Susan H Eshleman

Johns Hopkins University, Baltimore, Maryland, United States

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Publications (153)947.94 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Fourth-generation HIV assays detect both antigen and antibody, facilitating detection of acute/early HIV infection. The Bio-Rad GS HIV Combo Ag/Ab assay (Bio-Rad Combo) is an enzyme immunoassay that simultaneously detects HIV p24 antigen and antibodies to HIV-1 and HIV-2 in serum or plasma.Objective To evaluate the performance of the Bio-Rad Combo assay for detection of HIV infection in adults from Southern Africa.Study designSamples were obtained from adults in Soweto and Vulindlela, South Africa and Dar es Salaam, Tanzania (300 HIV-positive samples; 300 HIV-negative samples; 12 samples from individuals previously classified as having acute/early HIV infection). The samples were tested with the Bio-Rad Combo assay. Additional testing was performed to characterize the 12 acute/early samples.ResultsAll 300 HIV-positive samples were reactive using the Bio-Rad Combo assay; false positive test results were obtained for 10 (3.3%) of the HIV-negative samples (sensitivity: 100%, 95% confidence interval [CI]: 98.8–100%); specificity: 96.7%, 95% CI: 94.0–98.4%). The assay detected 10 of the 12 infections classified as acute/early. The two infections that were not detected had viral loads < 400 copies/mL; one of those samples contained antiretroviral drugs consistent with antiretroviral therapy.Conclusions The Bio-Rad Combo assay correctly classified the majority of study specimens. The specificity reported here may be higher than that seen in other settings, since HIV-negative samples were pre-screened using a different fourth-generation test. The assay also had high sensitivity for detection of acute/early infection. False-negative test results may be obtained in individuals who are virally suppressed.
    Journal of Clinical Virology 11/2014; · 3.47 Impact Factor
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    ABSTRACT: We compared the serologic response to HIV infection in Ugandan women with HIV subtype A (n=82) and D (n=32) infection using a limiting antigen avidity assay (LAg-Avidity assay); 2,614 samples were analyzed. Study participants were followed a median of 6.6 years after HIV seroconversion. Samples were classified as assay positive if they had a LAg-Avidity assay result <1.5 normalized optical density units (OD-n). Women with subtype D infection were more likely to have delayed antibody maturation. During the first two years after seroconversion, the mean time that women had an assay positive result (mean duration of recent infection, MDRI) was longer for women with subtype D infection than women with subtype A infection (267.9 days, 95% CI: 231.2-308.2 vs. 167.3 days, 95% CI: 151.8-185.9 days, p<0.01). The MDRI was also longer for women with subtype D infection after excluding low viral load samples and samples from women on antiretroviral therapy (ART). Women infected for >2 years were also more likely to be misclassified as recently infected in they had subtype D infection. Women with subtype D infection were also more likely to have antibody waning compared to women with subtype A infection. These findings may be related to the higher pathogenicity of subtype D HIV infection and are relevant to use of the LAg-Avidity assay for cross-sectional HIV incidence estimation in populations where subtype D infection is prevalent.
    AIDS Research and Human Retroviruses 10/2014; · 2.46 Impact Factor
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    ABSTRACT: US guidelines recommend at least annual HIV testing for those at risk. This analysis assessed frequency and correlates of infrequent HIV testing and late diagnosis among black men who have sex with men (BMSM).
    JAIDS Journal of Acquired Immune Deficiency Syndromes 09/2014; · 4.39 Impact Factor
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    ABSTRACT: HIV RNA levels are usually high early in HIV infection. In the HPTN 061 study, men were tested for HIV infection every six months; six (21.4%) of 28 men who acquired HIV infection during the study had low or undetectable HIV RNA at the time of HIV diagnosis. Antiretroviral drugs were not detected at the time of HIV diagnosis. False-negative HIV test results were obtained for two men using multiple assays. Antiretroviral drug resistance mutations were detected in HIV from one man. Additional studies are needed to identify factors associated with low HIV RNA levels during early HIV infection.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 08/2014; · 4.39 Impact Factor
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    ABSTRACT: In a randomized trial comparing nevirapine (NVP)-based versus lopinavir/ritonavir (LPV/r)-based antiretroviral therapy (ART) in HIV-infected children [primary endpoint discontinuation of study treatment for any reason or virologic failure by week 24] aged 2 months to 3 years, we assessed whether clinical, virologic, immunologic and safety outcomes varied by prior single-dose NVP exposure (PrNVP) for prevention of mother-to-child HIV transmission and other covariates.
