HIV Nucleic Acid Amplification Testing Research Articles

False-positive HIV nucleic acid amplification testing during CAR T-cell therapy

Advancements in immunotherapy have opened a new era in oncology, to include genetic modification of human T-cells to express a chimeric antigen receptor (CAR) that enables targeted tumor recognition (Kochenderfer et al., 2015; Lee et al., 2015; Maus and Levine 2016; Rosenberg et al., 2008). Herein, we report a false-positive HIV testing in a patient who had undergone CAR T-cell therapy created with a lentiviral vector.

Screening for acute HIV infection in community-based settings: Cost-effectiveness and impact on transmissions

To determine cost-effectiveness of three community-based acute HIV infection (AHI) testing algorithms compared to HIV antibody testing alone by focusing on the potential of averting new infections occurring within a one-year time horizon among men who have sex with men (MSM). Data sources for model parameters included actual cost and prevalence data derived from a community-based AHI screening program in San Diego, and published studies. Main outcome measure was costs per infection averted (IA). The lower end of the cost range of discounted lifetime costs of an HIV infection (i.e. $236,948) was used for defining cost-effectiveness. The most sensitive algorithm for AHI detection, which was based on HIV nucleic acid amplification testing, was estimated to prevent between 5 and 45 transmissions, with simulated costs per infection averted between $965 and $141,256 when compared to HIV antibody testing alone. AHI testing was cost-effective in preventing new HIV infections among at risk MSM in San Diego, and also among other MSM populations with similar HIV prevalence but lower proportions of AHI diagnoses. These results indicate that community-based AHI testing among MSM in the United States can pay for itself over the long run.

Risk Factors for Acute and Early HIV Infection Among Men Who Have Sex With Men (MSM) in San Diego, 2008 to 2014: A Cohort Study.

The objectives of this study were to identify risk factors associated with acute and early HIV infection (AEH) among men who have sex with men (MSM) undergoing community HIV testing and to compare demographics in those diagnosed with AEH with those diagnosed at chronic stage of HIV infection.In this retrospective cohort study, we analyzed risk factors associated with AEH among 8925 unique MSM (including 200 with AEH [2.2%] and 219 [2.5%] with newly diagnosed chronic HIV infection) undergoing community-based, confidential AEH screening in San Diego, California.The combination of condomless receptive anal intercourse (CRAI) plus ≥5 male partners, CRAI with an HIV-positive male, CRAI with a person who injects drugs, and prior syphilis diagnosis were significant predictors of AEH in the multivariable Cox regression model. Individuals reporting ≥1 of these 4 risk factors had a hazard ratio of 4.6 for AEH. MSM diagnosed with AEH differed in race (P = 0.005; more reported white race [P = 0.001], less black race [P = 0.030], trend toward less Native American race [P = 0.061]), when compared to those diagnosed with chronic HIV infection, while there was no difference observed regarding age.We established a multivariate model for the predicting risk of AEH infection in a cohort of MSM undergoing community HIV screening, which could be potentially used to discern those in need of further HIV nucleic acid amplification testing for community screening programs that do not test routinely for AEH. In addition, we found that race differed between those diagnosed with AEH and those diagnosed at chronic stage of HIV infection underlining the need for interventions that reduce stigma and promote the uptake of HIV testing for black MSM.

Performance of an alternative HIV diagnostic algorithm using the ARCHITECT HIV Ag/Ab Combo assay and potential utility of sample-to-cutoff ratio to discriminate primary from established infection

BackgroundThe ARCHITECT HIV Ag/Ab Combo assay has a wide dynamic range for determining the sample-to-cutoff ratio (S/CO) values compared to other diagnostic HIV antibody assays. ObjectivesDetermine the performance of an HIV testing algorithm that uses the ARCHITECT combo assay in the clinical setting and explore the utility of the signal-to-cutoff (S/CO) ratio to predict acute HIV-1 infection status. Study designA retrospective analysis of clinical samples from a hospital and referral population screened for HIV-1 infection between May 2011 and March 2013. Repeatedly reactive samples were tested using the Multispot HIV-1/HIV-2 rapid test and depending on that result, confirmatory orthogonal testing used the Western blot (WB) for HIV-1, Immunoblot for HIV-2 and nucleic acid amplification testing (NAAT) for HIV RNA. ResultsA total of 21,317 test results were evaluated of which 509 were ARCHITECT repeatedly reactive; of these, 422 were Multispot-reactive only for HIV-1 (413 WB-positive; 9 indeterminate), 4 were Multispot-reactive for both HIV-1 and HIV-2 (one HIV-2 immunoblot-positive with 17 HIV-2 RNA copies/mL) and 83 were Multispot-non-reactive of which 15 were HIV-1 RNA positive and represented acute HIV-1 infection. There was an association among the ARCHITECT S/CO (median; IQR) values for antibody-negative (0.14; 0.11–0.16), acute infection (33; 2.1–76) and established HIV-1 infection (794; 494–1,029) (Kruskal–Wallis, p<0.0001). ConclusionsThe ARCHITECT combo assay with Multispot confirmation and reserved use of HIV-1 WB, HIV-2 Immunoblot and HIV NAAT for Multispot dual HIV-1/2 infection, and NAAT alone for Multispot-negative specimens, had a suitable test performance for detecting acute and established HIV infection.

