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1. Demographics of sources of HIV-1 transmission in Zambia: a molecular epidemiology analysis in the HPTN 071 PopART study

Author

Agyei, Yaw, Beyers, Nulda, Bock, Peter, Bond, Virginia, Bwalya, Justin, Cori, Anne, Deventer, Anneen, Dunbar, Rory, El-Sadr, Wafaa, Emel, Lynda, Floyd, Sian, Griffith, Sam, Hargreaves, James, Hauck, Katharina, Headen, Tanette, Hoddinott, Graeme, James, Anelet, Jennings, Karen, Kanema, Sarah, Kosloff, Barry, Kruger, James, Kumar, Ramya, Macleod, David, Makola, Nozizwe, Mandla, Nomtha, Miller, Eric, Moore, Ayana, Mwenge, Lawrence, Noble, Heather, Phiri, Mwelwa, Pickles, Michael, Sabapathy, Kalpana, Sakala, Ephraim, Sauter, Rafael, Shanaube, Kwame, Silumesi, Andrew, Sista, Nirupama, Skalland, Tim, Smith, Peter, Thomas, Ranjeeta, Vermund, Sten, White, Rhonda, Wilson, Ethan, Yang, Blia, Yuhas, Krista, Bowden, Rory, Calvez, Vincent, Essex, Max, Grabowski, Kate, Gupta, Ravindra, Herbeck, Joshua, Kagaayi, Joseph, Kaleebu, Pontiano, Lingappa, Jairam, Moyo, Sikhulile, Novitsky, Vladimir, Ndung’u, Thumbi, Pillay, Deenan, Quinn, Thomas, Rambaut, Andrew, Seeley, Janet, Ssemwanga, Deogratius, Tanser, Frank, Wawer, Maria, Hall, Matthew, Golubchik, Tanya, Bonsall, David, Abeler-Dörner, Lucie, Limbada, Mohammed, Schaap, Ab, de Cesare, Mariateresa, MacIntyre-Cockett, George, Otecko, Newton, Probert, William, Ratmann, Oliver, Bulas Cruz, Ana, Piwowar-Manning, Estelle, Burns, David N, Cohen, Myron S, Donnell, Deborah J, Eshleman, Susan H, Simwinga, Musonda, Fidler, Sarah, Hayes, Richard, Ayles, Helen, and Fraser, Christophe

Published
2024
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2. CD101 genetic variants modify regulatory and conventional T cell phenotypes and functions

Author

Richert-Spuhler, Laura E, Mar, Corinne M, Shinde, Paurvi, Wu, Feinan, Hong, Ting, Greene, Evan, Hou, Sharon, Thomas, Katherine, Gottardo, Raphael, Mugo, Nelly, de Bruyn, Guy, Celum, Connie, Baeten, Jared M, Lingappa, Jairam R, Lund, Jennifer M, Wald, Anna, Campbell, Mary S, Corey, Lawrence, Coombs, Robert W, Hughes, James P, Magaret, Amalia, McElrath, M Juliana, Morrow, Rhoda, Mullins, James I, Coetzee, David, Fife, Kenneth, Were, Edwin, Essex, Max, Makhema, Joseph, Katabira, Elly, Ronald, Allan, Bukusi, Elizabeth, Cohen, Craig, Kapiga, Saidi, Manongi, Rachel, Farquhar, Carey, John-Stewart, Grace, Kiarie, James, Delany-Moretlwe, Sinead, Rees, Helen, Gray, Glenda, McIntyre, James, Mugo, Nelly Rwamba, Donnell, Deborah, Frenkel, Lisa, Hendrix, Craig W, Tumwesigye, Elioda, Ndase, Patrick, Bukusi, Eliabeth, Wangisi, Jonathan, Campbell, James, and Tappero, Jordan

Subjects
Clinical Research, HIV/AIDS, Prevention, Genetics, Infectious Diseases, Aetiology, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Underpinning research, Inflammatory and immune system, Adult, Antigens, CD, B-Lymphocytes, Cell Lineage, Dendritic Cells, Female, Gene Expression Profiling, Gene Expression Regulation, Genetic Predisposition to Disease, HIV Infections, HIV-1, Humans, Immunity, Innate, Immunophenotyping, Male, Monocytes, Mutation, Phenotype, Receptors, CCR5, Receptors, CXCR4, T-Lymphocytes, Regulatory, Partners in Prevention HSV/HIV Transmission Study, and the Partners PrEP Study Teams, CD101, HIV acquisition, T cell, host genetic variation, immune quiescence, inflammation, inflammatory homeostasis
Abstract

We recently reported that the risk of sexually acquired HIV-1 infection is increased significantly by variants in the gene encoding CD101, a protein thought to modify inflammatory responses. Using blood samples from individuals with and without these variants, we demonstrate that CD101 variants modify the prevalence of circulating inflammatory cell types and show that CD101 variants are associated with increased proinflammatory cytokine production by circulating T cells. One category of CD101 variants is associated with a reduced capacity of regulatory T cells to suppress T cell cytokine production, resulting in a reduction in the baseline level of immune quiescence. These data are supported by transcriptomics data revealing alterations in the intrinsic regulation of antiviral pathways and HIV resistance genes in individuals with CD101 variants. Our data support the hypothesis that CD101 contributes to homeostatic regulation of bystander inflammation, with CD101 variants altering heterosexual HIV-1 acquisition by facilitating increased prevalence and altered function of T cell subsets.

Published
2021

3. High incidence of tuberculosis in the first year of antiretroviral therapy in the Botswana National antiretroviral therapy programme between 2011 and 2015.

Author

Mupfumi, Lucy, Moyo, Sikhulile, Shin, Sanghyuk S, Wang, Qiao, Zetola, Nicola, Molebatsi, Kesaobaka, Nnawa, Judith, Kgwaadira, Botshelo T, Bewlay, Lesedi, Chebani, Tony, Iketleng, Thato, Mogashoa, Tuelo, Makhema, Joseph, Musonda, Rosemary M, Essex, Max, Kasvosve, Ishmael, and Gaseitsiwe, Simani

Subjects
Tuberculosis, Clinical Research, Prevention, Infectious Diseases, Rare Diseases, HIV/AIDS, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Infection, Good Health and Well Being, Adult, Antiretroviral Therapy, Highly Active, Botswana, CD4 Lymphocyte Count, Female, HIV Infections, Humans, Incidence, Male, Middle Aged, Multivariate Analysis, Proportional Hazards Models, Retrospective Studies, Risk Factors, Time Factors, Viral Load, HIV-1 viral load, incidence, isoniazid preventive therapy, tuberculosis preventive therapy, tuberculosis, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Virology
Abstract