    The Pediatric Infectious Disease Journal 08/2014; 33(8):846-854. · 3.14 Impact Factor
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    ABSTRACT: Multi-assay algorithms (MAAs) can be used to estimate HIV incidence in cross-sectional surveys. We compared the performance of two MAAs that use HIV diversity as one of four biomarkers for analysis of HIV incidence.
    PLoS ONE 06/2014; 9(6):e101043. · 3.53 Impact Factor
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    ABSTRACT: Background Although several interventions have shown reduced HIV incidence in clinical trials, the community-level effect of effective interventions on the epidemic when scaled up is unknown. We investigated whether a multicomponent, multilevel social and behavioural prevention strategy could reduce HIV incidence, increase HIV testing, reduce HIV risk behaviour, and change social and behavioural norms. Methods For this phase 3 cluster-randomised controlled trial, 34 communities in four sites in Africa and 14 communities in Thailand were randomly allocated in matched pairs to receive 36 months of community-based voluntary counselling and testing for HIV (intervention group) or standard counselling and testing alone (control group) between January, 2001, and December, 2011. The intervention was designed to make testing more accessible in communities, engage communities through outreach, and provide support services after testing. Randomisation was done by a computer-generated code and was not masked. Data were collected at baseline (n=14 567) and after intervention (n=56 683) by cross-sectional random surveys of community residents aged 18–32 years. The primary outcome was HIV incidence and was estimated with a cross-sectional multi-assay algorithm and antiretroviral drug screening assay. Thailand was excluded from incidence analyses because of low HIV prevalence. This trial is registered at ClinicalTrials.gov, number NCT00203749. Findings The estimated incidence of HIV in the intervention group was 1·52% versus 1·81% in the control group with an estimated reduction in HIV incidence of 13·9% (relative risk [RR] 0·86, 95% CI 0·73–1·02; p=0·082). HIV incidence was significantly reduced in women older than 24 years (RR=0·70, 0·54–0·90; p=0·0085), but not in other age or sex subgroups. Community-based voluntary counselling and testing increased testing rates by 25% overall (12–39; p=0·0003), by 45% (25–69; p<0·0001) in men and 15% (3–28; p=0·013) in women. No overall effect on sexual risk behaviour was recorded. Social norms regarding HIV testing were improved by 6% (95% CI 3–9) in communities in the intervention group. Interpretation These results are sufficiently robust, especially when taking into consideration the combined results of modest reductions in HIV incidence combined with increases in HIV testing and reductions in HIV risk behaviour, to recommend the Project Accept approach as an integral part of all interventions (including treatment as prevention) to reduce HIV transmission at the community level. Funding US National Institute of Mental Health, the Division of AIDS of the US National Institute of Allergy and Infectious Diseases, and the Office of AIDS Research of the US National Institutes of Health.
    The Lancet Global Health. 05/2014; 2(5):e267–e277.
