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1. Uptake of Human Papilloma Virus vaccine among young women living in fishing communities in Wakiso and Mukono districts, Uganda.

Author

Laban, Muteebwa, Nanyonjo, Gertrude, Wambuzi, Mathias, Ssetaala, Ali, Basalirwa, Geofrey, Muramuzi, Dan, Lugemwa, Jacqueline, Okech, Brenda, and Mirzazadeh, Ali

Abstract

Human Papilloma Virus (HPV) is a preventable cause of cervical cancer, the commonest cancer among women in Uganda. The Uganda Ministry of Health included the HPV vaccine in the free routine immunization schedule since 2015. Five years after this policy, we assessed the uptake of the HPV vaccine and associated socio-demographic factors among young women living in fishing communities in Central Uganda in 2020. We analyzed secondary data from 94 young women aged 9-25 years who were recruited from the two fishing communities (Kasenyi landing site and Koome Island) in a primary study that aimed to promote awareness of maternal and childhood vaccines. We assessed uptake of the HPV vaccine as the proportion of participants who self-reported to have ever received at least one dose of the HPV vaccine. We assessed the socio-demographic factors associated with HPV vaccine uptake using a modified Poisson regression model adjusted for clustering by study site in STATA version 17. The mean (standard deviation) age of study participants was 21.1 (3.1) years and most (81.9%) of them were from Kasenyi landing site. The uptake of the HPV vaccine was 10.6% [95% Confidence Interval (CI) 5.6, 18.9]. After adjusting for covariates, being 13-19 years old (adjusted prevalence ratio [aPR] 5.52, 95%CI 1.69, 18.00) and of Catholic religion (aPR 5.55, 95%CI 1.53, 20.16) were significantly associated with HPV vaccine uptake. The HPV vaccine uptake was very low, despite the reported 99% national coverage of HPV vaccination program for the first dose at the end of 2019. Age and religion showed to be important determinants of the HPV vaccine uptake. Reasons for such very low uptake of HPV vaccinations need to be carefully assessed to find effective strategies to improve it.

Published
2024

2. Long-term non-progression and risk factors for disease progression among children living with HIV in Botswana and Uganda: A retrospective cohort study

Author

Samuel Kyobe, Grace Kisitu, Savannah Mwesigwa, John Farirai, Eric Katagirya, Gaone Retshabile, Lesedi Williams, Angela Mirembe, Lesego Ketumile, Misaki Wayengera, John Mukisa, Gaseene Sebetso, Thabo Diphoko, Marion Amujal, Edgar Kigozi, Fred Katabazi, Ronald Oceng, Busisiwe Mlotshwa, Koketso Morapedi, Betty Nsangi, Edward Wampande, Masego Tsimako, Chester Brown, Ishmael Kasvosve, Moses Joloba, Gabriel Anabwani, Sununguko Mpoloka, Graeme Mardon, Adeodata Kekitiinwa, Neil A. Hanchard, Jacqueline Kyosiimire–Lugemwa, Mogomotsi Matshaba, and Dithan Kiragga

Subjects
LTNP, HIV progression, Pediatric, Africa, Infectious and parasitic diseases, RC109-216
Abstract

Objectives: We utilize a large retrospective study cohort derived from electronic medical records to estimate the prevalence of long-term non-progression (LTNP) and determine the factors associated with progression among children infected with HIV in Botswana and Uganda. Methods: Electronic medical records from large tertiary HIV clinical centers in Botswana and Uganda were queried to identify LTNP children 0-18 years enrolled between June 2003 and May 2014 and extract demographic and nutritional parameters. Multivariate subdistribution hazard analyses were used to examine demographic factors and nutritional status in progression in the pre-antiretroviral therapy era. Results: Between the two countries, 14,246 antiretroviral therapy-naïve children infected with HIV were enrolled into clinical care. The overall proportion of LTNP was 6.3% (9.5% in Botswana vs 5.9% in Uganda). The median progression-free survival for the cohort was 6.3 years, although this was lower in Botswana than in Uganda (6.6 vs 8.8 years; P

Published
2024
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3. Identification of a Clade-Specific HLA-C*03:02 CTL Epitope GY9 Derived from the HIV-1 p17 Matrix Protein

Author

Samuel Kyobe, Savannah Mwesigwa, Gyaviira Nkurunungi, Gaone Retshabile, Moses Egesa, Eric Katagirya, Marion Amujal, Busisiwe C. Mlotshwa, Lesedi Williams, Hakim Sendagire, on behalf of the CAfGEN Consortium, Dithan Kiragga, Graeme Mardon, Mogomotsi Matshaba, Neil A. Hanchard, Jacqueline Kyosiimire-Lugemwa, and David Robinson

Subjects
HIV control, HLA-C*03:02, immunoinformatics, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Efforts towards an effective HIV-1 vaccine have remained mainly unsuccessful. There is increasing evidence for a potential role of HLA-C-restricted CD8+ T cell responses in HIV-1 control, including our recent report of HLA-C*03:02 among African children. However, there are no documented optimal HIV-1 CD8+ T cell epitopes restricted by HLA-C*03:02; additionally, the structural influence of HLA-C*03:02 on epitope binding is undetermined. Immunoinformatics approaches provide a fast and inexpensive method to discover HLA-restricted epitopes. Here, we employed immunopeptidomics to identify HLA-C*03:02 CD8+ T cell epitopes. We identified a clade-specific Gag-derived GY9 (GTEELRSLY) HIV-1 p17 matrix epitope potentially restricted to HLA-C*03:02. Residues E62, T142, and E151 in the HLA-C*03:02 binding groove and positions p3, p6, and p9 on the GY9 epitope are crucial in shaping and stabilizing the epitope binding. Our findings support the growing evidence of the contribution of HLA-C molecules to HIV-1 control and provide a prospect for vaccine strategies.

Published
2024
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4. An Empirical Study on E-Learning Uptake by Teaching Staff at Makerere University Business School

Author

Bada, Joseph Kizito, Asianzu, Elizabeth, Lugemwa, Brian, Namataba, Josephine, and Milburga, Atceru

Abstract

The introduction of practical e-learning pedagogy to university teaching staff brings new opportunities for teaching and learning. Most teaching staff have not been exposed to use of a learning management system. The junior teaching staff at Makerere University Business School (MUBS) were trained to use e-learning tools with the Modular Object-oriented Dynamic Learning Management System (Moodle) as the platform for teaching. Moodle was selected for two reasons: it is open source and available for free download and it has good in-built pedagogical tools. The training course introduced new pedagogical tools that included online lessons, online assessment and collaborative tools in education (wiki, discussion forum). The participants evaluated the e-learning environment as the last activity in the course. The evaluation was done using questionnaires. The results indicate that the staff acquired good e-learning pedagogical skills at the end of the course. Further, results showed acceptance of e-learning by course instructors and usefulness of e-learning, with course instructors expressing their intention to use e-learning in teaching. The study shows that perceived usefulness influences behavioral intention more than perceived ease of use of the learning management system.

Published
2020

6. Voluntariness of consent in paediatric HIV clinical trials: a mixed-methods, cross-sectional study of participants in the CHAPAS-4 and ODYSSEY trials in Uganda

Author

Imelda K Tamwesigire, Francis Bajunirwe, Annabelle South, Diana Gibb, Anna Turkova, Deborah Ford, Abbas Lugemwa, Victor Musiime, and Shafic Makumbi

Subjects
Medicine
Abstract

Objectives To examine the voluntariness of consent in paediatric HIV clinical trials and the associated factors.Design Mixed-methods, cross-sectional study combining a quantitative survey conducted concurrently with indepth interviews.Setting and participants From January 2021 to April 2021, we interviewed parents of children on first-line or second-line Anti-retroviral therapy (ART) in two ongoing paediatric HIV clinical trials [CHAPAS-4 (ISRCTN22964075) and ODYSSEY (ISRCTN91737921)] at the Joint Clinical Research Centre Mbarara, Uganda.Outcome measures The outcome measures were the proportion of parents with voluntary consent, factors affecting voluntariness and the sources of external influence. Parents rated the voluntariness of their consent on a voluntariness ladder. Indepth interviews described participants’ lived experiences and were aimed at adding context.Results All 151 parents randomly sampled for the survey participated (84% female, median age 40 years). Most (67%) gave a fully voluntary decision, with a score of 10 on the voluntariness ladder, whereas 8% scored 9, 9% scored 8, 6% scored 7, 8% scored 6 and 2.7% scored 4. Trust in medical researchers (adjusted OR 9.90, 95% CI 1.01 to 97.20, p=0.049) and male sex of the parent (adjusted OR 3.66, 95% CI 1.00 to 13.38, p=0.05) were positively associated with voluntariness of consent. Prior research experience (adjusted OR 0.31, 95% CI 0.12 to 0.78, p=0.014) and consulting (adjusted OR 0.25. 95% CI 0.10 to 0.60, p=0.002) were negatively associated with voluntariness. Consultation and advice came from referring health workers (36%), spouses (29%), other family members (27%), friends (15%) and researchers (7%). The indepth interviews (n=14) identified the health condition of the child, advice from referring health workers and the opportunity to access better care as factors affecting the voluntariness of consent.Conclusions This study demonstrated a high voluntariness of consent, which was enhanced among male parents and by parents’ trust in medical researchers. Prior research experience of the child and advice from health workers and spouses were negatively associated with the voluntariness of parents’ consent. Female parents and parents of children with prior research experience may benefit from additional interventions to support voluntary participation.

Published
2024
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7. Uptake of Human Papilloma Virus vaccine among young women living in fishing communities in Wakiso and Mukono districts, Uganda.

Author

Muteebwa Laban, Gertrude Nanyonjo, Mathias Wambuzi, Ali Ssetaala, Geofrey Basalirwa, Dan Muramuzi, Jacqueline Kyosiimire Lugemwa, Brenda Okech, and Ali Mirzazadeh

Subjects
Public aspects of medicine, RA1-1270
Abstract

Human Papilloma Virus (HPV) is a preventable cause of cervical cancer, the commonest cancer among women in Uganda. The Uganda Ministry of Health included the HPV vaccine in the free routine immunization schedule since 2015. Five years after this policy, we assessed the uptake of the HPV vaccine and associated socio-demographic factors among young women living in fishing communities in Central Uganda in 2020. We analyzed secondary data from 94 young women aged 9-25 years who were recruited from the two fishing communities (Kasenyi landing site and Koome Island) in a primary study that aimed to promote awareness of maternal and childhood vaccines. We assessed uptake of the HPV vaccine as the proportion of participants who self-reported to have ever received at least one dose of the HPV vaccine. We assessed the socio-demographic factors associated with HPV vaccine uptake using a modified Poisson regression model adjusted for clustering by study site in STATA version 17. The mean (standard deviation) age of study participants was 21.1 (3.1) years and most (81.9%) of them were from Kasenyi landing site. The uptake of the HPV vaccine was 10.6% [95% Confidence Interval (CI) 5.6, 18.9]. After adjusting for covariates, being 13-19 years old (adjusted prevalence ratio [aPR] 5.52, 95%CI 1.69, 18.00) and of Catholic religion (aPR 5.55, 95%CI 1.53, 20.16) were significantly associated with HPV vaccine uptake. The HPV vaccine uptake was very low, despite the reported 99% national coverage of HPV vaccination program for the first dose at the end of 2019. Age and religion showed to be important determinants of the HPV vaccine uptake. Reasons for such very low uptake of HPV vaccinations need to be carefully assessed to find effective strategies to improve it.

Published
2024
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8. HIV specific Th1 responses are altered in Ugandans with HIV and Schistosoma mansoni coinfection

Author

Andrew Ekii Obuku, Jacqueline Kyosiimire Lugemwa, Andrew Abaasa, Moses Joloba, Song Ding, Justin Pollara, Guido Ferrari, Alexandre Harari, Giuseppe Pantaleo, and Pontiano Kaleebu

Subjects
HIV-1, Schistosomiasis, Immune responses, Down modulation, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Fishing communities surrounding Lake Victoria in Uganda have HIV prevalence of 28% and incidence rates of 5 per 100 person years. More than 50% of the local fishermen are infected with Schistosoma mansoni (S. mansoni). We investigated the role of S. mansoni coinfection as a possible modifier of immune responses against HIV. Using polychromatic flow cytometry and Gran-ToxiLux assays, HIV specific responses, T cell phenotypes, antibody-dependent cell-mediated cytotoxic (ADCC) potency and titres were compared between participants with HIV-S. mansoni coinfection and participants with HIV infection alone. Results S. mansoni coinfection was associated with a modified pattern of anti-HIV responses, including lower frequency of bifunctional (IFNγ + IL-2 − TNF-α+) CD4 T cells, higher overall CD4 T cell activation and lower HIV ADCC antibody titres, compared to participants with HIV alone. Conclusions These results support the hypothesis that S. mansoni infection affects T cell and antibody responses to HIV in coinfected individuals.

Published
2023
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9. Long-term non-progression and risk factors for disease progression among children living with HIV in Botswana and Uganda: A retrospective cohort study

Author

Kyobe, Samuel, Kisitu, Grace, Mwesigwa, Savannah, Farirai, John, Katagirya, Eric, Retshabile, Gaone, Williams, Lesedi, Mirembe, Angela, Ketumile, Lesego, Wayengera, Misaki, Mukisa, John, Sebetso, Gaseene, Diphoko, Thabo, Amujal, Marion, Kigozi, Edgar, Katabazi, Fred, Oceng, Ronald, Mlotshwa, Busisiwe, Morapedi, Koketso, Nsangi, Betty, Wampande, Edward, Tsimako, Masego, Brown, Chester, Kasvosve, Ishmael, Joloba, Moses, Anabwani, Gabriel, Mpoloka, Sununguko, Mardon, Graeme, Kekitiinwa, Adeodata, Hanchard, Neil A., Kyosiimire–Lugemwa, Jacqueline, Matshaba, Mogomotsi, and Kiragga, Dithan

Published
2024
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10. Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

