Evaluation of the Performance of Three Biomarker Assays for Recent HIV Infection Using a Well-Characterized HIV-1 Subtype C Incidence Cohort

2019 ◽  
Vol 35 (7) ◽  
pp. 615-627
Author(s):  
Elizabeth Gonese ◽  
Peter H. Kilmarx ◽  
Cari van Schalkwyk ◽  
Eduard Grebe ◽  
Kuda Mutasa ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Subtype C ◽  
Recent Hiv Infection ◽  
Hiv 1

scholarly journals Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhen Wang ◽  
Bin Zhao ◽  
Minghui An ◽  
Wei Song ◽  
Xue Dong ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Hiv Infection ◽  
Northeast China ◽  
Transmitted Drug Resistance ◽  
Newly Diagnosed ◽  
Resistance Mutations ◽  
Shenyang City ◽  
Subtype B ◽  
Recent Hiv Infection ◽  
Hiv 1

Abstract Background To assess transmitted drug resistance (TDR) to tenofovir (TDF)/emtricitabine (FTC), using as pre-exposure prophylaxis, among newly diagnosed human immunodeficiency virus-1 (HIV-1)-infected residents in Shenyang city, northeast China. Methods Demographic and epidemiological information of all newly diagnosed HIV-1 infected residents in Shenyang city from 2016 to 2018 were anonymously collected from the local HIV epidemic database. HIV-1 pol sequences were amplified from RNA in cryopreserved plasma samples and sequenced directly. Viral subtypes were inferred with phylogenetic analysis and drug resistance mutations (DRMs) were determined according to the Stanford HIVdb algorithm. Recent HIV infection was determined with HIV Limiting Antigen avidity electro immunoassay. Results A total of 2176 sequences (92.4%, 2176/2354) were obtained; 70.9% (1536/2167) were CRF01_AE, followed by CRF07_BC (18.0%, 391/2167), subtype B (4.7%, 102/2167), other subtypes (2.6%, 56/2167), and unique recombinant forms (3.8%, 82/2167). The prevalence of TDR was 4.9% (107/2167), among which, only 0.6% (13/2167) was resistance to TDF/FTC. Most of these subjects had CRF01_AE strains (76.9%, 10/13), were unmarried (76.9%, 10/13), infected through homosexual contact (92.3%, 12/13), and over 30 years old (median age: 33). The TDF/FTC DRMs included K65R (8/13), M184I/V (5/13), and Y115F (2/13). Recent HIV infection accounted for only 23.1% (3/13). Most cases were sporadic in the phylogenetic tree, except two CRF01_AE sequences with K65R (Bootstrap value: 99%). Conclusions The prevalence of TDR to TDF/FTC is low among newly diagnosed HIV-infected cases in Shenyang, suggesting that TDR may have little impact on the protective effect of the ongoing CROPrEP project in Shenyang city.

scholarly journals Effect of HIV Envelope Vaccination on the Subsequent Antibody Response to HIV Infection

mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Zanele Ditse ◽  
Nonhlanhla N. Mkhize ◽  
Michael Yin ◽  
Michael Keefer ◽  
David C. Montefiori ◽  
...  
Keyword(s):  
Immune Responses ◽  
Hiv Infection ◽  
South African ◽  
Phase 1 ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Tier 2 ◽  
Subtype C ◽  
Hiv Envelope ◽  
Hiv 1

ABSTRACT Analysis of breakthrough HIV-1 infections could elucidate whether prior vaccination primes relevant immune responses. Here, we measured HIV-specific antibody responses in 14 South African volunteers who acquired HIV infection after participating in phase 1/2 trials of envelope-containing immunogens. Serum samples were collected annually following HIV-1 infection from participants in trials HVTN 073 (subtype C, DNA/MVA, phase 1 trial, n = 1), HVTN 086 (subtype C, DNA/MVA/gp140 protein, phase 1 trial, n = 2), and HVTN 204 (multisubtype, DNA/adenovirus serotype 5 [Ad5], phase 2 trial, n = 7) and 4 placebo recipients. Binding and neutralizing antibody responses to Env proteins and peptides were determined pre- and post-HIV infection using an enzyme-linked immunosorbent assay and the TZM-bl cell neutralization assay, respectively. HIV-infected South African individuals served as unvaccinated controls. Binding antibodies to gp41, V3, V2, the membrane-proximal external region (MPER), and the CD4 binding site were detected from the first year of HIV-1 subtype C infection, and the levels were similar in vaccinated and placebo recipients. Neutralizing antibody responses against tier 1A viruses were detected in all participants, with the highest titers being to a subtype C virus, MW965.26. No responses were observed just prior to infection, indicating that vaccine-primed HIV-specific antibodies had waned. Sporadic neutralization activity against tier 2 isolates was observed after 2 to 3 years of HIV infection, but these responses were similar in the vaccinated and placebo groups as well as the unvaccinated controls. Our data suggest that prior vaccination with these immunogens did not alter the antibody responses to HIV-1 infection, nor did it accelerate the development of HIV neutralization breadth. IMPORTANCE There is a wealth of information on HIV-specific vaccine-induced immune responses among HIV-uninfected participants; however, data on immune responses among participants who acquire HIV after vaccination are limited. Here we show that HIV-specific binding antibody responses in individuals with breakthrough HIV infections were not affected by prior vaccination with HIV envelope-containing immunogens. We also found that these vectored vaccines did not prime tier 2 virus-neutralizing antibody responses, which are thought to be required for prevention against HIV acquisition, or accelerate the development of neutralization breadth. Although this study is limited, such studies can provide insights into whether vaccine-elicited antibody responses are boosted by HIV infection to acquire broader neutralizing activity, which may help to identify antigens relevant to the design of more effective vaccines.