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    ABSTRACT: Analysis of samples from Uganda using serologic HIV incidence assays reveal that individuals with subtype D infection often have weak humoral immune responses to HIV infection. It is unclear whether this reflects a poor initial response to infection or a waning antibody response later in infection. Samples (N = 2614) were obtained from 114 women aged 18-45 years in the Ugandan Genital Shedding and Disease Progression Study cohort (2001-2009; 82 subtype A, 32 subtype D; median 23 samples/women, range 3-41 samples, median follow-up of 6.6 years). Samples were analyzed using the BED capture immunoassay (cutoff, 0.8 OD-n) and the avidity assay (cutoff, 90% Avidity Index). Antibody maturation was assessed by having the BED capture enzyme immunoassay (BED-CEIA) or avidity value exceed the assay cutoff 1 or 2 years after infection. The waning antibody response was measured by having the BED-CEIA or avidity value fall >20% below the maximum value. For the BED-CEIA, 8 women with subtype A infection and 3 women with subtype D infection never progressed previously the cutoff value (median, 5.9 years follow-up after infection). Six women with subtype D infection never achieved an avidity index >90%. Subtype did not impact the proportion of women whose assay values regressed by >20% of the maximal value (for BED-CEIA: 33% for A, 41% for D, P = 0.51; for avidity: 1% for A, 6% for D, P = 0.19). The higher frequency of misclassification of individuals with long-term subtype D infection as recently infected using serologic incidence assays reflects a weak initial antibody response to HIV infection that is sustained over time.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2014; 65(4):390-6. · 4.39 Impact Factor
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    ABSTRACT: Antiretroviral drugs are used for the treatment and prevention of HIV infection. Non-adherence to antiretroviral drug regimens can compromise their clinical efficacy and lead to emergence of drug-resistant HIV. Clinical trials evaluating antiretroviral regimens for HIV treatment and prevention can also be compromised by poor adherence and non-disclosed off-study antiretroviral drug use. This report describes the development and validation of a high throughput, qualitative method for the identification of antiretroviral drugs using high-resolution mass spectrometry (HRMS) for the retrospective assessment of off-study antiretroviral drug use and the determination of potential antiretroviral therapy (ART) non-compliance. Serum standards were prepared that contained 15 antiretroviral drugs: 9 protease inhibitors (PIs), 4 nucleotide/nucleoside reverse transcriptase inhibitors (NRTIs), and 2 non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs). Analytical separation was achieved on a Hypersil Gold PFP (100×3 mm) column and the eluent was analyzed using the Thermo Exactive Orbitrap mass spectrometer (Exactive-MS) operated in full scan mode. Limit of identification, signal intensity precision, retention time analysis, selectivity, and carryover studies were conducted. Concordance with liquid chromatographic-tandem mass spectrometric (LC-MS/MS) methods was evaluated using remnant plasma samples from a clinical trial. The limit of identification ranged from 5-10 ng/ml for 14 drugs (9 PIs, 1 NNRTI, 4 NRTIs) and was 150 ng/ml for 1 NNRTI. Precision studies with high and low control mixtures revealed signal intensity coefficients of variation of 3.0-27.5%. The Exactive-MS method was selective for the compounds of interest. Overall, concordance ranged from 89.1%-100% for the screening of antiretroviral drugs in clinical plasma specimens as compared to LC-MS/MS methods. Using the Exactive-MS, we developed and validated a highly selective, robust method for the multiplexed detection of 15 antiretroviral drugs.
    Clinica chimica acta; international journal of clinical chemistry 03/2014; · 2.54 Impact Factor
