Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-30 (of 36 Records) |
Query Trace: Masciotra S[original query] |
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Neisseria gonorrhoeae antimicrobial susceptibility trends in Bangkok, Thailand, 2015-21: Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP)
Kittiyaowamarn R , Girdthep N , Cherdtrakulkiat T , Sangprasert P , Tongtoyai J , Weston E , Borisov A , Dunne EF , Chinhiran K , Woodring J , Ngarmjiratam N , Masciotra S , Frankson R , Sirivongrangson P , Unemo M , Wi T . JAC Antimicrob Resist 2023 5 (6) dlad139 OBJECTIVES: Rising antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a global public health concern. Many ceftriaxone-resistant cases have been linked to Asia. In the WHO/CDC global Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP), we conducted AMR surveillance at two clinical sites in Bangkok, Thailand, 2015-21. METHODS: Urethral discharge samples, from males with urethral discharge and/or dysuria, were Gram-stained and cultured. ETEST was performed to determine AMR. EGASP MIC alert values, CLSI and EUCAST breakpoints were used. RESULTS: In 2015-21, gonococcal isolates were cultured from 1928 cases; most (64.1%) were males reporting having sex with females. The sensitivity and specificity of Gram-stained microscopy compared with culture for detection of gonococci were 97.5% and 96.6%, respectively. From 2015 to 2021, the azithromycin MIC(90) increased from 0.125 to 1 mg/L, and the MIC(90) of ceftriaxone and cefixime increased from 0.008 and ≤0.016 mg/L to 0.032 and 0.064 mg/L, respectively. Eight EGASP MIC alert values (in seven isolates) were identified. Five alert values were for cefixime (all resistant according to EUCAST breakpoints) and three for azithromycin (all resistant according to EUCAST breakpoints). The average annual resistance to ciprofloxacin during 2015-21 was 92%. CONCLUSIONS: A continuous high susceptibility to ceftriaxone, Thailand's first-line gonorrhoea treatment, was found. However, the increasing MICs of ceftriaxone, cefixime and azithromycin are a substantial threat, especially considering these are the last remaining options for the treatment of gonorrhoea. To monitor AMR, continuous and quality-assured gonococcal AMR surveillance such as the Thai WHO/CDC EGASP, ideally including WGS, is imperative globally. |
The feasibility of modified HIV and antiretroviral drug testing using self-collected dried blood spots from men who have sex with men.
Luo W , Sullivan V , Chavez PR , Wiatrek SE , Zlotorzynska M , Martin A , Rossetti R , Sanchez T , Sullivan P , MacGowan RJ , Owen SM , Masciotra S . BMC Infect Dis 2021 21 (1) 423 BACKGROUND: In the US, one in six men who have sex with men (MSM) with HIV are unaware of their HIV infection. In certain circumstances, access to HIV testing and viral load (VL) monitoring is challenging. The objective of this study was to evaluate the feasibility of conducting laboratory-based HIV and antiretroviral (ARV) drug testing, and VL monitoring as part of two studies on self-collected dried blood spots (DBS). METHODS: Participants were instructed to collect DBS by self-fingerstick in studies that enrolled MSM online. DBS from the first study (N = 1444) were tested with HIV serological assays approved by the Food and Drug Administration (FDA). A subset was further tested with laboratory-modified serological and VL assays, and ARV levels were measured by mass spectrometry. DBS from the second study (N = 74) were only tested to assess VL monitoring. RESULTS: In the first study, the mail back rate of self-collected DBS cards was 62.9%. Ninety percent of DBS cards were received at the laboratory within 2 weeks from the day of collection, and 98% of the cards had sufficient spots for one assay. Concordance between FDA-approved and laboratory-modified protocols was high. The samples with undetectable ARV had higher VL than samples with at least one ARV drug. In the second study, 70.3% participants returned self-collected DBS cards, and all had sufficient spots for VL assay. High VL was observed in samples from participants who reported low ARV adherence. CONCLUSIONS: In these studies, MSM were able to collect and provide adequate DBS for HIV testing. The FDA-approved and laboratory-modified testing algorithms performed similarly. DBS collected at home may be feasible for HIV testing, ARV measurement, and monitoring viral suppression. |
Broadly neutralizing HIV-1 antibody reactivity in HIV tests: implications for diagnostics
Smith T , Masciotra S , Luo W , Sullivan V , Switzer WM , Johnson JA , Heneine W . AIDS 2021 35 (10) 1561-1565 OBJECTIVE: Passive immunization with broadly neutralizing antibodies (bNAbs) is under evaluation for HIV prevention. BNAbs target gp120 or gp41, two HIV envelope antigens commonly present in diagnostic tests. Depending on bNAb type and dose administered to humans, serum levels can reach ∼1 mg/mL and wane over several weeks to months. We investigated the reactivity of bNAbs in HIV serological tests to inform diagnostic testing practices for persons treated with these products. DESIGN METHODS: The anti-gp120 bNAbs VRCO1, PGT121, PGT145, 3BNC117, 10-1074, and N6 and anti-gp41 bNAbs 10E8 and 10E8v4 were tested with the laboratory-based Bio-Rad Ag/Ab Combo assay, the point-of-care single-use Determine Combo, OraQuick, Reveal G4, SureCheck, Uni-Gold, INSTI and DPP HIV 1/2 assays, and the supplemental Geenius and HIV-1 Western blot assays. RESULTS: At 1 mg/mL, all bNAbs were nonreactive in four screening tests. OraQuick, SureCheck, Reveal G4, and INSTI detected at least two bNAbs each; SureCheck exhibited reactivity to six bNAbs. Geenius was HIV-1 indeterminate (gp160+) with all bNAbs except PGT121, which was HIV antibody-negative. HIV-1 Western blot was indeterminate (gp41+/gp160+) with 10E8 and 10E8v4 and negative with the remaining bNAbs. There was no correlation between the test antigen construct(s) and bNAb reactivity. CONCLUSION: We identified a laboratory-based Ag/Ab EIA and three single-use rapid HIV tests that are nonreactive against a panel of bNAbs supporting some diagnostic tests can distinguish HIV-1 infection events among persons receiving bNAb immunoprophylaxis. Evaluation of HIV diagnostic tests prior to clinical use may identify suitable serologic assays for persons administered bNAbs. |
Prevalence and trends in HIV infection and testing among adults in the United States: The National Health and Nutrition Examination Surveys, 1999-2018
McQuillan GM , Kruszon-Moran D , Gu Q , Masciotra S , Storandt R . J Acquir Immune Defic Syndr 2020 Publish Ahead of Print (5) 523-529 BACKGROUND: HIV antibody testing has been included in the National Health and Nutrition Examination Survey, for ages 18-49 since 1999 and for ages 18-59 years since 2009 enabling estimation of trends in HIV prevalence as part of national surveillance in the U.S. household population. Self-reported HIV testing and antiretroviral (ARV) use was also included in the survey since 1999. SETTING: A continuous household-based probability sample of the U.S. population. METHODS: From 1999-2018, 29,020 participants age 18-49 years were tested for HIV antibody and 34,092 participants age 18-59 years were asked about self-report of any previous HIV testing. RESULTS: HIV prevalence was 0.41% among those aged 18-59 in 2009-2018 with a non-significant trend over time among those aged 18-49 years from 1999-2002 to 2015-2018. However, significant declines in prevalence were seen among those aged 18-39 years (0.37% to 0.11%), women (0.22% to 0.06%) and non-Hispanic black persons (2.14% to 0.80%). Participants age aged 18-39 self-reported a decline in HIV testing while those aged 40-49 and 50-59 years, non-Hispanic black persons and women reported an increase in getting a HIV test. Prevalence of infection and self-reported history of HIV testing varied by demographic and risk groups. HIV testing among HIV positive persons was 83.9%. ARV therapy among those HIV positive was under 50%. CONCLUSION: Though total HIV prevalence and previous self-reported HIV testing remained stable for the last 20 years, there were significant declines in age and demographic subgroups. Prevalence for both outcomes varied by demographic and risk variables. |
Do I Have HIV or Not? Lack of RNA Detection and the Case for Sensitive DNA Testing.