OBJECTIVE:Tuberculosis (TB) remains one of the leading causes of mortality and morbidity among people living with HIV. We sought to estimate the incidence of TB in a national database of HIV-infected patients receiving antiretroviral therapy (ART) in Botswana. DESIGN:A retrospective analysis of HIV-infected adult patients (≥18years) who initiated ART between 2011 and 2015 in the Botswana ART program. METHODS:Multivariable analysis using Cox regression included sex, age, viral load and CD4 counts. RESULTS:Of 45,729 patients, with a median follow-up of 1·7 years Q1, Q3: 0·5,3·1), 1,791 patients developed TB over a median of 1·5 years (Q1, Q3: 0·3,3·1) of follow-up (IR 1·9 per 100 py; 95% CI 1·8-2·0). At baseline, the median CD4+ T-cell count was 272 cells/μl (Q1:Q3 146, 403). The risk of TB was greatest within the first year of ART (IR 2·9 per 100 py; 95% CI 2·7-3·1) and in patients with CD4 counts below 50 cells/μl (IR 8·3/100 py; 95% CI 7·1-9·7). Patients with viral loads above 10,000 copies/ml at 3 months post ART initiation had two-times higher risk of TB, HR 2.5 (95% CI 1·8-2·3). CONCLUSIONS:We report a high incidence of TB within the first year of ART and in patients with advanced immunodeficiency. Improved screening strategies and virologic monitoring during this early period on ART, coupled with TB preventative treatment, will reduce the burden of TB.

Published
2019

4. Doravirine-associated resistance mutations in antiretroviral therapy naïve and experienced adults with HIV-1 subtype C infection in Botswana

Author

Bareng, Ontlametse T., Seselamarumo, Sekgabo, Seatla, Kaelo K., Choga, Wonderful T., Bakae, Blessing, Maruapula, Dorcas, Kelentse, Nametso, Moraka, Natasha O., Mokaleng, Baitshepi, Mokgethi, Patrick T., Ditlhako, Tsotlhe R., Pretorius-Holme, Molly, Mbulawa, Mpaphi B., Lebelonyane, Refeletswe, Bile, Ebi Celestin, Gaolathe, Tendani, Shapiro, Roger, Makhema, Joseph M., Lockman, Shahin, Essex, Max, Novitsky, Vlad, Mpoloka, Sununguko W., Moyo, Sikhulile, and Gaseitsiwe, Simani

Published
2022
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6. CD101 genetic variants modify regulatory and conventional T cell phenotypes and functions

Author

Celum, Connie, Wald, Anna, Lingappa, Jairam R., Baeten, Jared M., Campbell, Mary S., Corey, Lawrence, Coombs, Robert W., Hughes, James P., Magaret, Amalia, McElrath, M. Juliana, Morrow, Rhoda, Mullins, James I., Coetzee, David, Fife, Kenneth, Were, Edwin, Essex, Max, Makhema, Joseph, Katabira, Elly, Ronald, Allan, Bukusi, Elizabeth, Cohen, Craig, Kapiga, Saidi, Manongi, Rachel, Farquhar, Carey, John-Stewart, Grace, Kiarie, James, Delany-Moretlwe, Sinead, Rees, Helen, de Bruyn, Guy, Gray, Glenda, McIntyre, James, Mugo, Nelly Rwamba, Donnell, Deborah, Frenkel, Lisa, Hendrix, Craig W., Tumwesigye, Elioda, Ndase, Patrick, Bukusi, Eliabeth, Wangisi, Jonathan, Campbell, James, Tappero, Jordan, Richert-Spuhler, Laura E., Mar, Corinne M., Shinde, Paurvi, Wu, Feinan, Hong, Ting, Greene, Evan, Hou, Sharon, Thomas, Katherine, Gottardo, Raphael, Mugo, Nelly, and Lund, Jennifer M.

Published
2021
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7. Global and regional epidemiology of HIV-1 recombinants in 1990–2015: a systematic review and global survey

Author

Abimiku, Alash'le G, Agwale, Simon, Archibald, Chris, Avidor, Boaz, Barbás, María Gabriela, Barre-Sinoussi, Francoise, Barugahare, Banson, Belabbes, El Hadj, Bertagnolio, Silvia, Birx, Deborah, Bobkov, Aleksei F, Brandful, James, Bredell, Helba, Brennan, Catherine A, Brooks, James, Bruckova, Marie, Buonaguro, Luigi, Buonaguro, Franco, Buttò, Stefano, Buvé, Anne, Campbell, Mary, Carr, Jean, Carrera, Alex, Carrillo, Manuel Gómez, Celum, Connie, Chaplin, Beth, Charles, Macarthur, Chatzidimitriou, Dimitrios, Chen, Zhiwei, Chijiwa, Katsumi, Cooper, David, Cunningham, Philip, Dagnra, Anoumou, de Gascun, Cillian F, Del Amo, Julia, Delgado, Elena, Dietrich, Ursula, Dwyer, Dominic, Ellenberger, Dennis, Ensoli, Barbara, Essex, Max, Gao, Feng, Fleury, Hervé, Fonjungo, Peter N, Foulongne, Vincent, Gadkari, Deepak A, García, Federico, Garsia, Roger, Gershy-Damet, Guy Michel, Glynn, Judith R, Goodall, Ruth, Grossman, Zehava, Lindenmeyer-Guimarães, Monick, Hahn, Beatrice, Hamers, Raph L, Hamouda, Osamah, Handema, Ray, He, Xiang, Herbeck, Joshua, Ho, David D, Holguin, Africa, Hosseinipour, Mina, Hunt, Gillian, Ito, Masahiko, Bel Hadj Kacem, Mohamed Ali, Kahle, Erin, Kaleebu, Pontiano, Kalish, Marcia, Kamarulzaman, Adeeba, Kang, Chun, Kanki, Phyllis, Karamov, Edward, Karasi, Jean-Claude, Kayitenkore, Kayitesi, Kelleher, Tony, Kitayaporn, Dwip, Kostrikis, Leondios G, Kucherer, Claudia, Lara, Claudia, Leitner, Thomas, Liitsola, Kirsi, Lingappa, Jai, Linka, Marek, Lorenzana de Rivera, Ivette, Lukashov, Vladimir, Maayan, Shlomo, Mayr, Luzia, McCutchan, Francine, Meda, Nicolas, Menu, Elisabeth, Mhalu, Fred, Mloka, Doreen, Mokili, John L, Montes, Brigitte, Mor, Orna, Morgado, Mariza, Mosha, Fausta, Moussi, Awatef, Mullins, James, Najera, Rafael, Nasr, Mejda, Ndembi, Nicaise, Neilson, Joel R, Nerurkar, Vivek R, Neuhann, Florian, Nolte, Claudine, Novitsky, Vlad, Nyambi, Philippe, Ofner, Marianna, Paladin, Fem J, Papa, Anna, Pape, Jean, Parkin, Neil, Parry, Chris, Peeters, Martine, Pelletier, Alexandra, Pérez-Álvarez, Lucía, Pillay, Deenan, Pinto, Angie, Quang, Trinh Duy, Rademeyer, Cecilia, Raikanikoda, Filimone, Rayfield, Mark A, Reynes, Jean-Marc, Rinke de Wit, Tobias, Robbins, Kenneth E, Rolland, Morgane, Rousseau, Christine, Salazar-Gonzales, Jesus, Salem, Hanan, Salminen, Mika, Salomon, Horacio, Sandstrom, Paul, Santiago, Mario L, Sarr, Abdoulaye D, Schroeder, Bryan, Segondy, Michel, Selhorst, Philippe, Sempala, Sylvester, Servais, Jean, Shaik, Ansari, Shao, Yiming, Slim, Amine, Soares, Marcelo A, Songok, Elijah, Stewart, Debbie, Stokes, Julie, Subbarao, Shambavi, Sutthent, Ruengpung, Takehisa, Jun, Tanuri, Amilcar, Tee, Kok Keng, Thapa, Kiran, Thomson, Michael, Tran, Tyna, Urassa, Willy, Ushijima, Hiroshi, van de Perre, Philippe, van der Groen, Guido, van Laethem, Kristel, van Oosterhout, Joep, van Sighem, Ard, van Wijngaerden, Eric, Vandamme, Anne-Mieke, Vercauteren, Jurgen, Vidal, Nicole, Wallace, Lesley, Williamson, Carolyn, Wolday, Dawit, Xu, Jianqing, Yang, Chunfu, Zhang, Linqi, Zhang, Rong, Hemelaar, Joris, Elangovan, Ramyiadarsini, Yun, Jason, Dickson-Tetteh, Leslie, Kirtley, Shona, Gouws-Williams, Eleanor, and Ghys, Peter D