scholarly journals Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses

2018 ◽  
Vol 92 (9) ◽  
Author(s):  
Manickam Ashokkumar ◽  
Shambhu G. Aralaguppe ◽  
Srikanth P. Tripathy ◽  
Luke Elizabeth Hanna ◽  
Ujjwal Neogi
Keyword(s):  
Hiv Infection ◽  
Biological Properties ◽  
Subtype C ◽  
Chronic Stage ◽  
Human Host ◽  
Molecular Features ◽  
Successful Infection ◽  
Hiv Research ◽  
Hiv 1 ◽  
Chimeric Viruses

ABSTRACT Adequate information on the precise molecular and biological composition of the viral strains that establish HIV infection in the human host will provide effective means of immunization against HIV infection. In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7-Luc-IRESs-NefΔgp120 to obtain chimeric viruses. Samples were obtained from eight infants who had recently become infected with HIV through mother-to-child transmission (MTCT) and two adults who acquired infection through the heterosexual route and were in the chronic stage of infection. Among the 250 clones tested, 65 chimeric viruses were infectious, and all belonged to HIV-1 subtype C. The 65 clones were analyzed for molecular features of the envelope, per-infectious-particle infectivity, coreceptor tropism, drug sensitivity, and sensitivity to broadly neutralizing antibodies. Based on genotypic and phenotypic analysis of the viral clones, we identified 10 TF viruses from the eight infants. The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection. CXCR6 coreceptor usage, in addition to that of the CCR5 coreceptor, which was used by all 65 chimeric viruses, was identified in 13 viruses. The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection. IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist. One of the frontier areas of HIV research which has not seen a breakthrough yet is vaccine research, which is because of the enormous genetic diversity of HIV-1 and the unique infectious fitness of the virus. Among the repertoire of viral variants, the virus that establishes successful infection (transmitted founder [TF] virus) has not been well characterized yet. An insight into the salient features of the TF virus would go a long way toward helping with the design of an effective vaccine against HIV. Here we studied the biological properties of recently transmitted viruses isolated from infants who acquired infection from the mother and have come up with unique characterizations for the TF virus that establishes infection in the human host.

scholarly journals Difficulties of Identifying the Early HIV Antibody Seroconversion Period Depending on the Confirmatory Assay

2020 ◽  
Vol 7 (5) ◽  
Author(s):  
Karl Stefic ◽  
Nadia Mahjoub ◽  
Céline Desouche ◽  
Marie Laure Néré ◽  
Damien Thierry ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Early Stage ◽  
Inclusion Criteria ◽  
Multicenter Studies ◽  
Recent Infection ◽  
Western Blots ◽  
Confirmatory Assay ◽  
Single Use ◽  
Recent Hiv Infection ◽  
Hiv 1

Abstract Background Identification of HIV infection at the early stage is valuable for patient management, for prevention, and for research purposes. In practice, identification of a recent HIV infection at diagnosis proves challenging after HIV antibody seroconversion but can be suspected using Western blots (WBs) or immunoblots (IBs) as confirmatory assays. Methods Five commercially available confirmatory assays were compared using 43 samples from recently infected individuals. This included 2 WBs (New LAV Blot I, Biorad, and HIV Blot 2.2, MP Biomedicals), 2 IBs (INNO-LIA HIV I/II, Fujirebio, and RecomLine HIV-1 & HIV-2, Mikrogen Diagnostik), and 1 immunochromatographic single-use assay (Geenius HIV1/2 supplemental assay, Biorad). Results Following the manufacturer’s recommendations for interpretation, the 2 WBs led to indeterminate results for 30% and 42% of the samples, suggesting recent infection, compared with 2%–7% for the 3 other assays. When interpreted based on the Fiebig classification, concordant stages were observed in 42% of samples, and only 49% were classified as early seroconversion by all 5 assays. For the remaining specimens, the distinction with chronic infection was highly variable depending on the assay (5%–100%). Conclusions Clinical laboratories must consider this variability, which must be kept in mind both for initial diagnosis and for multicenter studies for which inclusion criteria refer to serological profiles by confirmatory assays.