Springer SA , Masciotra S , Johnson JA , Campbell S . Open Forum Infect Dis 2020 7 (11) ofaa478 We present a case of a 20-year-old male who had ambiguous HIV test results after entering new provider care and whose status was later complicated by undetectable viral RNA off antiretroviral therapy (ART). Verifying HIV infection status may occasionally require sensitive DNA testing that might need to be considered in diagnostic guidelines to resolve diagnosis and ensure appropriate ART management. |
Evaluation of rapid testing algorithms for venue-based anonymous HIV testing among non-HIV-positive men who have sex with men, National HIV Behavioral Surveillance (NHBS), 2017
Whitby S , Smith A , Rossetti R , Chapin-Bardales J , Martin A , Wejnert C , Masciotra S . J Community Health 2020 45 (6) 1228-1235 HIV rapid testing algorithms (RTAs) using any two orthogonal rapid tests (RTs) allow for on-site confirmation of infection. RTs vary in performance characteristics therefore the selection of RTs in an algorithm may affect identification of infection, particularly if acute. National HIV Behavioral Surveillance (NHBS) assessed RTAs among men who have sex with men recruited using anonymous venue-based sampling. Different algorithms were evaluated among participants who self-reported never having received a positive HIV test result prior to the interview. NHBS project areas performed sequential or parallel RTs using whole blood. Participants with at least one reactive RT were offered anonymous linkage to care and provided a dried blood spot (DBS) for testing at CDC. Discordant results (RT-1 reactive/RT-2 non-reactive) were tested at CDC with lab protocols modified for DBS. DBS were also tested for HIV-1 RNA (VL) and antiretroviral (ARV) drug levels. Of 6500 RTAs, 238 were RT-1 reactive; of those, 97.1% (231/238) had concordant results (RT-1/RT-2 reactive) and 2.9% (7/238) had discordant results. Five DBS associated with discordant results were available for confirmation at CDC. Four had non-reactive confirmatory test results that implied RT-1 false reactivity; one had ambiguous confirmatory test results which was non-reactive in further testing. Regardless of order and type of RT used, RTAs demonstrated high concordant results in the population surveyed. Additional laboratory testing on DBS following discordant results confirmed no infection. Implementing RTAs in the context of anonymous venue-based HIV testing could be an option when laboratory follow-up is not practicable. |
Performance evaluation of the Aptima HIV-1 RNA Quant assay on the Panther system using the standard and dilution protocols
Rossetti R , Smith T , Luo W , Taussig J , Valentine-Graves M , Sullivan P , Ingersoll JM , Kraft CS , Ethridge S , Wesolowski L , Delaney KP , Owen SM , Johnson JA , Masciotra S . J Clin Virol 2020 129 104479 BACKGROUND: Currently, FDA-approved HIV-1 viral load (VL) assays use venipuncture-derived plasma. The Hologic Panther system uses 0.7mL total volume for the Aptima HIV-1 Quant Assay standard (APT-Quant-std) and dilution (APT-Quant-dil) protocols. However, smaller plasma volumes from fingerstick whole blood (FSB) collected in EDTA-microtainer tubes (MCT) could provide an easier sample collection method for HIV-1 VL testing. OBJECTIVES: To evaluate the performance of the APT-Quant-std compared to the Roche CAP/CTM and Abbott m2000RT VL assays and an alternative APTQuant 1:7 dilution protocol, the latter using 100muL of MCT-derived plasma from FSB. STUDY DESIGN: Linearity was determined using commercial HIV-1 RNA plasma controls. Dilutions ranging 1.56-2.95 log10 copies/mL were prepared to determine the APT-Quant-dil Limit of Quantitation (LOQ) using Probit analysis. Specificity of APT-Quant-std was calculated using 326 HIVnegative samples. To evaluate agreement, 329 plasma specimens were tested with APT-Quant-std, CAP/CTM, and m2000RT. Forty-seven matched venipuncture and MCT-derived plasma specimens were tested with APT-Quant-std and APT-Quant-dil. RESULTS: Among the RNA controls, specificity was 99.69 % for APT-Quant-std. The R2 values were 0.988 (APT-Quant-std/CAP/CTM), 0.980 (APT-Quant-std/ m2000RT), and 0.997 (APT-Quant-std/APT-Quant-dil). The APT-Quant-dil LOQ was estimated at 2.7 log10 copies/mL (500 copies/mL) (95 %CI 2.62-2.87). At 2.3 log10 copies/mL (200 copies/mL), the overall agreement was 91.0 % for APT-Quant-std/CAP/CTM, 85.7 % for APT-Quant-std/m2000RT, and 82.9 % for APT-Quant-std/APT-Quant-dil. Quantified APT-Quant-std results were on average 0.2 log10 copies/mL higher than CAP/CTM and m2000RT and 0.14 log10 copies/mL higher than APT-Quant-dil. CONCLUSION: APT-Quant showed similar performance compared to the CAP/CTM and m2000RT assays and remains sensitive and accurate using the dilution protocol. |
Performance evaluation of the MedMira reveal G4 LAB S/P and POC HIV antibody rapid screening tests using plasma and whole blood specimens
Rossetti R , Smith T , Luo W , Masciotra S . J Clin Virol 2020 127 104344 BACKGROUND: The Reveal G4 antibody rapid test is FDA-approved for HIV-1 detection using the versions LAB S/P and POC in CLIA-moderate complexity settings with serum/plasma and whole blood, respectively. The same Reveal tests are CE-marked for HIV-1 and HIV-2 detection in laboratory and point-of-care (POC) settings. OBJECTIVE: We compared the performance of G4 LAB S/P with plasma and POC with whole blood (blood) for detecting early and established HIV-1/HIV-2 infections. STUDY DESIGN: Matched well-characterized plasma and simulated blood were used to evaluate: sensitivity in 104 HIV-1 and 55 HIV-2 established infections, specificity in 49 HIV-negative, and reactivity in early HIV-1 infection in a performance panel (n=38) and 18 plasma panels from seroconverters (SCs, n=183). Median number of days after first RNA-positive was calculated for 13 SCs. Impact of viral suppression (VS) was evaluated in 3 SCs receiving early antiretroviral therapy (ART). RESULTS: Sensitivity was 100 % for HIV-1 and 98.18 % for HIV-2, while specificity was 100 %. All 38 plasma and blood become reactive by Fiebig stage V. Of 18 SCs, 10 had similar reactivity in plasma/blood, 7 showed delayed reactivity in blood, and 1 was nonreactive in plasma/blood. The median days for a G4-reactive after first RNApositive was 13 for plasma and 14 for blood. Long-term VS had no impact on G4 reactivity. CONCLUSIONS: Overall reactivity in early HIV-1 infections is delayed by one day in blood compared to plasma. If FDA-approved for POC settings, the G4 POC is a fast sensitive screening tool for HIV-1/HIV-2-specific IgG even during VS. |