Published
2020
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8. Quantifying HIV transmission flow between high-prevalence hotspots and surrounding communities: a population-based study in Rakai, Uganda

Author

Ayles, Helen, Bowden, Rory, Calvez, Vincent, Cohen, Myron, Dennis, Anne, Essex, Max, Fidler, Sarah, Frampton, Dan, Hayes, Richard, Herbeck, Josh, Kaleebu, Pontiano, Kityo, Cissy, Lingappa, Jairam, Novitsky, Vladimir, Paton, Nick, Rambaut, Andrew, Seeley, Janet, Ssemwanga, Deogratius, Tanser, Frank, Lutalo, Tom, Galiwango, Ronald, Makumbi, Fred, Sewankambo, Nelson K., Nabukalu, Dorean, Ndyanabo, Anthony, Ssekasanvu, Joseph, Nakawooya, Hadijja, Nakukumba, Jessica, Kigozi, Grace N., Nantume, Betty S., Resty, Nampijja, Kambasu, Jedidah, Nalugemwa, Margaret, Nakabuye, Regina, Ssebanobe, Lawrence, Nankinga, Justine, Kayiira, Adrian, Nanfuka, Gorreth, Ahimbisibwe, Ruth, Tomusange, Stephen, Galiwango, Ronald M., Nakalanzi, Margaret, Otobi, Joseph O., Ankunda, Denis, Ssembatya, Joseph L., Ssemanda, John B., Kato, Emmanuel, Kairania, Robert, Kisakye, Alice, Batte, James, Ludigo, James, Nampijja, Abisagi, Watya, Steven, Nehemia, Kighoma, Anyokot, Sr. Margaret, Mwinike, Joshua, Kibumba, George, Ssebowa, Paschal, Mondo, George, Wasswa, Francis, Nantongo, Agnes, Kakembo, Rebecca, Galiwango, Josephine, Ssemango, Geoffrey, Redd, Andrew D., Santelli, John, Kennedy, Caitlin E., Wagman, Jennifer, Tobian, Aaron, Ratmann, Oliver, Kagaayi, Joseph, Hall, Matthew, Golubchick, Tanya, Kigozi, Godfrey, Xi, Xiaoyue, Wymant, Chris, Nakigozi, Gertrude, Abeler-Dörner, Lucie, Bonsall, David, Gall, Astrid, Hoppe, Anne, Kellam, Paul, Bazaale, Jeremiah, Kalibbala, Sarah, Laeyendecker, Oliver, Lessler, Justin, Nalugoda, Fred, Chang, Larry W, de Oliveira, Tulio, Pillay, Deenan, Quinn, Thomas C, Reynolds, Steven J, Spencer, Simon E F, Ssekubugu, Robert, Serwadda, David, Wawer, Maria J, Gray, Ronald H, Fraser, Christophe, and Grabowski, M Kate

Published
2020
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9. Health Impact and Cost-Effectiveness of HIV Testing, Linkage, and Early Antiretroviral Treatment in the Botswana Combination Prevention Project

Author

Resch, Stephen C., Foote, Julia H. A., Wirth, Kathleen E., Lasry, Arielle, Scott, Justine A., Moore, Janet, Shebl, Fatma M., Gaolathe, Tendani, Feser, Mary K., Lebelonyane, Refeletswe, Hyle, Emily P., Mmalane, Mompati O., Bachanas, Pamela, Yu, Liyang, Makhema, Joseph M., Holme, Molly Pretorius, Essex, Max, Alwano, Mary Grace, Lockman, Shahin, and Freedberg, Kenneth A.

Published
2022
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10. Antiretroviral Therapy for the Prevention of HIV-1 Transmission

Author

Cohen, Myron S, Chen, Ying Q, McCauley, Marybeth, Gamble, Theresa, Hosseinipour, Mina C, Kumarasamy, Nagalingeswaran, Hakim, James G, Kumwenda, Johnstone, Grinsztejn, Beatriz, Pilotto, Jose HS, Godbole, Sheela V, Chariyalertsak, Suwat, Santos, Breno R, Mayer, Kenneth H, Hoffman, Irving F, Eshleman, Susan H, Piwowar-Manning, Estelle, Cottle, Leslie, Zhang, Xinyi C, Makhema, Joseph, Mills, Lisa A, Panchia, Ravindre, Faesen, Sharlaa, Eron, Joseph, Gallant, Joel, Havlir, Diane, Swindells, Susan, Elharrar, Vanessa, Burns, David, Taha, Taha E, Nielsen-Saines, Karin, Celentano, David D, Essex, Max, Hudelson, Sarah E, Redd, Andrew D, and Fleming, Thomas R

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Health Sciences, Immunology, Medical Microbiology, Prevention, Clinical Research, Infectious Diseases, Clinical Trials and Supportive Activities, HIV/AIDS, Infection, Good Health and Well Being, Adult, Anti-Retroviral Agents, Disease Transmission, Infectious, Female, Follow-Up Studies, HIV Infections, HIV Seropositivity, HIV-1, Humans, Intention to Treat Analysis, Kaplan-Meier Estimate, Male, Middle Aged, Risk, Sexual Partners, Young Adult, HPTN 052 Study Team, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundAn interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission.MethodsWe randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1-negative partner in an intention-to-treat analysis.ResultsIndex participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant.ConclusionsThe early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners. (Funded by the National Institute of Allergy and Infectious Diseases; HPTN 052 ClinicalTrials.gov number, NCT00074581 .).