Author

Mehar (nee Abdulla), Amina Farhana, Abraham, Pattamukkil, Abrams, Elaine, Acero, Judith, Agaba, Gerald Muzorah, Ahimbisibwe, Grace, Ainebyoona, Barbara, Akobye, Winnie, Akhalwaya, Yasmeen, Akoojee, Nazim, Ali, Shabinah S., Amuge, Pauline, Andrea, Catherine, Muñoz Fernandez, Maria Angeles, Ankunda, Rogers, Rutebarika, Diana Antonia, Anugulruengkitt, Suvaporn, Apollo, Tsitsi, Archary, Moherndran, Arendze, Ronelle, Ategeka, Juliet, Atim, Eunice, Atwine, Lorna, Babiker, Abdel, Babirye, Sarah, Babu, Enock, Bagirigomwa, Edward, Baita, Angella, Balamusani, David, Baliram, Patsy, Baliruno, David, Ball, Colin, Balwa, Henry, Bamford, Alasdair, Bandi, Srini, Barker, Dominique, Barlow-Mosha, Linda, Bbuye, Dickson, Begum, Shazia, Behuhuma, Osee, Bernays, Sarah, Besigye, Rogers, Bester, Maria, Bhiri, Joyline, Bilardi, Davide, Bird, Kristien, Bollen, Pauline, Borg, Chiara, Borges Da Silva, Anne-Marie, Brown, Jackie, Bruno, Elena, Bunupuradah, Torsak, Burger, David, Buthelezi, Nomzamo, Bwakura-Dangarembizi, Mutsa, Byaruhanga, Africanus, Calvert, Joanna, Casey, Petronelle, Cassim, Haseena, Cebekhulu, Sphiwee, Chailert, Sanuphong, Chalermpantmetagul, Suwalai, Chamjamrat, Wanna, Chan, Man, Chandiwana, Precious, Chankun, Thannapat, Chanthaburanun, Sararut, Chanto, Nuttawut, Chidziva, Ennie, Chikowore, Minenhle, Chimanzi, Joy, Chinwong, Dujrudee, Chitongo, Stuart, Chitsamatanga, Moses, Choga, Joshua, Chutima, Duangrat, Clayden, Polly, Coelho, Alexandra, Colbers, Angela, Compagnucci, Alexandra, Constança Mendes, Ana, Conway, Magda, Cotton, Mark F, Crawley, Jane, Cressey, Tim R, Crisp, Jacky, Matos, Ana Cristina, Dadan, Sumaya, Daglish, Jacqui, Danaviah, Siva, Daniel, Tseleng, De Rossi, Anita, Denjanta, Sukanda, Dobbels, Els, Dowie, Maria, Dube, Prosper, Dube, Benedictor, Dudakia, Nimisha, Elwana, Alice, Epalza, Cristina, Eram, David, Erasmus, Juan, Erim, Peter, Escosa Garcia, Luis, Essack, Zaakirah, Estepa, Carolina, Etima, Monica, Fernandes, Alexandre, Fernandez, Maite, Fitzgerald, Felicity, Flynn, Jacquie, Ford, Deborah, Fortuny Guasch, Claudia, Foster, Caroline, Fourie, George, Fourie, Yolandie, Foxall, Sophie, Frank, Derusha, Gandhi, Kate, Garcia, India, Gartner, Kathleen, Gasa, Joshua, Gasa, Gugu, Giaquinto, Carlo, Gibb, Diana M, Gomez Rico, Coral, Gomez-Pena, Daniel, Gondo, Secrecy, Goodman, Anna, Gorreti Nakalema, Maria, Gozhora, Winnie, Greetanukroh, Pisut, Gregorio Maranon, Biobanco, Grossele, Tiziana, Gwande, Shamiso, Gwaze, Tapiwa, Gwenzi, Tsitsi, Hakim, James, Hakiza, Emmanuel, Kaka, Abdul Hamid, Harley, Ashley, Isaacs, Mornay, Isabirye, Richard, Ishemunyoro, Wilber, Jacobs, Tom, Jafta, Lungile, Jamil, Nasir, Janse van Rensburg, Anita Janse, Jeaven, Vinesh, Mellado Peña, Maria José, Jourdain, Gonzague, Juliet, Katabalwa, Jumpimai, Thidarat, Junkaew, Raungwit, Jupimai, Thidarat, Kaahwa, Winfred, Kabasonga, Mildred, Kaboggoza, Olivia, Kadhuba, Rose Jacqueline, Kaewbundit, Ampika, Kaewmamueng, Kanyanee, Kafufu, Bosco, Kakayi, Brenda, Kamboua, Phakamas, Kanjanavanit, Suparat, Kasangaki, Gladys, Kasipong, Naruporn, Kasozi, Miriam, Kataike, Hajira, Katemba, Chrispus, Kaudha, Elizabeth, Kekane, Nkata, Kekitiinwa, Adeodata R, Keminyeto, Edridah, Khamduang, Woottichai, Khamjakkaew, Warunee, Khamkon, Jiraporn, Khannak, Sasipass, Khatngam, Orapin, Khayanchoomnoom, Tassawan, Khumalo, Busi, Khunene, Mirriam, Khusuwan, Suwimon, Kibalama, Phionah, Kibenge, Robinah, Kirabira, Anthony, Kityo, Cissy M, Kiyimba, Lameck, Klein, Nigel, Klinprung, Soraya, Kobbe, Robin, Kobusingye, Olivia, Kobusungye, Josephine, Kongponoi, Areerat, Königs, Christoph, Koole, Olivier, Kouakam, Christelle, Krueduangkam, Nitinart, Kruenual, Namthip, Kunjaroenrut, Nuananong, Kyambadde, Raymonds, Kyobutungi, Priscilla, Kyomuhendo, Flavia, Kyomukama, Erinah, Lakha, Reshma, Langa, Cleopatra, Laomanit, Laddawan, Lebotsa, Emily, Leenasirimakul, Prattana, Lekku, Lawrence, Lensen, Sarah, Leroy, Valériane, Li, Jin, Liberty, Afaaf, Limplertjareanwanich, Juthamas, Little, Emma, Lugemwa, Abbas, Lutalo, Ezra, Jimenez, Jose Luis, Lyall, Hermione, MacDonald, Candice, Machache, Gladness, Madlala, Penelope, Madonsela, Tryphina, Maduna, Nomfundo, Maena, Joel, Mahanontharit, Apicha, Makanga, Collin, Makola, Candice, Makumbi, Shafic, Malgraaf, Lucille, Mamiane, Angelous, Mantkowski, Felicia, Mapfumo, Wendy, Marques, Laura, Mugagga, Agnes Mary, Maseko, Lindiwe, Masienyane, Tshepiso, Mathiba, Ruth, Matimba, Farai, Mawlana, Sajeeda, Mayanja, Emmanuel, Mayat, Fatima, Mbabazi, Ritah, Mbadaliga, Nokuthula, Mbasani, Faith, McClaughlin, Kathleen, McIlleron, Helen, Meethaisong, Watchara, Mendez Garcia, Patricia, Miwanda, Annet, Miranda, Carlota, Mkhize, Siphiwe, Mmolawa, Kgosimang, Mngqibisa, Rosie, Mohamed, Fatima, Moloantoa, Tumelo, Monametsi, Maletsatsi, Montero, Samuel, Moore, Cecilia L, Mosia, Rejoice, Moyo, Columbus, Mthethwa, Mumsy, Mudzingwa, Shepherd, Mudzviti, Tawona, Mujuru, Hilda, Mujyambere, Emmanuel, Mukanganiki, Trust, Mukisa Williams, Cynthia, Mulder, Mark, Mulima, Disan, Mulindwa, Alice, Mumbiro, Vivian, Mupambireyi, Zivai, Murciano Cabeza, Alba, Murungi, Herbert, Murungu, Dorothy, Musarurwa, Sandra, Musiime, Victor, Musiime, Alex V, Musisi, Maria, Musoke, Philippa, Musoke Nakirya, Barbara, Musoro, Godfrey, Musumba, Sharif, Mustafa, Sobia, Mutsai, Shirley, Mwesigwa Rubondo, Phyllis, Naabalamba, Mariam, Nagawa, Immaculate, Naidoo, Allemah, Nakabuye, Shamim, Nakabuye, Sarah, Nakalanzi, Sarah, Nalubwama, Justine, Nalugo, Annet, Nalusiba, Stella, Namajja, Clementine, Namanda, Sylvia, Namayanja, Paula, Nambi, Esther, Namuddu, Rachael Kikabi, Namukwaya, Stella, Namuli, Florence, Namusanje, Josephine, Namwanje, Rosemary, Nanan-kanjee, Anusha, Nanduudu, Annet, Nankunda, Charity, Baddokwaya, Joanita Nankya, Nannungi, Maria, Nansamba, Winnie, Nanthapisal, Kesdao, Nanyonjo, Juliet, Na-Rajsima, Sathaporn, Nasaazi, Claire, Nascimento, Helena, Nastouli, Eleni, Songtaweesin, Wipaporn Natalie, Nathoo, Kusum, Natuhurira, Ian, Nazzinda, Rashidah, Ncgaba, Thabisa, Ndigendawani, Milly, Ndlovu, Makhosonke, Nentsa, Georgina, Ngampiyaskul, Chaiwat, Ngcobo, Ntombenhle, Ngo Giang Huong, Nicole, Ngwaru, Pia, Nhema, Ruth, Ninsiima, Emily, Ninsiima, Gloria, Nkalo Phiri, Misheck, Noguera Julian, Antoni, Nolan, Monica, Noppakaorattanamanee, Thornthun, Nsibuka Kisekka, Muzamil, Nsirim, Eniola, Nundlal, Rashina, Nunes, Rosita, Nyantsa, Lungile, Nyati, Mandisa, O'Riordan, Sean, Ocitti Labeja, Paul, Odoch, Denis, Oguntimehin, Rachel, Ojok, Martin, Onen, Geoffrey, Orange, Wilma, Ounchanum, Pradthana, Ouma, Benson, Padrao, Andreia, Pako, Deborah, Parker, Anna, Pasko-Szcech, Malgorzata, Patel, Reena, Peongjakta, Rukchanok, Petpranee, Turian, Phillips, Tasmin, Philps, Jackie, Picault, Laura, Pieterse, Sonja, Pinheiro, Helena, Pongprapass, Supawadee, Pozniak, Anton, Prendergast, Andrew, Prieto Tato, Luis, Puangmalai, Patcharee, Puthanakit, Thanyawee, Rakgokong, Modiehi, Ramos, Helena, Ramsagar, Nastassja, Rau, Cornelius, Riault, Yoann, Rojo Conejo, Pablo, Clark, Basiimwa Roy, Rubanga, Eddie, Rubinga, Baker, Ruklao, Chutima, Runarassamee, Pattira, Saenjum, Chalermpong, Saewtrakool, Chayakorn, Saidi, Yacine, Sainz Costa, Talia, Saisaengjan, Chutima, Sakwa, Rebecca, Sarfati, Tatiana, Sbisi, Noshalaza, Scheppers, Dihedile, Schultze-Strasser, Stephan, Schulze-Sturm, Ulf, Scott, Karen, Seeley, Janet, Serunjogi, Robert, Sewnarain, Leora, Shakeshaft, Clare, Sidhoo, Subashinie, Shibemba, Mercy, Shingadia, Delane, Singh, Sheleika, Sirirungsi, Wasna, Sithebe, Sibongile, Smit, Theresa, Smith, Kurt, Smuts, Marlize, Spyer, Moira, Sripaoraya, Worathip, Srirompotong, Ussanee, Srisuk, Warunee, Ssenyonga, Mark, Sudsaard, Patamawadee, Sukrakanchana, Praornsuda, Tearsansern, Pathanee, Teixeira, Carla, Than-in-at, Kanchana, Thapwai, Thitiwat, Thaweesombat, Yupawan, Thewsoongnoen, Jutarat, Thiébaut, Rodolphe, Thomason, Margaret, Thrasyvoulou, Laura, Thungkham, Khanungnit, Tikabibamu, Judith, Tinago, Gloria, Trairat, Ketmookda, Tudor-Williams, Gareth, Tukamushaba, Mercy, Tukwasibwe, Deogratiuos, Tumusiime, Julius, Tuna, Joana, Turkova, Anna, Turner, Rebecca, Udomvised, Arttasid, Vadee, Aasia, Van Huyssteen, Hesti, Van Looy, Nadine, Variava, Ebrahim, Vaughan-Gordon, Yvonne, Vecchia, Giulio, Violari, Avy, Vowden, Richard, Waalewijn, Hylke, Wampamba, Rebecca, Welch, Steve, Weller, Ian, Weza, Sibusisiwe, White, Ellen, White, Ian, Widuch, Kaja, Wilkes, Helen, Wimonklang, Sookpanee, Wynne, Ben, Yingyong, Pacharaporn, Nakawungu, Zaam Zinda, Zuidewind, Peter, Ahimbisibwe, Grace Miriam, Mosia, Nozibusiso Rejoice, Fortuny, Clàudia, Bwakura-Dangarembizi, Mutsa F, Mujuru, Hilda A, Kityo, Cissy, Ferrand, Rashida A, and Rojo, Pablo

Published
2023
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11. Schistosoma mansoni infection alters the host pre-vaccination environment resulting in blunted Hepatitis B vaccination immune responses.

Author

Roshell Muir, Talibah Metcalf, Slim Fourati, Yannic Bartsch, Jacqueline Kyosiimire-Lugemwa, Glenda Canderan, Galit Alter, Enoch Muyanja, Brenda Okech, Teddy Namatovu, Irene Namara, Annemarie Namuniina, Ali Ssetaala, Juliet Mpendo, Annet Nanvubya, Paul Kato Kitandwe, Bernard S Bagaya, Noah Kiwanuka, Jacent Nassuna, Victoria Menya Biribawa, Alison M Elliott, Claudia J de Dood, William Senyonga, Priscilla Balungi, Pontiano Kaleebu, Yunia Mayanja, Matthew Odongo, Jennifer Connors, Pat Fast, Matt A Price, Paul L A M Corstjens, Govert J van Dam, Anatoli Kamali, Rafick Pierre Sekaly, and Elias K Haddad

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

Schistosomiasis is a disease caused by parasitic flatworms of the Schistosoma spp., and is increasingly recognized to alter the immune system, and the potential to respond to vaccines. The impact of endemic infections on protective immunity is critical to inform vaccination strategies globally. We assessed the influence of Schistosoma mansoni worm burden on multiple host vaccine-related immune parameters in a Ugandan fishing cohort (n = 75) given three doses of a Hepatitis B (HepB) vaccine at baseline and multiple timepoints post-vaccination. We observed distinct differences in immune responses in instances of higher worm burden, compared to low worm burden or non-infected. Concentrations of pre-vaccination serum schistosome-specific circulating anodic antigen (CAA), linked to worm burden, showed a significant bimodal distribution associated with HepB titers, which was lower in individuals with higher CAA values at month 7 post-vaccination (M7). Comparative chemokine/cytokine responses revealed significant upregulation of CCL19, CXCL9 and CCL17 known to be involved in T cell activation and recruitment, in higher CAA individuals, and CCL17 correlated negatively with HepB titers at month 12 post-vaccination. We show that HepB-specific CD4+ T cell memory responses correlated positively with HepB titers at M7. We further established that those participants with high CAA had significantly lower frequencies of circulating T follicular helper (cTfh) subpopulations pre- and post-vaccination, but higher regulatory T cells (Tregs) post-vaccination, suggesting changes in the immune microenvironment in high CAA could favor Treg recruitment and activation. Additionally, we found that changes in the levels of innate-related cytokines/chemokines CXCL10, IL-1β, and CCL26, involved in driving T helper responses, were associated with increasing CAA concentration. This study provides further insight on pre-vaccination host responses to Schistosoma worm burden which will support our understanding of vaccine responses altered by pathogenic host immune mechanisms and memory function and explain abrogated vaccine responses in communities with endemic infections.

Published
2023
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12. Clinical, metabolic, and immunological characterisation of adult Ugandan patients with new-onset diabetes and low vitamin D status

Author

Davis Kibirige, Isaac Sekitoleko, Priscilla Balungi, Jacqueline Kyosiimire-Lugemwa, and William Lumu

Subjects
Vitamin D deficiency, Vitamin D insufficiency, Newly diagnosed diabetes, African population, Uganda, Sub-Saharan Africa, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Abstract Background Low vitamin D concentrations are associated with metabolic derangements, notably insulin resistance and pancreatic beta-cell dysfunction in Caucasian populations. Studies on its association with the clinical, metabolic, and immunologic characteristics in black African adult populations with new-onset diabetes are limited. This study aimed to describe the clinical, metabolic, and immunologic characteristics of a black Ugandan adult population with recently diagnosed diabetes and hypovitaminosis D. Methods Serum vitamin D concentrations were measured in 327 participants with recently diagnosed diabetes. Vitamin D deficiency, vitamin D insufficiency, and normal vitamin D status were defined as serum 25 hydroxyvitamin D levels of

Published
2022
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14. Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Author