scholarly journals Simian-Human Immunodeficiency Virus SHIV.CH505 Infection of Rhesus Macaques Results in Persistent Viral Replication and Induces Intestinal Immunopathology

2019 ◽  
Vol 93 (18) ◽  
Author(s):  
Katharine J. Bar ◽  
Ernesto Coronado ◽  
Tiffany Hensley-McBain ◽  
Megan A. O’Connor ◽  
Jessica M. Osborn ◽  
...  
Keyword(s):  
T Cells ◽  
Hiv Infection ◽  
Viral Replication ◽  
Cell Function ◽  
Immune Cell ◽  
Rhesus Macaques ◽  
Subtype C ◽  
Viral Kinetics ◽  
Hiv 1

ABSTRACTSimian-human immunodeficiency viruses (SHIVs) have been utilized to test vaccine efficacy and characterize mechanisms of viral transmission and pathogenesis. However, the majority of SHIVs currently available have significant limitations in that they were developed using sequences from chronically HIV-infected individuals or uncommon HIV subtypes or were optimized for the macaque model by serially passaging the engineered virusin vitroorin vivo. Recently, a newly developed SHIV, SHIV.C.CH505.375H.dCT (SHIV.CH505), which incorporates vpu-env (gp140) sequences from a transmitted/founder HIV-1 subtype C strain, was shown to retain attributes of primary HIV-1 strains. However, a comprehensive analysis of the immunopathology that results from infection with this virus, especially in critical tissue compartments like the intestinal mucosa, has not been completed. In this study, we evaluated the viral dynamics and immunopathology of SHIV.CH505 in rhesus macaques. In line with previous findings, we found that SHIV.CH505 is capable of infecting and replicating efficiently in rhesus macaques, resulting in peripheral viral kinetics similar to that seen in pathogenic SIV and HIV infection. Furthermore, we observed significant and persistent depletions of CCR5+and CCR6+CD4+T cells in mucosal tissues, decreases in CD4+T cells producing Th17 cell-associated cytokines, CD8+T cell dysfunction, and alterations of B cell and innate immune cell function, indicating that SHIV.CH505 elicits intestinal immunopathology typical of SIV/HIV infection. These findings suggest that SHIV.CH505 recapitulates the early viral replication dynamics and immunopathogenesis of HIV-1 infection of humans and thus can serve as a new model for HIV-1 pathogenesis, treatment, and prevention research.IMPORTANCEThe development of chimeric SHIVs has been instrumental in advancing our understanding of HIV-host interactions and allowing forin vivotesting of novel treatments. However, many of the currently available SHIVs have distinct drawbacks and are unable to fully reflect the features characteristic of primary SIV and HIV strains. Here, we utilize rhesus macaques to define the immunopathogenesis of the recently developed SHIV.CH505, which was designed without many of the limitations of previous SHIVs. We observed that infection with SHIV.CH505 leads to peripheral viral kinetics and mucosal immunopathogenesis comparable with those caused by pathogenic SIV and HIV. Overall, these data provide evidence of the value of SHIV.CH505 as an effective model of SIV/HIV infection and an important tool that can be used in future studies, including preclinical testing of new therapies or prevention strategies.

scholarly journals Evaluation of the Abbott ARCHITECT HIV Ag/Ab combo assay for determining recent HIV-1 infection

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0242641
Author(s):  
Kelly A. Curtis ◽  
Donna L. Rudolph ◽  
Yi Pan ◽  
Kevin Delaney ◽  
Kathryn Anastos ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Diagnostic Test ◽  
Diagnostic Algorithm ◽  
The United States ◽  
Hiv Incidence ◽  
Test Protocol ◽  
Recent Infection ◽  
Recent Hiv Infection ◽  
Hiv 1 ◽  
Abbott Architect