Published
2016

11. Transient Increase in Herpes Simplex Virus Type 2 (HSV-2)–Associated Genital Ulcers Following Initiation of Antiretroviral Therapy in HIV/HSV-2–Coinfected Individuals

Author

Fife, Kenneth H, Mugwanya, Kenneth, Thomas, Katherine K, Baeten, Jared M, Celum, Connie, Bukusi, Elizabeth, de Bruyn, Guy, Mujugira, Andrew, Vwalika, Bellington, Wald, Anna, Lingappa, Jairam R, Lingappa, Jairam, Campbell, Mary, Corey, Lawrence, Coombs, Robert W, Hughes, James P, Magaret, Amalia, McElrath, M Juliana, Morrow, Rhoda, Mullins, James I, Coetzee, David, Fife, Kenneth, Were, Edwin, Essex, Max, Makhema, Joseph, Katabira, Elly, Ronald, Allan, Allen, Susan, Kayitenkore, Kayitesi, Karita, Etienne, Cohen, Craig, Kanweka, William, Kapiga, Saidi, Manongi, Rachel, Farquhar, Carey, John-Stewart, Grace, Kiarie, James, Inambao, Mubiana, Delany-Moretlwe, Sinead, Rees, Helen, Gray, Glenda, McIntyre, James, and Mugo, Nelly Rwamba

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Clinical Research, HIV/AIDS, Sexually Transmitted Infections, Infectious Diseases, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Infection, Acyclovir, Adult, Antiretroviral Therapy, Highly Active, Coinfection, Female, HIV Infections, Herpes Genitalis, Herpesvirus 2, Human, Humans, Immune Reconstitution Inflammatory Syndrome, Incidence, Male, Middle Aged, Ulcer, Partners in Prevention HSV/HIV Transmission Study Team, acyclovir, antiretroviral therapy, herpes simplex virus, human immunodeficiency virus, Biological Sciences, Medical and Health Sciences, Microbiology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundImmune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)-infected persons beginning antiretroviral therapy (ART) has been incompletely characterized for herpes simplex virus type 2 (HSV-2).MethodsWe evaluated genital ulcer disease (GUD) and HSV-2-associated GUD at quarterly visits or when spontaneously reported at monthly visits in 3381 HIV/HSV-2-coinfected individuals in a placebo-controlled trial of suppressive acyclovir therapy to prevent HIV transmission, 349 of whom initiated ART during the study. Incidence was calculated for months before and after ART initiation, and incidence rate ratios (IRRs) were calculated.ResultsGUD incidence increased from 15.0 episodes per 100 person-years before ART to 26.9 episodes per 100 person-years in the first full quarter after ART initiation (IRR, 1.83;P= .03), and the incidence of HSV-2-associated GUD increased from 8.1 to 19.0 episodes per 100 person-years (IRR, 2.20;P= .02). Subsequently, the incidence of GUD was similar to that before ART, although the numbers were small. Persons receiving suppressive acyclovir had fewer GUD episodes, but the IRR after beginning ART was similar in the acyclovir and placebo groups.ConclusionsInitiation of ART in HIV/HSV-2-coinfected persons is associated with a transient increase in GUD and HSV-2 GUD. Acyclovir reduces the incidence of GUD but does not prevent an increase in GUD incidence during the first quarter following initiation of ART.

Published
2016

12. Effect of Condom Use on Per-act HSV-2 Transmission Risk in HIV-1, HSV-2-discordant Couples

Author

Magaret, Amalia S, Mujugira, Andrew, Hughes, James P, Lingappa, Jairam, Bukusi, Elizabeth A, DeBruyn, Guy, Delany-Moretlwe, Sinead, Fife, Kenneth H, Gray, Glenda E, Kapiga, Saidi, Karita, Etienne, Mugo, Nelly R, Rees, Helen, Ronald, Allan, Vwalika, Bellington, Were, Edwin, Celum, Connie, Wald, Anna, Baeten, Jared M, Campbell, Mary, Corey, Lawrence, Coombs, Robert W, Magaret, Amalia, McElrath, M Juliana, Morrow, Rhoda, Mullins, James I, Coetzee, David, Fife, Kenneth, Essex, Max, Makhema, Joseph, Katabira, Elly, Allen, Susan, Kayitenkore, Kayitesi, Bukusi, Elizabeth, Cohen, Craig, Kanweka, William, Manongi, Rachel, Farquhar, Carey, John-Stewart, Grace, Kiarie, James, Inambao, Mubiana, de Bruyn, Guy, Gray, Glenda, McIntyre, James, and Mugo, Nelly Rwamba

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, HIV/AIDS, Sexually Transmitted Infections, Infectious Diseases, Prevention, Aetiology, 2.2 Factors relating to the physical environment, Infection, Reproductive health and childbirth, Good Health and Well Being, Condoms, Disease Transmission, Infectious, Family Characteristics, Female, HIV Infections, Herpes Genitalis, Herpesvirus 2, Human, Humans, Infection Control, Male, Risk Assessment, Partners in Prevention HSV/HIV Transmission Study Team, HIV, HSV-2, condom, efficacy, transmission, Biological Sciences, Medical and Health Sciences, Microbiology, Clinical sciences
Abstract

BackgroundThe efficacy of condoms for protection against transmission of herpes simplex virus type 2 (HSV-2) has been examined in a variety of populations with different effect measures. Often the efficacy has been assessed as change in hazard of transmission with consistent vs inconsistent use, independent of the number of acts. Condom efficacy has not previously measured on a per-act basis.MethodsWe examined the per-act HSV-2 transmission rates with and without condom use among 911 African HSV-2 and human immunodeficiency virus type 1 (HIV-1) serodiscordant couples followed for an average of 18 months in an HIV prevention study. Infectivity models were used to associate the log10 probability of HSV-2 transmission over monthly risk periods with reported numbers of protected and unprotected sex acts. Condom efficacy was computed as the proportionate reduction in transmission risk for protected relative to unprotected sex acts.ResultsTransmission of HSV-2 occurred in 68 couples, including 17 with susceptible women and 51 with susceptible men. The highest rate of transmission was from men to women: 28.5 transmissions per 1000 unprotected sex acts. We found that condoms were differentially protective against HSV-2 transmission by sex; condom use reduced per-act risk of transmission from men to women by 96% (P < .001) and marginally from women to men by 65% (P = .060).ConclusionsCondoms are recommended as an effective preventive method for heterosexual transmission of HSV-2.