Could HIV-1 RNA be an option as the second step in the HIV diagnostic algorithm
Masciotra S , Luo W , Rossetti R , Smith T , Ethridge S , Delaney KP , Wesolowski LG , Owen SM . Sex Transm Dis 2020 47 S26-S31 BACKGROUND: There is benefit to early HIV-1 diagnosis and treatment, but there is no FDA-approved quantitative assay with a diagnostic claim. We compared the performance of the Hologic Aptima HIV-1 Quant (APT-Quant) and Aptima HIV-1 Qual (APT-Qual) assays for diagnostic use and the performance of a diagnostic algorithm consisting of Bio-Rad BioPlex 2200 HIV Ag-Ab assay (BPC) followed by APT-Quant (two-test) compare to BPC followed by Geenius HIV-1/2 supplemental assay (Geenius) with reflex to APT-Qual (three-test). METHODS: 524 plasma, which included 419 longitudinal specimens from HIV-1 seroconverters (78 were after initiating antiretroviral therapy (ART)) and 105 from ART-naive persons with established HIV-1 infections, were used to evaluate APT-Quant performance for diagnostic use. Specimens from 200 HIV-negative persons were used to measure specificity. For the algorithm comparison, BPC-reactive specimens were evaluated with the two-test or three-test algorithm. McNemar's test was used to compare performance. RESULTS: APT-Quant detected more samples early in infection compared with APT-Qual. APT-Quant specificity was 99.8%. Before ART initiation, the algorithms performed similarly among samples from different stages of infection. After ART initiation, the three-test algorithm performed significantly better (p=0.0233). CONCLUSIONS: APT-Quant has excellent performance for diagnostic use. The two-test algorithm works well in ART-naive samples, but its performance decreases after the IgG response is elicited and with ART-induced suppressed viremia. Providing confirmation and VL with one test result could be advantageous for patient care. However, additional factors and challenges associated with the implementation of this two-test algorithm such as cost, specimen type and collection need further evaluation. |
Evaluation of the performance of the Cepheid Xpert HIV-1 Viral Load Assay for quantitative and diagnostic uses
Wesolowski L , Fowler W , Luo W , Sullivan V , Masciotra S , Smith T , Rossetti R , Delaney K , Oraka E , Chavez P , Ethridge S , Switzer WM , Owen SM . J Clin Virol 2019 122 104214 BACKGROUND: Cepheid's Xpert HIV-1 Viral Load (Xpert VL), a simplified, automated, single-use quantitative assay used with the GeneXpert System, is not FDA approved. OBJECTIVES: Using stored plasma, we conducted a study to assess the ability of Xpert VL to quantify viral load relative to the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 (Cobas VL) and to examine the use of the Xpert VL as a qualitative diagnostic test. STUDY DESIGN: Following HIV-1 viral stock dilutions, we conducted a probit analysis to identify the concentration where 95 % of specimens had quantified VLs. We also examined Xpert and Cobas log VL correlation in linearity panels; compared the proportion of 220 seroconverter specimens with virus detected using McNemar's test; and tested specimens from persons with untreated, established HIV-1 infection (n=149) and uninfected persons (n=497). Furthermore, we examined Xpert VL as a qualitative test in seroconverter specimens with early (n=20) and later (n=68) acute infections. RESULTS: At 1.80 log10 copies/mL, 95 % of specimens had quantifiable virus using Xpert VL. Xpert and Cobas VLs were highly correlated (R(2)=0.994). The proportion of seroconverter specimens with virus detected using Cobas and with Xpert VL was not statistically different (p=0.0578). Xpert VL detected 97.9 % of established infections, and specificity was 99.80 % (95 % CI 98.87%-99.99%). Xpert VL detected 90 % and 98.5 % of early and later acute infections, respectively. CONCLUSIONS: If approved, Xpert VL could allow U.S. laboratories that cannot bring on large, complex testing platforms to conduct HIV monitoring. An approval for diagnostic use may provide timely identification of HIV infections. |
Performance of an alternative laboratory-based HIV diagnostic testing algorithm using HIV-1 RNA viral load
Pitasi MA , Patel SN , Wesolowski LG , Masciotra S , Luo W , Owen SM , Delaney KP . Sex Transm Dis 2019 47 S18-S25 BACKGROUND: Since 2014, the recommended algorithm for laboratory diagnosis of HIV infection in the United States has consisted of an HIV-1/2 antigen/antibody (Ag/Ab) test followed by an HIV-1/2 antibody (Ab) differentiation test and, if necessary, a diagnostic HIV-1 nucleic acid test (NAT) to resolve discordant or indeterminate results. METHODS: Using stored specimens from persons seeking HIV testing who had not received a previous diagnosis or treatment, we compared the performance of a three-step alternative algorithm consisting of an Ag/Ab test followed by a quantitative HIV-1 RNA viral load assay and, if viral load is not detected, an Ab differentiation test, to that of the recommended algorithm. We calculated the sensitivity and specificity of five Ag/Ab tests and the proportion of specimens correctly classified by the alternative algorithm compared to the recommended algorithm. Results were examined separately for specimens classified as early infection, established infection, and false-reactive screening RESULTS: Sensitivity and specificity were similar among all Ag/Ab tests. Viral load quantification correctly classified all specimens from early infection, all false-reactive screening specimens, and the majority of specimens from established infection. CONCLUSIONS: Although cost, regulatory barriers, test availability, and the ability to differentiate early from established infection must be considered, this alternative algorithm can potentially decrease the total number of tests performed and reduce turnaround time, thereby streamlining HIV diagnosis and initiation of treatment. |
The concordance of the limiting antigen and the Bio-Rad avidity assays in persons from Estonia infected mainly with HIV-1 CRF06_cpx
