Laboratory Diagnosis and Monitoring of HIV Infection

2019 ◽  
Author(s):  
Anna Jeffery- Smith ◽  
C. Y. William Tong
Keyword(s):  
Hiv Infection ◽  
Sensitivity And Specificity ◽  
Point Of Care ◽  
Fourth Generation ◽  
Third Generation ◽  
Window Period ◽  
P24 Antigen ◽  
Exposure Risks ◽  
Positive Results ◽  
Hiv 1

In the majority of UK laboratories initial testing for HIV is now performed using a fourth generation test, which is a combination test for antibody to HIV and p24 antigen. These tests should be able to detect antibody to both HIV-1 and HIV-2. In addition, due to the heterogeneity of the virus they should be able to reliably detect antibody to the main circulating subtypes of HIV-1, i.e. group M (Major), O (Outlier), and N (non-M, non-O). The p24 antigen is an HIV capsid protein which is produced in large quantities during initial infection, prior to seroconversion. The sensitivity and specificity of fourth generation tests is typically > 99%. However, all positive results need further confirmation tests, as discussed below. Third generation laboratory assays only test for the presence of antibody to HIV. Though it includes the detection of IgM (which is not included in second generation assays), they do not detect early infection with isolated HIV antigen prior to seroconversion. Point-of-care testing for HIV is performed in the clinic or at bedside. Like laboratory based assays these tests can be either third or fourth generation. The sensitivity and specificity of point-of-care tests is considered lower than that of laboratory tests, and all positive results require confirmation with a laboratory assay. The window period is the length of time following infection with HIV until the appearance of laboratory markers of HIV infection in the blood. This period varies depending on which marker, i.e. antibody or antigen, is being tested for. The window period for fourth-generation tests is between eleven days and one month. Patients being counselled prior to this testing should be advised that a negative result does not cover risk exposures in the preceding month. These patients should be advised to have repeat testing if they have any further exposure risks in the preceding month prior to testing. For third-generation tests the window period is up to three months, correlating with the amount of time it may take for antibodies to HIV to develop.

scholarly journals Reduction of Diagnostic Window by New Fourth-Generation Human Immunodeficiency Virus Screening Assays †

1998 ◽  
Vol 36 (8) ◽  
pp. 2235-2239 ◽  
Author(s):  
Bernard Weber ◽  
El Hadji Mbargane Fall ◽  
Annemarie Berger ◽  
Hans Wilhelm Doerr
Keyword(s):  
Hiv Infection ◽  
Fourth Generation ◽  
Third Generation ◽  
Serum Samples ◽  
Immunodeficiency Virus ◽  
Hiv Antigen ◽  
Diagnostic Window ◽  
P24 Antigen ◽  
Culture Supernatants ◽  
Hiv 1

In order to reduce the diagnostic window between the time of human immunodeficiency virus (HIV) infection and laboratory diagnosis, new screening enzyme-linked immunosorbent assays (ELISAs) which permit the simultaneous detection of HIV antigen and antibody have been developed. Two fourth-generation assays, HIV DUO (Biomérieux) and HIV Combi (Boehringer Mannheim), for the combined detection of HIV antigen and antibody, were compared with a third-generation assay (HIV-1/HIV-2 3rd Generation Plus enzyme immunoassay [EIA]; Abbott) and a p24 antigen test (HIV-1 Ag monoclonal; Abbott). A total of 17 seroconversion panels, 15 cell culture supernatants infected with different HIV type 1 (HIV-1) subtypes, and 255 potentially cross-reactive serum samples were tested. Ten seroconversions were detected an average of 8.1 days earlier with HIV DUO and 7.5 days earlier with HIV Combi than with the third-generation ELISA. Overall, in the 17 seroconversion panels tested, HIV DUO detected HIV-1 infection an average of 4.8 days and HIV Combi detected infection an average of 4.4 days earlier than HIV-1/HIV-2 3rd Generation Plus EIA. HIV antigen was detected with HIV DUO and HIV Combi in all of the 15 cell culture supernatants infected with different HIV-1 subtypes, including subtype O. With fourth-generation assays, considerably fewer false-positive results (n = 4 to 6) were obtained, in comparison with the third-generation EIA (n = 18). Fourth-generation assays permit an earlier diagnosis of HIV infection than third-generation antibody screening assays through the detection of p24 antigen, which may be present in serum samples from individuals with recent HIV infection prior to seroconversion.