Mehar (nee Abdulla), Amina Farhana, Abraham, Pattamukkil, Abrams, Elaine, Acero, Judith, Agaba, Gerald Muzorah, Ahimbisibwe, Grace, Ainebyoona, Barbara, Akobye, Winnie, Akhalwaya, Yasmeen, Akoojee, Nazim, Ali, Shabinah S., Amuge, Pauline, Andrea, Catherine, Muñoz Fernandez, Maria Angeles, Ankunda, Rogers, Rutebarika, Diana Antonia, Anugulruengkitt, Suvaporn, Apollo, Tsitsi, Archary, Moherndran, Arendze, Ronelle, Ategeka, Juliet, Atim, Eunice, Atwine, Lorna, Babiker, Abdel, Babirye, Sarah, Babu, Enock, Bagirigomwa, Edward, Baita, Angella, Balamusani, David, Baliram, Patsy, Baliruno, David, Ball, Colin, Balwa, Henry, Bamford, Alasdair, Bandi, Srini, Barker, Dominique, Barlow-Mosha, Linda, Bbuye, Dickson, Begum, Shazia, Behuhuma, Osee, Bernays, Sarah, Besigye, Rogers, Bester, Maria, Bhiri, Joyline, Bilardi, Davide, Bird, Kristien, Bollen, Pauline, Borg, Chiara, Borges Da Silva, Anne-Marie, Brown, Jackie, Bruno, Elena, Bunupuradah, Torsak, Burger, David, Buthelezi, Nomzamo, Bwakura-Dangarembizi, Mutsa, Byaruhanga, Africanus, Calvert, Joanna, Casey, Petronelle, Cassim, Haseena, Cebekhulu, Sphiwee, Chailert, Sanuphong, Chalermpantmetagul, Suwalai, Chamjamrat, Wanna, Chan, Man, Chandiwana, Precious, Chankun, Thannapat, Chanthaburanun, Sararut, Chanto, Nuttawut, Chidziva, Ennie, Chikowore, Minenhle, Chimanzi, Joy, Chinwong, Dujrudee, Chitongo, Stuart, Chitsamatanga, Moses, Choga, Joshua, Chutima, Duangrat, Clayden, Polly, Coelho, Alexandra, Colbers, Angela, Compagnucci, Alexandra, Constança Mendes, Ana, Conway, Magda, Cotton, Mark F., Crawley, Jane, Cressey, Tim R., Crisp, Jacky, Matos, Ana Cristina, Dadan, Sumaya, Daglish, Jacqui, Danaviah, Siva, Daniel, Tseleng, De Rossi, Anita, Denjanta, Sukanda, Dobbels, Els, Dowie, Maria, Dube, Prosper, Dube, Benedictor, Dudakia, Nimisha, Elwana, Alice, Epalza, Cristina, Eram, David, Erasmus, Juan, Erim, Peter, Escosa Garcia, Luis, Essack, Zaakirah, Estepa, Carolina, Etima, Monica, Fernandes, Alexandre, Fernandez, Maite, Fitzgerald, Felicity, Flynn, Jacquie, Ford, Deborah, Fortuny Guasch, Claudia, Foster, Caroline, Fourie, George, Fourie, Yolandie, Foxall, Sophie, Frank, Derusha, Gandhi, Kate, Garcia, India, Gartner, Kathleen, Gasa, Joshua, Gasa, Gugu, Giaquinto, Carlo, Gibb, Diana M., Gomez Rico, Coral, Gomez-Pena, Daniel, Gondo, Secrecy, Goodman, Anna, Gorreti Nakalema, Maria, Gozhora, Winnie, Greetanukroh, Pisut, Gregorio Maranon, Biobanco, Grossele, Tiziana, Gwande, Shamiso, Gwaze, Tapiwa, Gwenzi, Tsitsi, Hakim, James, Hakiza, Emmanuel, Kaka, Abdul Hamid, Harley, Ashley, Isaacs, Mornay, Isabirye, Richard, Ishemunyoro, Wilber, Jacobs, Tom, Jafta, Lungile, Jamil, Nasir, Janse van Rensburg, Anita Janse, Jeaven, Vinesh, Mellado Peña, Maria José, Jourdain, Gonzague, Juliet, Katabalwa, Jumpimai, Thidarat, Junkaew, Raungwit, Jupimai, Thidarat, Kaahwa, Winfred, Kabasonga, Mildred, Kaboggoza, Olivia, Kadhuba, Rose Jacqueline, Kaewbundit, Ampika, Kaewmamueng, Kanyanee, Kafufu, Bosco, Kakayi, Brenda, Kamboua, Phakamas, Kanjanavanit, Suparat, Kasangaki, Gladys, Kasipong, Naruporn, Kasozi, Miriam, Kataike, Hajira, Katemba, Chrispus, Kaudha, Elizabeth, Kekane, Nkata, Kekitiinwa, Adeodata R., Keminyeto, Edridah, Khamduang, Woottichai, Khamjakkaew, Warunee, Khamkon, Jiraporn, Khannak, Sasipass, Khatngam, Orapin, Khayanchoomnoom, Tassawan, Khumalo, Busi, Khunene, Mirriam, Khusuwan, Suwimon, Kibalama, Phionah, Kibenge, Robinah, Kirabira, Anthony, Kityo, Cissy M., Kiyimba, Lameck, Klein, Nigel, Klinprung, Soraya, Kobbe, Robin, Kobusingye, Olivia, Kobusungye, Josephine, Kongponoi, Areerat, Königs, Christoph, Koole, Olivier, Kouakam, Christelle, Krueduangkam, Nitinart, Kruenual, Namthip, Kunjaroenrut, Nuananong, Kyambadde, Raymonds, Kyobutungi, Priscilla, Kyomuhendo, Flavia, Kyomukama, Erinah, Lakha, Reshma, Langa, Cleopatra, Laomanit, Laddawan, Lebotsa, Emily, Leenasirimakul, Prattana, Lekku, Lawrence, Lensen, Sarah, Leroy, Valériane, Li, Jin, Liberty, Afaaf, Limplertjareanwanich, Juthamas, Little, Emma, Lugemwa, Abbas, Lutalo, Ezra, Jimenez, Jose Luis, Lyall, Hermione, MacDonald, Candice, Machache, Gladness, Madlala, Penelope, Madonsela, Tryphina, Maduna, Nomfundo, Maena, Joel, Mahanontharit, Apicha, Makanga, Collin, Makola, Candice, Makumbi, Shafic, Malgraaf, Lucille, Mamiane, Angelous, Mantkowski, Felicia, Mapfumo, Wendy, Marques, Laura, Mugagga, Agnes Mary, Maseko, Lindiwe, Masienyane, Tshepiso, Mathiba, Ruth, Matimba, Farai, Mawlana, Sajeeda, Mayanja, Emmanuel, Mayat, Fatima, Mbabazi, Ritah, Mbadaliga, Nokuthula, Mbasani, Faith, McClaughlin, Kathleen, McIlleron, Helen, Meethaisong, Watchara, Mendez Garcia, Patricia, Miwanda, Annet, Miranda, Carlota, Mkhize, Siphiwe, Mmolawa, Kgosimang, Mngqibisa, Rosie, Mohamed, Fatima, Moloantoa, Tumelo, Monametsi, Maletsatsi, Montero, Samuel, Moore, Cecilia L., Mosia, Rejoice, Moyo, Columbus, Mthethwa, Mumsy, Mudzingwa, Shepherd, Mudzviti, Tawona, Mujuru, Hilda, Mujyambere, Emmanuel, Mukanganiki, Trust, Mukisa Williams, Cynthia, Mulder, Mark, Mulima, Disan, Mulindwa, Alice, Mumbiro, Vivian, Mupambireyi, Zivai, Murciano Cabeza, Alba, Murungi, Herbert, Murungu, Dorothy, Musarurwa, Sandra, Musiime, Victor, Musiime, Alex V., Musisi, Maria, Musoke, Philippa, Musoke Nakirya, Barbara, Musoro, Godfrey, Musumba, Sharif, Mustafa, Sobia, Mutsai, Shirley, Mwesigwa Rubondo, Phyllis, Naabalamba, Mariam, Nagawa, Immaculate, Naidoo, Allemah, Nakabuye, Shamim, Nakabuye, Sarah, Nakalanzi, Sarah, Nalubwama, Justine, Nalugo, Annet, Nalusiba, Stella, Namajja, Clementine, Namanda, Sylvia, Namayanja, Paula, Nambi, Esther, Namuddu, Rachael Kikabi, Namukwaya, Stella, Namuli, Florence, Namusanje, Josephine, Namwanje, Rosemary, Nanan-kanjee, Anusha, Nanduudu, Annet, Nankunda, Charity, Baddokwaya, Joanita Nankya, Nannungi, Maria, Nansamba, Winnie, Nanthapisal, Kesdao, Nanyonjo, Juliet, Na-Rajsima, Sathaporn, Nasaazi, Claire, Nascimento, Helena, Nastouli, Eleni, Songtaweesin, Wipaporn Natalie, Nathoo, Kusum, Natuhurira, Ian, Nazzinda, Rashidah, Ncgaba, Thabisa, Ndigendawani, Milly, Ndlovu, Makhosonke, Nentsa, Georgina, Ngampiyaskul, Chaiwat, Ngcobo, Ntombenhle, Ngo Giang Huong, Nicole, Ngwaru, Pia, Nhema, Ruth, Ninsiima, Emily, Ninsiima, Gloria, Nkalo Phiri, Misheck, Noguera Julian, Antoni, Nolan, Monica, Noppakaorattanamanee, Thornthun, Nsibuka Kisekka, Muzamil, Nsirim, Eniola, Nundlal, Rashina, Nunes, Rosita, Nyantsa, Lungile, Nyati, Mandisa, O'Riordan, Sean, Ocitti Labeja, Paul, Odoch, Denis, Oguntimehin, Rachel, Ojok, Martin, Onen, Geoffrey, Orange, Wilma, Ounchanum, Pradthana, Ouma, Benson, Padrao, Andreia, Pako, Deborah, Parker, Anna, Pasko-Szcech, Malgorzata, Patel, Reena, Peongjakta, Rukchanok, Petpranee, Turian, Phillips, Tasmin, Philps, Jackie, Picault, Laura, Pieterse, Sonja, Pinheiro, Helena, Pongprapass, Supawadee, Pozniak, Anton, Prendergast, Andrew, Prieto Tato, Luis, Puangmalai, Patcharee, Puthanakit, Thanyawee, Rakgokong, Modiehi, Ramos, Helena, Ramsagar, Nastassja, Rau, Cornelius, Riault, Yoann, Rojo Conejo, Pablo, Clark, Basiimwa Roy, Rubanga, Eddie, Rubinga, Baker, Ruklao, Chutima, Runarassamee, Pattira, Saenjum, Chalermpong, Saewtrakool, Chayakorn, Saidi, Yacine, Sainz Costa, Talia, Saisaengjan, Chutima, Sakwa, Rebecca, Sarfati, Tatiana, Sbisi, Noshalaza, Scheppers, Dihedile, Schultze-Strasser, Stephan, Schulze-Sturm, Ulf, Scott, Karen, Seeley, Janet, Serunjogi, Robert, Sewnarain, Leora, Shakeshaft, Clare, Sidhoo, Subashinie, Shibemba, Mercy, Shingadia, Delane, Singh, Sheleika, Sirirungsi, Wasna, Sithebe, Sibongile, Smit, Theresa, Smith, Kurt, Smuts, Marlize, Spyer, Moira, Sripaoraya, Worathip, Srirompotong, Ussanee, Srisuk, Warunee, Ssenyonga, Mark, Sudsaard, Patamawadee, Sukrakanchana, Praornsuda, Tearsansern, Pathanee, Teixeira, Carla, Than-in-at, Kanchana, Thapwai, Thitiwat, Thaweesombat, Yupawan, Thewsoongnoen, Jutarat, Thiébaut, Rodolphe, Thomason, Margaret, Thrasyvoulou, Laura, Thungkham, Khanungnit, Tikabibamu, Judith, Tinago, Gloria, Trairat, Ketmookda, Tudor-Williams, Gareth, Tukamushaba, Mercy, Tukwasibwe, Deogratiuos, Tumusiime, Julius, Tuna, Joana, Turkova, Anna, Turner, Rebecca, Udomvised, Arttasid, Vadee, Aasia, Van Huyssteen, Hesti, Van Looy, Nadine, Variava, Ebrahim, Vaughan-Gordon, Yvonne, Vecchia, Giulio, Violari, Avy, Vowden, Richard, Waalewijn, Hylke, Wampamba, Rebecca, Welch, Steve, Weller, Ian, Weza, Sibusisiwe, White, Ellen, White, Ian, Widuch, Kaja, Wilkes, Helen, Wimonklang, Sookpanee, Wynne, Ben, Yingyong, Pacharaporn, Nakawungu, Zaam Zinda, Zuidewind, Peter, Chan, Man K, Bollen, Pauline D J, Bwakura-Dangarembizi, Mutsa F, Kekitiinwa, Adeodata R, Cotton, Mark F, Ahimbisibwe, Grace Miriam, Ali, Shabinah, Kityo, Cissy M, Ferrand, Rashida A, Gibb, Diana M, and Burger, David M

Published
2022
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15. Once-daily dolutegravir-based antiretroviral therapy in infants and children living with HIV from age 4 weeks: results from the below 14 kg cohort in the randomised ODYSSEY trial

Author

Mehar (nee Abdulla), Amina Farhana, Abraham, Pattamukkil, Abrams, Elaine, Acero, Judith, Agaba, Gerald Muzorah, Ahimbisibwe, Grace, Ainebyoona, Barbara, Akobye, Winnie, Akhalwaya, Yasmeen, Akoojee, Nazim, Ali, Shabinah S., Amuge, Pauline, Andrea, Catherine, Muñoz Fernandez, Maria Angeles, Ankunda, Rogers, Rutebarika, Diana Antonia, Anugulruengkitt, Suvaporn, Apollo, Tsitsi, Archary, Moherndran, Arendze, Ronelle, Ategeka, Juliet, Atim, Eunice, Atwine, Lorna, Babiker, Abdel, Babirye, Sarah, Babu, Enock, Bagirigomwa, Edward, Baita, Angella, Balamusani, David, Baliram, Patsy, Baliruno, David, Ball, Colin, Balwa, Henry, Bamford, Alasdair, Bandi, Srini, Barker, Dominique, Barlow-Mosha, Linda, Bbuye, Dickson, Begum, Shazia, Behuhuma, Osee, Bernays, Sarah, Besigye, Rogers, Bester, Maria, Bhiri, Joyline, Bilardi, Davide, Bird, Kristien, Bollen, Pauline, Borg, Chiara, Borges Da Silva, Anne-Marie, Brown, Jackie, Bruno, Elena, Bunupuradah, Torsak, Burger, David, Buthelezi, Nomzamo, Bwakura-Dangarembizi, Mutsa, Byaruhanga, Africanus, Calvert, Joanna, Casey, Petronelle, Cassim, Haseena, Cebekhulu, Sphiwee, Chailert, Sanuphong, Chalermpantmetagul, Suwalai, Chamjamrat, Wanna, Chan, Man, Chandiwana, Precious, Chankun, Thannapat, Chanthaburanun, Sararut, Chanto, Nuttawut, Chidziva, Ennie, Chikowore, Minenhle, Chimanzi, Joy, Chinwong, Dujrudee, Chitongo, Stuart, Chitsamatanga, Moses, Choga, Joshua, Chutima, Duangrat, Clayden, Polly, Coelho, Alexandra, Colbers, Angela, Compagnucci, Alexandra, Constança Mendes, Ana, Conway, Magda, Cotton, Mark F., Crawley, Jane, Cressey, Tim R., Crisp, Jacky, Matos, Ana Cristina, Dadan, Sumaya, Daglish, Jacqui, Danaviah, Siva, Daniel, Tseleng, De Rossi, Anita, Denjanta, Sukanda, Dobbels, Els, Dowie, Maria, Dube, Prosper, Dube, Benedictor, Dudakia, Nimisha, Elwana, Alice, Epalza, Cristina, Eram, David, Erasmus, Juan, Erim, Peter, Escosa Garcia, Luis, Essack, Zaakirah, Estepa, Carolina, Etima, Monica, Fernandes, Alexandre, Fernandez, Maite, Fitzgerald, Felicity, Flynn, Jacquie, Ford, Deborah, Fortuny Guasch, Claudia, Foster, Caroline, Fourie, George, Fourie, Yolandie, Foxall, Sophie, Frank, Derusha, Gandhi, Kate, Garcia, India, Gartner, Kathleen, Gasa, Joshua, Gasa, Gugu, Giaquinto, Carlo, Gibb, Diana M., Gomez Rico, Coral, Gomez-Pena, Daniel, Gondo, Secrecy, Goodman, Anna, Gorreti Nakalema, Maria, Gozhora, Winnie, Greetanukroh, Pisut, Gregorio Maranon, Biobanco, Grossele, Tiziana, Gwande, Shamiso, Gwaze, Tapiwa, Gwenzi, Tsitsi, Hakim, James, Hakiza, Emmanuel, Kaka, Abdul Hamid, Harley, Ashley, Isaacs, Mornay, Isabirye, Richard, Ishemunyoro, Wilber, Jacobs, Tom, Jafta, Lungile, Jamil, Nasir, Janse van Rensburg, Anita Janse, Jeaven, Vinesh, Mellado Peña, Maria José, Jourdain, Gonzague, Juliet, Katabalwa, Jumpimai, Thidarat, Junkaew, Raungwit, Jupimai, Thidarat, Kaahwa, Winfred, Kabasonga, Mildred, Kaboggoza, Olivia, Kadhuba, Rose Jacqueline, Kaewbundit, Ampika, Kaewmamueng, Kanyanee, Kafufu, Bosco, Kakayi, Brenda, Kamboua, Phakamas, Kanjanavanit, Suparat, Kasangaki, Gladys, Kasipong, Naruporn, Kasozi, Miriam, Kataike, Hajira, Katemba, Chrispus, Kaudha, Elizabeth, Kekane, Nkata, Kekitiinwa, Adeodata R., Keminyeto, Edridah, Khamduang, Woottichai, Khamjakkaew, Warunee, Khamkon, Jiraporn, Khannak, Sasipass, Khatngam, Orapin, Khayanchoomnoom, Tassawan, Khumalo, Busi, Khunene, Mirriam, Khusuwan, Suwimon, Kibalama, Phionah, Kibenge, Robinah, Kirabira, Anthony, Kityo, Cissy M., Kiyimba, Lameck, Klein, Nigel, Klinprung, Soraya, Kobbe, Robin, Kobusingye, Olivia, Kobusungye, Josephine, Kongponoi, Areerat, Königs, Christoph, Koole, Olivier, Kouakam, Christelle, Krueduangkam, Nitinart, Kruenual, Namthip, Kunjaroenrut, Nuananong, Kyambadde, Raymonds, Kyobutungi, Priscilla, Kyomuhendo, Flavia, Kyomukama, Erinah, Lakha, Reshma, Langa, Cleopatra, Laomanit, Laddawan, Lebotsa, Emily, Leenasirimakul, Prattana, Lekku, Lawrence, Lensen, Sarah, Leroy, Valériane, Li, Jin, Liberty, Afaaf, Limplertjareanwanich, Juthamas, Little, Emma, Lugemwa, Abbas, Lutalo, Ezra, Jimenez, Jose Luis, Lyall, Hermione, MacDonald, Candice, Machache, Gladness, Madlala, Penelope, Madonsela, Tryphina, Maduna, Nomfundo, Maena, Joel, Mahanontharit, Apicha, Makanga, Collin, Makola, Candice, Makumbi, Shafic, Malgraaf, Lucille, Mamiane, Angelous, Mantkowski, Felicia, Mapfumo, Wendy, Marques, Laura, Mugagga, Agnes Mary, Maseko, Lindiwe, Masienyane, Tshepiso, Mathiba, Ruth, Matimba, Farai, Mawlana, Sajeeda, Mayanja, Emmanuel, Mayat, Fatima, Mbabazi, Ritah, Mbadaliga, Nokuthula, Mbasani, Faith, McClaughlin, Kathleen, McIlleron, Helen, Meethaisong, Watchara, Mendez Garcia, Patricia, Miwanda, Annet, Miranda, Carlota, Mkhize, Siphiwe, Mmolawa, Kgosimang, Mngqibisa, Rosie, Mohamed, Fatima, Moloantoa, Tumelo, Monametsi, Maletsatsi, Montero, Samuel, Moore, Cecilia L., Mosia, Rejoice, Moyo, Columbus, Mthethwa, Mumsy, Mudzingwa, Shepherd, Mudzviti, Tawona, Mujuru, Hilda, Mujyambere, Emmanuel, Mukanganiki, Trust, Mukisa Williams, Cynthia, Mulder, Mark, Mulima, Disan, Mulindwa, Alice, Mumbiro, Vivian, Mupambireyi, Zivai, Murciano Cabeza, Alba, Murungi, Herbert, Murungu, Dorothy, Musarurwa, Sandra, Musiime, Victor, Musiime, Alex V., Musisi, Maria, Musoke, Philippa, Musoke Nakirya, Barbara, Musoro, Godfrey, Musumba, Sharif, Mustafa, Sobia, Mutsai, Shirley, Mwesigwa Rubondo, Phyllis, Naabalamba, Mariam, Nagawa, Immaculate, Naidoo, Allemah, Nakabuye, Shamim, Nakabuye, Sarah, Nakalanzi, Sarah, Nalubwama, Justine, Nalugo, Annet, Nalusiba, Stella, Namajja, Clementine, Namanda, Sylvia, Namayanja, Paula, Nambi, Esther, Namuddu, Rachael Kikabi, Namukwaya, Stella, Namuli, Florence, Namusanje, Josephine, Namwanje, Rosemary, Nanan-kanjee, Anusha, Nanduudu, Annet, Nankunda, Charity, Baddokwaya, Joanita Nankya, Nannungi, Maria, Nansamba, Winnie, Nanthapisal, Kesdao, Nanyonjo, Juliet, Na-Rajsima, Sathaporn, Nasaazi, Claire, Nascimento, Helena, Nastouli, Eleni, Songtaweesin, Wipaporn Natalie, Nathoo, Kusum, Natuhurira, Ian, Nazzinda, Rashidah, Ncgaba, Thabisa, Ndigendawani, Milly, Ndlovu, Makhosonke, Nentsa, Georgina, Ngampiyaskul, Chaiwat, Ngcobo, Ntombenhle, Ngo Giang Huong, Nicole, Ngwaru, Pia, Nhema, Ruth, Ninsiima, Emily, Ninsiima, Gloria, Nkalo Phiri, Misheck, Noguera Julian, Antoni, Nolan, Monica, Noppakaorattanamanee, Thornthun, Nsibuka Kisekka, Muzamil, Nsirim, Eniola, Nundlal, Rashina, Nunes, Rosita, Nyantsa, Lungile, Nyati, Mandisa, O'Riordan, Sean, Ocitti Labeja, Paul, Odoch, Denis, Oguntimehin, Rachel, Ojok, Martin, Onen, Geoffrey, Orange, Wilma, Ounchanum, Pradthana, Ouma, Benson, Padrao, Andreia, Pako, Deborah, Parker, Anna, Pasko-Szcech, Malgorzata, Patel, Reena, Peongjakta, Rukchanok, Petpranee, Turian, Phillips, Tasmin, Philps, Jackie, Picault, Laura, Pieterse, Sonja, Pinheiro, Helena, Pongprapass, Supawadee, Pozniak, Anton, Prendergast, Andrew, Prieto Tato, Luis, Puangmalai, Patcharee, Puthanakit, Thanyawee, Rakgokong, Modiehi, Ramos, Helena, Ramsagar, Nastassja, Rau, Cornelius, Riault, Yoann, Rojo Conejo, Pablo, Clark, Basiimwa Roy, Rubanga, Eddie, Rubinga, Baker, Ruklao, Chutima, Runarassamee, Pattira, Saenjum, Chalermpong, Saewtrakool, Chayakorn, Saidi, Yacine, Sainz Costa, Talia, Saisaengjan, Chutima, Sakwa, Rebecca, Sarfati, Tatiana, Sbisi, Noshalaza, Scheppers, Dihedile, Schultze-Strasser, Stephan, Schulze-Sturm, Ulf, Scott, Karen, Seeley, Janet, Serunjogi, Robert, Sewnarain, Leora, Shakeshaft, Clare, Sidhoo, Subashinie, Shibemba, Mercy, Shingadia, Delane, Singh, Sheleika, Sirirungsi, Wasna, Sithebe, Sibongile, Smit, Theresa, Smith, Kurt, Smuts, Marlize, Spyer, Moira, Sripaoraya, Worathip, Srirompotong, Ussanee, Srisuk, Warunee, Ssenyonga, Mark, Sudsaard, Patamawadee, Sukrakanchana, Praornsuda, Tearsansern, Pathanee, Teixeira, Carla, Than-in-at, Kanchana, Thapwai, Thitiwat, Thaweesombat, Yupawan, Thewsoongnoen, Jutarat, Thiébaut, Rodolphe, Thomason, Margaret, Thrasyvoulou, Laura, Thungkham, Khanungnit, Tikabibamu, Judith, Tinago, Gloria, Trairat, Ketmookda, Tudor-Williams, Gareth, Tukamushaba, Mercy, Tukwasibwe, Deogratiuos, Tumusiime, Julius, Tuna, Joana, Turkova, Anna, Turner, Rebecca, Udomvised, Arttasid, Vadee, Aasia, Van Huyssteen, Hesti, Van Looy, Nadine, Variava, Ebrahim, Vaughan-Gordon, Yvonne, Vecchia, Giulio, Violari, Avy, Vowden, Richard, Waalewijn, Hylke, Wampamba, Rebecca, Welch, Steve, Weller, Ian, Weza, Sibusisiwe, White, Ellen, White, Ian, Widuch, Kaja, Wilkes, Helen, Wimonklang, Sookpanee, Wynne, Ben, Yingyong, Pacharaporn, Nakawungu, Zaam Zinda, Zuidewind, Peter, Mujuru, Hilda A, Kityo, Cissy M, Turner, Rebecca M, Ali, Shabinah, Nathoo, Kusum J, Mosala, Modehei, Kekitiinwa, Adeodata R, Rojo, Pablo, and Gibb, Diana M