Huik K , Soodla P , Pauskar M , Owen SM , Luo W , Murphy G , Jogeda EL , Kallas E , Rajasaar H , Avi R , Masciotra S , Lutsar I . PLoS One 2019 14 (5) e0217048 BACKGROUND: Serological assays to determine HIV incidence have contributed to estimates of HIV incidence, monitoring of HIV spread, and evaluation of prevention strategies. Two frequently used incidence assays are the Sedia HIV-1 LAg-Avidity EIA (LAg) and the Bio-Rad avidity incidence (BRAI) assays with a mean duration of recent infection (MDRI) of 130 and 240 days for subtype B infections, respectively. Little is known about how these assays perform with recombinant HIV-1 strains. We evaluated the concordance of these assays in a population infected mainly with HIV-1 CRF06_cpx. MATERIAL/METHODS: Remnant serum samples (n = 288) collected from confirmed, newly-diagnosed HIV-positive persons from Estonia in 2013 were tested. Demographic and clinical data were extracted from clinical databases. LAg was performed according to the manufacturer's protocol and BRAI testing was done using a validated protocol. Samples with LAg-pending or BRAI-invalid results were reclassified as recent if they were from persons with viral loads <1000 copies/mL or were reclassified as long-term if presenting with AIDS. RESULTS: In total 325 new HIV infections were diagnosed in 2013 in Estonia. Of those 276 persons were tested with both LAg and BRAI. Using assay results only, the recency rate was 44% and 70% by LAg and BRAI, respectively. The majority of samples (92%) recent by LAg were recent by BRAI. Similarly, 89% of samples long-term by BRAI were long-term by LAg. After clinical information was included in the analysis, the recency rate was 44% and 62% for LAg and BRAI, respectively. The majority of samples (86%) recent by LAg were recent by BRAI and 91% of long-term infections by BRAI were long-term by LAg. CONCLUSIONS: Comparison of LAg and BRAI results in this mostly CRF06_cpx-infected population showed good concordance for incidence classification. Our finding of a higher recency rate with BRAI in this population is likely related to the longer MDRI for this assay. |
Evaluation of the performance of three biomarker assays for recent HIV infection using a well-characterized HIV-1 subtype C incidence cohort
Gonese E , Kilmarx P , van Schalkwyk C , Grebe E , Mutasa K , Ntozini R , Parekh B , Dobbs T , Duong Pottinger Y , Masciotra S , Owen M , Nachega J , van Zyl G , Hargrove J . AIDS Res Hum Retroviruses 2019 35 (7) 615-627 BACKGROUND: Biomarkers for detecting early HIV infection and estimating HIV incidence should minimise False-Recent Rates (FRRs) while maximising Mean Duration of Recent Infection (MDRIs). We compared BED capture enzyme immunoassay (BED), Sedia Limiting Antigen Avidity EIA (LAg) and Bio-Rad avidity incident incidence (BRAI) assays using samples from Zimbabwean postpartum women infected with clade C HIV. METHODS: We calculated MDRIs using 590 samples from 351 seroconverting postpartum women, and FRRs using samples from 2,825 women known to be HIV-positive for >12 months. RESULTS: Antibody kinetics were more predictable with LAg and had higher precision compared to BED or BRAI. BRAI also exhibited more variability, and avidity reversal in some cases. For BED, LAg and BRAI, used alone or with viral load (VL), MDRI values in days were: BED - 188 and 170 at normalized optical density (ODn) 0.8; LAg - 104 and 100 at ODn cut-off 1.5; BRAI - 135 and 134 at Avidity Index cut-off 30%. Corresponding FRRs were: BRAI 1.1% and 1.0% and LAg 0.57% and 0.35%: these were 3.8 - 10.9 times lower than BED values of 4.8% and 3.8 Conclusion: BRAI and LAg have significantly lower FRRs and MDRIs than in published studies, and much lower than BED and could be used to estimate incidence in perinatal women and to measure population level HIV incidence in HIV control operations in Africa. BRAI and LAg have significantly lower FRRs and MDRIs than in published studies, and much lower than BED. These improved methods could be used to estimate incidence in perinatal women and to measure population level HIV incidence in HIV control operations in Africa. |
A generalizable method for estimating duration of HIV infections using clinical testing history and HIV test results
Pilcher CD , Porco TC , Facente SN , Grebe E , Delaney KP , Masciotra S , Kassanjee R , Busch MP , Murphy G , Owen SM , Welte A . AIDS 2019 33 (7) 1231-1240 OBJECTIVE: To determine the precision of new and established methods for estimating duration of HIV infection. DESIGN: A retrospective analysis of HIV testing results from serial samples in commercially-available panels, taking advantage of extensive testing previously conducted on 53 seroconverters. METHODS: We initially investigated four methods for estimating infection timing: 1) "Fiebig stages" based on test results from a single specimen; 2) an updated "4 gen" method similar to Fiebig stages but using antigen/antibody tests in place of the p24 antigen test; 3) modeling of "viral ramp-up" dynamics using quantitative HIV-1 viral load data from antibody-negative specimens; and 4) using detailed clinical testing history to define a plausible interval and best estimate of infection time. We then investigated a "two-step method" using data from both methods 3 and 4, allowing for test results to have come from specimens collected on different days. RESULTS: Fiebig and "4 gen" staging method estimates of time since detectable viremia had similar and modest correlation with observed data. Correlation of estimates from both new methods (3 and 4), and from a combination of these two ("2-step method") was markedly improved and variability significantly reduced when compared with Fiebig estimates on the same specimens. CONCLUSIONS: The new "two-step" method more accurately estimates timing of infection and is intended to be generalizable to more situations in clinical medicine, research, and surveillance than previous methods. An online tool is now available that enables researchers/clinicians to input data related to method 4, and generate estimated dates of detectable infection. |
Characteristics of persons who inject drugs with recent HIV infection in the United States: National HIV Behavioral Surveillance, 2012