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    ABSTRACT: Use of antiretroviral treatment for HIV-1 infection has decreased AIDS-related morbidity and mortality and prevents sexual transmission of HIV-1. However, the best time to initiate antiretroviral treatment to reduce progression of HIV-1 infection or non-AIDS clinical events is unknown. We reported previously that early antiretroviral treatment reduced HIV-1 transmission by 96%. We aimed to compare the effects of early and delayed initiation of antiretroviral treatment on clinical outcomes. The HPTN 052 trial is a randomised controlled trial done at 13 sites in nine countries. We enrolled HIV-1-serodiscordant couples to the study and randomly allocated them to either early or delayed antiretroviral treatment by use of permuted block randomisation, stratified by site. Random assignment was unblinded. The HIV-1-infected member of every couple initiated antiretroviral treatment either on entry into the study (early treatment group) or after a decline in CD4 count or with onset of an AIDS-related illness (delayed treatment group). Primary events were AIDS clinical events (WHO stage 4 HIV-1 disease, tuberculosis, and severe bacterial infections) and the following serious medical conditions unrelated to AIDS: serious cardiovascular or vascular disease, serious liver disease, end-stage renal disease, new-onset diabetes mellitus, and non-AIDS malignant disease. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00074581. 1763 people with HIV-1 infection and a serodiscordant partner were enrolled in the study; 886 were assigned early antiretroviral treatment and 877 to the delayed treatment group (two individuals were excluded from this group after randomisation). Median CD4 counts at randomisation were 442 (IQR 373-522) cells per μL in patients assigned to the early treatment group and 428 (357-522) cells per μL in those allocated delayed antiretroviral treatment. In the delayed group, antiretroviral treatment was initiated at a median CD4 count of 230 (IQR 197-249) cells per μL. Primary clinical events were reported in 57 individuals assigned to early treatment initiation versus 77 people allocated to delayed antiretroviral treatment (hazard ratio 0·73, 95% CI 0·52-1·03; p=0·074). New-onset AIDS events were recorded in 40 participants assigned to early antiretroviral treatment versus 61 allocated delayed initiation (0·64, 0·43-0·96; p=0·031), tuberculosis developed in 17 versus 34 patients, respectively (0·49, 0·28-0·89, p=0·018), and primary non-AIDS events were rare (12 in the early group vs nine with delayed treatment). In total, 498 primary and secondary outcomes occurred in the early treatment group (incidence 24·9 per 100 person-years, 95% CI 22·5-27·5) versus 585 in the delayed treatment group (29·2 per 100 person-years, 26·5-32·1; p=0·025). 26 people died, 11 who were allocated to early antiretroviral treatment and 15 who were assigned to the delayed treatment group. Early initiation of antiretroviral treatment delayed the time to AIDS events and decreased the incidence of primary and secondary outcomes. The clinical benefits recorded, combined with the striking reduction in HIV-1 transmission risk previously reported, provides strong support for earlier initiation of antiretroviral treatment. US National Institute of Allergy and Infectious Diseases.
    The Lancet Infectious Diseases 03/2014; · 19.45 Impact Factor
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    ABSTRACT: BACKGROUND: HPTN 046 compared the efficacy and safety of infant nevirapine (NVP) among HIV-exposed breastfed infants randomized at 6 weeks to 6 months to t NVP or placebo to prevent postnatal infection: we report final 18-month outcomes. METHODS: Randomized, placebo-controlled trial in 4 African countries. Infant diagnostic HIV testing was performed regularly from birth through 18 months. Kaplan-Meier analysis was used to assess 18-month cumulative infant HIV infection, HIV infection/or death, and mortality rates. RESULTS: Between 6 weeks and 6 months, postnatal HIV infection rates were significantly lower among infants receiving daily NVP from 6 weeks to 6 months 1.1% [95% confidence interval (CI): 0.2% to 1.8%], compared with placebo 2.4% (95% CI: 1.3% to 2.6%), P = 0.049, but not significantly lower thereafter. Eighteen-month postnatal infection rates were low: 2.2% (95% CI: 1.1% to 3.3%) versus 3.1% (95% CI: 1.9% to 4.4%), respectively, P = 0.28. Mortality and HIV infection/death did not differ between arms at any age. Infants of women receiving antiretroviral therapy (ART) for their own health had the lowest 18-month postnatal infection rates (0.5%, 95% CI: 0.0% to 1.1%). However, HIV infection/death rates at 18 months were not significantly different for infants of mothers on ART (3.7%, 95% CI: 1.9% to 5.5%), and infants of mothers with CD4 counts of ≥ 350 cells per cubic millimeter not receiving ART (4.8%, 95% CI: 2.7% to 6.8%; P = 0.46). There were no differences in adverse events between study arms. CONCLUSIONS: This trial demonstrated early but not late differences in postnatal HIV transmission among infants randomized at age 6 weeks to extended NVP or placebo, underscoring the importance of continued prophylaxis throughout breastfeeding.
    J Acquir Immune Defic Syndr. 03/2014; 65(3):366-74.
