Nondisclosure of HIV Status in a Clinical Trial Setting: Antiretroviral Drug Screening Can Help Distinguish Between Newly Diagnosed and Previously Diagnosed HIV Infection

Marzinke, Mark A.; Clarke, William; Wang, Lei; Cummings, Vanessa; Liu, Ting Yuan; Piwowar‐Manning, Estelle; Breaud, Autumn; Griffith, Sam; Buchbinder, Susan; Shoptaw, Steven; Rı́o, Carlos del; Magnus, Manya; Mannheimer, Sharon; Fields, Sheldon D.; Mayer, Kenneth H.; Wheeler, Darrell P.; Koblin, Beryl A.; Eshleman, Susan H.; Fogel, Jessica M.

doi:10.1093/cid/cit672

Cited by 52 publications

(64 citation statements)

References 10 publications

(13 reference statements)

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“…One of these individuals was most likely an elite controller and the other was virally suppressed from ART; nondisclosure of ART was common in this cohort. 8 In these 2 cases, HIV infection was missed at the study site at all 3 study visits (enrollment, 6 months, and 12 months). In one case, false-negative test results were also obtained when samples from the follow-up visits were tested at the centralized laboratory using the same assay; in the other case, weak positive results were obtained at the centralized laboratory.…”

Section: Discussionmentioning

confidence: 99%

Failure to Identify HIV-Infected Individuals in a Clinical Trial Using a Single HIV Rapid Test for Screening

Piwowar‐Manning¹,

Fogel²,

Laeyendecker³

et al. 2014

HIV Clinical Trials

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Background In the HIV Prevention Trials Network (HPTN) 061 study, 8 (2.3%) of 348 HIV-infected participants identified as HIV uninfected at study enrollment using a single HIV rapid test for screening were found to be HIV infected after additional testing. Objectives To evaluate the performance of different HIV assays for detection of HIV infection in HPTN 061 participants with missed infection and individuals with viral suppression. Methods Plasma samples from 8 HPTN 061 participants, 17 elite controllers, and 101 individuals on antiretroviral treatment (ART) were tested for HIV with 3 rapid tests, 2 laboratory-based immunoassays, and a Western blot assay. The HPTN 061 samples were also tested with 2 HIV RNA assays and an antiretroviral drug assay. Results Of the 8 HPTN 061 participants with missed infection, 1 was an elite controller, 1 was taking ART, 2 were missed because of testing or clerical errors, 1 had recent HIV infection (identified using a multi-assay algorithm), and 3 had acute HIV infection. Two (1.7%) of 118 individuals with viral suppression (both taking ART) had at least 1 false-negative test. Conclusions In clinical trials, HIV infections can be missed for a variety of reasons. Using more than one assay to screen for HIV infection may reduce the number of missed infections.

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Section: Discussionmentioning

confidence: 99%

Failure to Identify HIV-Infected Individuals in a Clinical Trial Using a Single HIV Rapid Test for Screening

Piwowar‐Manning¹,

Fogel²,

Laeyendecker³

et al. 2014

HIV Clinical Trials

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“…At the time when HPTN 061 was performed, there were no ARV drugs approved for PrEP for sexual HIV transmission. Many of the men in HPTN 061 who reported no current or prior ARV drug use had ARV drugs detected in study samples (21). In most cases, the drugs detected were consistent with ART regimens recommended at the time of the study.…”

Section: Discussionmentioning

confidence: 83%

“…This allowed us to explore whether the men enrolled in HPTN 073 were using any other ARV drugs. In a previous study, we analyzed ARV drug use among HIV-infected men in the HPTN 061 study (2009 to 2011), which enrolled 1,553 Black MSM in six cities in the United States, including the three sites in HPTN 073 (19,21). At the time when HPTN 061 was performed, there were no ARV drugs approved for PrEP for sexual HIV transmission.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of a Multidrug Assay for Monitoring Adherence to a Regimen for HIV Preexposure Prophylaxis in a Clinical Study, HIV Prevention Trials Network 073