Chapin-Bardales J , Masciotra S , Smith A , Hoots BE , Martin A , Switzer WM , Luo W , Owen SM , Paz-Bailey G . AIDS Behav 2019 23 (12) 3277-3285 We evaluated characteristics associated with recent HIV infection among persons who inject drugs (PWID) from 19 U.S. cities who participated in 2012 National HIV Behavioral Surveillance. Recent infection was defined as having a reactive HIV test, a Bio-Rad Avidity index cutoff </= 30%, no reported HIV diagnosis >/= 12 months before interview, and no evidence of viral suppression. Of 8667 PWID, 50 (0.6%) were recently HIV infected. Having a greater number of sex partners (>/= 2 partners vs. 0) [prevalence ratio (PR) 4.7, 95% confidence interval (CI) 1.3-17.8], injecting heroin and other drugs (PR 3.0, 95% CI 1.3-6.6) or exclusively non-heroin drugs (PR 5.9, 95% CI 1.7-20.7) compared to injecting only heroin, and having male-male sex in the past year (PR 7.1, 95% CI 3.0-16.6) were associated with recent infection. Promoting not only safe injection practices but also safe sex practices will be key to preventing new HIV infections. |
Undisclosed HIV infection among men who have sex with men in National HIV Behavioral Surveillance, 2014
Hoots BE , Wejnert C , Martin A , Haaland R , Masciotra S , Sionean C , Smith A , Switzer WM , Paz-Bailey G . AIDS 2019 33 (5) 913-918 OBJECTIVE: As a proxy for undiagnosed HIV, CDC's National HIV Behavioral Surveillance (NHBS) monitors participants who report being unaware of their infection, defined as self-reporting an HIV-negative or unknown status during the interview but testing positive for HIV infection. We validated the NHBS measure of awareness among men who have sex with men (MSM) in 2014. DESIGN: We tested dried blood spots (DBS) from MSM who reported being unaware of their infection for seven antiretrovirals (ARVs). MSM unaware with >/=1 ARV detected were defined as misreporters. METHODS: Weighted percentages and 95% confidence intervals were calculated to compare characteristics among misreporters, non-misreporters, and those who self-reported as HIV-positive. Viral load (VL) was quantified with a validated assay using DBS. RESULTS: Of 1,818 HIV-positive MSM, 299 (16%) self-reported as HIV-negative or unknown infection status. Of these 299, 145 (49%) were considered misreporters based on ARV detection. Among the unaware, misreporters were more likely than non-misreporters to be older and have health insurance. Compared to self-reported HIV-positive MSM, misreporters were more likely to be black, be bisexual, and have perceived discrimination. Of 138 misreporters with VL data, 116 (84%) had an undetectable VL. CONCLUSIONS: ARV testing revealed that half of MSM classified as unaware of their infection misreported their status. While off-label PrEP use might explain the presence of ARVs, it is unlikely since many misreporters were virally suppressed, suggesting they were on HIV therapy. Biomarker validation of behavioral data can improve data quality and usefulness in NHBS and other studies. |
Performance evaluation of the Bio-Rad Geenius HIV 1/2 supplemental assay
Luo W , Sullivan V , Smith T , Peters PJ , Gay C , Westheimer E , Cohen SE , Owen SM , Masciotra S . J Clin Virol 2018 111 24-28 BACKGROUND: In the US, the HIV diagnostic algorithm for laboratory settings recommends the use of an HIV-1/HIV-2 differentiation supplemental assay after an initial reactive antigen/antibody (Ag/Ab) assay result. Since the discontinuation of the Multispot HIV-1/HIV-2 Rapid Test (MS), the Geenius HIV-1/2 Supplemental assay (Geenius) is the only FDA-approved supplemental differentiation test. OBJECTIVE: We compared the performance of Geenius to MS and Western Blot (WB). STUDY DESIGN: The relative seroconversion plasma reactivity of Geenius and MS was assessed using a 50% cumulative frequency analysis from 17 HIV-1 seroconverters. In addition, previously characterized plasma specimens, 186 HIV-1 positive, 100 HIV-2 positive, and 93 Ag/Ab-positive/HIV-1 RNA-negative, were tested with Geenius v1.1 software. McNemar's test was used for paired comparison analysis. A subset of 48 specimens were retested with the upgraded Geenius v1.3 software. RESULTS: In HIV-1 seroconverters, the relative seroconversion reactivity was 2.5 and 2 days before the first positive HIV-1 WB for Geenius and MS, respectively. In HIV-1 positive samples, Geenius performed similarly to HIV-1 WB (p=0.1687) and MS (p=0.8312). In HIV-2 positive samples, Geenius underperformed compared to HIV-2 WB (p=0.0005) and MS (p=0.0012). When using the upgraded software among the HIV-1 positive and Ag/Ab-reactive/HIV-1 RNA-negative samples, gp140 reactivity decreased without affecting characterization of HIV-2 samples. CONCLUSIONS: With HIV-1 samples, Geenius, WB and MS performance was similar as supplemental tests. The updated Geenius software reduced false gp140 reactivity, but had no impact on identifying true HIV-2 infections. Further evaluation will assess the impact of the Geenius software update on final diagnostic interpretations. |
A strategy for PrEP clinicians to manage ambiguous HIV test results during follow-up visits
Smith DK , Switzer WM , Peters P , Delaney KP , Granade TC , Masciotra S , Shouse L , Brooks JT . Open Forum Infect Dis 2018 5 (8) ofy180 Prompt determination of HIV infection status is critical during follow-up visits for patients taking pre-exposure prophylaxis (PrEP) medication. Those who are uninfected can then continue safely taking PrEP, and those few who have acquired HIV infection can initiate an effective treatment regimen. However, a few recent cases have been reported of ambiguous HIV test results using common testing algorithms in PrEP patients. We review published reports of such cases and testing options that can be used to clarify true HIV status in these situations. In addition, we review the benefits and risks of 3 antiretroviral management options in these patients: (1) continue PrEP while conducting additional HIV tests, (2) initiate antiretroviral therapy for presumptive HIV infection while conducting confirmatory tests, or (3) discontinue PrEP to reassess HIV status after a brief antiretroviral-free interval. A clinical consultation resource is also provided. |
Characterization of real-time microarrays for simultaneous detection of HIV-1, HIV-2, and hepatitis viruses.