Does qualitative viral load testing shorten the window period for diagnosing HIV in individuals attending for post-exposure prophylaxis?

2020 ◽  
Vol 31 (9) ◽  
pp. 816-819
Author(s):  
Gary Whitlock ◽  
Nneka Nwokolo ◽  
Keyword(s):  
Viral Load ◽  
Hiv Infection ◽  
Point Of Care ◽  
Fourth Generation ◽  
Post Exposure Prophylaxis ◽  
Hiv Incidence ◽  
Post Exposure ◽  
Window Period ◽  
Hiv Test ◽  
Exposure Prophylaxis

A fourth-generation HIV test is conventionally performed at baseline for individuals given HIV post-exposure prophylaxis (PEP). However, early HIV infection may be missed by fourth-generation tests especially in settings of high HIV incidence, meaning that recently infected individuals are potentially at risk of transmitting HIV. In 2013, HIV incidence in PEP recipients at the 56 Dean Street clinic was 7.6 per 100 person-years. We therefore wished to see if using a point-of-care PCR HIV test in such individuals would shorten the testing window period and pick up early infections that would be undiagnosed by conventional tests. We compared HIV detection in PEP recipients using the Cepheid GeneXpert® HIV-1 Qual viral load (Qual VL) assay with the standard HIV tests used in our clinical service. Between March 2017 and August 2018, a Qual VL assay was performed in addition to standard baseline HIV tests in consented PEP recipients. Of 494 consented PEP recipients, 476 had valid Qual VL assay results. Of these, 474 (99.6%) had a negative Qual VL result and were also negative on standard baseline HIV tests. Two (0.4%) tested positive for HIV on Qual VL. One of these patients was also HIV-positive on all baseline HIV tests. The other had discordant baseline point-of-care HIV test results. Although no additional HIV infections were diagnosed in PEP recipients using Qual VL, in one individual, it provided confirmation of new HIV infection more quickly than the standard HIV testing pathway.

The performance of the Alere HIV combo point-of-care test on stored serum samples; useful for detection of early HIV-1 infections?

2017 ◽  
Vol 94 (5) ◽  
pp. 331-333 ◽  
Author(s):  
Carla van Tienen ◽  
Sharona Rugebregt ◽  
Sandra Scherbeijn ◽  
Hannelore Götz ◽  
Corine Geurts van Kessel
Keyword(s):  
Hiv Infection ◽  
Point Of Care ◽  
Acute Infection ◽  
Rapid Test ◽  
Public Health Department ◽  
Laboratory Setting ◽  
Serum Samples ◽  
Point Of Care Test ◽  
P24 Antigen ◽  
Hiv 1

IntroductionThe Alere HIV-1/2 Antigen/Antibody Combo point-of-care test is a commercially available 4th-generation rapid test for the diagnosis of HIV infection, including acute infection. We evaluated the sensitivity of this test in samples from patients with acute, recent or chronic HIV-1 infection.MethodsA validation of the test was performed using 89 HIV-positive serum samples collected in 2008–2016, that were stored at −20°C. Twenty-three samples were only p24-positive (acute infection); 49 samples were antibody-positive and p24-positive (recent infection); 17 samples were only antibody-positive (chronic infection). HIV infection was confirmed by standard-of-care assays and PCR. Samples came from patients attending an outpatient clinic for STDs at the Public Health Department and from patients within the Erasmus Medical Center, Rotterdam, the Netherlands.ResultsThe overall sensitivity of the test for diagnosing HIV infection based on detection of p24 antigen and/or antibodies was 92% (95% CI 86% to 98%) (82/89). In acute sera with only p24 antigen positivity, the sensitivity of the test decreased to 65% (95% CI 46% to 85%) (15/23). When both antibody and antigen testing were positive, the p24 sensitivity was only 24% (95% CI 12% to 36%) (12/49), but in these sera the final test result was positive in all sera (49/49) due to the positive antibody component.ConclusionsIn a laboratory setting, this test has an overall sensitivity of 92% to detect any stage of HIV-1 infection using sera specimens. It performs relatively well in detecting early HIV and may be beneficial as an initial screening in patients with a recent exposure to HIV. Additional testing in a laboratory setting remains mandatory as a proportion of acute HIV-1 infections are missed with this test.

scholarly journals Identifying HIV infection in South African women: How does a fourth generation HIV rapid test perform?