Published
2016

13. Demographics of sources of HIV-1 transmission in Zambia: a molecular epidemiology analysis in the HPTN 071 PopART study

Author

Hall, Matthew, primary, Golubchik, Tanya, additional, Bonsall, David, additional, Abeler-Dörner, Lucie, additional, Limbada, Mohammed, additional, Kosloff, Barry, additional, Schaap, Ab, additional, de Cesare, Mariateresa, additional, MacIntyre-Cockett, George, additional, Otecko, Newton, additional, Probert, William, additional, Ratmann, Oliver, additional, Bulas Cruz, Ana, additional, Piwowar-Manning, Estelle, additional, Burns, David N, additional, Cohen, Myron S, additional, Donnell, Deborah J, additional, Eshleman, Susan H, additional, Simwinga, Musonda, additional, Fidler, Sarah, additional, Hayes, Richard, additional, Ayles, Helen, additional, Fraser, Christophe, additional, Agyei, Yaw, additional, Beyers, Nulda, additional, Bock, Peter, additional, Bond, Virginia, additional, Bwalya, Justin, additional, Cori, Anne, additional, Deventer, Anneen, additional, Dunbar, Rory, additional, El-Sadr, Wafaa, additional, Emel, Lynda, additional, Floyd, Sian, additional, Griffith, Sam, additional, Hargreaves, James, additional, Hauck, Katharina, additional, Headen, Tanette, additional, Hoddinott, Graeme, additional, James, Anelet, additional, Jennings, Karen, additional, Kanema, Sarah, additional, Kruger, James, additional, Kumar, Ramya, additional, Macleod, David, additional, Makola, Nozizwe, additional, Mandla, Nomtha, additional, Miller, Eric, additional, Moore, Ayana, additional, Mwenge, Lawrence, additional, Noble, Heather, additional, Phiri, Mwelwa, additional, Pickles, Michael, additional, Sabapathy, Kalpana, additional, Sakala, Ephraim, additional, Sauter, Rafael, additional, Shanaube, Kwame, additional, Silumesi, Andrew, additional, Sista, Nirupama, additional, Skalland, Tim, additional, Smith, Peter, additional, Thomas, Ranjeeta, additional, Vermund, Sten, additional, White, Rhonda, additional, Wilson, Ethan, additional, Yang, Blia, additional, Yuhas, Krista, additional, Bowden, Rory, additional, Calvez, Vincent, additional, Essex, Max, additional, Grabowski, Kate, additional, Gupta, Ravindra, additional, Herbeck, Joshua, additional, Kagaayi, Joseph, additional, Kaleebu, Pontiano, additional, Lingappa, Jairam, additional, Moyo, Sikhulile, additional, Novitsky, Vladimir, additional, Ndung’u, Thumbi, additional, Pillay, Deenan, additional, Quinn, Thomas, additional, Rambaut, Andrew, additional, Seeley, Janet, additional, Ssemwanga, Deogratius, additional, Tanser, Frank, additional, and Wawer, Maria, additional

Published
2023
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14. Toll-like receptor gene variants and bacterial vaginosis among HIV-1 infected and uninfected African women.

Author

Mackelprang, Romel D, Scoville, Caitlin Wright, Cohen, Craig R, Ondondo, Raphael Omusebe, Bigham, Abigail W, Celum, Connie, Campbell, Mary S, Essex, Max, Wald, Anna, Kiarie, James, Ronald, Allan, Gray, Glenda, Lingappa, Jairam R, and Partners in Prevention HSV/HIV Transmission Study Team

Subjects
Partners in Prevention HSV/HIV Transmission Study Team, Humans, Vaginosis, Bacterial, AIDS-Related Opportunistic Infections, Case-Control Studies, Polymorphism, Single Nucleotide, Adult, Africa, Female, Toll-Like Receptors, Vaginosis, Bacterial, Polymorphism, Single Nucleotide, Immunology
Abstract

Bacterial vaginosis (BV) is a common vaginal syndrome associated with altered microflora that increases the risk of preterm delivery and acquisition of sexually transmitted diseases. The cause of BV is unknown although toll-like receptors (TLRs), that are central to innate immune responses, may be important. We evaluated associations between TLR SNPs and BV among HIV-1 infected and uninfected African women. Logistic regression was used to assess associations between SNPs (N=99) in TLRs 2-4, 7-9 and BV (as classified by Nugent's criteria). Among HIV-1 uninfected women, TLR7 rs5743737 and TLR7 rs1634323 were associated with a decreased risk of BV, whereas TLR7 rs179012 was associated with an increased risk. TLR2 SNP rs3804099 was associated with a decreased risk of BV among HIV-1 infected women. Our findings indicate that there may be differences in TLR association with BV among HIV-1 infected and HIV-1 uninfected women.

Published
2015

15. Plasma Cytokine Levels and Risk of HIV Type 1 (HIV-1) Transmission and Acquisition: A Nested Case-Control Study Among HIV-1–Serodiscordant Couples

Author

Kahle, Erin M, Team, for the Partners in Prevention HSV HIV Transmission Study, Bolton, Michael, Hughes, James P, Donnell, Deborah, Celum, Connie, Lingappa, Jairam R, Ronald, Allan, Cohen, Craig R, de Bruyn, Guy, Fong, Youyi, Katabira, Elly, McElrath, M Juliana, Baeten, Jared M, Wald, Anna, Lingappa, Jairam, Magaret, Amalia, Corey, Lawrence, Coetzee, David, Fife, Kenneth, Were, Edwin, Essex, Max, Makhema, Joseph, Bukusi, Elizabeth, Cohen, Craig, Allen, Susan, Kanweka, William, Kapiga, Saidi, Manongi, Rachel, Farquhar, Carey, John-Stewart, Grace, Kiarie, James, Inambao, Mubiana, Farm, Orange, Delany-Moretlwe, Sinead, Rees, Helen, Gray, Glenda, McIntyre, James, and Mugo, Nelly Rwamba

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Sexually Transmitted Infections, Infectious Diseases, HIV/AIDS, Infection, Good Health and Well Being, Adult, Africa South of the Sahara, Case-Control Studies, Cytokines, Female, HIV Infections, HIV-1, Humans, Male, Risk Factors, Sexual Partners, Young Adult, HIV-1 acquisition, immune activation, Africa, Partners in Prevention HSV/HIV Transmission Study Team, Biological Sciences, Medical and Health Sciences, Microbiology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundA heightened proinflammatory state has been hypothesized to enhance human immunodeficiency virus type 1 (HIV-1) transmission - both susceptibility of HIV-1-exposed persons and infectiousness of HIV-1-infected persons.MethodsUsing prospective data from heterosexual African couples with HIV-1 serodiscordance, we conducted a nested case-control analysis to assess the relationship between cytokine concentrations and the risk of HIV-1 acquisition. Case couples (n = 120) were initially serodiscordant couples in which HIV-1 was transmitted to the seronegative partner during the study; control couples (n = 321) were serodiscordant couples in which HIV-1 was not transmitted to the seronegative partner. Differences in a panel of 30 cytokines were measured using plasma specimens from both HIV-1-susceptible and HIV-1-infected partners. Plasma was collected before seroconversion for cases.ResultsFor both HIV-1-infected and HIV-1-susceptible partners, cases and controls had significantly different mean responses in cytokine panels (P < .001, by the Hotelling T(2) test), suggesting a broadly different pattern of immune activation for couples in which HIV-1 was transmitted, compared with couples without transmission. Individually, log10 mean concentrations of interleukin 10 (IL-10) and CXCL10 were significantly higher for both HIV-1-susceptible and HIV-1-infected case partners, compared with HIV-1-susceptible and HIV-1-infected control partners (P < .01 for all comparisons). In multivariate analysis, HIV-1 transmission was significantly associated with elevated CXCL10 concentrations in HIV-1-susceptible partners (P = .001) and with elevated IL-10 concentrations in HIV-1-infected partners (P = .02).ConclusionsImmune activation, as measured by levels of cytokine markers, particularly elevated levels of IL-10 and CXCL1, are associated with increased HIV-1 susceptibility and infectiousness.