Published
2022
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16. Efficacy and safety of dolutegravir or darunavir in combination with lamivudine plus either zidovudine or tenofovir for second-line treatment of HIV infection (NADIA): week 96 results from a prospective, multicentre, open-label, factorial, randomised, non-inferiority trial

Author

Kambugu, Andrew, Kaimal, Arvind, Castelnuovo, Barbara, Kiiza, Daniel, Asienzo, Jesca, Kisembo, John, Nsubuga, John, Okwero, Max, Muyise, Rhona, Kityo, Cissy, Nasaazi, Claire, Nakiboneka, Dridah L., Mugerwa, Henry, Namusanje, Josephine, Najjuuko, Theresa, Masaba, Timothy, Serumaga, Timothy, Alinaitwe, Adolf, Arinda, Allan, Rweyora, Angela, Ategeka, Gilbert, Kangah, Mary Goretti, Lugemwa, Abbas, Kasozi, Mariam, Tukumushabe, Phionah, Akunda, Rogers, Makumbi, Shafic, Musumba, Sharif, Myalo, Sula, Ahuura, John, Namusisi, Annet Mary, Kibirige, Daniel, Kiweewa, Francis, Mirembe, Grace, Mabonga, Habert, Wandege, Joseph, Nakakeeto, Josephine, Namubiru, Sharon, Nansalire, Winfred, Siika, Abraham Mosigisi, Kwobah, Charles Meja, Mboya, Chris Sande, Mokaya, Martha Mokeira Bisieri, Karoney, Mercy Jelagat, Cheruiyot, Priscilla Chepkorir, Cherutich, Salinah, Njuguna, Simon Wachira, Kirui, Viola Cherotich, Borok, Margaret, Chidziva, Ennie, Musoro, Godfrey, Hakim, James, Bhiri, Joyline, Phiri, Misheck, Mudzingwa, Shepherd, Manyanga, Tadios, Kiragga, Agnes, Banegura, Anchilla Mary, Hoppe, Anne, Balyegisawa, Apolo, Agwang, Betty, Isaaya, Brian, Tumwine, Constantine, Odongpiny, Eva Laker A., Musaazi, Joseph, Paton, Nicholas, Senkungu, Peter, Walimbwa, Stephen, Kamara, Yvonne, Amperiize, Mathius, Allen, Elizabeth, Opondo, Charles, Mohammed, Perry, van Rein-van der Horst, Willemijn, Van Delft, Yvon, Boateng, Fafa Addo, Namara, Doreen, Kaleebu, Pontiano, Ojoo, Sylvia, Bwakura, Tapiwanashe, Katana, Milly, Venter, Francois, Phiri, Sam, Walker, Sarah, Paton, Nicholas I, Siika, Abraham, and Odongpiny, Eva Laker A

Published
2022
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17. Dolutegravir dosing for children with HIV weighing less than 20 kg: pharmacokinetic and safety substudies nested in the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Author

Waalewijn, Hylke, Chan, Man K, Bollen, Pauline D J, Mujuru, Hilda A, Makumbi, Shafic, Kekitiinwa, Adeodata R, Kaudha, Elizabeth, Sarfati, Tatiana, Musoro, Godfrey, Nanduudu, Annet, Lugemwa, Abbas, Amuge, Pauline, Moore, Cecilia L, Rojo, Pablo, Giaquinto, Carlo, Colbers, Angela, Gibb, Diana M, Ford, Deborah, Turkova, Anna, and Burger, David M

Published
2022
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19. Borrowing information across patient subgroups in clinical trials, with application to a paediatric trial

Author

Turner, Rebecca M., Turkova, Anna, Moore, Cecilia L., Bamford, Alasdair, Archary, Moherndran, Barlow-Mosha, Linda N., Cotton, Mark F., Cressey, Tim R., Kaudha, Elizabeth, Lugemwa, Abbas, Lyall, Hermione, Mujuru, Hilda A., Mulenga, Veronica, Musiime, Victor, Rojo, Pablo, Tudor-Williams, Gareth, Welch, Steven B., Gibb, Diana M., Ford, Deborah, and White, Ian R.

Published
2022
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20. Borrowing information across patient subgroups in clinical trials, with application to a paediatric trial

Author

Rebecca M. Turner, Anna Turkova, Cecilia L. Moore, Alasdair Bamford, Moherndran Archary, Linda N. Barlow-Mosha, Mark F. Cotton, Tim R. Cressey, Elizabeth Kaudha, Abbas Lugemwa, Hermione Lyall, Hilda A. Mujuru, Veronica Mulenga, Victor Musiime, Pablo Rojo, Gareth Tudor-Williams, Steven B. Welch, Diana M. Gibb, Deborah Ford, Ian R. White, and and the ODYSSEY Trial Team

Subjects
Paediatric trials, Subgroups, Small samples, Bayesian analysis, Borrowing information, Medicine (General), R5-920
Abstract

Abstract Background Clinical trial investigators may need to evaluate treatment effects in a specific subgroup (or subgroups) of participants in addition to reporting results of the entire study population. Such subgroups lack power to detect a treatment effect, but there may be strong justification for borrowing information from a larger patient group within the same trial, while allowing for differences between populations. Our aim was to develop methods for eliciting expert opinions about differences in treatment effect between patient populations, and to incorporate these opinions into a Bayesian analysis. Methods We used an interaction parameter to model the relationship between underlying treatment effects in two subgroups. Elicitation was used to obtain clinical opinions on the likely values of the interaction parameter, since this parameter is poorly informed by the data. Feedback was provided to experts to communicate how uncertainty about the interaction parameter corresponds with relative weights allocated to subgroups in the Bayesian analysis. The impact on the planned analysis was then determined. Results The methods were applied to an ongoing non-inferiority trial designed to compare antiretroviral therapy regimens in 707 children living with HIV and weighing ≥ 14 kg, with an additional group of 85 younger children weighing

Published
2022
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21. Identification of a Clade-Specific HLA-C*03:02 CTL Epitope GY9 Derived from the HIV-1 p17 Matrix Protein.

Author

Kyobe, Samuel, Mwesigwa, Savannah, Nkurunungi, Gyaviira, Retshabile, Gaone, Egesa, Moses, Katagirya, Eric, Amujal, Marion, Mlotshwa, Busisiwe C., Williams, Lesedi, Sendagire, Hakim, Kiragga, Dithan, Mardon, Graeme, Matshaba, Mogomotsi, Hanchard, Neil A., Kyosiimire-Lugemwa, Jacqueline, and Robinson, David

Subjects
EXTRACELLULAR matrix proteins, HIV, HISTOCOMPATIBILITY class I antigens, VACCINE effectiveness, EPITOPES, T cells
Abstract

Efforts towards an effective HIV-1 vaccine have remained mainly unsuccessful. There is increasing evidence for a potential role of HLA-C-restricted CD8+ T cell responses in HIV-1 control, including our recent report of HLA-C*03:02 among African children. However, there are no documented optimal HIV-1 CD8+ T cell epitopes restricted by HLA-C*03:02; additionally, the structural influence of HLA-C*03:02 on epitope binding is undetermined. Immunoinformatics approaches provide a fast and inexpensive method to discover HLA-restricted epitopes. Here, we employed immunopeptidomics to identify HLA-C*03:02 CD8+ T cell epitopes. We identified a clade-specific Gag-derived GY9 (GTEELRSLY) HIV-1 p17 matrix epitope potentially restricted to HLA-C*03:02. Residues E62, T142, and E151 in the HLA-C*03:02 binding groove and positions p3, p6, and p9 on the GY9 epitope are crucial in shaping and stabilizing the epitope binding. Our findings support the growing evidence of the contribution of HLA-C molecules to HIV-1 control and provide a prospect for vaccine strategies. [ABSTRACT FROM AUTHOR]

Published
2024
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22. Prevalence of suicidal ideation and attempted suicide amongst women and girls in South Asia: A systematic review and meta-analysis

Author

Hoimonty Mazumder, Tony Lugemwa, Md Monir Hossain Shimul, Easter Protiva Gain, M. Mahbub Hossain, and Kenneth D. Ward

Subjects
Suicidal ideation, Attempted suicide, Suicide attempts, South Asia, Women suicidal behavior, Suicidal behavior, Psychiatry, RC435-571
Abstract

A growing body of literature suggests an increased risk of suicidal ideation and attempted suicide among women and girls in South Asia. This systematic review and meta-analysis aimed to appraise the current evidence and estimate the prevalence of suicidal ideation and attempted suicide in this population. We systematically searched nine (9) bibliographic databases (PubMed, ASU, Embase, WoS, CINAHL, PsycInfo, PsycArticles, HSNE, and NAHC) and additional sources through December 17, 2021, for studies that reported the prevalence of suicidal ideation or attempted suicide. Random-effect models were used to estimate pooled prevalence.Of 30 eligible studies, 27 reported suicidal ideation and 12 reported attempted suicide. The pooled prevalence of overall suicidal ideation and attempted suicide were 17% (95% CI:14.00–20.00, n ​= ​39674) and 5% (95% CI: 4.00–7.00, n ​= ​20791), respectively. Thirteen studies enrolled adult women from the general population, nine recruited adolescent girls, and eight recruited female medical/university students. The pooled estimate of suicidal ideation was higher among adults, whereas attempted suicide was found to be higher among adolescents. These findings on suicidal ideation and attempted suicide suggest a heavy epidemiological and psychosocial burden among South Asian women and girls that necessitates a gender-sensitive integrated multi-sectoral approach.

Published
2022
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23. 19β,28-Epoxy-18α-olean-3β-ol-2-furoate from Allobetulin (19β,28-Epoxy-18α-olean-3β-ol)

Author

Fulgentius Nelson Lugemwa

Subjects
19β,28-Epoxy-18α-olean-3β-ol-2-furoate, betulin, allobetulin, iodine, 2-furoyl chloride, esterification, Inorganic chemistry, QD146-197
Abstract

The E ring of betulin rearranges and forms a cyclic ether when treated with an acid. Treatment of betulin with iodine generated hydrogen iodide in situ, which went on to promote the rearrangement at C-19 and C-20, followed by cyclization to form allobetulin. A reaction of allobetulin with 2-furoyl chloride yielded 19β,28-Epoxy-18α-olean-3β-ol-2-furoate.

Published
2022
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25. ODYSSEY clinical trial design: a randomised global study to evaluate the efficacy and safety of dolutegravir-based antiretroviral therapy in HIV-positive children, with nested pharmacokinetic sub-studies to evaluate pragmatic WHO-weight-band based dolutegravir dosing

Author

Cecilia L. Moore, Anna Turkova, Hilda Mujuru, Adeodata Kekitiinwa, Abbas Lugemwa, Cissy M. Kityo, Linda N. Barlow-Mosha, Tim R. Cressey, Avy Violari, Ebrahim Variava, Mark F. Cotton, Moherndran Archary, Alexandra Compagnucci, Thanyawee Puthanakit, Osee Behuhuma, Yacine Saϊdi, James Hakim, Pauline Amuge, Lorna Atwine, Victor Musiime, David M. Burger, Clare Shakeshaft, Carlo Giaquinto, Pablo Rojo, Diana M. Gibb, Deborah Ford, and the ODYSSEY Trial Team

Subjects
Randomized control trial, Basket trial, HIV, Paediatric, Efficacy, Safety, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Dolutegravir (DTG)-based antiretroviral therapy (ART) is highly effective and well-tolerated in adults and is rapidly being adopted globally. We describe the design of the ODYSSEY trial which evaluates the efficacy and safety of DTG-based ART compared with standard-of-care in children and adolescents. The ODYSSEY trial includes nested pharmacokinetic (PK) sub-studies which evaluated pragmatic World Health Organization (WHO) weight-band-based DTG dosing and opened recruitment to children

Published
2021
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26. Islet autoantibody positivity in an adult population with recently diagnosed diabetes in Uganda.

Author

Davis Kibirige, Isaac Sekitoleko, Priscilla Balungi, Jacqueline Kyosiimire-Lugemwa, William Lumu, Angus G Jones, Andrew T Hattersley, Liam Smeeth, and Moffat J Nyirenda

Subjects
Medicine, Science
Abstract

AimsThis study aimed to investigate the frequency of islet autoantibody positivity in adult patients with recently diagnosed diabetes in Uganda and its associated characteristics.MethodsAutoantibodies to glutamic acid decarboxylase-65 (GADA), zinc transporter 8 (ZnT8-A), and tyrosine phosphatase (IA-2A) were measured in 534 adult patients with recently diagnosed diabetes. Islet autoantibody positivity was defined based on diagnostic thresholds derived from a local adult population without diabetes. The socio-demographic, clinical, and metabolic characteristics of islet autoantibody-positive and negative participants were then compared. The differences in these characteristics were analysed using the x2 test for categorical data and the Kruskal Wallis test for continuous data. Multivariate analysis was performed to identify predictors of islet autoantibody positivity.ResultsThirty four (6.4%) participants were positive for ≥1 islet autoantibody. GADA, IA-2A and ZnT8-A positivity was detected in 17 (3.2%), 10 (1.9%), and 7 (1.3%) participants, respectively. Compared with those negative for islet autoantibodies, participants positive for islet autoantibodies were more likely to live in a rural area (n = 18, 52.9% Vs n = 127, 25.5%, p = 0.005), to be initiated on insulin therapy (n = 19, 55.9% Vs n = 134, 26.8%, pConclusionThe prevalence of islet autoantibody positivity was relatively low, suggesting that pancreatic autoimmunity is a rare cause of new-onset diabetes in this adult Ugandan population. Living in a rural area and being initiated on insulin therapy were independently associated with islet autoantibody positivity in this study population.