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    ABSTRACT: To evaluate factors associated with misclassification by the limiting-antigen avidity (LAg-avidity) assay among individuals with long-standing HIV infection. Samples were obtained from the Multicenter AIDS Cohort Study and AIDS Linked to the IntraVenous Experience cohort (1089 samples from 667 individuals, 595 samples collected 2-4 years and 494 samples collected 4-8 years after HIV seroconversion). Paired samples from both time points were available for 422 (63.3%) of the 667 individuals. Samples were considered to be misclassified if the LAg-avidity assay result was 1.5 or less normalized optical density (OD-n) units. Overall, 4.8% (52/1089) of the samples were misclassified, including 1.8% [16/884, 95% confidence interval (CI) 1.09-3.06%] of samples from individuals with viral loads above 400 copies/ml and 1.4% (10/705) of samples from individuals with viral loads above 400 copies/ml and CD4 cell counts above 200 cells/μl (95% CI 0.68-2.60%). Age, race, sex, and mode of HIV acquisition were not associated with misclassification. In an adjusted analysis, viral load below 400 copies/ml [adjusted odds ratio (aOR) 3.72, 95% CI 1.61-8.57], CD4 cell count below 50 cells/μl (aOR 5.41, 95% CI 1.86-15.74), and low LAg-avidity result (≤1.5 OD-n) from the earlier time point (aOR 5.60, 95% CI 1.55-20.25) were significantly associated with misclassification. The manufacturer of the LAg-avidity assay recommends excluding individuals from incidence surveys who are receiving antiretroviral therapy, are elite suppressors, or have AIDS (CD4 cell count <200 cells/μl). The results of this study indicate that those exclusions do not remove all sources of assay misclassification among individuals with long-standing HIV infection.
    AIDS (London, England) 02/2014; · 6.56 Impact Factor
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    ABSTRACT: American Black men who have sex with men (MSM) are disproportionately affected by HIV, but the factors associated with this concentrated epidemic are not fully understood. Black MSM were enrolled in 6 US cities to evaluate a multi-component prevention intervention, with the current analysis focusing on the correlates of being newly diagnosed with HIV compared to being HIV-uninfected or previously diagnosed with HIV. HPTN 061 enrolled 1553 Black MSM whose median age was 40; 30% self-identified exclusively as gay or homosexual, 29% exclusively as bisexual, and 3% as transgender. About 1/6(th) (16.2%) were previously diagnosed with HIV (PD); of 1263 participants without a prior HIV diagnosis 7.6% were newly diagnosed (ND). Compared to PD, ND Black MSM were younger (p<0.001); less likely to be living with a primary partner (p<0.001); more likely to be diagnosed with syphilis (p<0.001), rectal gonorrhea (p = 0.011) or chlamydia (p = 0.020). Compared to HIV-uninfected Black MSM, ND were more likely to report unprotected receptive anal intercourse (URAI) with a male partner in the last 6 months (p<0.001); and to be diagnosed with syphilis (p<0.001), rectal gonorrhea (p = 0.004), and urethral (p = 0.025) or rectal chlamydia (p<0.001). They were less likely to report female (p = 0.002) or transgender partners (p = 0.018). Multivariate logistic regression analyses found that ND Black MSM were significantly more likely than HIV-uninfected peers to be unemployed; have STIs, and engage in URAI. Almost half the men in each group were poor, had depressive symptoms, and expressed internalized homophobia. ND HIV-infected Black MSM were more likely to be unemployed, have bacterial STIs and engage in URAI than other Black MSM. Culturally-tailored programs that address economic disenfranchisement, increase engagement in care, screen for STIs, in conjunction with safer sex prevention interventions, may help to decrease further transmission in this heavily affected community.
    PLoS ONE 01/2014; 9(1):e87298. · 3.53 Impact Factor
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    ABSTRACT: 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.
    HIV Clinical Trials 01/2014; 15(2):62-8. · 2.14 Impact Factor
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    ABSTRACT: A limiting antigen avidity enzyme immunoassay (HIV-1 LAg-Avidity assay) was recently developed for cross-sectional HIV incidence estimation. We evaluated the performance of the LAg-Avidity assay alone and in multi-assay algorithms (MAAs) that included other biomarkers. Performance of testing algorithms was evaluated using 2,282 samples from individuals in the United States collected 1 month to >8 years after HIV seroconversion. The capacity of selected testing algorithms to accurately estimate incidence was evaluated in three longitudinal cohorts. When used in a single-assay format, the LAg-Avidity assay classified some individuals infected >5 years as assay positive and failed to provide reliable incidence estimates in cohorts that included individuals with long-term infections. We evaluated >500,000 testing algorithms, that included the LAg-Avidity assay alone and MAAs with other biomarkers (BED capture immunoassay [BED-CEIA], BioRad-Avidity assay, HIV viral load, CD4 cell count), varying the assays and assay cutoffs. We identified an optimized 2-assay MAA that included the LAg-Avidity and BioRad-Avidity assays, and an optimized 4-assay MAA that included those assays, as well as HIV viral load and CD4 cell count. The two optimized MAAs classified all 845 samples from individuals infected >5 years as MAA negative and estimated incidence within a year of sample collection. These two MAAs produced incidence estimates that were consistent with those from longitudinal follow-up of cohorts. A comparison of the laboratory assay costs of the MAAs was also performed, and we found that the costs associated with the optimal two assay MAA were substantially less than with the four assay MAA. The LAg-Avidity assay did not perform well in a single-assay format, regardless of the assay cutoff. MAAs that include the LAg-Avidity and BioRad-Avidity assays, with or without viral load and CD4 cell count, provide accurate incidence estimates.