Published
2015

16. Global and regional molecular epidemiology of HIV-1, 1990–2015: a systematic review, global survey, and trend analysis

Author

Abimiku, Alash'le G, Agwale, Simon, Archibald, Chris, Avidor, Boaz, Barbás, María Gabriela, Barre-Sinoussi, Francoise, Barugahare, Banson, Belabbes, El Hadj, Bertagnolio, Silvia, Birx, Deborah, Bobkov, Aleksei F, Brandful, James, Bredell, Helba, Brennan, Catherine A, Brooks, James, Bruckova, Marie, Buonaguro, Luigi, Buonaguro, Franco, Buttò, Stefano, Buve, Anne, Campbell, Mary, Carr, Jean, Carrera, Alex, Carrillo, Manuel Gómez, Celum, Connie, Chaplin, Beth, Charles, Macarthur, Chatzidimitriou, Dimitrios, Chen, Zhiwei, Chijiwa, Katsumi, Cooper, David, Cunningham, Philip, Dagnra, Anoumou, de Gascun, Cillian F, Del Amo, Julia, Delgado, Elena, Dietrich, Ursula, Dwyer, Dominic, Ellenberger, Dennis, Ensoli, Barbara, Essex, Max, Gao, Feng, Fleury, Herve, Fonjungo, Peter N, Foulongne, Vincent, Gadkari, Deepak A, García, Federico, Garsia, Roger, Gershy-Damet, Guy Michel, Glynn, Judith R, Goodall, Ruth, Grossman, Zehava, Lindenmeyer-Guimarães, Monick, Hahn, Beatrice, Hamers, Raph L, Hamouda, Osamah, Handema, Ray, He, Xiang, Herbeck, Joshua, Ho, David D, Holguin, Africa, Hosseinipour, Mina, Hunt, Gillian, Ito, Masahiko, Bel Hadj Kacem, Mohamed Ali, Kahle, Erin, Kaleebu, Pontiano Kaleebu, Kalish, Marcia, Kamarulzaman, Adeeba, Kang, Chun, Kanki, Phyllis, Karamov, Edward, Karasi, Jean-Claude, Kayitenkore, Kayitesi, Kelleher, Tony, Kitayaporn, Dwip, Kostrikis, Leondios G, Kucherer, Claudia, Lara, Claudia, Leitner, Thomas, Liitsola, Kirsi, Lingappa, Jai, Linka, Marek, Lorenzana de Rivera, Ivette, Lukashov, Vladimir, Maayan, Shlomo, Mayr, Luzia, McCutchan, Francine, Meda, Nicolas, Menu, Elisabeth, Mhalu, Fred, Mloka, Doreen, Mokili, John L, Montes, Brigitte, Mor, Orna, Morgado, Mariza, Mosha, Fausta, Moussi, Awatef, Mullins, James, Najera, Rafael, Nasr, Mejda, Ndembi, Nicaise, Neilson, Joel R, Nerurkar, Vivek R, Neuhann, Florian, Nolte, Claudine, Novitsky, Vlad, Nyambi, Philippe, Ofner, Marianna, Paladin, Fem J, Papa, Anna, Pape, Jean, Parkin, Neil, Parry, Chris, Peeters, Martine, Pelletier, Alexandra, Pérez-Álvarez, Lucía, Pillay, Deenan, Pinto, Angie, Quang, Trinh Duy, Rademeyer, Cecilia, Raikanikoda, Filimone, Rayfield, Mark A, Reynes, Jean-Marc, Rinke de Wit, Tobias, Robbins, Kenneth E, Rolland, Morgane, Rousseau, Christine, Salazar-Gonzales, Jesus, Salem, Hanan, Salminen, Mika, Salomon, Horacio, Sandstrom, Paul, Santiago, Mario L, Sarr, Abdoulaye D, Schroeder, Bryan, Segondy, Michel, Selhorst, Philippe, Sempala, Sylvester, Servais, Jean, Shaik, Ansari, Shao, Yiming, Slim, Amine, Soares, Marcelo A, Songok, Elijah, Stewart, Debbie, Stokes, Julie, Subbarao, Shambavi, Sutthent, Ruengpung, Takehisa, Jun, Tanuri, Amilcar, Tee, Kok Keng, Thapa, Kiran, Thomson, Michael, Tran, Tyna, Urassa, Willy, Ushijima, Hiroshi, van de Perre, Philippe, van der Groen, Guido, van Laethem, Kristel, van Oosterhout, Joep, van Sighem, Ard, van Wijngaerden, Eric, Vandamme, Anne-Mieke, Vercauteren, Jurgen, Vidal, Nicole, Wallace, Lesley, Williamson, Carolyn, Wolday, Dawit, Xu, Jianqing, Yang, Chunfu, Zhang, Linqi, Zhang, Rong, Hemelaar, Joris, Elangovan, Ramyiadarsini, Yun, Jason, Dickson-Tetteh, Leslie, Fleminger, Isabella, Kirtley, Shona, Williams, Brian, Gouws-Williams, Eleanor, and Ghys, Peter D

Published
2019
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17. Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial

Author

Grinsztejn, Beatriz, Hosseinipour, Mina C, Ribaudo, Heather J, Swindells, Susan, Eron, Joseph, Chen, Ying Q, Wang, Lei, Ou, San-San, Anderson, Maija, McCauley, Marybeth, Gamble, Theresa, Kumarasamy, Nagalingeshwaran, Hakim, James G, Kumwenda, Johnstone, Pilotto, Jose HS, Godbole, Sheela V, Chariyalertsak, Suwat, de Melo, Marineide Gonçalves, Mayer, Kenneth H, Eshleman, Susan H, Piwowar-Manning, Estelle, Makhema, Joseph, Mills, Lisa A, Panchia, Ravindre, Sanne, Ian, Gallant, Joel, Hoffman, Irving, Taha, Taha E, Nielsen-Saines, Karin, Celentano, David, Essex, Max, Havlir, Diane, Cohen, Myron S, and Team, the HPTN 052-ACTG Study

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Health Sciences, Immunology, Medical Microbiology, Infectious Diseases, Clinical Research, Clinical Trials and Supportive Activities, HIV/AIDS, Prevention, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Infection, Good Health and Well Being, AIDS-Related Opportunistic Infections, Acquired Immunodeficiency Syndrome, Adult, Anti-Retroviral Agents, CD4 Lymphocyte Count, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Disease Progression, Drug Administration Schedule, Female, HIV-1, Humans, Intention to Treat Analysis, Kaplan-Meier Estimate, Kidney Failure, Chronic, Liver Diseases, Male, Neoplasms, Proportional Hazards Models, Time Factors, Tuberculosis, Pulmonary, Young Adult, HPTN 052-ACTG Study Team, Public Health and Health Services, Microbiology, Clinical sciences, Medical microbiology, Epidemiology
Abstract

BackgroundUse 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.MethodsThe 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.Findings1763 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.InterpretationEarly 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.FundingUS National Institute of Allergy and Infectious Diseases.