Published
2022
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27. Simplified dolutegravir dosing for children with HIV weighing 20 kg or more: pharmacokinetic and safety substudies of the multicentre, randomised ODYSSEY trial

Author

Bollen, Pauline D J, Moore, Cecilia L, Mujuru, Hilda A, Makumbi, Shafic, Kekitiinwa, Adeodata R, Kaudha, Elisabeth, Parker, Anna, Musoro, Godfrey, Nanduudu, Annet, Lugemwa, Abbas, Amuge, Pauline, Hakim, James G, Rojo, Pablo, Giaquinto, Carlo, Colbers, Angela, Gibb, Diana M, Ford, Deborah, Turkova, Anna, and Burger, David M

Published
2020
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28. Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

Author

Turkova, Anna, primary, White, Ellen, additional, Kekitiinwa, Adeodata R, additional, Mumbiro, Vivian, additional, Kaudha, Elizabeth, additional, Liberty, Afaaf, additional, Ahimbisibwe, Grace Miriam, additional, Moloantoa, Tumelo, additional, Srirompotong, Ussanee, additional, Mosia, Nozibusiso Rejoice, additional, Puthanakit, Thanyawee, additional, Kobbe, Robin, additional, Fortuny, Clàudia, additional, Kataike, Hajira, additional, Bbuye, Dickson, additional, Na-Rajsima, Sathaporn, additional, Coelho, Alexandra, additional, Lugemwa, Abbas, additional, Bwakura-Dangarembizi, Mutsa F, additional, Klein, Nigel, additional, Mujuru, Hilda A, additional, Kityo, Cissy, additional, Cotton, Mark F, additional, Ferrand, Rashida A, additional, Giaquinto, Carlo, additional, Rojo, Pablo, additional, Violari, Avy, additional, Gibb, Diana M, additional, Ford, Deborah, additional, Mehar (nee Abdulla), Amina Farhana, additional, Abraham, Pattamukkil, additional, Abrams, Elaine, additional, Acero, Judith, additional, Agaba, Gerald Muzorah, additional, Ahimbisibwe, Grace, additional, Ainebyoona, Barbara, additional, Akobye, Winnie, additional, Akhalwaya, Yasmeen, additional, Akoojee, Nazim, additional, Ali, Shabinah S., additional, Amuge, Pauline, additional, Andrea, Catherine, additional, Muñoz Fernandez, Maria Angeles, additional, Ankunda, Rogers, additional, Rutebarika, Diana Antonia, additional, Anugulruengkitt, Suvaporn, additional, Apollo, Tsitsi, additional, Archary, Moherndran, additional, Arendze, Ronelle, additional, Ategeka, Juliet, additional, Atim, Eunice, additional, Atwine, Lorna, additional, Babiker, Abdel, additional, Babirye, Sarah, additional, Babu, Enock, additional, Bagirigomwa, Edward, additional, Baita, Angella, additional, Balamusani, David, additional, Baliram, Patsy, additional, Baliruno, David, additional, Ball, Colin, additional, Balwa, Henry, additional, Bamford, Alasdair, additional, Bandi, Srini, additional, Barker, Dominique, additional, Barlow-Mosha, Linda, additional, Begum, Shazia, additional, Behuhuma, Osee, additional, Bernays, Sarah, additional, Besigye, Rogers, additional, Bester, Maria, additional, Bhiri, Joyline, additional, Bilardi, Davide, additional, Bird, Kristien, additional, Bollen, Pauline, additional, Borg, Chiara, additional, Borges Da Silva, Anne-Marie, additional, Brown, Jackie, additional, Bruno, Elena, additional, Bunupuradah, Torsak, additional, Burger, David, additional, Buthelezi, Nomzamo, additional, Bwakura-Dangarembizi, Mutsa, additional, Byaruhanga, Africanus, additional, Calvert, Joanna, additional, Casey, Petronelle, additional, Cassim, Haseena, additional, Cebekhulu, Sphiwee, additional, Chailert, Sanuphong, additional, Chalermpantmetagul, Suwalai, additional, Chamjamrat, Wanna, additional, Chan, Man, additional, Chandiwana, Precious, additional, Chankun, Thannapat, additional, Chanthaburanun, Sararut, additional, Chanto, Nuttawut, additional, Chidziva, Ennie, additional, Chikowore, Minenhle, additional, Chimanzi, Joy, additional, Chinwong, Dujrudee, additional, Chitongo, Stuart, additional, Chitsamatanga, Moses, additional, Choga, Joshua, additional, Chutima, Duangrat, additional, Clayden, Polly, additional, Colbers, Angela, additional, Compagnucci, Alexandra, additional, Constança Mendes, Ana, additional, Conway, Magda, additional, Crawley, Jane, additional, Cressey, Tim R, additional, Crisp, Jacky, additional, Matos, Ana Cristina, additional, Dadan, Sumaya, additional, Daglish, Jacqui, additional, Danaviah, Siva, additional, Daniel, Tseleng, additional, De Rossi, Anita, additional, Denjanta, Sukanda, additional, Dobbels, Els, additional, Dowie, Maria, additional, Dube, Prosper, additional, Dube, Benedictor, additional, Dudakia, Nimisha, additional, Elwana, Alice, additional, Epalza, Cristina, additional, Eram, David, additional, Erasmus, Juan, additional, Erim, Peter, additional, Escosa Garcia, Luis, additional, Essack, Zaakirah, additional, Estepa, Carolina, additional, Etima, Monica, additional, Fernandes, Alexandre, additional, Fernandez, Maite, additional, Fitzgerald, Felicity, additional, Flynn, Jacquie, additional, Fortuny Guasch, Claudia, additional, Foster, Caroline, additional, Fourie, George, additional, Fourie, Yolandie, additional, Foxall, Sophie, additional, Frank, Derusha, additional, Gandhi, Kate, additional, Garcia, India, additional, Gartner, Kathleen, additional, Gasa, Joshua, additional, Gasa, Gugu, additional, Gomez Rico, Coral, additional, Gomez-Pena, Daniel, additional, Gondo, Secrecy, additional, Goodman, Anna, additional, Gorreti Nakalema, Maria, additional, Gozhora, Winnie, additional, Greetanukroh, Pisut, additional, Gregorio Maranon, Biobanco, additional, Grossele, Tiziana, additional, Gwande, Shamiso, additional, Gwaze, Tapiwa, additional, Gwenzi, Tsitsi, additional, Hakim, James, additional, Hakiza, Emmanuel, additional, Kaka, Abdul Hamid, additional, Harley, Ashley, additional, Isaacs, Mornay, additional, Isabirye, Richard, additional, Ishemunyoro, Wilber, additional, Jacobs, Tom, additional, Jafta, Lungile, additional, Jamil, Nasir, additional, Janse van Rensburg, Anita Janse, additional, Jeaven, Vinesh, additional, Mellado Peña, Maria José, additional, Jourdain, Gonzague, additional, Juliet, Katabalwa, additional, Jumpimai, Thidarat, additional, Junkaew, Raungwit, additional, Jupimai, Thidarat, additional, Kaahwa, Winfred, additional, Kabasonga, Mildred, additional, Kaboggoza, Olivia, additional, Kadhuba, Rose Jacqueline, additional, Kaewbundit, Ampika, additional, Kaewmamueng, Kanyanee, additional, Kafufu, Bosco, additional, Kakayi, Brenda, additional, Kamboua, Phakamas, additional, Kanjanavanit, Suparat, additional, Kasangaki, Gladys, additional, Kasipong, Naruporn, additional, Kasozi, Miriam, additional, Katemba, Chrispus, additional, Kekane, Nkata, additional, Keminyeto, Edridah, additional, Khamduang, Woottichai, additional, Khamjakkaew, Warunee, additional, Khamkon, Jiraporn, additional, Khannak, Sasipass, additional, Khatngam, Orapin, additional, Khayanchoomnoom, Tassawan, additional, Khumalo, Busi, additional, Khunene, Mirriam, additional, Khusuwan, Suwimon, additional, Kibalama, Phionah, additional, Kibenge, Robinah, additional, Kirabira, Anthony, additional, Kityo, Cissy M, additional, Kiyimba, Lameck, additional, Klinprung, Soraya, additional, Kobusingye, Olivia, additional, Kobusungye, Josephine, additional, Kongponoi, Areerat, additional, Königs, Christoph, additional, Koole, Olivier, additional, Kouakam, Christelle, additional, Krueduangkam, Nitinart, additional, Kruenual, Namthip, additional, Kunjaroenrut, Nuananong, additional, Kyambadde, Raymonds, additional, Kyobutungi, Priscilla, additional, Kyomuhendo, Flavia, additional, Kyomukama, Erinah, additional, Lakha, Reshma, additional, Langa, Cleopatra, additional, Laomanit, Laddawan, additional, Lebotsa, Emily, additional, Leenasirimakul, Prattana, additional, Lekku, Lawrence, additional, Lensen, Sarah, additional, Leroy, Valériane, additional, Li, Jin, additional, Limplertjareanwanich, Juthamas, additional, Little, Emma, additional, Lutalo, Ezra, additional, Jimenez, Jose Luis, additional, Lyall, Hermione, additional, MacDonald, Candice, additional, Machache, Gladness, additional, Madlala, Penelope, additional, Madonsela, Tryphina, additional, Maduna, Nomfundo, additional, Maena, Joel, additional, Mahanontharit, Apicha, additional, Makanga, Collin, additional, Makola, Candice, additional, Makumbi, Shafic, additional, Malgraaf, Lucille, additional, Mamiane, Angelous, additional, Mantkowski, Felicia, additional, Mapfumo, Wendy, additional, Marques, Laura, additional, Mugagga, Agnes Mary, additional, Maseko, Lindiwe, additional, Masienyane, Tshepiso, additional, Mathiba, Ruth, additional, Matimba, Farai, additional, Mawlana, Sajeeda, additional, Mayanja, Emmanuel, additional, Mayat, Fatima, additional, Mbabazi, Ritah, additional, Mbadaliga, Nokuthula, additional, Mbasani, Faith, additional, McClaughlin, Kathleen, additional, McIlleron, Helen, additional, Meethaisong, Watchara, additional, Mendez Garcia, Patricia, additional, Miwanda, Annet, additional, Miranda, Carlota, additional, Mkhize, Siphiwe, additional, Mmolawa, Kgosimang, additional, Mngqibisa, Rosie, additional, Mohamed, Fatima, additional, Monametsi, Maletsatsi, additional, Montero, Samuel, additional, Moore, Cecilia L, additional, Mosia, Rejoice, additional, Moyo, Columbus, additional, Mthethwa, Mumsy, additional, Mudzingwa, Shepherd, additional, Mudzviti, Tawona, additional, Mujuru, Hilda, additional, Mujyambere, Emmanuel, additional, Mukanganiki, Trust, additional, Mukisa Williams, Cynthia, additional, Mulder, Mark, additional, Mulima, Disan, additional, Mulindwa, Alice, additional, Mupambireyi, Zivai, additional, Murciano Cabeza, Alba, additional, Murungi, Herbert, additional, Murungu, Dorothy, additional, Musarurwa, Sandra, additional, Musiime, Victor, additional, Musiime, Alex V, additional, Musisi, Maria, additional, Musoke, Philippa, additional, Musoke Nakirya, Barbara, additional, Musoro, Godfrey, additional, Musumba, Sharif, additional, Mustafa, Sobia, additional, Mutsai, Shirley, additional, Mwesigwa Rubondo, Phyllis, additional, Naabalamba, Mariam, additional, Nagawa, Immaculate, additional, Naidoo, Allemah, additional, Nakabuye, Shamim, additional, Nakabuye, Sarah, additional, Nakalanzi, Sarah, additional, Nalubwama, Justine, additional, Nalugo, Annet, additional, Nalusiba, Stella, additional, Namajja, Clementine, additional, Namanda, Sylvia, additional, Namayanja, Paula, additional, Nambi, Esther, additional, Namuddu, Rachael Kikabi, additional, Namukwaya, Stella, additional, Namuli, Florence, additional, Namusanje, Josephine, additional, Namwanje, Rosemary, additional, Nanan-kanjee, Anusha, additional, Nanduudu, Annet, additional, Nankunda, Charity, additional, Baddokwaya, Joanita Nankya, additional, Nannungi, Maria, additional, Nansamba, Winnie, additional, Nanthapisal, Kesdao, additional, Nanyonjo, Juliet, additional, Nasaazi, Claire, additional, Nascimento, Helena, additional, Nastouli, Eleni, additional, Songtaweesin, Wipaporn Natalie, additional, Nathoo, Kusum, additional, Natuhurira, Ian, additional, Nazzinda, Rashidah, additional, Ncgaba, Thabisa, additional, Ndigendawani, Milly, additional, Ndlovu, Makhosonke, additional, Nentsa, Georgina, additional, Ngampiyaskul, Chaiwat, additional, Ngcobo, Ntombenhle, additional, Ngo Giang Huong, Nicole, additional, Ngwaru, Pia, additional, Nhema, Ruth, additional, Ninsiima, Emily, additional, Ninsiima, Gloria, additional, Nkalo Phiri, Misheck, additional, Noguera Julian, Antoni, additional, Nolan, Monica, additional, Noppakaorattanamanee, Thornthun, additional, Nsibuka Kisekka, Muzamil, additional, Nsirim, Eniola, additional, Nundlal, Rashina, additional, Nunes, Rosita, additional, Nyantsa, Lungile, additional, Nyati, Mandisa, additional, O'Riordan, Sean, additional, Ocitti Labeja, Paul, additional, Odoch, Denis, additional, Oguntimehin, Rachel, additional, Ojok, Martin, additional, Onen, Geoffrey, additional, Orange, Wilma, additional, Ounchanum, Pradthana, additional, Ouma, Benson, additional, Padrao, Andreia, additional, Pako, Deborah, additional, Parker, Anna, additional, Pasko-Szcech, Malgorzata, additional, Patel, Reena, additional, Peongjakta, Rukchanok, additional, Petpranee, Turian, additional, Phillips, Tasmin, additional, Philps, Jackie, additional, Picault, Laura, additional, Pieterse, Sonja, additional, Pinheiro, Helena, additional, Pongprapass, Supawadee, additional, Pozniak, Anton, additional, Prendergast, Andrew, additional, Prieto Tato, Luis, additional, Puangmalai, Patcharee, additional, Rakgokong, Modiehi, additional, Ramos, Helena, additional, Ramsagar, Nastassja, additional, Rau, Cornelius, additional, Riault, Yoann, additional, Rojo Conejo, Pablo, additional, Clark, Basiimwa Roy, additional, Rubanga, Eddie, additional, Rubinga, Baker, additional, Ruklao, Chutima, additional, Runarassamee, Pattira, additional, Saenjum, Chalermpong, additional, Saewtrakool, Chayakorn, additional, Saidi, Yacine, additional, Sainz Costa, Talia, additional, Saisaengjan, Chutima, additional, Sakwa, Rebecca, additional, Sarfati, Tatiana, additional, Sbisi, Noshalaza, additional, Scheppers, Dihedile, additional, Schultze-Strasser, Stephan, additional, Schulze-Sturm, Ulf, additional, Scott, Karen, additional, Seeley, Janet, additional, Serunjogi, Robert, additional, Sewnarain, Leora, additional, Shakeshaft, Clare, additional, Sidhoo, Subashinie, additional, Shibemba, Mercy, additional, Shingadia, Delane, additional, Singh, Sheleika, additional, Sirirungsi, Wasna, additional, Sithebe, Sibongile, additional, Smit, Theresa, additional, Smith, Kurt, additional, Smuts, Marlize, additional, Spyer, Moira, additional, Sripaoraya, Worathip, additional, Srisuk, Warunee, additional, Ssenyonga, Mark, additional, Sudsaard, Patamawadee, additional, Sukrakanchana, Praornsuda, additional, Tearsansern, Pathanee, additional, Teixeira, Carla, additional, Than-in-at, Kanchana, additional, Thapwai, Thitiwat, additional, Thaweesombat, Yupawan, additional, Thewsoongnoen, Jutarat, additional, Thiébaut, Rodolphe, additional, Thomason, Margaret, additional, Thrasyvoulou, Laura, additional, Thungkham, Khanungnit, additional, Tikabibamu, Judith, additional, Tinago, Gloria, additional, Trairat, Ketmookda, additional, Tudor-Williams, Gareth, additional, Tukamushaba, Mercy, additional, Tukwasibwe, Deogratiuos, additional, Tumusiime, Julius, additional, Tuna, Joana, additional, Turkova, Anna, additional, Turner, Rebecca, additional, Udomvised, Arttasid, additional, Vadee, Aasia, additional, Van Huyssteen, Hesti, additional, Van Looy, Nadine, additional, Variava, Ebrahim, additional, Vaughan-Gordon, Yvonne, additional, Vecchia, Giulio, additional, Vowden, Richard, additional, Waalewijn, Hylke, additional, Wampamba, Rebecca, additional, Welch, Steve, additional, Weller, Ian, additional, Weza, Sibusisiwe, additional, White, Ian, additional, Widuch, Kaja, additional, Wilkes, Helen, additional, Wimonklang, Sookpanee, additional, Wynne, Ben, additional, Yingyong, Pacharaporn, additional, Nakawungu, Zaam Zinda, additional, and Zuidewind, Peter, additional

Published
2023
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29. Exome Sequencing Reveals a Putative Role for HLA-C*03:02 in Control of HIV-1 in African Pediatric Populations

Author

Samuel Kyobe, Savannah Mwesigwa, Grace P. Kisitu, John Farirai, Eric Katagirya, Angella N. Mirembe, Lesego Ketumile, Misaki Wayengera, Fred Ashaba Katabazi, Edgar Kigozi, Edward M. Wampande, Gaone Retshabile, Busisiwe C. Mlotshwa, Lesedi Williams, Koketso Morapedi, Ishmael Kasvosve, Jacqueline Kyosiimire-Lugemwa, Betty Nsangi, Masego Tsimako-Johnstone, Chester W. Brown, Moses Joloba, Gabriel Anabwani, Lukhele Bhekumusa, Sununguko W. Mpoloka, Graeme Mardon, Mogomotsi Matshaba, Adeodata Kekitiinwa, and Neil A. Hanchard

Subjects
AIDS, childhood HIV, long-term non-progression, genetics, genomics, Genetics, QH426-470
Abstract

Human leucocyte antigen (HLA) class I molecules present endogenously processed antigens to T-cells and have been linked to differences in HIV-1 disease progression. HLA allelotypes show considerable geographical and inter-individual variation, as does the rate of progression of HIV-1 disease, with long-term non-progression (LTNP) of disease having most evidence of an underlying genetic contribution. However, most genetic analyses of LTNP have occurred in adults of European ancestry, limiting the potential transferability of observed associations to diverse populations who carry the burden of disease. This is particularly true of HIV-1 infected children. Here, using exome sequencing (ES) to infer HLA allelotypes, we determine associations with HIV-1 LTNP in two diverse African pediatric populations. We performed a case-control association study of 394 LTNPs and 420 rapid progressors retrospectively identified from electronic medical records of pediatric HIV-1 populations in Uganda and Botswana. We utilized high-depth ES to perform high-resolution HLA allelotyping and assessed evidence of association between HLA class I alleles and LTNP. Sixteen HLA alleles and haplotypes had significantly different frequencies between Uganda and Botswana, with allelic differences being more prominent in HLA-A compared to HLA-B and C allelotypes. Three HLA allelotypes showed association with LTNP, including a novel association in HLA-C (HLA-B∗57:03, aOR 3.21, Pc = 0.0259; B∗58:01, aOR 1.89, Pc = 0.033; C∗03:02, aOR 4.74, Pc = 0.033). Together, these alleles convey an estimated population attributable risk (PAR) of non-progression of 16.5%. We also observed novel haplotype associations with HLA-B∗57:03-C∗07:01 (aOR 5.40, Pc = 0.025) and HLA-B∗58:01-C∗03:02 (aOR 4.88, Pc = 0.011) with a PAR of 9.8%, as well as a previously unreported independent additive effect and heterozygote advantage of HLA-C∗03:02 with B∗58:01 (aOR 4.15, Pc = 0.005) that appears to limit disease progression, despite weak LD (r2 = 0.18) between these alleles. These associations remained irrespective of gender or country. In one of the largest studies of HIV in Africa, we find evidence of a protective effect of canonical HLA-B alleles and a novel HLA-C association that appears to augment existing HIV-1 control alleles in pediatric populations. Our findings outline the value of using multi-ethnic populations in genetic studies and offer a novel HIV-1 association of relevance to ongoing vaccine studies.