2011 ◽  
Vol 1 (1) ◽  
Author(s):  
Kapila Bhowan ◽  
Emma Kalk ◽  
Sonjiha Khan ◽  
Gayle Sherman
Keyword(s):  
South Africa ◽  
Hiv Infection ◽  
Point Of Care ◽  
Post Partum ◽  
Rapid Test ◽  
African Women ◽  
Fourth Generation ◽  
Third Generation ◽  
Detection Rates ◽  
Hiv Antibodies

Background: HIV rapid tests (RT) play an important role in tackling the HIV pandemic in South Africa. Third generation RT that detect HIV antibodies are currently used to diagnose HIV infection at the point of care. Determine Combo (DC) is the first fourth generation RT that detects both p24 antigen (p24Ag) and HIV antibodies (Ab), theoretically reducing the window period and increasing detection rates. Early detection of maternal HIV infection is important to mitigate the high risk of vertical transmission associated with acute maternal infection. Objectives: We assessed the performance of the DC RT against third generation RT in antenatal and post-partum women. Methods: Third generation RT Advance Quality and Acon were used in a serial algorithm to diagnose HIV infection in antenatal and post-partum women over six months at a tertiary hospital in Johannesburg, South Africa. This data provided the reference against which the DC RT was compared on plasma and whole blood samples. Results: The 1019 participants comprised 345 (34%) antenatal and 674 (66%) post-partum women. Ninety women (8.8%) tested HIV-positive of whom 59 (66%) were tested antenatally, and 31 (34%) post-partum yielding prevalence rates of 17.1% and 4.6% respectively. The sensitivity and specificity of the Ab component of DC on plasma antenatally was 100% (93.8% – 100%) and 100% (98.6% – 100%) respectively and post-partum was 100% (88.9% – 100%) and 99.6% (98.8% – 99.9%) respectively. One false positive and not a single true positive p24Ag was detected. Of 505 post-partum women who tested HIV-negative 6–12 months prior to enrolment, 12 (2.4%) seroconverted. Conclusion: The fourth generation DC offered no advantage over current third generation RT in the diagnosis of HIV infection.

scholarly journals Streptavidin-conjugated gold nanoclusters as ultrasensitive fluorescent sensors for early diagnosis of HIV infection

2018 ◽  
Vol 4 (11) ◽  
pp. eaar6280 ◽  
Author(s):  
Aditya Dileep Kurdekar ◽  
L. A. Avinash Chunduri ◽  
C. Sai Manohar ◽  
Mohan Kumar Haleyurgirisetty ◽  
Indira K. Hewlett ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Limit Of Detection ◽  
Gold Nanoclusters ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Metal Nanoclusters ◽  
Detection Range ◽  
In Silico Studies ◽  
P24 Antigen ◽  
Hiv 1

We have engineered streptavidin-labeled fluorescent gold nanoclusters to develop a gold nanocluster immunoassay (GNCIA) for the early and sensitive detection of HIV infection. We performed computational simulations on the mechanism of interaction between the nanoclusters and the streptavidin protein via in silico studies and showed that gold nanoclusters enhance the binding to the protein, by enhancing interaction between the Au atoms and the specific active site residues, compared to other metal nanoclusters. We also evaluated the role of glutathione conjugation in binding to gold nanoclusters with streptavidin. As proof of concept, GNCIA achieved a sensitivity limit of detection of HIV-1 p24 antigen in clinical specimens of 5 pg/ml, with a detection range up to1000 pg/ml in a linear dose-dependent manner. GNCIA demonstrated a threefold higher sensitivity and specificity compared to enzyme-linked immunosorbent assay for the detection of HIV p24 antigen. The specificity of the immunoassay was 100% when tested with plasma samples negative for HIV-1 p24 antigen and positive for viruses such as hepatitis B virus, hepatitis C virus, and dengue. GNCIA could be developed into a universal labeling technology using the relevant capture and detector antibodies for the specific detection of antigens of various pathogens in the future.

