Browsing by Author "Eshleman, Susan H."

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    Comparison of cross-sectional HIV incidence assay results from dried blood spots and plasma
    (Public Library of Science, 2017-02-23) Schlusser, Katherine E.; Pilcher, Christopher; Kallas, Esper G.; Santos, Breno R.; Deeks, Steven G.; Facente, Shelley; Keating, Sheila M.; Busch, Michael P.; Murphy, Gary; Welte, Alex; Quinn, Thomas; Eshleman, Susan H.; Laeyendecker, Oliver
    Background: Assays have been developed for cross-sectional HIV incidence estimation using plasma samples. Large scale surveillance programs are planned using dried blood spot (DBS) specimens for incidence assessment. However, limited information exists on the performance of HIV cross-sectional incidence assays using DBS. Methods: The assays evaluated were: Maxim HIV-1 Limiting Antigen Avidity EIA (LAg-Avidity), Sedia HIV-1 BED-Capture EIA (BED-CEIA), and CDC modified BioRad HIV-1/2 Plus O Avidity-based Assay (CDC-BioRad Avidity) using pre-determined cutoff values. 100 matched HIV-1 positive plasma and DBS samples, with known duration of infection, from the Consortium for the Evaluation and Performance of HIV Incidence Assays repository were tested. All assays were run in duplicate. To examine the degree of variability within and between results for each sample type, both categorical and continuous results were analyzed. Associations were assessed with Bland Altman, R2 values and Cohen’s kappa coefficient (ĸ). Results: Intra-assay variability using the same sample type was similar for all assays (R2 0.96 to 1.00). The R2 values comparing DBS and plasma results for LAg-Avidity, BED-CEIA, and CDC-BioRad Avidity were 0.96, 0.94, and 0.84, respectively. The concordance and ĸ values between DBS and plasma for all three assays were >87% and >0.64, respectively. The Bland-Altman analysis showed significant differences between plasma and DBS samples. For all three assays, a higher number of samples were classified as recent infections using DBS samples. Conclusions: DBS and plasma sample results were highly correlated. However, when compared to plasma, each assay performed somewhat differently in DBS at the lower and higher ends of the dynamic range. DBS samples were more likely to be classified as recently infected by all three assays, which may lead to overestimation of incidence in surveys using performance criteria derived for plasma samples.
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    Effect of Universal Testing and Treatment on HIV Incidence — HPTN 071 (PopART)
    (Massachusetts Medical Society, 2019-07) Hayes, Richard J.; Donnell, Deborah; Floyd, Sian; Mandla, Nomtha; Bwalya, Justin; Sabapathy, Kalpana; Yang, Blia; Phiri, Mwelwa; Schaap, Ab; Eshleman, Susan H.; Piwowar-Manning, Estelle; Kosloff, Barry; James, Anelet; Skalland, Timothy; Wilson, Ethan; Emel, Lynda; Macleod, David; Dunbar, Rory; Simwinga, Musonda; Makola, Nozizwe; Bond, Virginia; Moore, Ayana; Griffith, Sam; Sista, Nirupama Deshmane; Vermund, Sten H.; El-Sadr, Wafaa; Burns, David N.; Hargreaves, James R.; Hauck, Katharina; Fraser, Christophe; Shanaube, Kwame; Bock, Peter; Beyers, Nulda; Ayles, Helen; Fidler, Sarah
    BACKGROUND: A universal testing and treatment strategy is a potential approach to reduce the incidence of human immunodeficiency virus (HIV) infection, yet previous trial results are inconsistent. METHODS: In the HPTN 071 (PopART) community-randomized trial conducted from 2013 through 2018, we randomly assigned 21 communities in Zambia and South Africa (total population, approximately 1 million) to group A (combination prevention intervention with universal antiretroviral therapy [ART]), group B (the prevention intervention with ART provided according to local guidelines [universal since 2016]), or group C (standard care). The prevention intervention included home-based HIV testing delivered by community workers, who also supported linkage to HIV care and ART adherence. The primary outcome, HIV incidence between months 12 and 36, was measured in a population cohort of approximately 2000 randomly sampled adults (18 to 44 years of age) per community. Viral suppression (<400 