Granade TC , Kodani M , Wells SK , Youngpairoj AS , Masciotra S , Curtis KM , Kamili S , Owen SM . J Virol Methods 2018 259 60-65 Real-time PCR assays for nucleic acid testing (NAT) of hepatitis viruses A-E and for HIV-1 and HIV-2 have been developed; however, a multiplex assay that can simultaneously detect all of these agents is not yet available. Standardized TaqMan assays for detection of hepatitis viruses A-E have been described and applied to TaqMan Array Cards (TAC) which are capable of multiple pathogen detection using a single set of optimized PCR conditions. Assays for three gene regions of HIV-1 (long-terminal repeat (LTR), gag, and polymerase) and HIV-2 (overlap of LTR and gag, protease and integrase) were designed using the hepatitis assay conditions. Nucleic acid extracts of HIV-1-infected samples (44 plasma, 41 whole blood, 20 HIV-1 viral stocks) were tested on the TAC cards; 98 were reactive (92%) with 70 in multiple gene regions. Twenty-four of the 27 (89%) HIV-2 specimens (10 plasma, 1 PBMC lysate, 6 whole blood and 10 plasmids containing HIV-2 polymerase) were detected on TAC. No HIV or hepatitis virus sequences were detected in 30 HIV-negative samples (specificity 100%). Three HBV and 18 HCV co-infections were identified in the HIV-1-infected specimens. Multi-pathogen detection using TAC could provide a rapid, sensitive and more efficient method of surveying for a variety of infectious disease nucleic acids. |
Detailed Transmission Network Analysis of a Large Opiate-Driven Outbreak of HIV Infection in the United States.
Campbell EM , Jia H , Shankar A , Hanson D , Luo W , Masciotra S , Owen SM , Oster AM , Galang RR , Spiller MW , Blosser SJ , Chapman E , Roseberry JC , Gentry J , Pontones P , Duwve J , Peyrani P , Kagan RM , Whitcomb JM , Peters PJ , Heneine W , Brooks JT , Switzer WM . J Infect Dis 2017 216 (9) 1053-1062 In January 2015, an outbreak of undiagnosed human immunodeficiency virus (HIV) infections among persons who inject drugs (PWID) was recognized in rural Indiana. By September 2016, 205 persons in this community of approximately 4400 had received a diagnosis of HIV infection. We report results of new approaches to analyzing epidemiologic and laboratory data to understand transmission during this outbreak. HIV genetic distances were calculated using the polymerase region. Networks were generated using data about reported high-risk contacts, viral genetic similarity, and their most parsimonious combinations. Sample collection dates and recency assay results were used to infer dates of infection. Epidemiologic and laboratory data each generated large and dense networks. Integration of these data revealed subgroups with epidemiologic and genetic commonalities, one of which appeared to contain the earliest infections. Predicted infection dates suggest that transmission began in 2011, underwent explosive growth in mid-2014, and slowed after the declaration of a public health emergency. Results from this phylodynamic analysis suggest that the majority of infections had likely already occurred when the investigation began and that early transmission may have been associated with sexual activity and injection drug use. Early and sustained efforts are needed to detect infections and prevent or interrupt rapid transmission within networks of uninfected PWID. |
Heightened HIV antibody responses in postpartum women as exemplified by recent infection assays: implications for incidence estimates
Hargrove J , van Schalkwyk C , Humphrey J , Mutasa K , Ntozini R , Owen M , Masciotra S , Parekh B , Duong YT , Dobbs T , Kilmarx P , Gonese E . AIDS Res Hum Retroviruses 2017 33 (9) 902-904 BACKGROUND: Laboratory assays that identify recent HIV infections are important for assessing impacts of interventions aimed at reducing HIV incidence. Kinetics of HIV humoral responses can vary with inherent assay properties, and between HIV subtypes, populations and physiological states. They are important in determining mean duration of recent infection (MDRI) for antibody-based assays for detecting recent HIV infections. METHODS: We determined MDRIs for BED-CEIA, LAg and BRAI assays for 101 seroconverting postpartum women, recruited in Harare in 1997- 2000 during the Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) Trial, comparing them against published MDRIs estimated from seroconverting cases in the general population. We also compared MDRIs for women who seroconverted either during the first nine months, or at later stages, postpartum. RESULTS: At cut-offs (C) of 0.8 for BED, 1.5 for LAg and 40% for BRAI, estimated MDRIs for postpartum mothers, were 192, 104 and 144 days, 33%, 32-41% and 52% lower than published estimates of 287, 152-177 and 298 days, respectively, for clade C samples from general populations. Point estimates of MDRI values were 7 - 19% shorter for women who seroconverted in the first 9- months postpartum, compared with those seroconverting later. CONCLUSIONS: MDRI values for three HIV incidence biomarkers are longer in the general population than among postpartum women, particularly those who recently gave birth, consistent with heightened immunologic activation soon after birth. Our results provide a caution that MDRI may vary significantly between subjects in different physiological states. |
Performance evaluation of the FDA-approved Determine HIV-1/2 Ag/Ab Combo assay using plasma and whole blood specimens
Masciotra S , Luo W , Westheimer E , Cohen SE , Gay CL , Hall L , Pan Y , Peters PJ , Owen SM . J Clin Virol 2017 91 95-100 BACKGROUND: The Determine HIV-1/2 Ag/Ab Combo (DC) rapid test can identify HIV-1 infection earlier than rapid antibody-only tests in plasma specimens. OBJECTIVES: We compared the performance of DC with a laboratory-based antigen/antibody (Ag/Ab) combo assay in plasma and evaluated antigen reactivity in whole blood specimens. STUDY DESIGN: We tested by DC 508 plasma specimens collected in a prospective study and 107 sequential plasma and simulated whole blood specimens from 20 seroconversion panels. Previous results using the ARCHITECT (ARC) Ag/Ab combo assay were compared to DC results. In seroconversion panels, the days from the first HIV1 RNA-positive test to first DC-reactive in plasma and whole blood was compared. McNemar's and Wilcoxon signed rank tests were used for statistical analysis. RESULTS: Of 415 HIV-positive samples, ARC detected 396 (95.4%) and DC 337 (81.2%) (p<0.0001). DC was reactive in 50.0% of ARC-reactive/MS-negative, 78.6% of ARC-reactive/MS-indeterminate, and 99.6% of ARC-reactive/MS-HIV-1-positive or -undifferentiated specimens. DC antigen reactivity was higher among ARC-reactive/MS-negative than MS-indeterminate samples. In 20 HIV-1 seroconversion panels, there was a significant difference between DC reactivity in plasma (91.1%) and whole blood (56.4%) (p<0.0001). DC with whole blood showed a significant delay in reactivity compared to plasma (p=0.008). CONCLUSIONS: In plasma, DC was significantly less sensitive than an instrumented laboratory-based Ag/Ab combo assay. DC in plasma was significantly more sensitive compared to whole blood in early HIV-1 infections. With the U.S. laboratory-based diagnostic algorithm, DC as the first step would likely miss a high proportion of HIV-1 infections in early stages of seroconversion. |