Published
2021
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31. Schistosoma mansoni infection alters the host pre-vaccination environment resulting in blunted Hepatitis B vaccination immune responses

Author

Muir, Roshell, primary, Metcalf, Talibah, additional, Fourati, Slim, additional, Bartsch, Yannic, additional, Kyosiimire-Lugemwa, Jacqueline, additional, Canderan, Glenda, additional, Alter, Galit, additional, Muyanja, Enoch, additional, Okech, Brenda, additional, Namatovu, Teddy, additional, Namara, Irene, additional, Namuniina, Annemarie, additional, Ssetaala, Ali, additional, Mpendo, Juliet, additional, Nanvubya, Annet, additional, Kitandwe, Paul Kato, additional, Bagaya, Bernard S., additional, Kiwanuka, Noah, additional, Nassuna, Jacent, additional, Biribawa, Victoria Menya, additional, Elliott, Alison M., additional, de Dood, Claudia J., additional, Senyonga, William, additional, Balungi, Priscilla, additional, Kaleebu, Pontiano, additional, Mayanja, Yunia, additional, Odongo, Matthew, additional, Connors, Jennifer, additional, Fast, Pat, additional, Price, Matt A., additional, Corstjens, Paul L. A. M., additional, van Dam, Govert J., additional, Kamali, Anatoli, additional, Sekaly, Rafick Pierre, additional, and Haddad, Elias K., additional

Published
2023
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32. Effect of ready-to-use supplementary food on mortality in severely immunocompromised HIV-infected individuals in Africa initiating antiretroviral therapy (REALITY): an open-label, parallel-group, randomised controlled trial

Author

Mugyenyi, Peter, Kityo, Cissy, Musiime, Victor, Wavamunno, Priscilla, Nambi, Esther, Ocitti, Paul, Ndigendawani, Milly, Kabahenda, Sheila, Kemigisa, Mable, Acen, Juliet, Olebo, David Francis, Mpamize, Gordon, Amone, Alex, Okweny, David, Mbonye, Andrew, Nambaziira, Florence, Rweyora, Angela, Kangah, Mary, Kabaswahili, Beatrice, Abach, James, Abongomera, George, Omongin, Joseph, Aciro, Irene, Philliam, Aleti, Arach, Beatrice, Ocung, Emmanuel, Amone, Geoffrey, Miles, Peter, Adong, Claudia, Tumsuiime, Constance, Kidega, Patrick, Otto, Ben, Apio, Florence, Baleeta, Keith, Mukuye, Andrew, Abwola, Mary, Ssennono, Fred, Baliruno, David, Tuhirwe, Stephen, Namisi, Ronald, Kigongo, Fredrick, Kikyonkyo, Dickson, Mushahara, Furaha, Tusiime, Julian, Musiime, Alex, Nankya, Agnes, Atwongyeire, Dickens, Sirikye, Sowal, Myalo, Sula, Noowe, Nelson, Lugemwa, Abbas, Kasozi, Mariam, Mwebe, Sandra, Atwine, Lorna, Senkindu, Tapson, Natuhurira, Ian, Katemba, Chrispus, Ninsiima, Emily, Acaku, Moses, Kyomuhangi, Joy, Ankunda, Rogers, Tukwasibwe, Deogratious, Ayesiga, Lillian, Hakim, James, Nathoo, Kusum, Bwakura-Dangarembizi, Mutsa, Reid, Andrew, Chidziva, Ennie, Mhute, Tawand, Tinago, Gloria, Bhiri, Joyline, Mudzingwa, Shepherd, Phiri, Misheck, Steamer, John, Nhema, Ruth, Warambwa, Colin, Musoro, Godfrey, Mutsai, Shirley, Nemasango, Beauty, Moyo, Columbus, Chitongo, Stuart, Rashirai, Kennias, Vhembo, Sydney, Mlambo, Brian, Nkomani, Sanele, Ndemera, Buxton, Willard, Marko, Berejena, Chipo, Musodza, Yeukai, Matiza, Patience, Mudenge, Boniface, Guti, Vongai, Etyang, Anthony, Agutu, Clara, Berkley, Jay, Maitland, Kathryn, Njuguna, Patricia, Mwaringa, Shalton, Etyang, Timothy, Awuondo, Ken, Wale, Stephen, Shangala, Jimmy, Kithunga, Jefwa, Mwarumba, Salim, Said Maitha, Salma, Mutai, Robert, Lozi Lewa, Margaret, Mwambingu, Gabriel, Mwanzu, Alfred, Kalama, Connie, Latham, Helen, Shikuku, Joyce, Fondo, Amos, Njogu, Anne, Khadenge, Connie, Mwakisha, Bryan, Siika, Abraham, Wools-Kaloustian, Kara, Nyandiko, Winston, Chepkorir-Cheruiyot, Priscilla, Sudoi, Allan, Wachira, Simon, Meli, Betty, Karoney, Mercy, Nzioka, Agnes, Tanui, Michael, Mokaya, Martha, Ekiru, Wilson, Mboya, Chris, Mwimali, Dorothy, Mengich, Cecilia, Choge, Julie, Injera, Wilfred, Njenga, Kennedy, Cherutich, Salinah, Anyango Orido, Millicent, Omondi Lwande, Gerald, Rutto, Peter, Mudogo, Alice, Kutto, Irene, Shali, Amina, Jaika, Linda, Jerotich, Hellen, Pierre, Mowlem, Mallewa, Jane, Kaunda, Symon, Van Oosterhout, Joep, O'Hare, Bernadette, Heydermann, Robert, Gonzalez, Carmen, Dzabala, Nettie, Kelly, Christine, Denis, Brigitte, Selemani, George, Nyondo- Mipando, Linda, Chirwa, Emmie, Banda, Peter, Mvula, Linley, Msuku, Harrison, Ziwoya, Milton, Manda, Yollam, Nicholas, Simon, Masesa, Clemens, Mwalukomo, Thandi, Makhaza, Lumbani, Sheha, Irene, Bwanali, Joseph, Limbuni, Molly, Gibb, Diana M, Thomason, Margaret J, Walker, Ann Sarah, Pett, Sarah L, Szubert, Alexander J, Griffiths, Anna, Wilkes, Helen, Rajapakse, Chathurika, Spyer, Moira J, Prendergast, Andrew J, Klein, Nigel, Rauchenberger, Mary, Van Looy, Nadine, Little, Emma, Fairbrother, Keith, Cowan, Frances, Seeley, Janet, Bernays, Sarah, Kawuma, Rachel, Mupambireyi, Zivai, Chepkorir, Priscilla, Melly, Betty, Walker, A Sarah, and Berkley, James A

Published
2018
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33. Lopinavir plus nucleoside reverse-transcriptase inhibitors, lopinavir plus raltegravir, or lopinavir monotherapy for second-line treatment of HIV (EARNEST): 144-week follow-up results from a randomised controlled trial

Author

Agweng, E, Awio, P, Bakeinyaga, G, Isabirye, C, Kabuga, U, Kasuswa, S, Katuramu, M, Kiweewa, F, Kyomugisha, H, Lutalo, E, Mulima, D, Musana, H, Musitwa, G, Musiime, V, Ndigendawan, M, Namata, H, Nkalubo, J, Labejja, P Ocitti, Okello, P, Olal, P, Pimundu, G, Segonga, P, Ssali, F, Tamale, Z, Tumukunde, D, Namala, W, Byaruhanga, R, Kayiwa, J, Tukamushaba, J, Abunyang, S, Eram, D, Denis, O, Lwalanda, R, Mugarura, L, Namusanje, J, Nankya, I, Ndashimye, E, Nabulime, E, Senfuma, O, Bihabwa, G, Buluma, E, Elbireer, A, Kamya, D, Katwere, M, Kiggundu, R, Komujuni, C, Laker, E, Lubwama, E, Mambule, I, Matovu, J, Nakajubi, A, Nakku, J, Nalumenya, R, Namuyimbwa, L, Semitala, F, Wandera, B, Wanyama, J, Mugerwa, H, Ninsiima, E, Ssenkindu, T, Mwebe, S, Atwine, L, William, H, Katemba, C, Acaku, M, Ssebutinde, P, Kitizo, H, Kukundakwe, J, Naluguza, M, Ssegawa, K, Namayanja, Nsibuka, F, Tuhirirwe, P, Fortunate, M, Acen, J, Achidri, J, Amone, A, Chamai, M, Ditai, J, Kemigisa, M, Kiconco, M, Matama, C, Mbanza, D, Nambaziira, F, Odoi, M Owor, Rweyora, A, Tumwebaze, G, Kalanzi, H, Katabaazi, J, Kiyingi, A, Mbidde, M, Mugenyi, M, Okong, P, Senoga, I, Abwola, M, Baliruno, D, Bwomezi, J, Kasede, A, Mudoola, M, Namisi, R, Ssennono, F, Tuhirwe, S, Amone, G, Abach, J, Aciro, I, Arach, B, Kidega, P, Omongin, J, Ocung, E, Odong, W, Philliam, A, Alima, H, Ahimbisibwe, B, Atuhaire, E, Atukunda, F, Bekusike, G, Bulegyeya, A, Kahatano, D, Kamukama, S, Kyoshabire, J, Nassali, A, Mbonye, A, Naturinda, T M, Ndukukire, Nshabohurira, A, Ntawiha, H, Rogers, A, Tibyasa, M, Kiirya, S, Atwongyeire, D, Nankya, A, Draleku, C, Nakiboneka, D, Odoch, D, Lakidi, L, Ruganda, R, Abiriga, R, Mulindwa, M, Balmoi, F, Kafuma, S, Moriku, E, Reid, A, Chidziva, E, Musoro, G, Warambwa, C, Tinago, G, Mutsai, S, Phiri, M, Mudzingwa, S, Bafana, T, Masore, V, Moyo, C, Nhema, R, Chitongo, S, Heyderman, Robert, Kabanga, Lucky, Kaunda, Symon, Kudzala, Aubrey, Lifa, Linly, Mallewa, Jane, Moore, Mike, Mtali, Chrissie, Musowa, George, Mwimaniwa, Grace, Sikwese, Rosemary, Ziwoya, Milton, Chitete, H Chimbaka B, Kamanga, S, Makwakwa, T Kayinga E, Mbiya, R, Mlenga, M, Mphande, T, Mtika, C, Mushani, G, Ndhlovu, O, Ngonga, M, Nkhana, I, Nyirenda, R, Cheruiyot, P, Kwobah, C, Ekiru, W Lokitala, Mokaya, M, Mudogo, A, Nzioka, A, Tanui, M, Wachira, S, Wools-Kaloustian, K, Alipalli, P, Chikatula, E, Kipaila, J, Kunda, I, Lakhi, S, Malama, J, Mufwambi, W, Mulenga, L, Mwaba, P, Mwamba, E, Namfukwe, M, Kerukadho, E, Ngwatu, B, Birungi, J, Boles, J, Burke, A, Castle, L, Ghuman, S, Kendall, L, Tebbs, S, Whittle, J, Wilkes, H, Young, N, Spyer, M, Kapuya, C, Kyomuhendo, F, Kyakundi, D, Mkandawire, N, Mulambo, S, Senyonjo, S, Angus, B, Arenas-Pinto, A, Palfreeman, A, Post, F, Ishola, D, Arribas, J, Colebunders, R, Floridia, M, Giuliano, M, Mallon, P, Walsh, P, De Rosa, M, Rinaldi, E, Weller, I, Gilks, C, Kangewende, A, Luyirika, E, Miiro, F, Ojoo, S, Phiri, S, Wapakabulo, A, Peto, T, Matenga, J, Cloherty, G, van Wyk, J, Norton, M, Lehrman, S, Lamba, P, Malik, K, Rooney, J, Snowden, W, Villacian, J, Hakim, James G, Thompson, Jennifer, Kityo, Cissy, Hoppe, Anne, Kambugu, Andrew, van Oosterhout, Joep J, Lugemwa, Abbas, Siika, Abraham, Mwebaze, Raymond, Mweemba, Aggrey, Abongomera, George, Thomason, Margaret J, Easterbrook, Philippa, Mugyenyi, Peter, Walker, A Sarah, and Paton, Nicholas I

Published
2018
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34. Immunologic, virologic and genetic studies of HIV-1 infected long-term non-progressors in Uganda

Author

Kyosiimire-Lugemwa, Jacqueline

Subjects
616.979201
Abstract

HIV -l-specific T -cell responses are preserved in HIV -1 infected individuals with non- progressing HIV -1 disease. Evaluation of HIV -I-specific T -cell functionality; T -cell phenotype; HLA class; subtype, RNA and DNA levels of HIV -1; and other factors in long- term non-progressors (LTNP) in comparison with rapid progressors (RP) could reveal novel correlates of protection against disease progression. We show that HIV -1 RNA viral load, proviral DNA load and lipopolysaccharide (LPS) were positively correlated with each other and negatively correlated with CD4 count. We show that IFN-y Gag-specific responses were higher in LTNP, whereas IFN-y Nef-specific responses were higher in RP. Nef-specific responses positively correlated with HIV-I RNA viral load, proviral DNA load and LPS. Flow cytometric analysis of HIV -l-specific responses showed that IFN -y +, CD I 07 a +IFN -y +, and IFN-y+TNF-a+ dual responses to Gag-p24 were higher in LTNP and correlated positively with CD4 count. Nef-specific responses in LTNP were predominantly polyfunctional. Among HIV-I-specific responses to Gag-pI7, Gag-p24 and Nef, only production of IFN- y+TNF-a+ in response to the Nef-specific pep tides correlated negatively with both RNA viral load and proviral DNA load and was a good correlate of protection. In analysis of perforin and degranulation, Nef-specific responses showed higher monofunctional CD8+CD 1 07a +PF in RP and CD8+CD107a+PF+ in LTNP. CD8+CD107a+PF positively correlated with RNA viral load, proviral DNA load and LPS and negatively correlated with CD4 T-cell count. IL- 21 levels in the CD8 T-cells of RP were higher than in the LTNP. CD4+CD45RA +CD38+HLADR+ T-celllevels, PD-l levels and CD8+ naive T-cells were higher in the LTNP. PD-1 levels and CD8+ naive T-cells correlated negatively with LPS and positively with CD4 count, PD-l also correlated negatively with RNA viral load. High CD8 naive T -cells and PD-I expression were good correlates of protection. T -cell regulatory levels were not significantly different in LTNP and RP. Correlates of rapid disease progression included high IFN-y Nef-specific responses and high monofunctional CD8+CDI07a+PF Nef-specific responses.

Published
2011

35. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treating uncomplicated malaria: a randomized trial to guide policy in Uganda.

Author

Yeka, Adoke, Dorsey, Grant, Kamya, Moses R, Talisuna, Ambrose, Lugemwa, Myers, Rwakimari, John Bosco, Staedke, Sarah G, Rosenthal, Philip J, Wabwire-Mangen, Fred, and Bukirwa, Hasifa

Subjects
Humans, Malaria, Falciparum, Ethanolamines, Artemisinins, Quinolines, Fluorenes, Antimalarials, Drug Therapy, Combination, Health Policy, Child, Child, Preschool, Infant, Uganda, Artemether, Lumefantrine, Malaria, Falciparum, Drug Therapy, Combination, Preschool, General Science & Technology
Abstract

BackgroundUganda recently adopted artemether-lumefantrine (AL) as the recommended first-line treatment for uncomplicated malaria. However, AL has several limitations, including a twice-daily dosing regimen, recommendation for administration with fatty food, and a high risk of reinfection soon after therapy in high transmission areas. Dihydroartemisinin-piperaquine (DP) is a new alternative artemisinin-based combination therapy that is dosed once daily and has a long post-treatment prophylactic effect. We compared the efficacy and safety of AL with DP in Kanungu, an area of moderate malaria transmission.Methodology/principal findingsPatients aged 6 months to 10 years with uncomplicated falciparum malaria were randomized to therapy and followed for 42 days. Genotyping was used to distinguish recrudescence from new infection. Of 414 patients enrolled, 408 completed follow-up. Compared to patients treated with artemether-lumefantrine, patients treated with dihydroartemisinin-piperaquine had a significantly lower risk of recurrent parasitaemia (33.2% vs. 12.2%; risk difference = 20.9%, 95% CI 13.0-28.8%) but no statistically significant difference in the risk of treatment failure due to recrudescence (5.8% vs. 2.0%; risk difference = 3.8%, 95% CI -0.2-7.8%). Patients treated with dihydroartemisinin-piperaquine also had a lower risk of developing gametocytaemia after therapy (4.2% vs. 10.6%, p = 0.01). Both drugs were safe and well tolerated.Conclusions/significanceDP is highly efficacious, and operationally preferable to AL because of a less intensive dosing schedule and requirements. Dihydroartemisinin-piperaquine should be considered for a role in the antimalarial treatment policy of Uganda.Trial registrationControlled-Trials.com ISRCTN75606663.