SENSITIVITY, SPECIFICITY, AND PREDICTIVE VALUE OF PHYSICAL EXAMINATION, CULTURE, AND OTHER LABORATORY STUDIES IN THE DIAGNOSIS DURING EARLY INFANCY OF VERTICALLY ACQUIRED HUMAN IMMUNODEFICIENCY VIRUS INFECTION

PEDIATRICS ◽  
1994 ◽  
Vol 94 (2) ◽  
pp. 274-275
Author(s):  
Susan E. Pacheco ◽  
William T. Shearer
Keyword(s):  
Clinical Trials ◽  
Physical Examination ◽  
Hiv Infection ◽  
Laboratory Studies ◽  
Diagnostic Laboratory ◽  
Predictive Values ◽  
P24 Antigen ◽  
Aids Clinical Trials ◽  
Sensitivity Specificity ◽  
Hiv 1

Purpose of the Study. To determine the HIV vertical transmission rate in an unselected group of infants born to HIV-infected mothers, and to examine the sensitivity, specificity, and positive and negative predictive values of physical examination and diagnostic laboratory studies (HIV culture, serum quantitative immunoglobulins and HIV-1 p24 antigen) in the diagnosis of HIV infection. Study Population. A group of 142 infants referred solely because they were born to HIV-infected mothers were selected for this study. Methods. Epidemiological and clinical data were obtained retrospectively from the Baylor Pediatric AIDS Clinical Trials Group HIV Infection Registry and medical records. The information recorded included results of physical examination and diagnostic laboratory tests (HIV culture, serum quantitative immunoglobulins, and HIV-1 p24 antigen). HIV cultures were performed according to a consensus protocol developed for the National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. Results. Of 142 infants whose HIV infection status was known at the time of the study, 17 (20%) had confirmed infection, and 68 (80%) had seroreverted with no evidence of infection. All HIV-infected infants were at least 3 months old when abnormal physical exam findings became apparent (lymphadenopathy and hepatosplenomegaly), but similar findings were noted in an equal number of HIV-uninfected infants. All infected infants available were HIV culture positive by 6 months of age (16/16). There was no positive cultures reported in the infants who seroreverted (32/32). Elevated immunoglobulins (IgG, IgA, IgM) were present by 6 months of age in a high percentage of infected infants. Nearly one-half of the uninfected infants had elevated immunoglobulin levels during the first 6 months of life, but in 50% of the cases it was IgG alone.

scholarly journals Hyperbaric hyperoxia exposure in suppressing human immunodeficiencyvirus replication: An experimental in vitro in peripheral mononuclear blood cells culture

2020 ◽  
Author(s):  
Retno Budiarti ◽  
Siti Qamariyah Khairunisa ◽  
Nasronudin ◽  
Kuntaman ◽  
Guritno
Keyword(s):  
Hiv Infection ◽  
Healthy Volunteers ◽  
Hyperbaric Oxygen ◽  
Experimental Unit ◽  
Control Group ◽  
P24 Antigen ◽  
Hyperbaric Exposure ◽  
Interferon Α2 ◽  
Hiv 1

Cellular immune has an important role in response HIV infection, which is attack the infected cells to activate signaling molecule. Hyperbaric Oxygen (HBO) worked as complementary treatment for HIV infection. The production of ROS and RNS molecules during hyperbaric exposure can affect gene expression which contributes to cellular adaptative response. This study was conducted to explore the mechanisms of cellular adaptive response to HIV infection during hyperbaric exposure. This study was carried on in vitro using healthy volunteers’ PBMCs (Peripheral Blood Mononuclear Cells) cultures infected with HIV-1. The study was conducted as a post- test only group design. The experimental unit was PBMC from venous blood of healthy volunteers which were cultured in vitro and infected by co-culturing with HIV-1 in MT4 cell line. The experimental unit consist of treatment and control group. Each group examined the expression of transcription factor NFκB, Interferon α, reverse transcriptase inhibitors (p21), and the amount of HIV-1 p24 antigen. There were increasingly significant differences in the expression of the trancription factor of NFκB, p21, and HIV-1 p24 antigen,as well as mRNA transcription of interferon α2 between treatment and controlgroup. By decreasing p24 antigen showed that HBO exposure was able to suppress HIV-1 replication. The exposure to hyperbaric oxygen at the pressure of 2.4 ATAand 98% oxygen wasable to produce ROS and RNS molecules, which play a role in cellular adaptive responses through increasing the expression of nfĸb, p21 and mRNA of interferon α2 plays a role in inhibition mechanism of HIV-1 replication in cells.

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