Doherty Institute - Research Publications

Permanent URI for this collection

http://hdl.handle.net/11343/113582

Filters

Reset filters

Settings
Statistics
Citations
Author: Lewin, Sharon ×

Search Results

Now showing 1 - 10 of 88
  • Item
    No Preview Available
    Adaptation of the intact proviral DNA assay to a nanowell-based digital PCR platform
    Tumpach, C ; Cochrane, CR ; Kim, Y ; Ong, J ; Rhodes, A ; Angelovich, TA ; Churchill, MJ ; Lewin, SR ; Telwatte, S ; Roche, M (MEDISCRIPT LTD, 2023-06)
    Quantification of intact proviruses is a critical measurement in HIV cure studies both in vitro and in vivo. The widely adopted 'intact proviral DNA assay' (IPDA), designed to discriminate and quantify genetically intact HIV proviruses based on detection of two HIV sequence-specific targets, was originally validated using Bio-Rad's droplet digital PCR technology (ddPCR). Despite its advantages, ddPCR is limited in multiplexing capability (two-channel) and is both labor- and time intensive. To overcome some of these limitations, we utilized a nanowell-based digital PCR platform (dPCR, QIAcuity from Qiagen) which is a fully automated system that partitions samples into nanowells rather than droplets. In this study we adapted the IPDA assay to the QIAcuity platform and assessed its performance relative to ddPCR. The dPCR could differentiate between intact, 5' defective and 3' defective proviruses and was sensitive to single HIV copy input. We found the intra-assay and inter-assay variability was within acceptable ranges (with coefficient of variation at or below 10%). When comparing the performance of the IPDA in ex vivo CD4+ T cells from people with HIV on antiretroviral therapy, there was a strong correlation in the quantification of intact (rs = 0.93; p < 0.001) and 3' defective proviruses (rs = 0.96; p < 0.001) with a significant but less strong correlation for 5' defective proviruses (rs = 0.7; p = 0.04). We demonstrate that the dPCR platform enables sensitive and accurate quantification of genetically intact and defective proviruses similar to the ddPCR system but with greater speed and efficiency. This flexible system can be further optimized in the future, to detect up to 5 targets, enabling a more precise detection of intact and potentially replication-competent proviruses.
  • Item
    No Preview Available
    Regional Analysis of Intact and Defective HIV Proviruses in the Brain of Viremic and Virally Suppressed People with HIV
    Angelovich, TA ; Cochrane, CR ; Zhou, J ; Tumpach, C ; Byrnes, SJ ; Eddine, JJ ; Waring, E ; Busman-Sahay, K ; Deleage, C ; Jenkins, TA ; Hearps, AC ; Turville, S ; Gorry, PR ; Lewin, SR ; Brew, BJ ; Estes, JD ; Roche, M ; Churchill, MJ (WILEY, 2023-10)
    Here, we provide the first regional analysis of intact and defective HIV reservoirs within the brain. Brain tissue from both viremic and virally suppressed people with HIV (PWH) harbored HIV pol DNA in all regions tested, with lower levels present in basal ganglia and cerebellum relative to frontal white matter. Intact proviruses were primarily found in the frontal white matter but also detected in other brain regions of PWH, demonstrating frontal white matter as a major brain reservoir of intact, potentially replication competent HIV DNA that persists despite antiretroviral therapy. ANN NEUROL 2023;94:798-802.
  • Item
    No Preview Available
    Combination Immune Checkpoint Blockade Enhances IL-2 and CD107a Production from HIV-Specific T Cells Ex Vivo in People Living with HIV on Antiretroviral Therapy
    Chiu, CY ; Chang, JJ ; Dantanarayana, A ; Solomon, A ; Evans, VA ; Pascoe, R ; Gubser, C ; Trautman, L ; Fromentin, R ; Chomont, N ; McMahon, JH ; Cameron, PU ; Rasmussen, TA ; Lewin, SR (AMER ASSOC IMMUNOLOGISTS, 2022-01-01)
    In people with HIV (PWH) on antiretroviral therapy (ART), immune dysfunction persists, including elevated expression of immune checkpoint (IC) proteins on total and HIV-specific T cells. Reversing immune exhaustion is one strategy to enhance the elimination of HIV-infected cells that persist in PWH on ART. We aimed to evaluate whether blocking CTL-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), T cell Ig domain and mucin domain 3 (TIM-3), T cell Ig and ITIM domain (TIGIT) and lymphocyte activation gene-3 (LAG-3) alone or in combination would enhance HIV-specific CD4+ and CD8+ T cell function ex vivo. Intracellular cytokine staining was performed using human PBMCs from PWH on ART (n = 11) and expression of CD107a, IFN-γ, TNF-α, and IL-2 was quantified with HIV peptides and Abs to IC. We found the following: 1) IC blockade enhanced the induction of CD107a and IL-2 but not IFN-γ and TNF-α in response to Gag and Nef peptides; 2) the induction of CD107a and IL-2 was greatest with multiple combinations of two Abs; and 3) Abs to LAG-3, CTLA-4, and TIGIT in combinations showed synergistic induction of IL-2 in HIV-specific CD8+ and CD107a and IL-2 production in HIV-specific CD4+ and CD8+ T cells. These results demonstrate that the combination of Abs to LAG-3, CTLA-4, or TIGIT can increase the frequency of cells expressing CD107a and IL-2 that associated with cytotoxicity and survival of HIV-specific CD4+ and CD8+ T cells in PWH on ART. These combinations should be further explored for an HIV cure.
  • Item
    Thumbnail Image
    Memory CD4+ T cells that co-express PD1 and CTLA4 have reduced response to activating stimuli facilitating HIV latency
    Rasmussen, TA ; Zerbato, JM ; Rhodes, A ; Tumpach, C ; Dantanarayana, A ; McMahon, JH ; Lau, JSY ; Chang, JJ ; Gubser, C ; Brown, W ; Hoh, R ; Krone, M ; Pascoe, R ; Chiu, CY ; Bramhall, M ; Lee, HJ ; Haque, A ; Fromentin, R ; Chomont, N ; Milush, J ; Van der Sluis, RM ; Palmer, S ; Deeks, SG ; Cameron, PU ; Evans, V ; Lewin, SR (CELL PRESS, 2022-10-18)
    Programmed cell death 1 (PD1) and cytotoxic T lymphocyte-associated protein 4 (CTLA4) suppress CD4+ T cell activation and may promote latent HIV infection. By performing leukapheresis (n = 21) and lymph node biopsies (n = 8) in people with HIV on antiretroviral therapy (ART) and sorting memory CD4+ T cells into subsets based on PD1/CTLA4 expression, we investigate the role of PD1 and CTLA 4 in HIV persistence. We show that double-positive (PD1+CTLA4+) cells in blood contain more HIV DNA compared with double-negative (PD1-CTLA4-) cells but still have a lower proportion of cells producing multiply spliced HIV RNA after stimulation as well as reduced upregulation of T cell activation and proliferation markers. Transcriptomics analyses identify differential expression of key genes regulating T cell activation and proliferation with MAF, KLRB1, and TIGIT being upregulated in double-positive compared with double-negative cells, whereas FOS is downregulated. We conclude that, in addition to being enriched for HIV DNA, double-positive cells are characterized by negative signaling and a reduced capacity to respond to stimulation, favoring HIV latency.