Prospective cohort study of HIV incidence and molecular characteristics of HIV among men who have sex with men(MSM) in Yunnan Province, China

BackgroundYunnan has the largest number of reported HIV/AIDS cases among all Chinese provinces, the reported prevalence of HIV among Yunnan men who have sex with men (MSM) passed 10%, while HIV incidence epidemic and molecular characteristics of new infected Yunnan MSM were not evaluated before.MethodsAn 18 months prospective followed up with a frequency of 3 month per visit were conducted among HIV seronegative MSM in Kunming cityduring 2009–2011. Interviewer-administrated questionnaires were carried out. Blood specimens were obtained to test for syphilis and HIV, in which HIV were evaluated by standard HIV enzyme immunoassay (EIA) and HIV nucleic acid amplification testing (NAAT). Near full-length regions of the HIV-1 were evaluated for subtyping, primary drug resistance mutations.ResultsDuring the follow-up 70.1% of the recruited 378 MSM retained in the cohort. Eleven MSM seroconverted to HIV and fifteen MSM seroconverted to syphilis. The HIV incidence and syphilis incidence was 3.5 (95% CI 1.8-6.2) cases /100 person year(PY) and 5.3 (95% CI 3.0-8.7) cases/100 PY, respectively. Multivariate analysis showed that baseline syphilis infection (aHR, 17.7), occupation (students vs. others [aHR, 5.7], retirees vs. others [aHR, 4.1]), bleeding experience after receptive anal intercourse (aHR,7.6), and minority ethnic(vs. Han) [aHR, 5.7] were independent risk factors for HIV seroconversion(each P<0.05). Among the 7/11 successfully amplified near full-length sequences, 71.4% (5/7) were CRF01_AE, and 28.6% (2/7) were CRF07_BC. Two HIV transmission pairs were detected among seroconverted minority ethnic MSM.ConclusionsHIV incidence was moderately high among Yunnan MSM. Yunnan province need to strengthen both HIV and syphilis screening among MSM population. Some subpopulations of MSM, such as students, retirees and minority ethnic groups require more HIV epidemic surveillance and strengthened behavior interventions. HIV subtypes and primary drug resistance should be continually monitored to track cross-group transmission of HIV strains.

Evaluation of application of pooling nucleic acid amplification testing in men who have sex with men population in China

Objective To evaluate the application of pooling HIV nucleic acid amplification testing (NAAT) among men who had sex with men (MSM) population, and to investigate suitable HIV screening strategy and the feasibility of calculation of HIV incidence using pooling NAAT among MSM population in China.Methods Four thousand eight hundred and fifty-six samples were collected from MSM population from April 2008 to September 2009 among with 4 156 were in Heilongjiang province and 700 were in Beijing in China. After standard testing with an HIV ELISA and WB confirmation testing, HIV antibody-negative samples were pooled and screened for HIV using NAAT.A three-stage pooling strategy was adopted.The HIV positive rate estimated by the four HIV screening strategies was calculated.In addition, 4 156 HIV positive specimens from Heilongjiang province were screened with the BED capture enzyme immunoassay (BED-CEIA).The HIV-1 incidences were estimated by BED-CEIA assay and pooling NAAT individually.ResultsOne hundred and forty-three of 4 856 subjects were HIV infected.130 were 3rd and 4th generation ELISA positive; 13 were antibody-negative but acutely HIV infected.According to the evaluation of four HIV screening strategies, routine HIV screening test together with pooling NAAT was more effective than other strategies for screening out window period generation ELISA+WB+pooling NAAT' were 2.68%(95% confidence interval CI=2.22%-3.14%), 2.82%(95%CI=2.35%-3.29%), 2.94%(95%CI=2.46%-3.42%) and 2.94%(95%CI=2.46%-3.42%), respectively.The differences were not significant (χ2=0.854 3, P=0.836 4).Of the 88 HIV positive samples from Heilongjiang province, 44 participants were tested as recent HIV infections by BED-CEIA assay. The estimated HIV-1 incidence was 2.36% (95%CI=1.63%-3.08%) and 2.92% (95%CI=1.01%-4.83%) based on BED-CEIA assay and pooling NAAT,respectively.Conclusions Pooling NAAT is a effective screening test in HIV negative population to detect window period infection among MSM population in China. Key words: Sexual behavior; Male; HIV; Nuclieic acids; HIV infections