Background Given the challenges and costs associated with implementing HIV-1 incidence assay testing, there is great interest in evaluating the use of commercial HIV diagnostic tests for determining recent HIV infection. A diagnostic test with the capability of providing reliable data for the determination of recent HIV infection without substantial modifications to the test protocol would have a significant impact on HIV surveillance. The Abbott ARCHITECT HIV Ag/Ab Combo Assay is an antigen/antibody immunoassay, which meets the criteria as the first screening test in the recommended HIV laboratory diagnostic algorithm for the United States. Methods In this study, we evaluated the performance characteristics of the ARCHITECT HIV Ag/Ab Combo signal-to-cutoff ratio (S/Co) for determining recent infection, including estimation of the mean duration of recent infection (MDRI) and false recent rate (FRR), and selection of recency cutoffs. Results The MDRI estimates for the S/Co recency cutoff of 400 is within the 4 to 12 months range recommended for HIV incidence assays, and the FRR rate for this cutoff was 1.5%. Additionally, ARCHITECT Combo S/Co values were compared relative to diagnostic test results from two prior prospective HIV-1 diagnostic studies in order to validate the use of the S/Co for both diagnostic and recency determination. Conclusion Dual-use of the ARCHITECT Combo assay data for diagnostic and incidence purposes would reduce the need for separate HIV incidence testing and allow for monitoring of recent infection for incidence estimation and other public health applications.

scholarly journals Association of recent HIV infection and in-utero HIV-1 transmission

AIDS ◽  
2011 ◽  
Vol 25 (11) ◽  
pp. 1357-1364 ◽  
Author(s):  
Taha E. Taha ◽  
Maria M. James ◽  
Donald R. Hoover ◽  
Jin Sun ◽  
Oliver Laeyendecker ◽  
...  
Keyword(s):  
Hiv Infection ◽  
In Utero ◽  
Recent Hiv Infection ◽  
Hiv 1

scholarly journals Tracing the origin and dynamics of the HIV-1 epidemic in Serbia

2014 ◽  
Vol 66 (2) ◽  
pp. 507-515 ◽  
Author(s):  
Marina Siljic ◽  
Dubravka Salemovic ◽  
Dj. Jevtovic ◽  
Ivana Pesic-Pavlovic ◽  
Sonja Zerjav ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Sexual Transmission ◽  
Intravenous Drug User ◽  
Subtype C ◽  
Subtype B ◽  
Sex With Men ◽  
Hiv 1 ◽  
Genetic Form ◽  
Subtype Distribution ◽  
Founder Strain

Since the first report of HIV infection in Serbia in 1985, the HIV-1 epidemic was very dynamic, changing the pattern in subtype distribution and prevailing transmission routes. To better understand the origin and epidemiological dynamics of HIV-1, we analyzed 266 (pol) sequences from Serbian patients diagnosed over a period of 14 years. Subtype distribution in Serbia is still marked by a prevailing subtype B genetic form. The transmission pattern, however, has changed from being intravenous drug user (IVDU) - driven to predominantly sexual transmission. The estimated time of initial founder strain introduction of sequences from Serbian IVDUs and MSM (men who have sex with men) is similar and dates back to the early 1980s, while introduction of subtype C occurred much more recently.

scholarly journals Evaluation of the Abbott ARCHITECT HIV Ag/Ab Combo Assay for Determining Recent HIV-1 Infection

2020 ◽  
Author(s):  
Kelly A. Curtis ◽  
Donna L. Rudolph ◽  
Yi Pan ◽  
Kevin Delaney ◽  
Kathryn Anastos ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Diagnostic Test ◽  
Diagnostic Algorithm ◽  
The United States ◽  
Hiv Incidence ◽  
Test Protocol ◽  
Recent Infection ◽  
Recent Hiv Infection ◽  
Hiv 1 ◽  
Abbott Architect

BackgroundGiven the challenges and costs associated with implementing HIV-1 incidence assay testing, there is great interest in evaluating the use of commercial HIV diagnostic tests for determining recent HIV infection. A diagnostic test with the capability of providing reliable data for the determination of recent HIV infection without substantial modifications to the test protocol would have a significant impact on HIV surveillance. The Abbott ARCHITECT HIV Ag/Ab Combo Assay is an antigen/antibody immunoassay, which meets the criteria as the first screening test in the recommended HIV laboratory diagnostic algorithm for the United States.MethodsIn this study, we evaluated the performance characteristics of the ARCHITECT HIV Ag/Ab Combo signal-to-cutoff ratio (S/Co) for determining recent infection, including estimation of the mean duration of recent infection (MDRI) and false recent rate (FRR), and selection of recency cutoffs.ResultsThe MDRI estimates for the S/Co recency cutoff of 400 is within the 4 to 12 months range recommended for HIV incidence assays, and the FRR rate for this cutoff was 1.5%. Additionally, ARCHITECT Combo S/Co values were compared relative to diagnostic test results from two prior prospective HIV-1 diagnostic studies in order to validate the use of the S/Co for both diagnostic and recency determination.ConclusionDual-use of the ARCHITECT Combo assay data for diagnostic and incidence purposes would reduce the need for separate HIV incidence testing and allow for monitoring of recent infection for incidence estimation and other public health applications.

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