copies of HIV RNA per milliliter) was assessed in all HIV-positive participants at 24 months. RESULTS: The population cohort included 48,301 participants. Baseline HIV prevalence was 21% or 22% in each group. Between months 12 and 36, a total of 553 new HIV infections were observed during 39,702 person-years (1.4 per 100 person-years; women, 1.7; men, 0.8). The adjusted rate ratio for group A as compared with group C was 0.93 (95% confidence interval [CI], 0.74 to 1.18; P=0.51) and for group B as compared with group C was 0.70 (95% CI, 0.55 to 0.88; P=0.006). The percentage of HIV-positive participants with viral suppression at 24 months was 71.9% in group A, 67.5% in group B, and 60.2% in group C. The estimated percentage of HIV-positive adults in the community who were receiving ART at 36 months was 81% in group A and 80% in group B. CONCLUSIONS: A combination prevention intervention with ART provided according to local guidelines resulted in a 30% lower incidence of HIV infection than standard care. The lack of effect with universal ART was unanticipated and not consistent with the data on viral suppression. In this trial setting, universal testing and treatment reduced the population-level incidence of HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 071 [PopArt] ClinicalTrials.gov number, NCT01900977. opens in new tab.)
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    Nevirapine versus ritonavir-boosted lopinavir for HIV-infected children
    (Massachusetts Medical Society, 2012) Violari, Avy; Paed, F. C.; Lindsey, Jane C.; Hughes, Michael D.; Mujuru, Hilda A.; Barlow-Mosha, Linda; Kamthunzi, Portia; Chi, Benjamin H.; Cotton, Mark F.; Moultrie, Harry; Khadse, Sandhya; Schimana, Werner; Bobat, Raziya; Purdue, Lynette; Eshleman, Susan H.; Abrams, Elaine J.; Millar, Linda; Petzold, Elizabeth; Mofenson, Lynne M.; Jean-Philippe, Patrick; Palumbo, Paul
    BACKGROUND: Nevirapine-based antiretroviral therapy is the predominant (and often the only) regimen available for children in resource-limited settings. Nevirapine resistance after exposure to the drug for prevention of maternal-to-child human immunodeficiency virus (HIV) transmission is common, a problem that has led to the recommendation of ritonavir-boosted lopinavir in such settings. Regardless of whether there has been prior exposure to nevirapine, the performance of nevirapine versus ritonavir-boosted lopinavir in young children has not been rigorously established. METHODS: In a randomized trial conducted in six African countries and India, we compared the initiation of HIV treatment with zidovudine, lamivudine, and either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 2 to 36 months of age who had no prior exposure to nevirapine. The primary end point was virologic failure or discontinuation of treatment by study week 24. RESULTS: A total of 288 children were enrolled; the median percentage of CD4+ T cells was 15%, and the median plasma HIV type 1 (HIV-1) RNA level was 5.7 log 10 copies per milliliter. The percentage of children who reached the primary end point was significantly higher in the nevirapine group than in the ritonavir-boosted lopinavir group (40.8% vs. 19.3%; P<0.001). Among the nevirapine-treated children with virologic failure for whom data on resistance were available, more than half (19 of 32) had resistance at the time of virologic failure. In addition, the time to a protocol-defined toxicity end point was shorter in the nevirapine group (P = 0.04), as was the time to death (P = 0.06). CONCLUSIONS: Outcomes were superior with ritonavir-boosted lopinavir among young children with no prior exposure to nevirapine. Factors that may have contributed to the suboptimal results with nevirapine include elevated viral load at baseline, selection for nevirapine resistance, background regimen of nucleoside reverse-transcriptase inhibitors, and the standard ramp-up dosing strategy. The results of this trial present policymakers with difficult choices. (Funded by the National Institute of Allergy and Infectious Diseases and others; P1060 ClinicalTrials.gov number, NCT00307151.) Copyright © 2012 Massachusetts Medical Society. All rights reserved.