Published
2008

36. Nucleoside reverse-transcriptase inhibitor cross-resistance and outcomes from second-line antiretroviral therapy in the public health approach: an observational analysis within the randomised, open-label, EARNEST trial

Author

Agweng, E, Awio, P, Bakeinyaga, G, Isabirye, C, Kabuga, U, Kasuswa, S, Katuramu, M, Kityo, C, Kiweewa, F, Kyomugisha, H, Lutalo, E, Mugyenyi, P, Mulima, D, Musana, H, Musitwa, G, Musiime, V, Ndigendawan, M, Namata, H, Nkalubo, J, Labejja, P Ocitti, Okello, P, Olal, P, Pimundu, G, Segonga, P, Ssali, F, Tamale, Z, Tumukunde, D, Namala, W, Byaruhanga, R, Kayiwa, J, Tukamushaba, J, Abunyang, S, Eram, D, Denis, O, Lwalanda, R, Mugarura, L, Namusanje, J, Nankya, I, Ndashimye, E, Nabulime, E, Senfuma, O, Bihabwa, G, Buluma, E, Easterbrook, P, Elbireer, A, Kambugu, A, Kamya, D, Katwere, M, Kiggundu, R, Komujuni, C, Laker, E, Lubwama, E, Mambule, I, Matovu, J, Nakajubi, A, Nakku, J, Nalumenya, R, Namuyimbwa, L, Semitala, F, Wandera, B, Wanyama, J, Mugerwa, H, Lugemwa, A, Ninsiima, E, Ssenkindu, T, Mwebe, S, Atwine, L, William, H, Katemba, C, Acaku, M, Ssebutinde, P, Kitizo, H, Kukundakwe, J, Naluguza, M, Ssegawa, K, Namayanja, Nsibuka, F, Tuhirirwe, P, Fortunate, M, Acen, J, Achidri, J, Amone, A, Chamai, M, Ditai, J, Kemigisa, M, Kiconco, M, Matama, C, Mbanza, D, Nambaziira, F, Odoi, M Owor, Rweyora, A, Tumwebaze, G, Kalanzi, H, Katabaazi, J, Kiyingi, A, Mbidde, M, Mugenyi, M, Mwebaze, R, Okong, P, Senoga, I, Abwola, M, Baliruno, D, Bwomezi, J, Kasede, A, Mudoola, M, Namisi, R, Ssennono, F, Tuhirwe, S, Abongomera, G, Amone, G, Abach, J, Aciro, I, Arach, B, Kidega, P, Omongin, J, Ocung, E, Odong, W, Philliam, A, Alima, H, Ahimbisibwe, B, Atuhaire, E, Atukunda, F, Bekusike, G, Bulegyeya, A, Kahatano, D, Kamukama, S, Kyoshabire, J, Nassali, A, Mbonye, A, Naturinda, T M, Ndukukire, Nshabohurira, A, Ntawiha, H, Rogers, A, Tibyasa, M, Kiirya, S, Atwongyeire, D, Nankya, A, Draleku, C, Nakiboneka, D, Odoch, D, Lakidi, L, Ruganda, R, Abiriga, R, Mulindwa, M, Balmoi, F, Kafuma, S, Moriku, E, Hakim, J, Reid, A, Chidziva, E, Musoro, G, Warambwa, C, Tinago, G, Mutsai, S, Phiri, M, Mudzingwa, S, Bafana, T, Masore, V, Moyo, C, Nhema, R, Chitongo, S, Heyderman, Robert, Kabanga, Lucky, Kaunda, Symon, Kudzala, Aubrey, Lifa, Linly, Mallewa, Jane, Moore, Mike, Mtali, Chrissie, Musowa, George, Mwimaniwa, Grace, Sikwese, Rosemary, van Oosterhout, Joep, Ziwoya, Milton, Chimbaka, H, Chitete, B, Kamanga, S, Makwakwa, T Kayinga E, Mbiya, R, Mlenga, M, Mphande, T, Mtika, C, Mushani, G, Ndhlovu, O, Ngonga, M, Nkhana, I, Nyirenda, R, Cheruiyot, P, Kwobah, C, Ekiru, W Lokitala, Mokaya, M, Mudogo, A, Nzioka, A, Siika, A, Tanui, M, Wachira, S, Wools-Kaloustian, K, Alipalli, P, Chikatula, E, Kipaila, J, Kunda, I, Lakhi, S, Malama, J, Mufwambi, W, Mulenga, L, Mwaba, P, Mwamba, E, Mweemba, A, Namfukwe, M, Kerukadho, E, Ngwatu, B, Birungi, J, Paton, N, Boles, J, Burke, A, Castle, L, Ghuman, S, Kendall, L, Hoppe, A, Tebbs, S, Thomason, M, Thompson, J, Walker, S, Whittle, J, Wilkes, H, Young, N, Spyer, M, Kapuya, C, Kyomuhendo, F, Kyakundi, D, Mkandawire, N, Mulambo, S, Senyonjo, S, Angus, B, Arenas-Pinto, A, Palfreeman, A, Post, F, Ishola, D, Arribas, J, Colebunders, R, Floridia, M, Giuliano, M, Mallon, P, Walsh, P, De Rosa, M, Rinaldi, E, Weller, I, Gilks, C, Kangewende, A, Luyirika, E, Miiro, F, Mwamba, P, Ojoo, S, Phiri, S, van Oosterhout, J, Wapakabulo, A, Peto, T, French, N, Matenga, J, Cloherty, G, van Wyk, J, Norton, M, Lehrman, S, Lamba, P, Malik, K, Rooney, J, Snowden, W, Villacian, J, Paton, Nicholas I, Kityo, Cissy, Thompson, Jennifer, Nankya, Immaculate, Bagenda, Leonard, Hoppe, Anne, Hakim, James, Kambugu, Andrew, van Oosterhout, Joep J, Kiconco, Mary, Bertagnolio, Silvia, Easterbrook, Philippa J, Mugyenyi, Peter, and Walker, A Sarah

Published
2017
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37. Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

Author

Turkova, A., White, E., Kekitiinwa, A.R., Mumbiro, V., Kaudha, E., Liberty, A., Ahimbisibwe, G.M., Moloantoa, T., Srirompotong, U., Mosia, N.R., Puthanakit, T., Kobbe, R., Fortuny, C., Kataike, H., Bbuye, D., Na-Rajsima, S., Coelho, A., Lugemwa, A., Bwakura-Dangarembizi, M.F., Klein, N., Mujuru, H.A., Kityo, C., Cotton, M.F., Ferrand, R.A., Giaquinto, C., Rojo, P., Violari, A., Burger, D.M., Colbers, A.P., Gibb, D.M., Ford, D., Turkova, A., White, E., Kekitiinwa, A.R., Mumbiro, V., Kaudha, E., Liberty, A., Ahimbisibwe, G.M., Moloantoa, T., Srirompotong, U., Mosia, N.R., Puthanakit, T., Kobbe, R., Fortuny, C., Kataike, H., Bbuye, D., Na-Rajsima, S., Coelho, A., Lugemwa, A., Bwakura-Dangarembizi, M.F., Klein, N., Mujuru, H.A., Kityo, C., Cotton, M.F., Ferrand, R.A., Giaquinto, C., Rojo, P., Violari, A., Burger, D.M., Colbers, A.P., Gibb, D.M., and Ford, D.

Abstract

Item does not contain fulltext, BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124-159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event

Published
2023

38. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treatment of malaria: a randomized trial.

Author

Kamya, Moses R, Yeka, Adoke, Bukirwa, Hasifa, Lugemwa, Myers, Rwakimari, John B, Staedke, Sarah G, Talisuna, Ambrose O, Greenhouse, Bryan, Nosten, François, Rosenthal, Philip J, Wabwire-Mangen, Fred, and Dorsey, Grant

Subjects
Clinical Sciences
Abstract

ObjectivesTo compare the efficacy and safety of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) for treating uncomplicated falciparum malaria in Uganda.DesignRandomized single-blinded clinical trial.SettingApac, Uganda, an area of very high malaria transmission intensity.ParticipantsChildren aged 6 mo to 10 y with uncomplicated falciparum malaria.InterventionTreatment of malaria with AL or DP, each following standard 3-d dosing regimens.Outcome measuresRisks of recurrent parasitemia at 28 and 42 d, unadjusted and adjusted by genotyping to distinguish recrudescences and new infections.ResultsOf 421 enrolled participants, 417 (99%) completed follow-up. The unadjusted risk of recurrent falciparum parasitemia was significantly lower for participants treated with DP than for those treated with AL after 28 d (11% versus 29%; risk difference [RD] 18%, 95% confidence interval [CI] 11%-26%) and 42 d (43% versus 53%; RD 9.6%, 95% CI 0%-19%) of follow-up. Similarly, the risk of recurrent parasitemia due to possible recrudescence (adjusted by genotyping) was significantly lower for participants treated with DP than for those treated with AL after 28 d (1.9% versus 8.9%; RD 7.0%, 95% CI 2.5%-12%) and 42 d (6.9% versus 16%; RD 9.5%, 95% CI 2.8%-16%). Patients treated with DP had a lower risk of recurrent parasitemia due to non-falciparum species, development of gametocytemia, and higher mean increase in hemoglobin compared to patients treated with AL. Both drugs were well tolerated; serious adverse events were uncommon and unrelated to study drugs.ConclusionDP was superior to AL for reducing the risk of recurrent parasitemia and gametocytemia, and provided improved hemoglobin recovery. DP thus appears to be a good alternative to AL as first-line treatment of uncomplicated malaria in Uganda. To maximize the benefit of artemisinin-based combination therapy in Africa, treatment should be integrated with aggressive strategies to reduce malaria transmission intensity.

Published
2007

39. Efficacy and safety of dolutegravir or darunavir in combination with lamivudine plus either zidovudine or tenofovir for second-line treatment of HIV infection (NADIA): week 96 results from a prospective, multicentre, open-label, factorial, randomised, non-inferiority trial

Author

Nicholas I Paton, Joseph Musaazi, Cissy Kityo, Stephen Walimbwa, Anne Hoppe, Apolo Balyegisawa, Jesca Asienzo, Arvind Kaimal, Grace Mirembe, Abbas Lugemwa, Gilbert Ategeka, Margaret Borok, Henry Mugerwa, Abraham Siika, Eva Laker A Odongpiny, Barbara Castelnuovo, Agnes Kiragga, Andrew Kambugu, Daniel Kiiza, John Kisembo, John Nsubuga, Max Okwero, Rhona Muyise, Claire Nasaazi, Dridah L. Nakiboneka, Josephine Namusanje, Theresa Najjuuko, Timothy Masaba, Timothy Serumaga, Adolf Alinaitwe, Allan Arinda, Angela Rweyora, Mary Goretti Kangah, Mariam Kasozi, Phionah Tukumushabe, Rogers Akunda, Shafic Makumbi, Sharif Musumba, Sula Myalo, John Ahuura, Annet Mary Namusisi, Daniel Kibirige, Francis Kiweewa, Habert Mabonga, Joseph Wandege, Josephine Nakakeeto, Sharon Namubiru, Winfred Nansalire, Abraham Mosigisi Siika, Charles Meja Kwobah, Chris Sande Mboya, Martha Mokeira Bisieri Mokaya, Mercy Jelagat Karoney, Priscilla Chepkorir Cheruiyot, Salinah Cherutich, Simon Wachira Njuguna, Viola Cherotich Kirui, Ennie Chidziva, Godfrey Musoro, James Hakim, Joyline Bhiri, Misheck Phiri, Shepherd Mudzingwa, Tadios Manyanga, Anchilla Mary Banegura, Betty Agwang, Brian Isaaya, Constantine Tumwine, Eva Laker A. Odongpiny, Nicholas Paton, Peter Senkungu, Yvonne Kamara, Mathius Amperiize, Elizabeth Allen, Charles Opondo, Perry Mohammed, Willemijn van Rein-van der Horst, Yvon Van Delft, Fafa Addo Boateng, Doreen Namara, Pontiano Kaleebu, Sylvia Ojoo, Tapiwanashe Bwakura, Milly Katana, Francois Venter, Sam Phiri, and Sarah Walker

Subjects
Ritonavir, Anti-HIV Agents, Pyridones, Epidemiology, Immunology, HIV Infections, Viral Load, Piperazines, Infectious Diseases, Lamivudine, Virology, Oxazines, HIV-1, Humans, RNA, Drug Therapy, Combination, Prospective Studies, Tenofovir, Heterocyclic Compounds, 3-Ring, Zidovudine, Darunavir
Abstract

WHO guidelines recommend dolutegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs) for second-line HIV therapy, with NRTI switching from first-line tenofovir to zidovudine. We aimed to examine whether dolutegravir is non-inferior to darunavir, the best-in-class protease inhibitor drug, and whether maintaining tenofovir in second-line therapy is non-inferior to switching to zidovudine.In this prospective, multicentre, open-label, factorial, randomised, non-inferiority trial (NADIA), participants with confirmed HIV first-line treatment failure (HIV-1 RNA ≥1000 copies per mL) were recruited at seven clinical sites in Kenya, Uganda, and Zimbabwe. Following a 2 × 2 factorial design and stratified by site and screening HIV-1 RNA concentration, participants were randomly assigned (1:1:1:1) to receive a 96-week regimen containing either dolutegravir (50 mg once daily) or ritonavir-boosted darunavir (800 mg of darunavir plus 100 mg of ritonavir once daily) in combination with either tenofovir (300 mg once daily) plus lamivudine (300 mg once daily) or zidovudine (300 mg twice daily) plus lamivudine (150 mg twice daily). The NRTI drugs allocated by randomisation were administered orally in fixed-dose combination pills; other drugs were administered orally as separate pills. The previously reported primary outcome was the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 48 weeks. Here, we report the main secondary outcome: the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 96 weeks (non-inferiority margin 12%). We analysed this outcome and safety outcomes in the intention-to-treat population, which excluded only those who were randomly assigned in error and withdrawn before receiving trial drugs. This study was registered at ClinicalTrials.gov, NCT03988452, and is complete.Between July 30 and Dec 18, 2019, we screened 783 patients and enrolled 465. One participant was randomly assigned in error and immediately withdrawn. The remaining 464 participants were randomly assigned to receive either dolutegravir (n=235) or ritonavir-boosted darunavir (n=229) and to receive lamivudine plus either tenofovir (n=233) or zidovudine (n=231). At week 96, 211 (90%) of 235 participants in the dolutegravir group and 199 (87%) of 229 participants in the darunavir group had HIV-1 RNA less than 400 copies per mL (percentage point difference 2·9, 95% CI -3·0 to 8·7), indicating non-inferiority. Nine (4%) participants (all in the dolutegravir group) developed dolutegravir resistance; no participants developed darunavir resistance (p=0·0023). In the other randomised comparison, 214 (92%) of 233 patients in the tenofovir group and 196 (85%) of 231 patients in the zidovudine group had HIV-1 RNA less than 400 copies per mL (percentage point difference 7·0, 95% CI 1·2 to 12·8), showing non-inferiority and indicating the superiority of tenofovir (p=0·019). The proportions of participants with any grade 3-4 adverse event were similar between the dolutegravir (26 [11%]) and darunavir (28 [12%]) groups and between the tenofovir (22 [9%]) and zidovudine (32 [14%]) groups. There were no deaths related to study medication.Dolutegravir-based and darunavir-based regimens maintain good viral suppression during 96 weeks; dolutegravir is non-inferior to darunavir but is at greater risk of resistance in second-line therapy. Tenofovir should be continued in second-line therapy, rather than being switched to zidovudine.Janssen.

Published
2022

40. Schistosoma mansoniinfection alters the host pre-vaccination environment resulting in blunted Hepatitis B vaccination immune responses

Author

Muir, Roshell, primary, Metcalf, Talibah, additional, Fourati, Slim, additional, Bartsch, Yannic, additional, Lugemwa, Jacqueline Kyosiimire, additional, Canderan, Glenda, additional, Alter, Galit, additional, Muyanja, Enoch, additional, Okech, Brenda, additional, Namatovu, Teddy, additional, Namara, Irene, additional, Namuniina, Annemarie, additional, Ssetaala, Ali, additional, Mpendo, Juliet, additional, Nanvubya, Annet, additional, Kitandwe, Paul Kato, additional, Bagaya, Bernard S., additional, Kiwanuka, Noah, additional, Nassuna, Jacent, additional, Biribawa, Victoria Menya, additional, Elliott, Alison M., additional, de Dood, Claudia J., additional, Senyonga, William, additional, Balungi, Priscilla, additional, Kaleebu, Pontiano, additional, Mayanja, Yunia, additional, Odongo, Mathew, additional, Fast, Pat, additional, Price, Matt A., additional, Corstjens, Paul L.A.M., additional, van Dam, Govert J., additional, Kamali, Anatoli, additional, Sekaly, Rafick Pierre, additional, and Haddad, Elias K, additional

Published
2023
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41. 1-[(1S,2S)-1,2-Bis(2-hydroxyphenyl)-2-pivaloylaminoethylamino]-2,2-dimethyl-1-propanone

Author

Fulgentius Nelson Lugemwa

Subjects
selective pivaloylation, 2-[(1S,2S)-1,2-diamino-2(2-hydroxyphenyl)ethyl]phenol, 1-[(1S,2S)-1,2-bis(2-hydroxyphenyl)-2-pivaloylaminoethylamino]-2,2-dimethyl-1-propanone, Inorganic chemistry, QD146-197
Abstract

When 2-[(1S,2S)-1,2-diamino-2(2-hydroxyphenyl)ethyl]phenol (I) was reacted with 2 mole equivalents of trimethyl acetic (pivalic) anhydride in tetrahydrofuran at room temperature, 1-[(1S,2S)-1,2-bis(2-hydroxyphenyl)-2-pivaloylaminoethylamino]-2,2-dimethyl-1-propanone (II) was obtained quantitatively as the only product. The structure of the product was determined using 1H- and 13C-NMR. The COSY spectrum indicated that the single –NH was coupled to the single benzylic proton, –CH. The versality of the transformation could be used to generate additional compounds for use in various research areas.