  • Item
    No Preview Available
    Multiparameter immunohistochemistry analysis of HIV DNA, RNA and immune checkpoints in lymph node tissue
    Richardson, ZA ; Deleage, C ; Tutuka, CSA ; Walkiewicz, M ; Del Rio-Estrada, PM ; Pascoe, RD ; Evans, VA ; Reyesteran, G ; Gonzales, M ; Roberts-Thomson, S ; Gonzalez-Navarro, M ; Torres-Ruiz, F ; Estes, JD ; Lewin, SR ; Cameron, PU (ELSEVIER, 2022-02)
    The main barrier to a cure for HIV is the persistence of long-lived and proliferating latently infected CD4+ T-cells despite antiretroviral therapy (ART). Latency is well characterized in multiple CD4+ T-cell subsets, however, the contribution of regulatory T-cells (Tregs) expressing FoxP3 as well as immune checkpoints (ICs) PD-1 and CTLA-4 as targets for productive and latent HIV infection in people living with HIV on suppressive ART is less well defined. We used multiplex detection of HIV DNA and RNA with immunohistochemistry (mIHC) on formalin-fixed paraffin embedded (FFPE) cells to simultaneously detect HIV RNA and DNA and cellular markers. HIV DNA and RNA were detected by in situ hybridization (ISH) (RNA/DNAscope) and IHC was used to detect cellular markers (CD4, PD-1, FoxP3, and CTLA-4) by incorporating the tyramide system amplification (TSA) system. We evaluated latently infected cell lines, a primary cell model of HIV latency and excisional lymph node (LN) biopsies collected from people living with HIV (PLWH) on and off ART. We clearly detected infected cells that coexpressed HIV RNA and DNA (active replication) and DNA only (latently infected cells) in combination with IHC markers in the in vitro infection model as well as LN tissue from PLWH both on and off ART. Combining ISH targeting HIV RNA and DNA with IHC provides a platform to detect and quantify HIV persistence within cells identified by multiple markers in tissue samples from PLWH on ART or to study HIV latency.
  • Item
    Thumbnail Image
    Multi-site assessment of rapid, point-of-care antigen testing for the diagnosis of SARS-CoV-2 infection in a low-prevalence setting: A validation and implementation study
    Muhi, S ; Tayler, N ; Hoang, T ; Ballard, SA ; Graham, M ; Rojek, A ; Kwong, JC ; Trubiano, JA ; Smibert, O ; Drewett, G ; James, F ; Gardiner, E ; Chea, S ; Isles, N ; Sait, M ; Pasricha, S ; Taiaroa, G ; McAuley, J ; Williams, E ; Gibney, KB ; Stinear, TP ; Bond, K ; Lewin, SR ; Putland, M ; Howden, BP ; Williamson, DA (ELSEVIER, 2021-04)
    BACKGROUND: In Australia, COVID-19 diagnosis relies on RT-PCR testing which is relatively costly and time-consuming. To date, few studies have assessed the performance and implementation of rapid antigen-based SARS-CoV-2 testing in a setting with a low prevalence of COVID-19 infections, such as Australia. METHODS: This study recruited participants presenting for COVID-19 testing at three Melbourne metropolitan hospitals during a period of low COVID-19 prevalence. The Abbott PanBioTM COVID-19 Ag point-of-care test was performed alongside RT-PCR. In addition, participants with COVID-19 notified to the Victorian Government were invited to provide additional swabs to aid validation. Implementation challenges were also documented. FINDINGS: The specificity of the Abbott PanBioTM COVID-19 Ag test was 99.96% (95% CI 99.73 - 100%). Sensitivity amongst participants with RT-PCR-confirmed infection was dependent upon the duration of symptoms reported, ranging from 77.3% (duration 1 to 33 days) to 100% in those within seven days of symptom onset. A range of implementation challenges were identified which may inform future COVID-19 testing strategies in a low prevalence setting. INTERPRETATION: Given the high specificity, antigen-based tests may be most useful in rapidly triaging public health and hospital resources while expediting confirmatory RT-PCR testing. Considering the limitations in test sensitivity and the potential for rapid transmission in susceptible populations, particularly in hospital settings, careful consideration is required for implementation of antigen testing in a low prevalence setting. FUNDING: This work was funded by the Victorian Department of Health and Human Services. The funder was not involved in data analysis or manuscript preparation.
  • Item
    Thumbnail Image
    8th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015).
