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1. 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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2. 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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3. Antiretroviral regimens in pregnancy and breast-feeding in Botswana

Author

Shapiro, R.L., Snowden, W., Martinez-Tristani, M., Mazhani, L., Essex, M., Souda, S., Lubega, E., Akhtar, M., Wester, C., Tuomola, R., Sharma, U., Handelsman, E., Mburu, K., Jayeoba, O., Moko, E., Leidner, J., Powis, K., Asmelash, A., Tumbare, E., Zwerski, S., Makhema, J., Moyo, S., Thior, I., McIntosh, K., van Widenfelt, E., Hughes, M.D., Ogwu, A., Kitch, D., Lockman, S., and Moffat, C.

Subjects
Highly active antiretroviral therapy -- Health aspects, HIV infection -- Drug therapy, HIV infection -- Prevention, Disease transmission -- Risk factors, Disease transmission -- Patient outcomes, Pregnancy -- Health aspects, Breast feeding -- Health aspects, HIV infection in pregnancy -- Drug therapy, HIV infection in pregnancy -- Prevention
Abstract

The study attempts to evaluate the most effective and safe highly active antiretroviral therapy (HAART) in preventing human immunedeficiency virus type -1 (HIV-1) transmission during pregnancy and breast-feeding. The results indicate that all regimes of HAART had positive outcomes in reducing HIV-1 transmission, with a overall rate of 1.1% between mother and infant.

Published
2010

5. Mapping the medical outcomes study HIV health survey (MOS-HIV) to the EuroQoL 5 Dimension (EQ-5D-3 L) utility index

Author

Shi, Yuan, Thompson, Jennifer, Walker, A Sarah, Paton, Nicholas I, Cheung, Yin Bun, 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, TM, 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, Kayinga, T, Makwakwa, 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, 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, Team, EARNEST Trial, UAM. Departamento de Medicina, and Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ)

Subjects
Adult, Male, Mean squared error, Medicina, Intraclass correlation, HIV Infections, lcsh:Computer applications to medicine. Medical informatics, Standard deviation, 03 medical and health sciences, 0302 clinical medicine, EQ-5D, Outcome Assessment, Health Care, Statistics, Covariate, Humans, 030212 general & internal medicine, Least-Squares Analysis, Africa South of the Sahara, Health utility, Mathematics, Medical outcomes study HIV health survey, Research, 030503 health policy & services, 1. No poverty, Public Health, Environmental and Occupational Health, General Medicine, Health Surveys, Regression, 3. Good health, Mapping, Ordinary least squares, Quality of Life, lcsh:R858-859.7, Female, 0305 other medical science, Body mass index
Abstract

Background: Mapping of health-related quality-of-life measures to health utility values can facilitate cost-utility evaluation. Regression-based methods tend to lead to shrinkage of variance. This study aims to map the Medical Outcomes Study HIV Health Survey (MOS-HIV) to EuroQoL 5 Dimensions (EQ-5D-3 L) utility index, and to characterize the performance of three mapping methods, including ordinary least squares (OLS), equi-percentile method (EPM), and a recently proposed method called Mean Rank Method (MRM). Methods: This is a secondary analysis of data from a randomized HIV treatment trial. Baseline data from 421 participants were used to develop mapping functions. Follow-up data from 236 participants was used to validate the mapping functions. Results: In the training dataset, MRM and OLS, but not EPM, reproduced the observed mean utility (0.731). MRM, OLS and EPM under-estimated the standard deviation by 0.3, 26.6 and 1.7%, respectively. MRM had the lowest mean absolute error (0.143) and highest intraclass correlation coefficient (0.723) with the observed utility values, whereas OLS had the lowest mean squared error (0.038) and highest R-squared (0.542). Regressing the MRM- and OLS-mapped utility values upon body mass index and log-viral load gave covariate associations comparable to those estimated from the observed utility data (all P > 0.10). EPM did not achieve this property. Findings from the validation data were similar. Conclusions: Functions are available for mapping the MOS-HIV to the EQ-5D-3 L utility values. MRM and OLS were comparable in terms of agreement with the observed utility values at the individual level. MRM had better performance at the group level in terms of describing the utility distribution. Trial registration: NCT00988039. Registered 30 September 2009., The EARNEST trial was funded by the European and Developing Countries Clinical Trials Partnership (EDCTP, Grant Code: IP.2007.33011.003) with contributions from the Medical Research Council, UK; Institito de Salud Carlos III, Spain (Grant A107/90015); Irish Aid, Ireland; Swedish International Development Cooperation Agency (SIDA), Sweden; Instituto Superiore di Sanita (ISS), Italy; The World Health Organisation; and Merck, USA. Substantive in-kind contributions were made by the Medical Research Council Clinical Trials Unit, UK [MC_UU_12023/23], CINECA, Bologna, Italy, Janssen Diagnostics, Beerse, Belgium; GSK/ViiV Healthcare Ltd., UK; Abbott Laboratories, USA. Trial medication was donated by AbbVie, Merck, Pfizer, GSK and Gilead. The Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi

Published
2019

7. Isolation and characterization of monoclonal antibodies raised against the reverse transcriptase of human immunodeficiency virus type 2 and cross-reactivity with that of type 1

Author

Snowden, W., Coughlan, N., Tisdale, M., and Stammers, D.K.

