Browsing by Author "Cohen, Myron S."

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    Blood and genital fluid viral load trajectories among treated and untreated persons with acute HIV infection in Malawi
    (Wolters Kluwer, 2022) Chen, Jane S.; Pettifor, Audrey E.; Nelson, Julie A. E.; Phiri, Sam; Pasquale, Dana K.; Kumwenda, Wiza; Kamanga, Gift; Cottrell, Mackenzie L.; Sykes, Craig; Kashuba, Angela D. M.; Tegha, Gerald; Krysiak, Robert; Thengolose, Isaac; Cohen, Myron S.; Hoffman, Irving F.; Miller, William C.; Rutstein, Sarah E.; Community and Global Health, Richard M. Fairbanks School of Public Health
    Background: Persons with acute HIV infection (AHI) are highly infectious and responsible for a disproportionate share of incident infections. Immediate antiretroviral therapy (ART) rapidly reduces blood viral loads (VLs), but genital VLs after ART initiation during AHI are less well described. Setting: Lilongwe, Malawi, 2012-2014. Methods: HIV-seronegative and HIV-serodiscordant persons aged ≥18 years were screened for AHI (RNA positive) and randomized to standard of care, behavioral intervention, or behavioral intervention plus short-term ART (raltegravir/emtricitabine/tenofovir) (1:2:2). Persons who were ART eligible under Malawi guidelines could receive first-line therapy. Blood and genital VLs were assessed at weeks 1, 4, 8, and 12. Fisher's Exact test was used to compare viral suppression by ART status. Results: Overall, 46 persons with AHI were enrolled; of whom, 17 started ART within 12 weeks. Median blood VL at AHI diagnosis was 836,115 copies/mL. At week 12, 7% (1/14) of those who initiated ART had a blood VL of ≥400 copies/mL, compared with 100% (23/23; P < 0.0001) of those who did not initiate ART (median VL: 61,605 copies/mL). Median genital VL at week 1 was 772 copies/mL, with 13 of 22 (59%) having VL of ≥400 copies/mL. At week 12, 0 of 10 (0%) of those who initiated ART had genital VL of ≥400 copies/mL, compared with 7 of 15 (47%) of those who did not initiate ART (P = 0.02). Conclusion: Although highly correlated, VLs in blood and genital fluids occupy discrete biological compartments with distinct virologic dynamics. Our results corroborate the dramatic reduction in both compartments after ART initiation. Increasing AHI screening and rapidly initiating treatment is key to interrupting transmission.
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    Effect of Bamlanivimab vs Placebo on Incidence of COVID-19 Among Residents and Staff of Skilled Nursing and Assisted Living Facilities: A Randomized Clinical Trial
    (AMA, 2021-06-03) Cohen, Myron S.; Nirula, Ajay; Mulligan, Mark J.; Novak, Richard M.; Marovich, Mary; Yen, Catherine; Stemer, Alexander; Mayer, Stockton M.; Wohl, David; Brengle, Blair; Montague, Brian T.; Frank, Ian; McCulloh, Russell J.; Fichtenbaum, Carl J.; Lipson, Brad; Gabra, Nashwa; Ramirez, Julio A.; Thai, Christine; Chege, Wairimu; Gomez Lorenzo, Margarita M.; Sista, Nirupama; Farrior, Jennifer; Clement, Meredith E.; Brown, Elizabeth R.; Custer, Kenneth L.; Van Naarden, Jacob; Adams, Andrew C.; Schade, Andrew E.; Dabora, Matan C.; Knorr, Jack; Price, Karen L.; Sabo, Janelle; Tuttle, Jay L.; Klekotka, Paul; Shen, Lei; Skovronsky, Daniel M.; IU School of Medicine-Northwest
    Importance Preventive interventions are needed to protect residents and staff of skilled nursing and assisted living facilities from COVID-19 during outbreaks in their facilities. Bamlanivimab, a neutralizing monoclonal antibody against SARS-CoV-2, may confer rapid protection from SARS-CoV-2 infection and COVID-19. Objective To determine the effect of bamlanivimab on the incidence of COVID-19 among residents and staff of skilled nursing and assisted living facilities. Design, Setting, and Participants Randomized, double-blind, single-dose, phase 3 trial that enrolled residents and staff of 74 skilled nursing and assisted living facilities in the United States with at least 1 confirmed SARS-CoV-2 index case. A total of 1175 participants enrolled in the study from August 2 to November 20, 2020. Database lock was triggered on January 13, 2021, when all participants reached study day 57. Interventions Participants were randomized to receive a single intravenous infusion of bamlanivimab, 4200 mg (n = 588), or placebo (n = 587). Main Outcomes and Measures The primary outcome was incidence of COVID-19, defined as the detection of SARS-CoV-2 by reverse transcriptase–polymerase chain reaction and mild or worse disease severity within 21 days of detection, within 8 weeks of randomization. Key secondary outcomes included incidence of moderate or worse COVID-19 severity and incidence of SARS-CoV-2 infection. Results The prevention population comprised a total of 966 participants (666 staff and 300 residents) who were negative at baseline for SARS-CoV-2 infection and serology (mean age, 53.0 [range, 18-104] years; 722 [74.7%] women). Bamlanivimab significantly reduced the incidence of COVID-19 in the prevention population compared with placebo (8.5% vs 15.2%; odds ratio, 0.43 [95% CI, 0.28-0.68]; P < .001; absolute risk difference, −6.6 [95% CI, −10.7 to −2.6] percentage points). Five deaths attributed to COVID-19 were reported by day 57; all occurred in the placebo group. Among 1175 participants who received study product (safety population), the rate of participants with adverse events was 20.1% in the bamlanivimab group and 18.9% in the placebo group. The most common adverse events were urinary tract infection (reported by 12 participants [2%] who received bamlanivimab and 14 [2.4%] who received placebo) and hypertension (reported by 7 participants [1.2%] who received bamlanivimab and 10 [1.7%] who received placebo). Conclusions and Relevance Among residents and staff in skilled nursing and assisted living facilities, treatment during August-November 2020 with bamlanivimab monotherapy reduced the incidence of COVID-19 infection. Further research is needed to assess preventive efficacy with current patterns of viral strains with combination monoclonal antibody therapy.