Published
2019
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42. Raltegravir-intensified initial antiretroviral therapy in advanced HIV disease in Africa: A randomised controlled trial.

Author

Cissy Kityo, Alexander J Szubert, Abraham Siika, Robert Heyderman, Mutsa Bwakura-Dangarembizi, Abbas Lugemwa, Shalton Mwaringa, Anna Griffiths, Immaculate Nkanya, Sheila Kabahenda, Simon Wachira, Godfrey Musoro, Chatu Rajapakse, Timothy Etyang, James Abach, Moira J Spyer, Priscilla Wavamunno, Linda Nyondo-Mipando, Ennie Chidziva, Kusum Nathoo, Nigel Klein, James Hakim, Diana M Gibb, A Sarah Walker, Sarah L Pett, and REALITY trial team

Subjects
Medicine
Abstract

BackgroundIn sub-Saharan Africa, individuals infected with HIV who are severely immunocompromised have high mortality (about 10%) shortly after starting antiretroviral therapy (ART). This group also has the greatest risk of morbidity and mortality associated with immune reconstitution inflammatory syndrome (IRIS), a paradoxical response to successful ART. Integrase inhibitors lead to significantly more rapid declines in HIV viral load (VL) than all other ART classes. We hypothesised that intensifying standard triple-drug ART with the integrase inhibitor, raltegravir, would reduce HIV VL faster and hence reduce early mortality, although this strategy could also risk more IRIS events.Methods and findingsIn a 2×2×2 factorial open-label parallel-group trial, treatment-naive adults, adolescents, and children >5 years old infected with HIV, with cluster of differentiation 4 (CD4) 0.7) and despite significantly greater VL suppression with raltegravir-intensified ART at 4 weeks (343/836 [41.0%] versus 113/841 [13.4%] with standard ART, p < 0.001) and 12 weeks (567/789 [71.9%] versus 415/803 [51.7%] with standard ART, p < 0.001). Through 48 weeks, there was no evidence of differences in mortality (aHR = 0.98 [95% CI 0.76-1.28], p = 0.91); in serious (aHR = 0.99 [0.81-1.21], p = 0.88), grade-4 (aHR = 0.88 [0.71-1.09], p = 0.29), or ART-modifying (aHR = 0.90 [0.63-1.27], p = 0.54) adverse events (the latter occurring in 59 [6.5%] participants with raltegravir-intensified ART versus 66 [7.3%] with standard ART); in events judged compatible with IRIS (occurring in 89 [9.9%] participants with raltegravir-intensified ART versus 86 [9.5%] with standard ART, p = 0.79) or in hospitalisations (aHR = 0.94 [95% CI 0.76-1.17], p = 0.59). At 12 weeks, one and two raltegravir-intensified participants had predicted intermediate-level and high-level raltegravir resistance, respectively. At 48 weeks, the nucleoside reverse transcriptase inhibitor (NRTI) mutation K219E/Q (p = 0.004) and the non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations K101E/P (p = 0.03) and P225H (p = 0.007) were less common in virus from participants with raltegravir-intensified ART, with weak evidence of less intermediate- or high-level resistance to tenofovir (p = 0.06), abacavir (p = 0.08), and rilpivirine (p = 0.07). Limitations of the study include limited clinical, radiological, and/or microbiological information for some participants, reflecting available services at the centres, and lack of baseline genotypes.ConclusionsAlthough 12 weeks of raltegravir intensification was well tolerated and reduced HIV viraemia significantly faster than standard triple-drug ART during the time of greatest risk for early death, this strategy did not reduce mortality or clinical events in this group and is not warranted. There was no excess of IRIS-compatible events, suggesting that integrase inhibitors can be used safely as part of standard triple-drug first-line therapy in severely immunocompromised individuals.Trial registrationClinicalTrials.gov NCT01825031.Trial registrationInternational Standard Randomised Controlled Trials Number ISRCTN 43622374.

Published
2018
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44. Schistosoma mansoniinfection alters the host pre-vaccination environment resulting in blunted Hepatitis B vaccination immune responses

Author

Roshell Muir, Talibah Metcalf, Slim Fourati, Yannic Bartsch, Jacqueline Kyosiimire Lugemwa, Glenda Canderan, Galit Alter, Enoch Muyanja, Brenda Okech, Teddy Namatovu, Irene Namara, Annemarie Namuniina, Ali Ssetaala, Juliet Mpendo, Annet Nanvubya, Paul Kato Kitandwe, Bernard S. Bagaya, Noah Kiwanuka, Jacent Nassuna, Victoria Menya Biribawa, Alison M. Elliott, Claudia J. de Dood, William Senyonga, Priscilla Balungi, Pontiano Kaleebu, Yunia Mayanja, Mathew Odongo, Pat Fast, Matt A. Price, Paul L.A.M. Corstjens, Govert J. van Dam, Anatoli Kamali, Rafick Pierre Sekaly, and Elias K Haddad

Subjects
Article
Abstract

The impact of endemic infections on protective immunity is critical to inform vaccination strategies. In this study, we assessed the influence ofSchistosoma mansoniinfection on host responses in a Ugandan fishing cohort given a Hepatitis B (HepB) vaccine. Concentrations of schistosome-specific circulating anodic antigen (CAA) pre-vaccination showed a significant bimodal distribution associated with HepB titers, which were lower in individuals with high CAA. We established that participants with high CAA had significantly lower frequencies of circulating T follicular helper (cTfh) subpopulations pre- and post-vaccination and higher regulatory T cells (Tregs) post-vaccination. Polarization towards higher frequencies of Tregs: cTfh cells can be mediated by changes in the cytokine environment favoring Treg differentiation. In fact, we observed higher levels of CCL17 and soluble IL-2R pre-vaccination (important for Treg recruitment and development), in individuals with high CAA that negatively associated with HepB titers. Additionally, alterations in pre-vaccination monocyte function correlated with HepB titers, and changes in innate-related cytokines/chemokine production were associated with increasing CAA concentration. We report, that by influencing the immune landscape, schistosomiasis has the potential to modulate immune responses to HepB vaccination. These findings highlight multipleSchistosoma-related immune associations that could explain abrogated vaccine responses in communities with endemic infections.Author SummarySchistosomiasis drives host immune responses for optimal pathogen survival, potentially altering host responses to vaccine-related antigen. Chronic schistosomiasis and co-infection with hepatotropic viruses are common in countries where schistosomiasis is endemic. We explored the impact ofSchistosoma mansoni(S. mansoni) infection on Hepatitis B (HepB) vaccination of individuals from a fishing community in Uganda. We demonstrate that high schistosome-specific antigen (circulating anodic antigen, CAA) concentration pre-vaccination, is associated with lower HepB antibody titers post-vaccination. We show higher pre-vaccination levels of cellular and soluble factors in instances of high CAA that are negatively associated with HepB antibody titers post-vaccination, which coincided with lower frequencies of circulating T follicular helper cell populations (cTfh), proliferating antibody secreting cells (ASCs), and higher frequencies of regulatory T cells (Tregs). We also show that monocyte function is important in HepB vaccine responses, and that high CAA is associated with alterations in the early innate cytokine/chemokine microenvironment. Our findings suggest that in individuals with high CAA and likely high worm burden, schistosomiasis creates and sustains an environment that is polarized against optimal host immune responses to the vaccine, which puts many endemic communities at risk for infection against HepB and other diseases that are preventable by vaccines.

Published
2023

45. Long-Term Non-Progression and Risk Factors for Disease Progression Among Children Living with HIV in Botswana and Uganda: A Retrospective Cohort Study

Author

Samuel Kyobe, Grace Paul Kisitu, Savannah Mwesigwa, John Farirai, Eric Katagirya, Gaone Retshabile, Lesedi Williams, Angela Mirembe, Lesego Ketumile, Misaki Wayengera, John Mukisa, Gaseene Sebetso, Thabo Diphoko, Marion Amujal, Edgar Kigozi, Fred Ashaba Katabazi, Ronald Oceng, Busisiwe C. Mlotshwa, Koketso Morapedi, Jacqueline Kyosiimire-Lugemwa, Betty Nsangi, Edward Wampande, Masego Tsimako-Johnstone, Chester W. Brown, Ishmael Kasvosve, Moses Joloba, Gabriel Anabwani, Sununguko Wata Mpoloka, Graeme Mardon, Dithan Kiragga, Neil A. Hanchard, Mogomotsi Sandy Matshaba, and Adeodata R. Kekitiinwa

Published
2023

46. Neuropsychiatric Manifestations and Sleep Disturbances in Children and Adolescents Randomised to Dolutegravir-Based Antiretroviral Therapy vs Standard-of-Care in the Odyssey Trial

Author

Anna Turkova, Ellen White, Adeodata R. Kekitiinwa, Vivian Mumbiro, Elizabeth Kaudha, Afaaf Liberty, Grace Miriam Ahimbisibwe, Tumelo Moloantoa, Ussanee Srirompotong, Nozibusiso Rejoice Mosia, Thanyawee Puthanakit, Robin Kobbe, Clàudia Fortuny, Hajira Kataike, Dickson Bbuye, Sathaporn Na-Rajsima, Alexandra Coelho, Abbas Lugemwa, Mutsa F. Bwakura-Dangarembizi, Nigel Klein, Hilda Mujuru, Cissy Kityo, Mark F. Cotton, Rashida Abbas Ferrand, Carlo Giaquinto, Pablo Rojo Conejo, Avy Violari, Diana M. Gibb, Deborah Ford, and ODYSSEY Trial Team

Published
2023

49. HIV specific Th1 responses are altered in Ugandans with schistosoma mansoni coinfection

Author

Andrew Ekii Obuku, Jacqueline Kyosimiire Lugemwa, Andrew Abaasa, Moses Joloba, Song Ding, Justin Pollara, Giuseppe Pantaleo, Guido Ferrari, Alexandre Harari, and Pontiano Kaleebu

Abstract

Fishing communities surrounding Lake Victoria in Uganda have HIV prevalence of 28% and incidence rates of 5 per 100 person years. More than 50% of the local fishermen are infected withSchistosoma mansoni(S. mansoni). We investigated the role ofS. mansonicoinfection as a possible modifier of immune responses against HIV. Using polychromatic flow cytometry and Gran-ToxiLux assays, HIV specific responses, T cell phenotypes, antibody-dependent cell-mediated cytotoxic (ADCC) potency and titres were compared between participants with HIV-S. mansonicoinfection and participants with HIV infection alone.S. mansonicoinfection was associated with a modified pattern of anti-HIV responses, including lower frequency of bifunctional (IFNγ + IL-2 − TNF-α+) CD4 T cells, higher overall CD4 T cell activation and lower HIV ADCC antibody titres, compared to participants with HIV alone. These results support the hypothesis thatS. mansoniinfection affects T cell and antibody responses to HIV in coinfected individuals.

Published
2022

50. The cost‐effectiveness of prophylaxis strategies for individuals with advanced HIV starting treatment in Africa

Author

Walker, Simon M., Cox, Edward, Revill, Paul, Musiime, Victor, Bwakura?Dangarembizi, Mutsa, Mallewa, Jane, Cheruiyot, Priscilla, Maitland, Kathryn, Ford, Nathan, Gibb, Diana M., Walker, A Sarah, Soares, Marta, Mugyenyi, P, Kityo, C, Musiime, V, Wavamunno, P, Nambi, E, Ocitti, P, Ndigendawani, M, Kabahenda, S, Kemigisa, M, Acen, J, Olebo, D, Mpamize, G, Amone, A, Okweny, D, Mbonye, A, Nambaziira, F, Rweyora, A, Kangah, M, Kabaswahili, V, Abach, J, Abongomera, G, Omongin, J, Aciro, I, Philliam, A, Arach, B, Ocung, E, Amone, G, Miles, P, Adong, C, Tumsuiime, C, Kidega, P, Otto, B, Apio, F, Baleeta, K, Mukuye, A, Abwola, M, Ssennono, F, Baliruno, D, Tuhirwe, S, Namisi, R, Kigongo, F, Kikyonkyo, D, Mushahara, F, Tusiime, J, Musiime, A, Nankya, A, Atwongyeire, D, Sirikye, S, Mula, S, Noowe, N, Lugemwa, A, Kasozi, M, Mwebe, S, Atwine, L, Senkindu, T, Natuhurira, T, Katemba, C, Ninsiima, E, Acaku, M, Kyomuhangi, J, Ankunda, R, Tukwasibwe, D, Ayesiga, L, Hakim, J, Nathoo, K, Bwakura?Dangarembizi, M, Reid, A, Chidziva, E, Mhute, T, Tinago, Gc, Bhiri, J, Mudzingwa, S, Phiri, M, Steamer, J, Nhema, R, Warambwa, C, Musoro, G, Mutsai, S, Nemasango, B, Moyo, C, Chitongo, S, Rashirai, K, Vhembo, S, Mlambo, B, Nkomani, S, Ndemera, B, Willard, M, Berejena, C, Musodza, Y, Matiza, P, Mudenge, B, Guti, V, Etyang, A, Agutu, C, Berkley, J, Maitland, K, Njuguna, P, Mwaringa, S, Etyang, T, Awuondo, K, Wale, S, Shangala, J, Kithunga, J, Mwarumba, S, Maitha, S Said, Mutai, R, Lewa, M Lozi, Mwambingu, G, Mwanzu, A, Kalama, C, Latham, H, Shikuku, J, Fondo, A, Njogu, A, Khadenge, C, Mwakisha, B, Siika, A, Wools?Kaloustian, K, Nyandiko, W, Cheruiyot, P, Sudoi, A, Wachira, S, Meli, B, Karoney, M, Nzioka, A, Tanui, M, Mokaya, M, Ekiru, W, Mboya, C, Mwimali, D, Mengich, C, Choge, J, Injera, W, Njenga, K, Cherutich, S, Orido, M Anyango, Lwande, G Omondi, Rutto, P, Mudogo, A, Kutto, I, Shali, A, Jaika, L, Jerotich, H, Pierre, M, Mallewa, J, Kaunda, S, Van Oosterhout, J, O'Hare, B, Heydermann, R, Gonzalez, C, Dzabala, N, Kelly, C, Denis, B, Selemani, G, Mipando, L Nyondo, Chirwa, E, Banda, P, Mvula, L, Msuku, H, Ziwoya, M, Manda, Y, Nicholas, S, Masesa, C, Mwalukomo, T, Makhaza, L, Sheha, I, Bwanali, J, Limbuni, M, Gibb, D, Thomason, M, Walker, As, Pett, S, Szubert, A, Griffiths, A, Wilkes, H, Rajapakse, C, Spyer, M, Prendergast, A, Klein, N, Rauchenberger, M, Van Looy, N, Little, E, Fairbrother, K, Cowan, F, Seeley, J, Bernays, S, Kawuma, R, Mupambireyi, Z, Kyomuhendo, F, Nakalanzi, S, Peshu, J, Ndaa, S, Chabuka, J, Mkandawire, N, Matandika, L, Kapuya, C, Weller, I, Malianga, E, Mwansambo, C, Miiro, F, Elyanu, P, Bukusi, E, Katabira, E, Mugurungi, O, Peto, T, Musoke, P, Matenga, J, Phiri, S, Lyall, H, Johnston, V, Fitzgerald, F, Post, F, Ssali, F, Arenas?Pinto, A, Turkova, A, and Bamford, A

Subjects
Cost benefit analysis, Practice guidelines (Medicine) -- Evaluation, HIV infection -- Diagnosis -- Care and treatment, Cost benefit analysis, Health
Abstract

: Introduction: Many HIV‐positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced‐prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4 Methods: The REALITY trial enrolled from June 2013 to April 2015. A decision‐analytic model was developed to estimate the cost‐effectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standard‐prophylaxis, enhanced‐prophylaxis, standard‐prophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhanced‐prophylaxis (CrAg‐positive) or standard‐prophylaxis (CrAg‐negative), the second to enhanced‐prophylaxis (CrAg‐positive) or enhanced‐prophylaxis without fluconazole (CrAg‐negative) and the third to standard‐prophylaxis with fluconazole (CrAg‐positive) or without fluconazole (CrAg‐negative). The model estimated costs, life‐years and quality‐adjusted life‐years (QALY) over 48 weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause. Results: Enhanced‐prophylaxis was cost‐effective at cost‐effectiveness thresholds of US$300 and US$500 per QALY with an incremental cost‐effectiveness ratio (ICER) of US$157 per QALY in the CD4 Conclusions: The REALITY enhanced‐prophylaxis package in individuals with advanced HIV starting ART reduces morbidity and mortality, is practical to administer and is cost‐effective. Efforts should continue to ensure that components are accessed at lowest available prices., Introduction In low‐ and middle‐income settings, more than a third of HIV‐positive individuals starting antiretroviral therapy (ART) present with advanced disease (CD4 ≤ 200 cells/mm[sup.3]); over half of these have [...]

Published
2020
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