Subjects
HIV infection -- Drug therapy, Monoclonal antibodies -- Physiological aspects, Cross reactions (Immunology) -- Physiological aspects, HIV (Viruses), Reverse transcriptase, Health
Abstract

Monoclonal antibodies to reverse transcriptase (RT) in HIV-2 were produced in mice to assist in the search for new RT inhibitors. Reverse transcriptase is the enzyme that plays a major role in the replication of HIV in host cells. The monoclonal antibodies produced in the mice were classified into three groups, all of which recognized a different part of the enzyme. One of the antibodies also reacts with RT of HIV-1. Information from the antibody reactions to RT will help researchers characterize the three-dimensional structure of RT. Current antiretroviral drugs such as AZT, ddI, and ddC act as RT inhibitors. Eventually, HIV develops resistance to these drugs. Characterizing the structure of RT will aid in the development of new RT-inhibiting drug therapies.

Published
1993

8. High Rate of HIV Resuppression After Viral Failure on First-line Antiretroviral Therapy in the Absence of Switch to Second-line Therapy

Author

Gupta, R. K., Goodall, R. L., Ranopa, M., Kityo, C., Munderi, P., Lyagoba, F., Mugarura, L., Gilks, C. F., Kaleebu, P., Pillay, D., Grosskurth, H., Kabuye, G., Nsibambi, D., Kasirye, R., Zalwango, E., Nakazibwe, M., Kikaire, B., Nassuna, G., Massa, R., Fadhiru, K., Namyalo, M., Zalwango, A., Generous, L., Khauka, P., Rutikarayo, N., Nakahima, W., Mugisha, A., Todd, J., Levin, J., Muyingo, S., Ruberantwari, A., Yirrell, D., Ndembi, N., Hughes, P., Aber, M., Medina Lara, A., Foster, S., Amurwon, J., Mugyenyi, P., Ssali, F., Tumukunde, D., Otim, T., Kabanda, J., Musana, H., Akao, J., Kyomugisha, H., Byamukama, A., Sabiiti, J., Komugyena, J., Wavamunno, P., Mukiibi, S., Drasiku, A., Byaruhanga, R., Labeja, O., Katundu, P., Tugume, S., Awio, P., Namazzi, A., Bakeinyaga, T. G., Katabira, H., Abaine, D., Tukamushaba, J., Anywar, W., Ojiambo, W., Angweng, E., Murungi, S., Haguma, W., Atwiine, S., Kigozi, J., Latif, A., Hakim, J., Robertson, V., Reid, A., Chidziva, E., Bulaya-Tembo, R., Musoro, G., Taziwa, F., Chimbetete, C., Chakonza, L., Mawora, A., Muvirimi, C., Tinago, G., Svovanapasis, P., Simango, M., Chirema, O., Machingura, J., Mutsai, S., Phiri, M., Bafana, T., Chirara, M., Muchabaiwa, L., Muzambi, M., Katabira, E., Ronald, A., Kambungu, A., Lutwama, F., Nanfuka, A., Walusimbi, J., Nabankema, E., Nalumenya, R., Namuli, T., Kulume, R., Namata, I., Nyachwo, L., Florence, A., Kusiima, A., Lubwama, E., Nairuba, R., Oketta, F., Buluma, E., Waita, R., Ojiambo, H., Sadik, F., Wanyama, J., Nabongo, P., Ochai, R., Muhweezi, D., Gilks, C., Boocock, K., Puddephatt, C., Winogron, D., Bohannon, J., Darbyshire, J., Gibb, M. D., Burke, A., Bray, D., Babiker, A., Walker, S. A., Wilkes, H., Rauchenberger, M., Sheehan, S., Peto, L., Taylor, K., Spyer, M., Ferrier, A., Naidoo, B., Dunn, D., Goodall, R., Nanfuka, R., Mufuka-Kapuya, C., Kapaata, A., Katuramur, M., Magala, R., Magambo, B., Mataruka, K., McCormick, A., Musunga, T., Nabankkema, M., Nkalubo, J., Nkurunziza, P., Parry, C., Nyanzi Wakholi, B., Weller, I., Bahendeka, S., Bassett, M., Chogo Wapakhabulo, A., Gazzard, B., Mapuchere, C., Mugurungi, O., Burke, C., Jones, S., Newland, C., Rahim, S., Rooney, J., Smith, M., Snowden, W., Steens, J.- M., Breckenridge, A., McLaren, A., Hill, C., Matenga, J., Pozniak, A., Serwadda, D., Peto, T., Palfreeman, A., and Borok, M.