    PLoS ONE 12/2013; 8(12):e82772. · 3.53 Impact Factor
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    ABSTRACT: In HIV-infected children, viral diversity tends to increase with age in the absence of antiretroviral treatment (ART). We measured HIV diversity in African children (ages 6-36 months) enrolled in a randomized clinical trial comparing two ART regimens (Cohort I of the P1060 trial). Children in this cohort were exposed to single dose nevirapine (sdNVP) at birth. HIV diversity was measured retrospectively using a high resolution melting (HRM) diversity assay. Samples were obtained from 139 children at the enrollment visit prior to ART initiation. Six regions of the HIV genome were analyzed: two in gag, one in pol, and three in env. A single numeric HRM score that reflects HIV diversity was generated for each region; composite HRM scores were also calculated (mean and median for all six regions). In multivariable median regression models using backwards selection that started with demographic and clinical variables, older age was associated with higher HRM scores (higher HIV diversity) in pol (P = 0.005) and with higher mean (P = 0.014) and median (P<0.001) HRM scores. In multivariable models adjusted for age, pre-treatment HIV viral load, pre-treatment CD4%, and randomized treatment regimen, higher HRM scores in pol were associated with shorter time to virologic suppression (P = 0.016) and longer time to study endpoints (virologic failure [VF], VF/death, and VF/off study treatment; P<0.001 for all measures). In this cohort of sdNVP-exposed, ART-naïve African children, higher levels of HIV diversity in the HIV pol region prior to ART initiation were associated with better treatment outcomes.
    PLoS ONE 12/2013; 8(11):e81213. · 3.53 Impact Factor
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    ABSTRACT: Accurate methods of HIV incidence determination are critically needed to monitor the epidemic and determine the population level impact of prevention trials. One such trial, Project Accept, a Phase III, community-randomized trial, evaluated the impact of enhanced, community-based voluntary counseling and testing on population-level HIV incidence. The primary endpoint of the trial was based on a single, cross-sectional, post-intervention HIV incidence assessment. Test performance of HIV incidence determination was evaluated for 403 multi-assay algorithms [MAAs] that included the BED capture immunoassay [BED-CEIA] alone, an avidity assay alone, and combinations of these assays at different cutoff values with and without CD4 and viral load testing on samples from seven African cohorts (5,325 samples from 3,436 individuals with known duration of HIV infection [1 month to >10 years]). The mean window period (average time individuals appear positive for a given algorithm) and performance in estimating an incidence estimate (in terms of bias and variance) of these MAAs were evaluated in three simulated epidemic scenarios (stable, emerging and waning). The power of different test methods to detect a 35% reduction in incidence in the matched communities of Project Accept was also assessed. A MAA was identified that included BED-CEIA, the avidity assay, CD4 cell count, and viral load that had a window period of 259 days, accurately estimated HIV incidence in all three epidemic settings and provided sufficient power to detect an intervention effect in Project Accept. In a Southern African setting, HIV incidence estimates and intervention effects can be accurately estimated from cross-sectional surveys using a MAA. The improved accuracy in cross-sectional incidence testing that a MAA provides is a powerful tool for HIV surveillance and program evaluation.