Performance evaluation of the point-of-care INSTI HIV-1/2 antibody test in early and established HIV infections
Adams S , Luo W , Wesolowski L , Cohen SE , Peters PJ , Owen SM , Masciotra S . J Clin Virol 2017 91 90-94 BACKGROUND: The flow-through INSTI HIV-1/HIV-2 Rapid Antibody (INSTI) test is a 60s FDA-approved test for HIV-1 and HIV-2 antibody testing using whole blood and plasma. OBJECTIVE: We evaluated the performance of INSTI using plasma and simulated whole blood specimens. STUDY DESIGN: INSTI's performance in plasma specimens from commercial seroconversion panels was assessed by estimating the relative sensitivity using a 50% cumulative frequency analysis and by comparing its performance with other FDA-approved rapid tests (RTs). INSTI was further evaluated using 320 HIV-1 plasma specimens collected during a cross-sectional study and with 107 HIV-1 and 24 HIV-2 simulated whole blood specimens. Sensitivity and specificity were calculated using 615 known HIV-1 group M/O and 80 HIV-2 (Western blot (WB)-positive), and 497 HIV-negative plasma specimens, respectively. RESULTS: In HIV-1 seroconversion panels, INSTI became reactive 9days before a positive WB. When compared to FDA-approved antibody-based lateral flow RTs, INSTI detected significantly more early infections. Among HIV-1-infected cross-sectional plasma samples, INSTI detected 23 (27%) of 85 Architect-positive/Multispot-negative or indeterminate specimens. For plasma specimens, the sensitivity was 99.84% for HIV-1 and 100% for HIV-2, and the specificity was 99.80%. Using simulated whole blood from seroconverters, INSTI performed similarly to plasma. CONCLUSIONS: INSTI performed significantly better than antibody-based lateral flow RTs during early stages of seroconversion. Sensitivity and specificity were within the manufacturer's reported ranges. Considering the observed test performance and the almost immediate results, INSTI is an accurate option to detect HIV-1/HIV-2 antibodies in point-of-care settings where lab testing is not feasible. |
Evaluation of dried blood spot protocols with the Bio-Rad GS HIV Combo Ag/Ab EIA and Geenius HIV 1/2 Supplemental Assay
Luo W , Davis G , Li L , Shriver MK , Mei J , Styer LM , Parker MM , Smith A , Paz-Bailey G , Ethridge S , Wesolowski L , Owen SM , Masciotra S . J Clin Virol 2017 91 84-89 OBJECTIVE: FDA-approved antigen/antibody combo and HIV-1/2 differentiation supplemental tests do not have claims for dried blood spot (DBS) use. We compared two DBS-modified protocols, the Bio-Rad GS HIV Combo Ag/Ab (BRC) EIA and Geenius HIV-1/2 (Geenius) Supplemental Assay, to plasma protocols and evaluated them in the CDC/APHL HIV diagnostic algorithm. METHODS: BRC-DBS p24 analytical sensitivity was calculated from serial dilutions of p24. DBS specimens included 11 HIV-1 seroconverters, 151 HIV-1-positive individuals, including 20 on antiretroviral therapy, 31 HIV-2-positive and one HIV-1/HIV-2-positive individuals. BRC-reactive specimens were tested with Geenius using the same DBS eluate. Matched plasma specimens were tested with BRC, an IgG/IgM immunoassay and Geenius. DBS and plasma results were compared using the McNemar's test. A DBS-algorithm applied to 348 DBS from high-risk individuals who participated in surveillance was compared to HIV status based on local testing algorithms. RESULTS: BRC-DBS detects p24 at a concentration 18 times higher than in plasma. In seroconverters, BRC-DBS detected more infections than the IgG/IgM immunoassay in plasma (p=0.0133), but fewer infections than BRC-plasma (p=0.0133). In addition, the BRC/Geenius-plasma algorithm identified more HIV-1 infections than the BRC/Geenius-DBS algorithm (p=0.0455). The DBS protocols correctly identified HIV status for established HIV-1 infections, including those on therapy, HIV-2 infections, and surveillance specimens. CONCLUSIONS: The DBS protocols exhibited promising performance and allowed rapid supplemental testing. Although the DBS algorithm missed some early infections, it showed similar results when applied to specimens from a high-risk population. Implementation of a DBS algorithm would benefit testing programs without capacity for venipuncture. |
Time until emergence of HIV test reactivity following infection with HIV-1: Implications for interpreting test results and retesting after exposure.
Delaney KP , Hanson DL , Masciotra S , Ethridge SF , Wesolowski L , Owen SM . Clin Infect Dis 2016 64 (1) 53-59 BACKGROUND: Understanding the period of time between an exposure resulting in infection with HIV and when a test can reliably detect the presence of that infection, i.e. the test window period, may benefit testing programs and clinicians in counseling patients about when the clinician and the patient can be confident a suspected exposure did not result in HIV infection. METHODS: We evaluated the intervals between reactivity of the Aptima HIV-1 RNA nucleic acid test (Aptima) and 20 FDA-approved HIV immunoassays using 222 longitudinally collected plasma specimens from HIV-1 seroconverters from the United States. A multi-model framework based upon two general approaches, interval-censored survival and binomial regression, was implemented to estimate the relative emergence of test reactivity, referred to in this report as an inter-test reactivity interval (ITRI). We then combined ITRI results with simulated data for the eclipse period, the time between exposure and detection of HIV virus by Aptima, to develop estimates of the window period for each test. RESULTS: The estimated ITRIs were shorter with each new class of HIV tests, ranging from 5.9 to 24.8 days. The 99th percentiles of the window period probability distribution ranged from 44 days for laboratory screening tests that detect both antigen and antibody to 65 days for the Western blot test. CONCLUSIONS: Our directly comparable estimates of the emergence of reactivity for 20 immunoassays are valuable to testing providers for interpreting negative HIV test results obtained shortly after exposure, and for counseling individuals on when to retest after an exposure. |
Mean Recency Period for Estimation of HIV-1 Incidence with the BED-Capture EIA and Bio-Rad Avidity in Persons Diagnosed in the United States with Subtype B
Hanson DL , Song R , Masciotra S , Hernandez A , Dobbs TL , Parekh BS , Owen SM , Green TA . PLoS One 2016 11 (4) e0152327 HIV incidence estimates are used to monitor HIV-1 infection in the United States. Use of laboratory biomarkers that distinguish recent from longstanding infection to quantify HIV incidence rely on having accurate knowledge of the average time that individuals spend in a transient state of recent infection between seroconversion and reaching a specified biomarker cutoff value. This paper describes five estimation procedures from two general statistical approaches, a survival time approach and an approach that fits binomial models of the probability of being classified as recently infected, as a function of time since seroconversion. We compare these procedures for estimating the mean duration of recent infection (MDRI) for two biomarkers used by the U.S. National HIV Surveillance System for determination of HIV incidence, the Aware BED EIA HIV-1 incidence test (BED) and the avidity-based, modified Bio-Rad HIV-1/HIV-2 plus O ELISA (BRAI) assay. Collectively, 953 specimens from 220 HIV-1 subtype B seroconverters, taken from 5 cohorts, were tested with a biomarker assay. Estimates of MDRI using the non-parametric survival approach were 198.4 days (SD 13.0) for BED and 239.6 days (SD 13.9) for BRAI using cutoff values of 0.8 normalized optical density and 30%, respectively. The probability of remaining in the recent state as a function of time since seroconversion, based upon this revised statistical approach, can be applied in the calculation of annual incidence in the United States. |