Published
2014

18. Immune activation markers in peripartum women in Botswana: association with feeding strategy and maternal morbidity.

Author

Russell, Elizabeth S, Mohammed, Terence, Smeaton, Laura, Jorowe, Baitshepi, MacLeod, Iain J, Hoffman, Risa M, Currier, Judith S, Moyo, Sikhulile, Essex, Max, and Lockman, Shahin

Subjects
Humans, HIV Infections, Tumor Necrosis Factor-alpha, Fibrin Fibrinogen Degradation Products, Interleukin-6, Interleukin-10, Anti-Retroviral Agents, CD4 Lymphocyte Count, Prognosis, Viral Load, Multivariate Analysis, Breast Feeding, Postpartum Period, Pregnancy, Infant Formula, Infant, Newborn, Botswana, Female, Interferon-gamma, Peripartum Period, Infant, Newborn, General Science & Technology
Abstract

Hormone levels shift the immune state in HIV-uninfected pregnant and breastfeeding women away from Th1 responses and toward regulation to permit fetal tolerance. Limited data exist on inflammation during pregnancy or postpartum in HIV-infected women, though certain inflammatory markers are associated with adverse health outcomes among HIV-infected persons. We measured hsCRP, D-dimer, IFN-γ, IL-6, IL-10 and TNF-α at 34 weeks gestation and six months postpartum in HIV-infected women from the Botswana Mashi PMTCT trial who were randomized to breastfeeding or formula-feeding. Differences in inflammatory markers between gestation and postpartum periods, and by randomized feeding method, were estimated using generalized estimating equations, adjusting for baseline plasma HIV-1 viral load, CD4 count, calendar time, and antiretroviral treatment status. Additionally, we studied the association between marker concentrations at six months postpartum and major adverse clinical events over the following 4.5 years, using case-cohort sampling and adjusted Cox proportional hazards models. In 86 breastfeeding and 75 formula-feeding women, hsCRP and D-dimer decreased significantly between 34 weeks gestation and six months postpartum, while IFN-γ increased. There was no significant association between inflammatory marker change and randomized feeding method after adjusting for multiple comparisons and removing outliers. In univariate analysis, TNF-α, D-dimer, and IFN-γ concentrations at six months postpartum were significant predictors of subsequent clinical events, and TNF-α remained significant in multivariate analysis (HR = 4.16, p = 0.001). In young HIV-infected women in Botswana inflammatory marker concentrations did not differ significantly between women who breast- vs. formula-fed. However, postpartum TNF-α level was predictive of subsequent adverse clinical event.

Published
2014

19. Contribution of Maternal Antiretroviral Therapy and Breastfeeding to 24-Month Survival in Human Immunodeficiency Virus-Exposed Uninfected Children : An Individual Pooled Analysis of African and Asian Studies

Author

Arikawa, Shino, Rollins, Nigel, Jourdain, Gonzague, Humphrey, Jean, Kourtis, Athena P., Hoffman, Irving, Essex, Max, Farley, Tim, Coovadia, Hoosen M., Gray, Glenda, Kuhn, Louise, Shapiro, Roger, Leroy, Valériane, Bollinger, Robert C., Onyango-Makumbi, Carolyne, Lockman, Shahin, Marquez, Carina, Doherty, Tanya, Dabis, François, Mandelbrot, Laurent, Le Coeur, Sophie, Rolland, Matthieu, Joly, Pierre, Newell, Marie-Louise, and Becquet, Renaud

Published
2018

29. Low rates of NRTI and NNRTI drug resistance among participants in the Botswana combination prevention program (BCPP) trial

Author

Moyo, Sikhulile, Gaseitsiwe, Simani, Zahralban-Steele, Melissa, Maruapula, Dorcas, Nkhisang, Tapiwa, Mokaleng, Baitshepi, Mohammed, Terence, Ditlhako, Tsotlhe R., Bareng, Ontlametse T., Mokgethi, Thatayaone P., van Widenfelt, Erik, Pretorius-Holme, Molly, Mine, Madisa O., Raizes, Elliot, Yankinda, Etienne Kadima, Wirth, Kathleen E., Gaolathe, Tendani, Makhema, Joseph M., Lockman, Shahin, Essex, Max, and Novitsky, Vlad

Published
2019
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32. AZT Trials to Reduce Perinatal HIV Transmission: A Debate about Science, Ethics and Resources

Author

McIntyre, James, Bagenda, Danstan, Musoke-Mudido, Philippa, Curtis, Hilary, Tomori, Oyewale, Laing, Richard, Green, Chris W., Wilkinson, David, Wallis, Robert S., del Río, Carlos, Kamarulzaman, Adeeba, Schüklenk, Udo, Lallemant, Marc, McIntosh, Kenneth, Le Coeur, Sophie, Vithayasai, Vicharn, Lek, Tun-Hoh, Hammer, Scott, Prescott, Nicholas, Essex, Max, de Bruyn, Maria, Mofenson, Lynne, Abubakar, Abdnasir M., Ray, Sunanda, and Berer, Marge

Published
1998

36. High Prevalence of Hepatitis B Virus Infection Among People With HIV in Rural and Periurban Communities in Botswana

Author

Phinius, Bonolo B, primary, Anderson, Motswedi, additional, Gobe, Irene, additional, Mokomane, Margaret, additional, Choga, Wonderful T, additional, Mutenga, Sharon R, additional, Mpebe, Gorata, additional, Pretorius-Holme, Molly, additional, Musonda, Rosemary, additional, Gaolathe, Tendani, additional, Mmalane, Mompati, additional, Shapiro, Roger, additional, Makhema, Joseph, additional, Lockman, Shahin, additional, Novitsky, Vlad, additional, Essex, Max, additional, Moyo, Sikhulile, additional, and Gaseitsiwe, Simani, additional

Published
2023
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39. HIV-1C in-House RNA-Based Genotyping Assay for Detection of Drug Resistance Mutations in Samples with Low-Level Viral Loads

Author

Bareng, Ontlametse T, primary, Choga, Wonderful T, additional, Maphorisa, Segomotso T, additional, Seselamarumo, Sekgabo, additional, Seatla, Kaelo K, additional, Mokgethi, Patrick T, additional, Maruapula, Dorcas, additional, Mogwele, Mompati L, additional, Ditshwanelo, Doreen, additional, Moraka, Natasha O, additional, Gobe, Irene, additional, Motswaledi, Modisa S, additional, Makhema, Joseph M, additional, Musonda, Rosemary, additional, Shapiro, Roger, additional, Essex, Max, additional, Novitsky, Vlad, additional, Moyo, Sikhulile, additional, and Gaseitsiwe, Simani, additional

Published
2022
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40. Prediction of Coreceptor Tropism in HIV-1 Subtype C in Botswana