    PLoS ONE 11/2013; 8(11):e78818. · 3.53 Impact Factor
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    ABSTRACT: Multi-assay algorithms (MAAs) can be used for cross-sectional HIV incidence estimation. We previously identified a robust MAA that includes the BED capture immunoassay (BED-CEIA), the BioRad-Avidity assay, viral load, and CD4 cell count. In this report, we evaluated MAAs that include a high resolution melting (HRM) diversity assay that does not require sequencing. HRM scores were determined for eight regions of the HIV genome (2 in gag, 1 in pol, and 5 in env). MAAs were evaluated that included the BED capture immunoassay (BED-CEIA), the BioRad-Avidity assay, viral load, and HRM score, using HRM scores from different regions and a range of region-specific HRM diversity assay cutoffs. Performance characteristics based on the proportion of samples classified as MAA positive by duration of infection were determined for each MAA, including the mean window period. Cross-sectional incidence estimates obtained using optimized MAAs were compared to longitudinal incidence estimates for three cohorts in the United States. The performance of the HRM-based MAA was nearly identical to that of the MAA that included CD4 cell count. The HRM-based MAA had a mean window period of 154 days and provided cross-sectional incidence estimates that were similar to those based on cohort follow-up._HIV diversity is a useful biomarker for HIV incidence estimation. MAAs that include the HRM diversity assay can provide accurate HIV incidence estimates using stored plasma or serum samples, without the need for CD4 cell counts.
    Journal of clinical microbiology 10/2013; · 4.23 Impact Factor
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    ABSTRACT: The HIV Prevention Trials Network 052 study enrolled serodiscordant couples. Index participants infected with human immunodeficiency virus reported no prior antiretroviral (ARV) treatment at enrollment. ARV drug testing was performed retrospectively using enrollment samples from a subset of index participants. ARV drugs were detected in 45 of 96 participants (46.9%) with an undetectable viral load, 2 of 48 (4.2%) with a low viral load, and 1 of 65 (1.5%) with a high viral load (P < .0001); they were also detected in follow-up samples from participants who were not receiving study-administered treatment. ARV drug testing may be useful in addition to self-report of ARV drug use in some clinical trial settings.
    The Journal of Infectious Diseases 10/2013; 208(10):1624-8. · 5.78 Impact Factor
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    ABSTRACT: In HPTN 061, 155 HIV-infected men reported no prior HIV diagnosis; 83 of those men had HIV viral loads <1,000 copies/mL at enrollment. Antiretroviral drug testing revealed that 65 (78.3%) of the 83 men were on antiretroviral treatment. Antiretroviral drug testing can help distinguish between newly-diagnosed and previously-diagnosed HIV infection.
    Clinical Infectious Diseases 10/2013; · 9.42 Impact Factor

Publication Stats

4k Citations
947.94 Total Impact Points

Institutions

  • 2006–2014
    • Johns Hopkins University
      • • Department of Pathology
      • • Department of Medicine
      Baltimore, Maryland, United States
  • 2013
    • Tan Tock Seng Hospital
      Tumasik, Singapore
  • 2011–2013
    • National Institute of Allergy and Infectious Diseases
      • Laboratory of Immunoregulation
      Maryland, United States
  • 2000–2013
    • Johns Hopkins Medicine
      • Department of Pathology
      Baltimore, Maryland, United States
  • 2012
    • University of the Witwatersrand
      • Perinatal HIV Research Unit
      Johannesburg, Gauteng, South Africa
  • 2009
    • Monogram Biosciences
      San Francisco, California, United States
  • 2007
    • Centers for Disease Control and Prevention
      Atlanta, Michigan, United States
    • Fred Hutchinson Cancer Research Center
      Seattle, Washington, United States
  • 2003
    • University of Miami Miller School of Medicine
      • Division of Hospital Medicine
      Miami, FL, United States
  • 2001–2002
    • University of California, Los Angeles
      • Department of Pediatrics
      Los Angeles, CA, United States
    • Stanford University
      • Division of Infectious Diseases
      Stanford, CA, United States
  • 1998–1999
    • Case Western Reserve University
      • • Department of Pathology (University Hospitals Case Medical Center)
      • • Department of Oral Pathology
      Cleveland, OH, United States