbial translocation (lipopolysaccharide, endotoxin antibody, and sCD14) did not change significantly during HIV-1 disease progression. Moreover, circulating immunoreactive cytokine levels either decreased or remained virtually unchanged throughout disease progression. These data suggest that microbial translocation and its subsequent inflammatory immune response do not have a causal relationship with HIV-1 disease progression in Africa.

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Section: Discussionmentioning

confidence: 85%

Microbial translocation, the innate cytokine response, and HIV-1 disease progression in Africa

Redd

Dabitao²,

Bream³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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111

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“…Furthermore, our previous studies have shown a high rate of false-recent misclassification among HIV-infected elite suppressors who have low or undetectable viral loads in the absence of ARV use. 23 In this study, ARV use was not associated with falserecent misclassification in multivariate models that also included HIV viral load.…”

Section: Discussionmentioning

confidence: 85%

Specificity of Four Laboratory Approaches for Cross-Sectional HIV Incidence Determination: Analysis of Samples from Adults with Known Nonrecent HIV Infection from Five African Countries

Laeyendecker

Brookmeyer

Mullis

et al. 2012

AIDS Research and Human Retroviruses

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Assays to determine cross-sectional HIV incidence misclassify some individuals with nonrecent HIV infection as recently infected, overestimating HIV incidence. We analyzed factors associated with false-recent misclassification in five African countries. Samples from 2197 adults from Botswana, Kenya, South Africa, Tanzania, and Uganda who were HIV infected > 12 months were tested using the (1) BED capture enzyme immunoassay (BED), (2) avidity assay, (3) BED and avidity assays with higher assay cutoffs (BED + avidity screen), and (4) multiassay algorithm (MAA) that includes the BED + avidity screen, CD4 cell count, and HIV viral load. Logistic regression identified factors associated with misclassification. False-recent misclassification rates and 95% confidence intervals were BED alone: 7.6% (6.6, 8.8); avidity assay alone: 3.5% (2.7, 4.3); BED + avidity screen: 2.2% (1.7, 2.9); and MAA: 1.2% (0.8, 1.8). The misclassification rate for the MAA was significantly lower than the rates for the other three methods (each p < 0.05). Misclassification rates were lower when the analysis was limited to subtype C-endemic countries, with the lowest rate obtained for the MAA [0.8% (0.2, 1.9)]. Factors associated with misclassification were for BED alone: country of origin, antiretroviral treatment (ART), viral load, and CD4 cell count; for avidity assay alone: country of origin; for BED + avidity screen: country of origin and ART. No factors were associated with misclassification using the MAA. In a multivariate model, these associations remained significant with one exception: the association of ART with misclassification was completely attenuated. A MAA that included CD4 cell count and viral load had lower false-recent misclassification than the BED or avidity assays (alone or in combination). Studies are underway to compare the sensitivity of these methods for detection of recent HIV infection.

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“…Serologic incidence assays have also been used as components of multiassay algorithms (MAAs) developed for cross-sectional HIV incidence estimation (3). Some MAAs also include nonserologic biomarkers, such as CD4 cell count, viral load, and antiretroviral testing or self-report, to help identify individuals with long-standing HIV infections (2,4,5).…”

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confidence: 99%

HIV Diversity as a Biomarker for HIV Incidence Estimation: Including a High-Resolution Melting Diversity Assay in a Multiassay Algorithm

et al. 2014

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pMultiassay algorithms (MAAs) can be used to estimate cross-sectional HIV incidence. We previously identified a robust MAA that includes the BED capture enzyme immunoassay (BED-CEIA), the Bio-Rad Avidity assay, viral load, and CD4 cell count. In this report, we evaluated MAAs that include a high-resolution melting (HRM) diversity assay that does not require sequencing. HRM scores were determined for eight regions of the HIV genome (2 in gag, 1 in pol, and 5 in env). The MAAs that were evaluated included the BED-CEIA, the Bio-Rad Avidity assay, viral load, and the HRM diversity assay, using HRM scores from different regions and a range of region-specific HRM diversity assay cutoffs. The performance characteristics based on the proportion of samples that were classified as MAA positive by duration of infection were determined for each MAA, including the mean window period. The cross-sectional incidence estimates obtained using optimized MAAs were compared to longitudinal incidence estimates for three cohorts in the United States. The performance of the HRM-based MAA was nearly identical to that of the MAA that included CD4 cell count. The HRM-based MAA had a mean window period of 154 days and provided cross-sectional incidence estimates that were similar to those based on cohort follow-up. HIV diversity is a useful biomarker for estimating HIV incidence. MAAs that include the HRM diversity assay can provide accurate HIV incidence estimates using stored blood plasma or serum samples without a requirement for CD4 cell count data.

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The Effect of Viral Suppression on Cross-Sectional Incidence Testing in the Johns Hopkins Hospital Emergency Department

Cited by 60 publications

References 21 publications

Microbial translocation, the innate cytokine response, and HIV-1 disease progression in Africa

Microbial translocation, the innate cytokine response, and HIV-1 disease progression in Africa

Specificity of Four Laboratory Approaches for Cross-Sectional HIV Incidence Determination: Analysis of Samples from Adults with Known Nonrecent HIV Infection from Five African Countries

HIV Diversity as a Biomarker for HIV Incidence Estimation: Including a High-Resolution Melting Diversity Assay in a Multiassay Algorithm

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