Author

Kotokwe, Kenanao, Moyo, Sikhulile, Zahralban-Steele, Melissa, Holme, Molly Pretorius, Melamu, Pinkie, Koofhethile, Catherine Kegakilwe, Choga, Wonderful Tatenda, Mohammed, Terence, Nkhisang, Tapiwa, Mokaleng, Baitshepi, Maruapula, Dorcas, Ditlhako, Tsotlhe, Bareng, Ontlametse, Mokgethi, Patrick, Boleo, Corretah, Makhema, Joseph, Lockman, Shahin, Essex, Max, Ragonnet-Cronin, Manon, Novitsky, Vlad, Gaseitsiwe, Simani, and Consortium, PANGEA Consortium PANGEA

Subjects
CXCR4, Infectious Diseases, Virology, X4-tropic viruses, R5-tropic viruses, CCR5, HIV-1C tropism
Abstract

It remains unknown whether the C-C motif chemokine receptor type 5 (CCR5) coreceptor is still the predominant coreceptor used by Human Immunodeficiency Virus-1 (HIV-1) in Botswana, where the HIV-1 subtype C predominates. We sought to determine HIV-1C tropism in Botswana using genotypic tools, taking into account the effect of antiretroviral treatment (ART) and virologic suppression. HIV-1 gp120 V3 loop sequences from 5602 participants were analyzed for viral tropism using three coreceptor use predicting algorithms/tools: Geno2pheno, HIV-1C Web Position-Specific Score Matrices (WebPSSM) and the 11/25 charge rule. We then compared the demographic and clinical characteristics of people living with HIV (PLWH) harboring R5- versus X4-tropic viruses using χ2 and Wilcoxon rank sum tests for categorical and continuous data analysis, respectively. The three tools congruently predicted 64% of viruses as either R5-tropic or X4-tropic. Geno2pheno and the 11/25 charge rule had the highest concordance at 89%. We observed a significant difference in ART status between participants harboring X4- versus R5-tropic viruses. X4-tropic viruses were more frequent among PLWH receiving ART (χ2 test, p = 0.03). CCR5 is the predominant coreceptor used by HIV-1C strains circulating in Botswana, underlining the strong potential for CCR5 inhibitor use, even in PLWH with drug resistance. We suggest that the tools for coreceptor prediction should be used in combination.

Published
2023
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42. Introduction: The Etiology of AIDS

Author

Essex, Max, Mboup, Souleymane, Essex, Max, editor, Mboup, Souleymane, editor, Kanki, Phyllis J., editor, Marlink, Richard G., editor, Tlou, Sheila D., editor, and Holme, Molly, editor

Published
2002
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43. HIV-1 Subtypes and Recombinants

Author

Renjifo, Boris, Essex, Max, Essex, Max, editor, Mboup, Souleymane, editor, Kanki, Phyllis J., editor, Marlink, Richard G., editor, Tlou, Sheila D., editor, and Holme, Molly, editor

Published
2002
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46. Undisclosed antiretroviral drug use in Botswana: implication for national estimates

Author

Moyo, Sikhulile, Gaseitsiwe, Simani, Powis, Kathleen M., Pretorius Holme, Molly, Mohammed, Terence, Zahralban-Steele, Melissa, Yankinde, Etienne K., Maphorisa, Comfort, Abrams, William, Lebelonyane, Refeletswe, Manyake, Kutlo, Sekoto, Tumalano, Mmalane, Mompati, Gaolathe, Tendani, Wirth, Kathleen E., Makhema, Joseph, Lockman, Shahin, Clarke, William, Essex, Max, and Novitsky, Vlad

Published
2018
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47. HIV-1 Langerhans' Cell Tropism Associated with Heterosexual Transmission of HIV

Author

Soto-Ramirez, Luis E., Renjifo, Boris, McLane, Mary F., Marlink, Richard, O'Hara, Carl, Sutthent, Ruengpung, Wasi, Chantapong, Vithayasai, Prakong, Vithayasai, Vicharn, Apichartpiyakul, Chatchawann, Auewarakul, Prasert, Cruz, Victor Peña, Chui, Dao-Shan, Osathanondh, Rapin, Mayer, Kenneth, Lee, Tun-Hou, and Essex, Max

Published
1996

49. HIV-1 drug resistance mutations among individuals with low-level viraemia while taking combination ART in Botswana

Author

Bareng, Ontlametse T, Moyo, Sikhulile, Zahralban-Steele, Melissa, Maruapula, Dorcas, Ditlhako, Tsotlhe, Mokaleng, Baitshepi, Mokgethi, Patrick, Choga, Wonderful T, Moraka, Natasha O, Pretorius-Holme, Molly, Mine, Madisa O, Raizes, Elliot, Molebatsi, Kesaobaka, Motswaledi, Modisa S, Gobe, Irene, Mohammed, Terence, Gaolathe, Tendani, Shapiro, Roger, Mmalane, Mompati, Makhema, Joseph M, Lockman, Shahin, Essex, Max, Novitsky, Vlad, and Gaseitsiwe, Simani

Subjects
Pharmacology, Microbiology (medical), Adult, Botswana, Anti-HIV Agents, Drug Resistance, HIV Infections, Viral Load, Infectious Diseases, Drug Resistance, Viral, HIV Seropositivity, Mutation, HIV-1, Humans, Pharmacology (medical), Viremia, Original Research
Abstract

Objectives To assess whether a single instance of low-level viraemia (LLV) is associated with the presence of drug resistance mutations (DRMs) and predicts subsequent virological failure (VF) in adults receiving ART in 30 communities participating in the Botswana Combination Prevention Project. Methods A total of 6078 HIV-1 C pol sequences were generated and analysed using the Stanford HIV drug resistance database. LLV was defined as plasma VL = 51–999 copies/mL and VF was defined as plasma VL ≥ 1000 copies/mL. Results Among 6078 people with HIV (PWH), 4443 (73%) were on ART for at least 6 months. Of the 332 persons on ART with VL > 50 copies/mL, 175 (4%) had VL ≥ 1000 copies/mL and 157 (4%) had LLV at baseline. The prevalence of any DRM was 57 (36%) and 78 (45%) in persons with LLV and VL ≥ 1000 copies/mL, respectively. Major DRMs were found in 31 (20%) with LLV and 53 (30%) with VL ≥ 1000 copies/mL (P = 0.04). Among the 135 PWH with at least one DRM, 17% had NRTI-, 35% NNRTI-, 6% PI- and 3% INSTI-associated mutations. Among the 3596 participants who were followed up, 1709 (48%) were on ART for ≥6 months at entry and had at least one subsequent VL measurement (median 29 months), 43 (3%) of whom had LLV. The OR of experiencing VF in persons with LLV at entry was 36-fold higher than in the virally suppressed group. Conclusions A single LLV measurement while on ART strongly predicted the risk of future VF, suggesting the use of VL > 50 copies/mL as an indication for more intensive adherence support with more frequent VL monitoring.

Published
2022

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