More on HIV Nucleic Acid Amplification Testing

Detection of acute and early HIV infection, despite its importance, has been difficult to accomplish. Pooled nucleic acid amplification testing (NAAT)

Detection of Acute HIV Infections in an Urban HIV Counseling and Testing Population in the United States

The southeastern United States has an increasing burden of HIV, particularly among blacks, women, and men who have sex with men. To evaluate HIV nucleic acid amplification testing (NAAT) and antibody-based algorithms in determination of HIV incidence, detection of acute HIV infections, and surveillance of drug-resistant virus transmission in the urban southeastern United States, we conducted a cross-sectional analysis of prospectively collected data from 2202 adults receiving HIV testing and counseling at 3 sites in Atlanta, GA from October 2002 through January 2004. After standard testing with an HIV enzyme immunoassay (EIA) and Western blot confirmation, HIV-positive specimens were tested with 2 standardized assays to detect recent infection. HIV antibody-negative specimens were pooled and screened for HIV using NAAT. Seventy (3.2%) of 2202 subjects were HIV infected. Only 66 were positive on the standard HIV antibody test; 4 were antibody-negative but acutely HIV infected. The overall annual HIV incidence was 1.1% (95% confidence interval [CI]: 0.4 to 1.8) based on the Vironostika-LS assay and 1.3% (95% CI: 0.6 to 2.1) based on the BED Incidence Enzyme Immunoassay (EIA). The prevalence of acute HIV infection was 1.8 per 1000 persons (95% CI: 0.7 to 4.6). The sensitivity of the current testing algorithm using an EIA and Western blot test for detectable infections was only 94.3% (95% CI: 86.2 to 97.8). All 3 of the acutely infected subjects genotyped had drug resistance mutations, and 1 had multiclass resistance. Adding NAAT-based screening to standard HIV antibody testing increased case identification by 6% and uncovered the first evidence of multidrug-resistant HIV transmission in Atlanta. Antibody tests alone are insufficient for public health practice in high-risk urban HIV testing settings.

Detection of HCV and HIV‐1 antibody negative infections in Scottish and Northern Ireland blood donations by nucleic acid amplification testing

To reduce the risk of transfusion-transmissible viruses entering the blood supply, the nucleic acid amplification testing (NAT) was implemented to screen Scottish and Northern Irish blood donations in minipools. After 5 years of NAT for hepatitis C virus (HCV) and 2 years for human immunodeficiency virus-1 (HIV-1), the yield of serologically negative, nucleic acid positive 'window donations' and cost-benefit of NAT is under review. When the Scottish National Blood Transfusion Service (SNBTS) implemented NAT in 1999, a fully automated 'black box' system was not available. Therefore, an 'in-house' assimilated NAT assay was developed, validated and implemented. The system is flexible and allows testing for additional viral markers to be introduced with relative ease. The HCV and HIV NAT assays have 95% detection levels of 7.25 IU/ml and 39.8 IU/ml, respectively, as determined by probit analysis. One HCV (1 in 1.9 million) and one HIV (1 in 0.77 million) window donation have been detected in 5 and 2 years, respectively, of NAT. The SNBTS NAT assays are robust and have performed consistently over the last 5 years. The design of the in-house system allowed HIV NAT to be added in 2003 at a relatively small additional cost per sample, although for both assays, the royalty fee far exceeds the cost of the test itself. Clearly NAT has a benefit in improving the safety of the blood supply although the risks of transfusion-transmitted viral infections, as reported in the Serious Hazards of Transfusion (SHOT) report, are extremely low. Also, in UK the yield of HCV antibody negative, NAT positive donations is far lower than predicted although the early detection of an HIV window period donation and the increase of HIV in the blood donor and general populations may provide a stronger case for HIV NAT. SUMMARY SENTENCE: The yield of HCV and HIV NAT in UK is significantly less than that anticipated from statistical models.

Acute HIV revisited: new opportunities for treatment and prevention.

Inability to recognize incident infection has traditionally limited both scientific and public health approaches to HIV disease. Recently, some laboratories have begun adding HIV nucleic acid amplification testing to HIV diagnostic testing algorithms so that acute (antibody-negative) HIV infections can be routinely detected within the first 1-3 weeks of exposure. In this review article, we will highlight critical opportunities for HIV treatment and prevention that are presented by these diagnostic strategies.

Acute HIV revisited: new opportunities for treatment and prevention

Inability to recognize incident infection has traditionally limited both scientific and public health approaches to HIV disease. Recently, some laboratories have begun adding HIV nucleic acid amplification testing to HIV diagnostic testing algorithms so that acute (antibody-negative) HIV infections can be routinely detected within the first 1–3 weeks of exposure. In this review article, we will highlight critical opportunities for HIV treatment and prevention that are presented by these diagnostic strategies.