    Pate, KM ; Pohlmeyer, C ; Walker-Sperling, V ; Foote, J ; Najarro, K ; Cryer, C ; Salgado, M ; Gama, L ; Engle, E ; Shirk, E ; Queen, S ; Chioma, S ; Vermillion, M ; Bullock, B ; Li, M ; Lyons, C ; Adams, R ; Zink, C ; Clements, J ; Mankowski, J ; Blankson, J ; Micci, L ; Ryan, E ; Fromentin, R ; Benne, C ; Chomont, N ; Lifson, J ; Paiardini, M ; Lee, S ; Chomont, N ; Fromentin, R ; Silicano, R ; Silicano, J ; Richman, D ; O'Doherty, U ; Palmer, S ; Burbelo, P ; Deeks, S ; Ghneim, K ; Ahlers, J ; Fourati, S ; Shive, C ; Cameron, M ; Mukerjee, P ; Ghannoum, M ; Rodriguez, B ; Deeks, S ; Lederman, M ; Sekaly, R ; Frange, P ; Faye, A ; Avettand-Fenoel, V ; Bellaton, E ; Deschamps, D ; Angin, M ; Caillat-Zucman, S ; Peytavin, G ; Le Chenadec, J ; Warszawski, J ; Rouzioux, C ; Saez-Cirion, A ; Chang, C ; Cameron, P ; Elliott, J ; Perelson, A ; Roche, M ; Dantanarayana, A ; Solomon, A ; Naranbhai, V ; Tenakoon, S ; Hoh, R ; McMahon, J ; Sikaris, K ; Hartogensis, W ; Bacchetti, P ; Hecht, F ; Lifson, J ; Deeks, S ; Lewin, S ; Byrareddy, S ; Arthos, J ; Cicala, C ; Reimann, K ; Parslow, T ; Santangelo, P ; Villinger, F ; Fauci, A ; Ansari, A ; George, M ; Weiser, B ; Burger, H ; Lewy, T ; Anastos, K ; Asmuth, D ; Somsouk, M ; Hunt, P ; Min, Z ; Miller, C ; Li, XD ; Hinkle, J ; Shaw, A ; Weaver, E ; Klein, G ; Viljoen, K ; Wendoh, J ; Karaoz, U ; Brodie, E ; Mulder, N ; Botha, G ; Kidzeru, E ; Butcher, J ; Gray, C ; Rosenthal, K ; Abimiku, A ; Cameron, B ; Stintzi, A ; Jaspan, H ; Schafer, J ; Evans, T ; Li, H ; Reeves, RK ; Kroon, M ; Dunning, L ; Hsiao, M ; Myer, L ; Crowell, CS ; Maiga, AI ; Sylla, M ; Taiwo, B ; Koné, N ; Murphy, RL ; Marcelin, A-G ; Traore, B ; Fofana, DB ; Chadwick, EG ; Ásbjörnsdóttir, KH ; Slyker, JA ; Wamalwa, D ; De Rosa, S ; Hughes, JP ; Rowhani-Rahbar, A ; Chohan, BH ; Benki-Nugent, S ; Tapia, K ; John-Stewart, GC ; Kizito, H ; Gaur, A ; Prasitsuebsai, W ; Rakhmanina, N ; Chokephaibulkit, K ; Fourie, J ; Bekker, L-G ; Shao, Y ; Bennett, S ; Quirk, E ; Prasitsuebsai, W ; Teeraananchai, S ; Truong, KH ; Ananworanich, J ; Chau, V ; Van Nguyen, L ; Kosalaraksa, ; Kurniati, N ; Sudjaritruk, T ; Chokephaibulkit, K ; Singtoroj, T ; Kerr, SJ ; Sohn, AH ; Lombaard, J ; Bunupuradah, T ; Flynn, P ; Ramapuram, J ; Ssali, F ; Crauwels, H ; Hoogstoel, A ; Van Eygen, V ; Stevens, M ; Boven, K ; Jao, J ; Myer, L ; Phillips, T ; Petro, G ; Zerbe, A ; Abrams, EJ ; Hanrahan, C ; Martinson, N ; Link-Barnes, G ; Msandiwa, R ; Chaisson, R ; Golub, J ; Evans, DH ; Schnippel, K ; Budgell, E ; Shearer, K ; Berhanu, R ; Long, L ; Rosen, S ; Schultze, A ; Efsen, AMW ; Post, FA ; Panteleev, A ; Furrer, H ; Miller, R ; Losso, MH ; Toibaro, J ; Skrahin, A ; Miro, JM ; Caylà, JA ; Girardi, E ; Bruyand, M ; Obel, N ; Podlekareva, DN ; Lundgren, JD ; Mocroft, A ; Kirk, O ; Baddeley, A ; Doherty, M ; Kanchar, A ; Matteelli, A ; Timimi, HB ; Getahun, H ; Hosseinipour, M ; Bisson, G ; Miyahara, S ; Sun, X ; Moses, A ; Riviere, C ; Kirui, FK ; Badal-Faesen, S ; Lagat, D ; Nyirenda, M ; Naidoo, K ; Hakim, J ; Mugyenyi, P ; Henostroza, G ; Leger, PD ; Lama, JR ; Mohapi, L ; Alave, J ; Mave, V ; Veloso, VG ; Pillay, S ; Kumarasamy, N ; Bao, J ; Hogg, E ; Jones, L ; Zolopa, A ; Kumwenda, J ; Gupta, A ; Cohen, M ; Chen, Y ; McCauley, M ; Gamble, T ; Hosseinipour, M ; Kumarasamy, N ; Hakim, J ; Kumwenda, N ; Brum, T ; Grinsztejn, B ; Godbole, S ; Chariyalertsak, S ; Santos, RB ; Mayer, K ; Hoffman, I ; Eshleman, S ; Piwowar-Manning, E ; Ou, S-S ; Cottle, L ; Makhema, J ; Mills, L ; Panchia, R ; Badal-Faesen, S ; Eron, J ; Gallant, J ; Havlir, D ; Swindells, S ; Elharrar, V ; Burns, D ; Taha, T ; Nielsen, K ; Celentano, D ; Essex, M ; Fleming, T ; Jean, K ; Puren, A ; Cutler, E ; Singh, B ; Bouscaillou, J ; Rain-Taljaard, R ; Taljjard, D ; Lissouba, P ; Peytavin, G ; Auvert, B ; Jenkins, L ; Nordio, J ; Vasarhelyi, K ; Nunez, A ; Barrios, R ; Rutherford, A ; Iwuji, C ; Dray-Spira, R ; Calmy, A ; Larmarange, J ; Orne-Gliemann, J ; Dabis, F ; Pillay, D ; Porter, K ; Barnabas, R ; van Rooyen, H ; Tumwesigye, E ; Brantley, J ; Baeten, J ; van Heerden, A ; Turyamureeba, B ; Joseph, P ; Krows, M ; Hughes, J ; Celum, C ; Eshleman, SH ; Hudelson, SE ; Ou, SS ; Redd, AD ; Swanstrom, R ; Porcella, SF ; Chen, YQ ; Piwowar-Manning, E ; McCauley, M ; Gamble, T ; Sievers, M ; Martens, CA ; Bruno, D ; Ping, L-H ; Dukhovlinova, E ; Quinn, TC ; Kumwenda, J ; Maliwichi, M ; Nhando, N ; Akelo, V ; Moyo, S ; Panchia, R ; Kumarasamy, N ; Chotirosniramit, N ; Rocha, MM ; Bustorff, F ; Grinsztejn, B ; Mayer, KH ; Hughes, JP ; Cohen, MS ; Haas, AD ; Tenthani, L ; Msukwa, MT ; Jahn, A ; Midiani, D ; Mhango, E ; Gadabu, O ; Tal, K ; Spörri, A ; Egger, M ; Chimbwandira, F ; van Oosterhout, JJ ; Keiser, O ; Rosenberg, N ; Mtande, T ; Saidi, F ; Stanley, C ; Jere, E ; Mwangomba, L ; Kumwenda, K ; Mofolo, I ; Mwale, M ; Chauma, A ; Miller, WC ; Hoffman, I ; Hosseinipour, MC ; Buzdugan, R ; McCoy, SI ; Watadzaushe, C ; Dufour, M-SK ; Petersen, M ; Dirawo, J ; Mushavi, A ; Mujuru, HA ; Mahomva, A ; Engelsmann, B ; Hakobyan, A ; Mugurungi, O ; Cowan, FM ; Padian, NS ; Lallemant, M ; Amzal, B ; Urien, S ; Sripan, P ; Cressey, T ; Ngo-Giang-Huong, N ; Rawangban, B ; Sabsanong, P ; Siriwachirachai, T ; Jarupanich, T ; Kanjanavikai, P ; Wanasiri, P ; Koetsawang, S ; Jourdain, G ; Le Cœur, S ; Ochoa-Moreno, I ; Mangenah, C ; Buzdugan, R ; Padian, NS ; Mccoy, SI ; Cowan, FM ; Bautista-Arredondo, S ; Wambura, M ; Hayes, R ; Grund, J ; Kapiga, S ; Mahler, H ; Mshana, G ; Kuringe, E ; Plotkin, M ; Bock, N ; Larke, N ; Changalucha, J ; Weiss, H ; Thirumurthy, H ; Akello, I ; Murray, K ; Masters, S ; Maman, S ; Omanga, E ; Agot, K ; Duwve, J ; Hoover, K ; Conrad, C ; Galang, R ; Hillman, D ; Hoots, B ; Patel, M ; Peters, P ; Pontones, P ; Roseberry, J ; Shields, J ; Waterhouse, D ; Weidle, P ; Galang, RR ; Gentry, J ; Peters, PJ ; Blosser, SJ ; Chapman, EL ; Conrad, C ; Duwve, JM ; Ganova-Raeva, L ; Heneine, W ; Hillman, D ; Jia, H ; Liu, L ; Luo, W ; Lovchik, J ; Masciotra, S ; Owen, SM ; Perez, A ; Peyrani, P ; Pontones, P ; Ramachandran, S ; Roseberry, JC ; Sandoval, M ; Shankar, A ; Thai, H ; Xia, G ; Khudyakov, Y ; Switzer, WM ; Mannheimer, S ; Hirsch-Moverman, Y ; Loquere, A ; Franks, J ; Hughes, J ; Ou, S-S ; Amico, KR ; Hendrix, C ; Dye, BJ ; Piwowar-Manning, E ; Marzinke, M ; Elharrar, V ; Stirratt, M ; Grant, RM ; Holtz, TH ; Chitwarakorn, A ; Curlin, ME ; Hughes, J ; Amico, KR ; Hendrix, C ; Dye, BJ ; Anderson, PL ; Ou, S-S ; Elharrar, V ; Eshleman, SH ; Stirratt, M ; Grant, RM ; Doherty, M ; Beusenberg, M ; Asamoah-Odei, E ; Lule, F ; Pendse, R ; Ghidinelli, M ; Lo, Y-R ; Reidner, G ; Donoghoe, M ; Vitoria, M ; Hirnschall, G ; Levi, J ; Raymond, A ; Pozniak, A ; Vernazza, P ; Kohler, P ; Ford, N ; Hill, A ; Wolff, M ; Cortes, CP ; Shepherd, BE ; Giganti, M ; Gowan, CM ; Rawat, A ; Uebel, KE ; Moore, D ; Yassi, A ; Wilkinson, L ; Harley, B ; Jacobs, S ; Cragg, C ; Kriel, E ; Solomon, S ; Peton, N ; Jennings, K ; Youngleson, M ; Grimsrud, A ; Joy, J ; Liang, R ; McCloskey, R ; Nguyen, T ; Brumme, C ; Colley, G ; Hogg, R ; Montaner, J ; Harrigan, PR ; Poon, A ; Klein, K ; Ratcliff, A ; Nickel, G ; Nankya, I ; Lobritz, M ; Gao, Y ; Shattock, R ; Arts, E ; Kinloch, NN ; Macmillan, DR ; Le, AQ ; Cotton, LA ; Mccloskey, R ; Bangsberg, DR ; Buchbinder, S ; Carrington, M ; Fuchs, J ; Harrigan, PR ; Koblin, B ; Markowitz, M ; Mayer, K ; Milloy, MJ ; Schechter, MT ; Wagner, T ; Walker, BD ; Carlson, JM ; Poon, AFY ; Brumme, ZL ; Mesplède, T ; Anstett, K ; Osman, N ; Hassounah, S ; Liang, J ; Han, Y ; Wainberg, M ; Demeulemeester, J ; Vets, S ; Schrijvers, R ; Madlala, P ; De Maeyer, M ; De Rijck, J ; Ndung'u, T ; Debyser, Z ; Gijsbers, R ; Prentice, H ; Tomaras, G ; Geraghty, D ; Apps, R ; Fong, Y ; Ehrenberg, P ; Rolland, M ; Kijak, G ; Nelson, W ; Decamp, A ; Shen, X ; Yates, N ; Zolla-Pazner, S ; Nitayaphan, S ; Rerks-Ngarm, S ; Pitisuttithum, P ; Ferrari, G ; Montefiori, D ; McElrath, J ; Bailer, R ; Koup, R ; O'Connell, R ; Robb, M ; Michael, N ; Kim, J ; Thomas, R ; Peterson, C ; Wang, J ; Polacino, P ; Holmes, M ; Hu, S-L ; Gregory, P ; Kiem, H-P ; Kaminski, R ; Hu, W ; Zhang, Y ; Karn, J ; Khalili, K ; Chew, G ; Fujita, T ; Clayton, K ; Ishii, N ; Abdel-Mohsen, M ; Liegler, T ; Hecht, F ; Ostrowski, M ; Shikuma, C ; Maurer, M ; Korman, A ; Deeks, S ; Ndhlovu, L ; Karn, J ; Das, B ; Dobrowolski, C ; Scully, E ; Deeks, S ; Gandhi, M ; Johnston, R ; Bunupuradah, T ; Kiertiburanakul, S ; Avihingsanon, A ; Chetchotisakd, P ; Techapornroong, M ; Leerattanapetch, N ; Kantipong, P ; Bowonwatanuwong, C ; Banchongkit, S ; Klinbuayaem, V ; Mekviwattanawan, S ; Nimitvilai, S ; Jirajariyavej, S ; Prasithsirikul, W ; Munsakul, W ; Bhakeecheep, S ; Chaivooth, S ; Phanuphak, P ; Cooper, DA ; Apornpong, T ; Kerr, SJ ; Emery, S ; Ruxrungtham, K ; Mills, T ; Andrade, J ; Diperri, G ; Van Lunzen, J ; Koenig, E ; Elion, R ; Cavassini, M ; Madruga, JV ; Brunetta, J ; Shamblaw, D ; Dejesus, E ; Cohen, C ; Plummer, A ; Liu, Y ; McCallister, S ; Gupta, S ; Pozniak, A ; Arribas, J ; Post, F ; Bloch, M ; Gathe, J ; Benson, P ; Custodio, J ; Abram, M ; Wei, X ; Cheng, A ; McCallister, S ; Fordyce, M ; Gatell, J ; Raffi, F ; Plettenberg, A ; Smith, D ; Portilla, J ; Hoffmann, C ; Arasteh, K ; Thompson, M ; Hagins, D ; Morales-Ramirez, J ; Xu, X ; Teppler, H ; Trahan, M-J ; Lamarre, V ; Metras, M-E ; Lapointe, N ; Kakkar, F ; Hwang, C ; Schürmann, D ; Sobotha, C ; Boffito, M ; Sevinsky, H ; Ray, N ; Ravindran, P ; Xiao, H ; Krystal, M ; Dicker, I ; Grasela, D ; Lataillade, M ; Brunet, L ; Moodie, EE ; Young, J ; Walmsley, S ; Hull, M ; Cooper, C ; Klein, MB ; Naggie, S ; Cooper, C ; Saag, M ; Yang, JC ; Stamm, LM ; Pang, PS ; McHutchison, JG ; Dieterich, D ; Sulkowski, MS ; Wyles, D ; Eron, JJ ; Lalezari, J ; Wang, C ; Ruane, PJ ; Blick, G ; Bhatti, L ; Hu, YB ; Co, M ; Gibbons, K ; Trinh, R ; Sulkowski, MS ; Casado, JL ; Bañon, S ; Quereda, C ; Moreno, A ; Elías, MJP ; Moreno, S ; Saeed, S ; Rollet-Kurhajec, K ; Strumpf, EC ; Klein, MB ; Rockstroh, JK ; Nelson, M ; Katlama, C ; Lalezari, J ; Mallolas, J ; Bloch, M ; Matthews, G ; Saag, MS ; Zamor, P ; Orkin, C ; Gress, J ; Shaughnessy, M ; Klopfer, S ; Platt, HL ; Robertson, M ; Sulkowski, M ; Lacombe, K ; Fontaine, H ; Dhiver, C ; Rosenthal, E ; Metivier, S ; Antonini-Michelle, T ; Valantin, MA ; Miailhes, P ; Harent, S ; Batisse, D ; Pageaux, G-P ; Aumaitre, H ; Dominguez, S ; Chas, J ; Allegre, T ; Lafeuillade, A ; De Truchis, P ; De Ledinghen, V ; Leroy, V ; Billaud, E ; Sogni, P ; Dabis, F ; Wittkop, L ; Duvivier, C ; Filipovics, A ; Fedchuk, L ; Bennai, Y ; Salmon, D ; Karim, QA ; Leask, K ; Kharsany, A ; Humphries, H ; Ntombela, F ; Samsunder, N ; Baxter, C ; Frohlich, J ; van der Elst, L ; Karim, SA ; Thirumurthy, H ; Masters, S ; Rao, S ; Murray, K ; Omanga, E ; Agot, K ; Marshall, BDL ; Elston, B ; Dobrer, S ; Montaner, J ; Kerr, T ; Wood, E ; Milloy, M-J ; Czaicki, N ; Njau, P ; Bautista-Arredondo, S ; Simba, O ; Padian, N ; McCoy, S ; Haber, N ; Tanser, F ; Herbst, K ; Pillay, D ; Bärnighausen, T ; Pettifor, A ; MacPhail, C ; Selin, A ; Gomez-Olivé, X ; Hughes, J ; Wagner, R ; Mabuza, W ; Mokoena, I ; Eshleman, S ; Piwowar-Manning, E ; Twine, R ; Julien, A ; Marcus, C ; Andrew, P ; Wang, J ; Xing, Y ; McKinstry, L ; Hamilton, E ; Agyei, Y ; Allison, S ; Sato, P ; Townley, E ; Tollman, S ; Kahn, K ; Solomon, MM ; Schechter, M ; Liu, AY ; McMahan, V ; Guanira, JV ; Hance, RJ ; Chariyalertsak, S ; Mayer, KH ; Grant, RM ; Liu, A ; Cohen, S ; Vittinghoff, E ; Anderson, P ; Doblecki-Lewis, S ; Bacon, O ; Chege, W ; Elion, R ; Buchbinder, S ; Kolber, M ; Henderson, F ; Taylor, A ; Chirwa, L ; Williams, T ; Borkowf, C ; Kasonde, M ; Mutanhaurwa, R ; Matlhaba, O ; Hageman, K ; Casillas, P ; Hosek, S ; Rudy, B ; Landovitz, R ; Kapogiannis, B ; Siberry, G ; Liu, N ; Rutledge, B ; Brothers, J ; Rooney, J ; Wilson, CM ; Hoagland, B ; Veloso, VG ; De Boni, RB ; Madruga, JV ; Kallas, EG ; Fernandes, NM ; Moreira, RI ; Liu, AY ; Grinsztejn, B ; Nair, G ; Justman, JE ; Piper, J ; Marzinke, M ; Hendrix, C ; Dai, J ; Pan, J ; Galaska, B ; Levy, L ; Shwartz, J ; McGowan, I ; Dezutti, C ; Xu, J ; Tang, W ; Zou, H ; Mahapatra, T ; Hu, Q ; Fu, G ; Wang, Z ; Lu, L ; Zhuang, M ; Chen, X ; Fu, J ; Yu, Y ; Lu, J ; Jiang, Y ; Geng, W ; Han, X ; Shang, H ; Wimonsate, W ; Pattanasin, S ; Sriporn, A ; Luechai, P ; Satumay, K ; Tippanonth, N ; Promda, N ; Holtz, T ; Chitwarakorn, A ; Dunne, E ; Chan, G ; Bennett, A ; Buskin, S ; Dombrowski, J ; Golden, M ; Grosso, A ; Stahlman, S ; Mothopeng, T ; Taruberekera, N ; Ouedraogo, G ; Ky-Zerbo, O ; Pitche, V ; Anato, S ; Sithole, B ; Mabuza, X ; Ceesay, N ; Diouf, D ; Trapence, G ; Umar, E ; Baral, S ; Khosropour, CM ; Katz, DA ; Dombrowski, JC ; Golden, MR ; Bavinton, BR ; Jin, F ; Prestage, G ; Zablotska, I ; Grinsztejn, B ; Phanuphak, N ; Friedman, RK ; Grulich, AE ; Sathane, I ; Horth, R ; Boothe, M ; Baltazar, CS ; Young, P ; Fisher, H ; Teodoro, E ; Gouveia, ML ; Lane, T ; Mcfarland, W ; Booth, R ; Davis, J ; Dvoryak, S ; Brewster, J ; Strathdee, S ; Latkin, C ; Joseph, B ; Milloy, MJ ; Nguyen, HH ; Bui, DD ; Dinh, TTT ; Nguyen, MS ; Tran, HT ; Le Hai Nguyen, ; Van Nguyen, TT ; Vu, QD ; Nhan, T ; Le, AKA ; Nguyen, BC ; Suthar, A ; Lo, Y-R ; Pham, HT ; Le, MG ; Nguyen, HL ; Kato, M ; Richardson, L ; Kerr, T ; Hogg, B ; Guillemi, S ; Montaner, J ; Wood, E ; Milloy, M-J ; Cousien, A ; Leclerc, P ; Morissette, C ; Bruneau, J ; Roy, É ; Yazdanpanah, Y ; Cox, J ; Bershteyn, A ; Klein, D ; Oishi, K ; Eckhoff, P ; Leisegang, R ; Mcmahon, J ; Hislop, M ; Stinson, K ; Boulle, A ; Elliott, J ; Maartens, G ; Kim, A ; Nganga, L ; Mukui, I ; Wamicwe, J ; Mwanyumba, S ; Bowen, N ; Wiesner, L ; De Cock, K ; Han, L ; Tang, W ; Best, J ; Zhang, Y ; Kim, J ; Liu, F ; Mollan, K ; Hudgens, M ; Bayus, B ; Terris-Prestholt, F ; Galler, S ; Yang, L ; Peeling, R ; Volberding, P ; Ma, B ; Yang, B ; Huang, S ; Fenton, K ; Wei, C ; Tucker, J ; Dombrowski, JC ; Hughes, JP ; Buskin, SE ; Simoni, JM ; Katz, D ; Fleming, M ; Nunez, A ; Golden, MR ; Schmitz, K ; Scheepers, E ; Okonji, E ; Kawooya, V ; Yotebieng, M ; Thirumurthy, H ; Moracco, KE ; Kawende, B ; Chalachala, JL ; Wenzi, LK ; Ravelomanana, NLR ; Edmonds, A ; Thompson, D ; Okitolonda, E ; Behets, F ; Musarandega, R ; Mahomva, A ; Robinson, J ; Tumbare, E ; Sen, PD ; Hakobyan, A ; Mushavi, A ; Domercant, JW ; Puttkammer, N ; Lu, L ; Francois, K ; Duncan, D ; Grand'Pierre, R ; Lowrance, D ; Adler, M ; Tih, PM ; Katayi, E ; Mboh, E ; Bonje, E ; Lem, E ; Awa, JC ; Lim, JR ; Duncan, D ; Petit, L ; Bianchi, F ; Welty, T ; Achu, MN ; Tayong, G ; Tene, G ; Mosoko, JJ ; Bolu, O ; Kieffer, MP ; Woelk, G ; Mpofu, D ; Cathcart, R ; Okala, SG ; King, DF ; Shattock, RJ ; Jacob, RA ; Moyo, T ; Schomaker, M ; Abrahams, F ; Pujol, BG ; Dorfman, J ; Valenzuela-Ponce, H ; Ávila-Ríos, S ; Garrido-Rodríguez, D ; García-Téllez, T ; Soto-Nava, M ; Escamilla-Gómez, T ; García-Morales, C ; Cortés-Álvarez, J ; Hernández-Juan, R ; Murakami-Ogasawara, A ; Mejía-Villatoro, C ; Pascale, J ; Porras, G ; Quant, C ; Lorenzana, I ; Meza, R ; Palou, E ; Manzanero, M ; Reyes-Terán, G ; Mailiiard, RB ; Smith, KN ; Piazza, P ; Mullins, JI ; Rinaldo, CR ; Planas, D ; Gosselin, A ; Monteiro, P ; Goulet, J-P ; Da Fonseca, S ; Cléret-Buhot, A ; Jenabian, M-A ; Routy, J-P ; Ancuta, P ; Jensen, K ; dela Pena-Ponce, MG ; Piatak, M ; Jacobs, W ; Fennelly, G ; Mollan, K ; Hudgens, M ; Kozlowski, P ; Amedee, A ; Estes, J ; Lifson, J ; Van Rompay, K ; Larsen, M ; De Paris, K ; Malatinkova, E ; De Spiegelaere, W ; Bonczkowski, P ; Kiselinova, M ; Vervisch, K ; Trypsteen, W ; Johnson, M ; Verhofstede, C ; de Looze, D ; Murray, C ; Loes, SK-D ; Vandekerckhove, L ; Fletcher, JLK ; Pinyakorn, S ; de Souza, M ; Akapirat, S ; Trichavaroj, R ; Pankam, T ; Kroon, E ; Colby, D ; Prueksakaew, P ; Suttichom, D ; Kim, JH ; Phanuphak, P ; Phanuphak, N ; Ananworanich, J ; Vandendriessche, A ; Mourez, T ; Lemée, V ; Debab, Y ; Peytavin, G ; Ladner, J ; Caron, F ; Plantier, J-C ; Leporrier, J ; Colby, D ; Phanuphak, N ; Sirivichayakul, S ; Prueksakaew, P ; Saengtawan, P ; Trichavaroj, R ; Crowell, T ; Kim, J ; Ananworanich, J ; Phanuphak, P ; Argento, E ; Duff, P ; Bingham, B ; Nguyen, P ; Strathdee, S ; Shannon, K ; Namey, E ; Perry, B ; Headley, J ; Yao, KA ; Ouattara, M ; Shighata, C ; Ferguson, M ; Lane, T ; Sibanyoni, M ; Manyuchi, A ; Osmand, T ; Marr, A ; Grasso, M ; Isdahl, Z ; Mutanha, N ; Makhubela, P ; Silima, M ; Zuma, N ; Struthers, H ; McIntyre, J ; Rees, H ; Venter, F ; Lancaster, K ; Lungu, T ; Hosseinipour, M ; Chadwick, K ; Dibb, Z ; Go, VF ; Pence, BW ; Powers, KA ; Hoffman, IF ; Miller, WC ; Sedaghat, A ; Karamouzian, M ; Sharifi, H ; Mirzazadeh, A ; Shokoohi, M ; Haghdoost, A ; Schwartz, S ; Lambert, A ; Phaswana-Mafuya, N ; Holland, C ; Kose, Z ; Mcingana, M ; Sweitzer, S ; Baral, S ; Grimsrud, A ; Lesosky, M ; Kalombo, C ; Bekker, L-G ; Myer, L ; Caballero, P ; Da Silva, CM ; Da Cruz, M ; Plazy, M ; ElFarouki, K ; Iwuji, C ; Okesola, N ; Orne-Gliemann, J ; Larmarange, J ; Newell, M-L ; Pillay, D ; Dabis, F ; Dray-Spira, R ; Rebeiro, PF ; Cesar, C ; Shepherd, BE ; De Boni, RB ; Cortés, C ; Rodriguez, F ; Belaunzarán-Zamudio, P ; Pape, JW ; Padgett, D ; Hoces, D ; McGowan, CC ; Cahn, P ; Pilcher, C ; Hatano, H ; Dasgupta, A ; Jones, D ; Torres, S ; Calderon, F ; Ospina-Norvell, C ; Hartogensis, W ; Demicco, E ; Geng, E ; Gandhi, M ; Havlir, D ; Wagner, A ; Njuguna, I ; Mugo, C ; Inwani, I ; Maleche-Obimbo, E ; Sherr, K ; Wamalwa, D ; John-Stewart, G ; Slyker, J ; Bandason, T ; Mchugh, G ; Ferrand, R ; Munyati, S ; Kranzer, K ; Chonzi, P ; Elyanu, P ; Magongo, E ; Asire, B ; Lukabwe, I ; Bitimwine, H ; Katureebe, C ; Achii, P ; Mulema, V ; Dziuban, E ; Sugandhi, N ; Musiime, V ; Namuwenge, N ; Musinguzi, J ; Manno, EC ; Bamford, A ; Conejo, PR ; Marquez, L ; Mellado, MJ ; Muñoz-Fernández, MÁ ; Spoulou, V ; Klein, N ; Ananworanich, J ; Della Negra, M ; Ziegler, JB ; Meanson, E ; Lyall, H ; Shingadia, D ; Di Biagio, A ; Giacomet, V ; Vibeke, R ; de Sousa Marques, HH ; Salo, E ; Volokha, A ; Scherpbier, HJ ; Niehues, T ; Levy, J ; Marczynska, M ; Mardarescu, M ; Reliquet, V ; Giaquinto, C ; Bernardi, S ; Palma, P ; Ronen, K ; Mcgrath, C ; Langat, A ; Kinuthia, J ; Omolo, D ; Singa, B ; Katana, A ; Nganga, L ; John-Stewart, G ; Krebs, E ; Min, JE ; Barrios, R ; Montaner, J ; Nosyk, B ; Kelly, S ; Shattock, A ; Kerr, C ; Stuart, R ; Papoyan, A ; Grigoryan, T ; Hovhannisyan, R ; Grigoryan, S ; Wilson, D ; Rajkotia, Y ; Zang, O ; Nguimkeu, P ; Djurovic, I ; Estill, J ; Ford, N ; Salazar-Vizcaya, L ; Haas, A ; Blaser, N ; Egger, M ; Habiyambere, V ; Keiser, O ; Chuma, B ; Koseki, S ; Musau, S ; Johns, B ; Gatome-Munyua, A ; Honermann, B ; Millett, G ; Lindsey, K ; Wijayaratne, S ; Sherwood, J ; MacAllister, J ; Le, A ; Taylor, J ; Dong, W ; McCloskey, R ; Woods, C ; Hayashi, K ; Milloy, M-J ; Harrigan, PR ; Poon, AF ; Brumme, ZL ; Garrido-Rodriguez, D ; Avila-Rios, S ; Valenzuela-Ponce, H ; García-Tellez, T ; Quiroz-Morales, V ; García-Morales, C ; Soto-Nava, M ; Murakami-Ogasawara, A ; Fernandez-Lopez, JC ; Terán, GR ; Alcami, J ; Bermejo, M ; Descours, B ; Mateos, E ; Lederman, MM ; Benkirane, M ; Coiras, M ; Purcell, D ; Jacobson, J ; Harty, L ; Jarman, K ; Lackovic, K ; Khoury, G ; Mota, T ; Lee, M ; Bernardi, G ; Saleh, S ; Sonza, S ; Lewin, S ; Capoferri, A ; Sievers, M ; Redd, A ; Cash, A ; Xu, D ; Porcella, SF ; Quinn, T ; Siliciano, RF ; Levis, M ; Ambinder, RF ; Durand, CM ; Lee, S-K ; Zhou, S ; Archin, N ; Margolis, D ; Swanstrom, R ; Alcaide, M ; Chisembele, M ; Malupande, E ; Arheart, K ; Jones, D ; Fischl, M ; Vicol, LA ; Hornsberger, A ; Pick, N ; Van Schalkwyk, J ; Bloomenthal, D ; Christilaw, J ; Money, D ; Pyra, M ; Heffron, R ; Mugo, NR ; Nanda, K ; Thomas, KK ; Celum, C ; Kourtis, AP ; Baeten, JM ; Ajibola, G ; Shapiro, R ; Zash, R ; Holmes, L ; Batlang, O ; Ramogothobeng, K ; Chilisa, F ; Bennett, K ; Makhema, J ; Lockman, S ; Powis, K ; Lippman, SA ; Pettifor, AP ; Neilands, TB ; MacPhail, C ; Peacock, D ; Maman, S ; Twine, R ; Selin, A ; Kahn, K ; Derksen, L ; Muula, A ; van Oosterhout, J ; van Lettow, M ; Matengeni, A ; Sodhi, S ; Katz, D ; Golden, M ; Hughes, J ; Farquhar, C ; Stekler, J ; Lippman, SA ; Moran, ME ; Ventura, A ; Castillo, LS ; Buchbinder, S ; Treves-Kagan, S ; Sevelius, JM ; Mavedzenge, SN ; Sibanda, E ; Mavengere, Y ; Hatzold, K ; Mugurungi, O ; Ncube, G ; Cowan, F ; Muffih, PT ; Mboh, E ; Fang, E ; Wainfen, W ; Fon, H ; Welty, T ; Shields, R ; Golden, M ; Bachireddy, C ; Izenberg, J ; Soule, M ; Dvoryak, S ; Altice, F ; Nosyk, B ; Min, JE ; Evans, E ; Li, L ; Liu, L ; Lima, V ; Wood, E ; Montaner, J ; Beletsky, L ; Gonzalez-Zuniga, P ; Rangel, G ; Werb, D ; Arredondo, J ; Strathdee, SA ; Lambdin, BH ; Nyandindi, C ; Bruce, D ; Sabuni, N ; Magimba, A ; Matiko, E ; Milloy, M-J ; Kerr, T ; Hogg, R ; Guillemi, S ; Montaner, J ; Wood, E ; Merlini, E ; Iannuzzi, F ; Bai, F ; Trunfio, M ; Bonora, S ; Calcagno, A ; Cannizzo, ES ; Basilissi, M ; Bini, T ; Monforte, AD ; Marchetti, G ; O'Brien, M ; Manches, O ; Wilen, C ; Wu, V ; Sunseri, N ; Bhardwaj, N ; Bego, MG ; Côté, ÉA ; Aschman, N ; Mercier, J ; Weissenhorn, W ; Cohen, ÉA ; Turrini, F ; Kajaste-Rudnitski, A ; Marelli, SS ; Van Lint, C ; Das, AT ; Berkout, B ; Vicenzi, E ; Simpson, S ; deSilva, T ; Yindom, L-M ; Leligdowicz, A ; Vincent, T ; Rowland-Jones, S ; Webb, GM ; Chew, GM ; Fujita, T ; Burwitz, BJ ; Wu, HL ; Reed, JS ; Hammond, KB ; Hansen, SG ; Maurer, M ; Korman, AJ ; Ndhlovu, LC ; Sacha, JB ; Esser, S ; Geisel, MHM ; Arendt, M ; Schulze, C ; Holzendorf, V ; Warnke, A ; Brockmeyer, NH ; Hower, M ; Schadendorf, D ; Neumann, T ; Eisele, L ; Erbel, R ; Moebus, S ; Jöckel, K-H ; Reinsch, N ; Hamzah, L ; Tiraboschi, JM ; Toby, M ; Iveson, H ; Mant, C ; John, C ; Burling, K ; Kulasegaram, R ; Teague, A ; Post, FA ; Fox, J ; Grant, P ; Kitch, D ; McComsey, G ; Collier, A ; Koletar, S ; Erlandson, K ; Yin, M ; Bartali, B ; Ha, B ; Melbourne, K ; Brown, T ; Sudjaritruk, T ; Bunupuradah, T ; Aurpibul, L ; Kosalaraksa, ; Kurniati, N ; Puthanakit, T ; Spinner, CD ; Kern, KE ; Noe, S ; von Werder, A ; Schwerdtfeger, C ; Schmid, RM ; Zink, A ; Wolf, E ; Iakoubov, R ; Paraskevis, D ; Nikolopoulos, G ; Sypsa, V ; Psichogiou, M ; Malliori, M ; Friedman, SR ; Hatzakis, A ; Thompson, LH ; Wertheim, JO ; Reza, T ; Wylie, JL ; Emmanuel, F ; Brooks, J ; Blanchard, JF ; Sandstrom, P ; Tee, KK ; Kantor, R ; Sungkanuparph, S ; Takebe, Y ; Li, P ; Ditangco, R ; Phanuphak, P ; Sirisanthana, T ; Sim, B ; Ratanasuwan, W ; Kantipong, P ; Mustafa, M ; Merati, TP ; Jiamsakul, A ; Singtoroj, T ; Kamarulzaman, A ; Sulaberidze, L ; Mirzazadeh, A ; Chikovani, I ; Shengelia, N ; Tsereteli, N ; Gotsadze, G ; Mulawa, M ; Reyes, H ; Foshee, V ; Halpern, C ; Kajula, L ; Maman, S ; Treves-Kagan, S ; Ayadi, AE ; Pettifor, A ; MacPhail, C ; Twine, R ; Maman, S ; Kahn, K ; Lippman, SA ; Camlin, CS ; Ssemmondo, E ; Chamie, G ; Kwarisiima, D ; Sang, N ; Bukusi, EA ; Cohen, CR ; Kamya, MR ; Havlir, D ; Schley, A ; Skowronska, E ; Okonji, E ; Scheepers, E ; Feldacker, C ; Myers, S ; Cesar, F ; Parades, Z ; Ferrao, C ; Citao, SC ; Mudender, F ; Golden, M ; Mark, J ; Kinuthia, J ; Osoti, A ; Gone, M ; Asila, V ; Parikh, S ; Krakowiak, D ; Betz, B ; Richardson, B ; Roxby, A ; Farquhar, C ; Pina, C ; Dange, A ; Neytra, S ; Kambli, H ; Karambe, S ; Chhabra, R ; Patel, V ; Ndlovu, B ; Hermanus, T ; Tumba, N ; Moore, P ; Jaggernath, M ; Walker, BD ; Morris, L ; Ndung'u, T ; Leitman, EM ; Hurst, J ; Mori, M ; Matthews, PC ; Frahm, N ; Kublin, J ; Gray, GE ; Goulder, PJ ; Demarco, T ; Rountree, W ; Hora, B ; Chen, Y ; Keinonen, S ; Racz, L ; Daniell, L ; Louzao, R ; Sanchez, A ; Busch, M ; Denny, T ; Gao, F ; Johnson, A ; Jacob, R ; Haeryfar, M ; Dikeakos, J ; Mohammed, T ; Gaseitsiwe, S ; Matlhagela, K ; Matsheka, M ; Moyo, S ; Musonda, R ; Moukambi, F ; Rabezanahary, H ; Rodrigues, V ; Estaquier, J ; Ndjoyi-Mbiguino, A ; Nzengui, GFN ; Kamdem, HM ; Bélec, L ; Viana, R ; Xaba, T ; Stojiljkovic, T ; Gunther, N ; Wallis, C ; Grimsrud, A ; Cornell, M ; Schomaker, M ; Fox, MP ; Orrell, C ; Prozesky, H ; Stinson, K ; Tanser, F ; Egger, M ; Myer, L ; Nsumba, MS ; Barbara, C ; Musomba, RZ ; Kaimal, A ; Ivan, K ; Isaac, L ; Laurence, J ; Rosalind, P-R ; Andrew, K ; Khan, A ; Hans, L ; Gonzales, L ; Carmona, S ; Hsiao, N-Y ; Brophy, J ; Lee, T ; Sauve, L ; Bitnun, A ; Singer, J ; Kakkar, F ; Lapointe, N ; Alimenti, A ; Money, D ; Vaudry, W ; Samson, L ; Singer, J ; Bitnun, A ; Lee, T ; Samson, L ; Brophy, J ; Money, D ; Alimenti, A ; Vaudry, W ; Kakkar, F ; Lapointe, N ; Sauve, L ; du Lou, AD ; Pannetier, J ; Ravalihasy, A ; Gosselin, A ; Supervie, V ; Bajos, N ; Lert, F ; Lydie, N ; Dray-Spira, R ; Kerani, R ; Herbeck, J ; Buskin, S ; Dombrowski, J ; Bennett, A ; Barash, E ; Barbee, L ; Golden, M ; Chang, L ; Grabowski, MK ; Ssekubugu, R ; Nalugoda, F ; Reynolds, S ; Lessler, J ; Moore, S ; Quinn, T ; Gray, R ; Serwadda, D ; Wawer, M ; Ramachandran, A ; Manabe, Y ; Rajasingham, R ; Shah, M ; Schwarz, M ; Flick, R ; Harawa, M ; Simon, K ; Kim, M ; Robison, J ; Ahmed, S ; Schramm, B ; Tayea, A ; Wolters, L ; Nicholas, S ; Masiku, CW ; Zolowere, DB ; Mhango, E ; Kandulu, JR ; Etard, J-F ; Amaros, I ; Szumilin, E ; Gueguen, M ; Ndulue, N ; Etsetowaghan, A ; Gabriel, C ; Ibrahim, J ; Seclen-Palacin, J ; Natumanya, E ; Nabitaka, L ; Bitarakwate, E ; Ismail, S ; Moshgabadi, N ; Galli, R ; Daly, A ; Ko, SMS ; Zhang, M ; Westgard, T ; Bulpitt, A ; Shackleton, CR (Wiley, 2015)
  • Item
    Thumbnail Image
    Multiply spliced HIV RNA is a predictive measure of virus production ex vivo and in vivo following reversal of HIV latency
    Zerbato, JM ; Khoury, G ; Zhao, W ; Gartner, MJ ; Pascoe, RD ; Rhodes, A ; Dantanarayana, A ; Gooey, M ; Anderson, J ; Bacchetti, P ; Deeks, SG ; McMahon, J ; Roche, M ; Rasmussen, TA ; Purcell, DFJ ; Lewin, SR (ELSEVIER, 2021-03)