Persistence of HIV Antibody Avidity in the Presence of Antiretroviral Therapy
Curtis K , Price K , Niedzwiedz P , Masciotra S , Owen M . AIDS Res Hum Retroviruses 2016 32 (6) 561-3 The effects of antiretroviral therapy (ART) on the performance of HIV incidence assays have been well-documented. In order to improve upon current assay approaches or focus the development of future assays, studies are needed to characterize the effects of ART on all candidate HIV incidence assays. In this study, we compared the performance of three antibody avidity-based HIV incidence assays, the LAg, Bio-Rad Avidity, and HIV-1 Multiplex assays, using a well-defined cohort of recent HIV-1 seroconverters composed of ART-naive HIV-1-infected individuals and those who received ART early or delayed in the course of infection. Differences in the performance of all three avidity-based incidence assays were noted with study subjects who received ART. The LAg assay and Multiplex total antibody measurements (nMFI) exhibited similar kinetics in reactivity, as these assays tended to fluctuate with changes in viral load. In the early ART group, all 7 subjects remained recent by both assays at time points >1 year post-seroconversion, and assay values declined dramatically post-delayed ART initiation. In contrast, the two-well, antibody-dissociation avidity assays, Bio-Rad Avidity and Multiplex avidity index measurements, continued to mature in the early ART group, though blunted relative to the ART naive group, and assay values remained stable after delayed ART initiation. In summary, although the HIV incidence assays evaluated in this study are all designed to measure antibody avidity, each assay is affected differently by ART-induced virus suppression, presumably due to the distinct assay formats and procedures for measuring avidity. |
Performance evaluation of the CHEMBIO DPP(R) (dual path platform) HIV-1/2 assay in early and established infections
Masciotra S , Price KA , Sprinkle P , Wesolowski L , Owen SM . J Clin Virol 2015 70 97-100 BACKGROUND: The availability of more accurate point-of-care technology could increase the number of persons aware of their HIV status. The DPP((R)) HIV-1/2 assay is the first dual path platform rapid test (RT) approved in the U.S. that also received the Clinical Laboratory Improvement Amendments (CLIA) waiver for use with oral fluid and fingerstick and venous whole blood. OBJECTIVE: To evaluate the performance of the DPP((R)) HIV-1/2 assay with plasma specimens. STUDY DESIGN: Sensitivity and specificity of the assay were calculated from 696 HIV-1 groups M (B and non-B subtypes) and O and HIV-2 (groups A and B) specimens and 505 HIV-negative specimens, respectively. Analysis of the assay performance in HIV-1 early infections was assessed by estimating the relative sensitivity of the RT before the Western blot (WB) becomes positive using a 50% cumulative frequency analysis and by comparing the reactivity with other Food and Drug Administration (FDA)-approved RTs. RESULTS: The sensitivity for established infection was 100% for HIV-1 and 100% for HIV-2. The specificity was 100%. The DPP((R)) HIV-1/2 assay performs similarly to most antibody-based RT approved by FDA in early HIV-1 infections. CONCLUSIONS: The DPP((R)) technology showed no significant improvement for detecting early infections over other lateral-flow RTs used in the U.S. Without more data on the DPP((R)) HIV-1/2 assay, especially from whole blood and oral fluid specimens collected during the early phase of infection, its performance as point-of-care technology remains to be assessed. |
Early HIV infections among men who have sex with men in five cities in the United States
Paz-Bailey G , Smith A , Masciotra S , Zhang W , Bingham T , Flynn C , German D , Al-Tayyib A , Magnus M , LaLota M , Rose CE , Owen SM . AIDS Behav 2015 19 (12) 2304-10 We tested blood samples from men who have sex with men (MSM) to detect early HIV infection. Early HIV included both acute (infected past 30 days) and recent (estimated recency past 240 days). Acute infections were defined as screen immunoassay (IA) negative/NAAT-positive or IA-positive/Multispot-negative/NAAT-positive. Recent infections were defined as avidity index cutoff <30 % on an avidity-based IA and, (1) not reporting antiretroviral therapy use or, (2) HIV RNA >150 copies/mL. Of 937 samples, 26 % (244) were HIV-infected and of these 5 % (12) were early. Of early infections, 2 were acute and 10 recent; most (8/12) were among black MSM. Early infection was associated with last partner of black race [adjusted relative risk (ARR) = 4.6, confidence intervals (CI) 1.2-17.3], receptive anal sex at last sex (ARR = 4.3, CI 1.2-15.0), and daily Internet use to meet partners/friends (ARR = 3.3, CI 1.1-9.7). Expanding prevention and treatment for black MSM will be necessary for reducing incidence in the United States. |
HIV reverse-transcriptase drug resistance mutations during early infection reveal greater transmission diversity than in envelope sequences.
Lipscomb JT , Switzer WM , Li JF , Masciotra S , Owen SM , Johnson JA . J Infect Dis 2014 210 (11) 1827-37 BACKGROUND: Drug resistance mutations (DRMs) can serve as distinct, non-polymorphic markers for evaluating diversity of expressed HIV-1. We screened for resistance mutations during early-acute viremia and examined the diversity in reverse transcriptase (RT) relative to envelope (env) in cases of transmitted drug resistance. METHODS: We evaluated 111 longitudinal plasma samples collected every 2-7 days from 15 individuals who seroconverted for HIV-1 infection in 1994-2000. The samples were screened with sensitive PCR assays for the commonly transmitted M41 L and K70R mutations, and for K65R, which was undetected by bulk sequencing. Mutation-positive samples were further characterized by clonal sequencing of RT and env V1-V3. RESULTS: Resistance mutations were detected in 4 of 15 seroconverters at 5-50 days of viral nucleic acid expression; most mutations disappeared around the time of seroconversion. Clonal sequencing verified low-level K65R at frequencies of 0.4%-4.9%. In each case, K65R co-existed unlinked with variants carrying 2-5 thymidine analog mutations at frequencies of 1.6%-23.0%. In one seroconverter, variants with M184 V and NNRTI mutations were also identified at first RNA expression. Each seroconverter displayed a homogeneous V1-V3 env population. CONCLUSIONS: Reverse transcriptase DRMs demonstrate that the breadth of variants in transmission may be greater than what is reflected in envelope sequences. |
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