Zhang

Clarke

Marzinke

et al. 2017

Antimicrob Agents Chemother

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Daily oral tenofovir disoproxil fumarate (TDF)-emtricitabine (FTC) is a safe and effective intervention for HIV preexposure prophylaxis (PrEP). We evaluated the performance of a qualitative assay that detects 20 antiretroviral (ARV) drugs (multidrug assay) in assessing recent PrEP exposure (detection limit, 2 to 20 ng/ml). Samples were obtained from 216 Black men who have sex with men (208 HIV-uninfected men and 8 seroconverters) who were enrolled in a study in the United States evaluating the acceptability of TDF-FTC PrEP (165 of the uninfected men and 5 of the seroconverters accepted PrEP). Samples from 163 of the 165 HIVuninfected men who accepted PrEP and samples from all 8 seroconverters were also tested for tenofovir (TFV) and FTC using a quantitative assay (detection limit for both drugs, 0.31 ng/ml). HIV drug resistance was assessed in seroconverter samples. The multidrug assay detected TFV and/or FTC in 3 (1.4%) of the 208 uninfected men at enrollment, 84 (40.4%) of the 208 uninfected men at the last study visit, and 1 (12.5%) of the 8 seroconverters. No other ARV drugs were detected. The quantitative assay confirmed all positive results from the multidrug assay and detected TFV and/or FTC in 9 additional samples (TFV range, 0.65 to 16.5 ng/ml; FTC range, 0.33 to 14.6 ng/ml). Resistance mutations were detected in 4 of the 8 seroconverter samples. The multidrug assay had 100% sensitivity and specificity for detecting TFV and FTC at drug concentrations consistent with daily PrEP use. The quantitative assay detected TFV and FTC at lower levels, which also might have provided protection against HIV infection.

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“…Marzinke et al 19 present an application of HRMS screening of antiretroviral (ARV) drugs for evaluating eligibility in a HIV clinical trial. The study examines a difficult consequence of HIV clinical trials: trials commonly attempt to recruit newly diagnosed, drug naïve patients; however, patients may be untruthful with regards to their knowledge of their HIV status as an attempt to obtain care by enrolling in the trial.…”

Section: Forensic Toxicologymentioning

confidence: 99%

Present and Future Applications of High Resolution Mass Spectrometry in the Clinic

Crutchfield

Clarke

2014

Discoveries

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High resolution mass spectrometers have directly enabled clinical applications of high clinical utility. These types of mass spectrometers are less known to the general public than their low resolution counterparts and are often ascribed to proteomics or biomarker discovery. This perception is rapidly changing as high resolution mass spectrometers see impact in the areas of clinical toxicology, forensic toxicology, microbiology, and molecular diagnostics as routine analyzers. Applications in these areas are made possible by the unique capacity of high resolution mass spectrometers, typically time-of flight or Orbitrap instruments, to characterize analytical species with sufficient mass resolution to better resolve molecular composition than lower resolution analyzers. This capacity confers a unique source of analytical specificity. In the future, this analytical specificity will likely be well applied to other clinical applications: mass spectrometry based tissue imaging, intraoperative determination of tumor boundaries, and evaluation of metabolic flux.

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Nondisclosure of HIV Status in a Clinical Trial Setting: Antiretroviral Drug Screening Can Help Distinguish Between Newly Diagnosed and Previously Diagnosed HIV Infection

Cited by 52 publications

References 10 publications

Failure to Identify HIV-Infected Individuals in a Clinical Trial Using a Single HIV Rapid Test for Screening

Failure to Identify HIV-Infected Individuals in a Clinical Trial Using a Single HIV Rapid Test for Screening

Evaluation of a Multidrug Assay for Monitoring Adherence to a Regimen for HIV Preexposure Prophylaxis in a Clinical Study, HIV Prevention Trials Network 073

Present and Future Applications of High Resolution Mass Spectrometry in the Clinic

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