    BACKGROUND: One strategy being pursued to clear latently infected cells that persist in people living with HIV (PLWH) on antiretroviral therapy (ART) is to activate latent HIV infection with a latency reversing agent (LRA). Surrogate markers that accurately measure virus production following an LRA are needed. METHODS: We quantified cell-associated unspliced (US), multiply spliced (MS) and supernatant (SN) HIV RNA by qPCR from total and resting CD4+ T cells isolated from seven PLWH on ART before and after treatment ex vivo with different LRAs, including histone deacetylase inhibitors (HDACi). MS and plasma HIV RNA were also quantified from PLWH on ART (n-11) who received the HDACi panobinostat. FINDINGS: In total and resting CD4+ T cells from PLWH on ART, detection of US RNA was common while detection of MS RNA was infrequent. Primers used to detect MS RNA, in contrast to US RNA, bound sites of the viral genome that are commonly mutated or deleted in PLWH on ART. Following ex vivo stimulation with LRAs, we identified a strong correlation between the fold change increase in SN and MS RNA, but not the fold change increase in SN and US RNA. In PLWH on ART who received panobinostat, MS RNA was significantly higher in samples with detectable compared to non0detectable plasma HIV RNA. INTERPRETATION: Following administration of an LRA, quantification of MS RNA is more likely to reflect an increase in virion production and is therefore a better indicator of meaningful latency reversal. FUNDING: NHMRC, NIH DARE collaboratory.
  • Item
    Thumbnail Image
    A clinical trial of non-invasive imaging with an anti-HIV antibody labelled with copper-64 in people living with HIV and uninfected controls
    McMahon, JH ; Zerbato, JM ; Lau, JSY ; Lange, JL ; Roche, M ; Tumpach, C ; Dantanarayana, A ; Rhodes, A ; Chang, J ; Rasmussen, TA ; Mackenzie, CA ; Alt, K ; Hagenauer, M ; Roney, J ; O'Bryan, J ; Carey, A ; McIntyre, R ; Beech, P ; O'Keefe, GJ ; Wichmann, CW ; Scott, FE ; Guo, N ; Lee, S-T ; Liu, Z ; Caskey, M ; Nussenzweig, MC ; Donnelly, PS ; Egan, G ; Hagemeyer, CE ; Scott, AM ; Lewin, SR (ELSEVIER, 2021-03)
    BACKGROUND: A research priority in finding a cure for HIV is to establish methods to accurately locate and quantify where and how HIV persists in people living with HIV (PLWH) receiving suppressive antiretroviral therapy (ART). Infusing copper-64 (64Cu) radiolabelled broadly neutralising antibodies targeting HIV envelope (Env) with CT scan and positron emission tomography (PET) identified HIV Env in tissues in SIV infected non-human primates . We aimed to determine if a similar approach was effective in people living with HIV (PLWH). METHODS: Unmodified 3BNC117 was compared with 3BNC117 bound to the chelator MeCOSar and 64Cu (64Cu-3BNC117) in vitro to assess binding and neutralization. In a clinical trial 64Cu-3BNC117 was infused into HIV uninfected (Group 1), HIV infected and viremic (viral load, VL >1000 c/mL; Group 2) and HIV infected aviremic (VL <20 c/mL; Group 3) participants using two dosing strategies: high protein (3mg/kg unlabeled 3BNC117 combined with <5mg 64Cu-3BNC117) and trace (<5mg 64Cu-3BNC117 only). All participants were screened for 3BNC117 sensitivity from virus obtained from viral outgrowth. Magnetic resonance imaging (MRI)/PET and pharmacokinetic assessments (ELISA for serum 3BNC117 concentrations and gamma counting for 64Cu) were performed 1, 24- and 48-hours post dosing. The trial (clincialtrials.gov NCT03063788) primary endpoint was comparison of PET standard uptake values (SUVs) in regions of interest (e.g lymph node groups and gastrointestinal tract). FINDINGS: Comparison of unmodified and modified 3BNC117 in vitro demonstrated no difference in HIV binding or neutralisation. 17 individuals were enrolled of which 12 were dosed including Group 1 (n=4, 2 high protein, 2 trace dose), Group 2 (n=6, 2 high protein, 4 trace) and Group 3 (n=2, trace only). HIV+ participants had a mean CD4 of 574 cells/microL and mean age 43 years. There were no drug related adverse effects and no differences in tissue uptake in regions of interest (e.g lymph node gut, pharynx) between the 3 groups. In the high protein dosing group, serum concentrations of 3BNC117 and gamma counts were highly correlated demonstrating that 64Cu-3BNC117 remained intact in vivo. INTERPRETATION: In PLWH on or off ART, the intervention of infusing 64Cu-3BNC117 and MRI/PET imaging over 48 hours, was unable to detect HIV-1 env expression in vivo. Future studies should investigate alternative radiolabels such as zirconium which have a longer half-life in vivo. FUNDING: Funded by the Alfred Foundation, The Australian Centre for HIV and Hepatitis Virology Research with additional support from the Division of AIDS, National Institute of Allergy and Infectious Disease, US National Institutes of Health (USAI126611). JHM and SRL are supported by the Australian National Health and Medical Research Council.
  • Item
    Thumbnail Image
    Interrupting antiretroviral therapy in HIV cure trials during COVID-19: Adaptation to low transmission settings
    Lau, JSY ; Rasmussen, TA ; Lewin, SR ; Ehm, A ; Martinez, C ; Burnett, C ; McMahon, JH (MEDISCRIPT LTD, 2021-03)