Subjects
Anti-HIV Agents, HIV, Viral Load, viral resuppression, Dideoxynucleosides, failure, resistance, Drug Combinations, Lamivudine, Africa, HIV/AIDS, Humans, Nevirapine, Viremia, Zidovudine
Abstract

In a randomized comparison of nevirapine or abacavir with zidovudine plus lamivudine, routine viral load monitoring was not performed, yet 27% of individuals with viral failure at week 48 experienced resuppression by week 96 without switching. This supports World Health Organization recommendations that suspected viral failure should trigger adherence counseling and repeat measurement before a treatment switch is considered.

Published
2013

9. Once- versus twice-daily abacavir and lamivudine in African children: the randomised controlled ARROW Trial

Author

Musiime, V, Kasirye, P, Naidoo-James, B, Nahirya-Ntege, P, Mhute, T, Cook, A, Mugarura, L, Munjoma, M, Thoofer, N, Ndashimye, E, Nankya, I, Spyer, M, Thomason, M, Snowden, W, Gibb, DM, Walker, AS, and ARROW Trial Team

Abstract

Background: Antiretroviral therapy (ART) adherence is critical for successful HIV treatment outcomes. Once-daily dosing could improve adherence. Plasma concentrations of once-daily vs twice-daily abacavir + lamivudine are bioequivalent in children, but no randomized trial has compared virological outcomes. Methods: Children taking abacavir + lamivudine-containing first-line regimens twice daily for more than 36 weeks in the ARROW trial (NCT02028676, ISRCTN24791884) were randomized to continue twice-daily vs move to once-daily abacavir + lamivudine (open-label). Co-primary outcomes were viral load suppression at week 48 (12% noninferiority margin, measured retrospectively) and lamivudine or abacavir-related grade 3/4 adverse events. Results: Six hundred and sixty-nine children (median 5 years, range 1–16) were randomized to twice daily (n = 333) vs once daily (n = 336) after median 1.8 years on twice-daily abacavir + lamivudine-containing first-line ART. Children were followed for median 114 weeks. At week 48, 242/331 (73%) twice daily vs 236/330 (72%) once daily had viral load less than 80 copies/ml [difference −1.6% (95% confidence interval −8.4,+5.2%) P = 0.65]; 79% twice daily vs 78% once daily had viral load less than 400 copies/ml (P = 0.76) (week 96 results similar). One grade 3/4 adverse event was judged uncertainly related to abacavir + lamivudine (hepatitis; once daily). At week 48, 9% twice daily vs 10% once daily reported missing one or more ART pills in the last 4 weeks (P = 0.74) and 8 vs 8% at week 96 (P = 0.90). Carers strongly preferred once-daily dosing. There was no difference between randomized groups in postbaseline drug-resistance mutations or drug-susceptibility; WHO 3/4 events; ART-modifying, grade 3/4 or serious adverse events; CD4% or weight-for-age/height-for-age (all P > 0.15). Conclusion: Once-daily abacavir + lamivudine was noninferior to twice daily in viral load suppression, with similar resistance, adherence, clinical, immunological and safety outcomes. Abacavir + lamivudine provides the first once-daily nucleoside backbone across childhood that can be used to simplify ART.

Published
2016

10. Why START? Reflections that led to the conduct of this large long-term strategic HIV trial

Author

Lundgren, J, Babiker, A, Gordin, F, Emery, S, Fätkenheuer, G, Molina, JM, Wood, R, Neaton, JD, Agan, BK, Alston-Smith, B, Arenas-Pinto, A, Arribas, JR, Baker, JV, Baxter, J, Belloso, WH, Brekke, K, Brew, B, Brobst, SW, Burman, W, Carey, C, Clark, R, Cooper, DA, Davey, RT, De La Rosa, G, Denning, ET, Dolan, M, Dore, G, Duprez, D, Emanuel, E, Grady, C, Grund, B, Hirschel, B, Hoen, B, Hudson, F, Johnson, MA, Kambili, C, Klingman, K, Kunisaki, KM, Landay, A, Ledergerber, B, Lehrman, SN, Martinez, A, Meger, S, Misar, K, Mitsuyasu, RT, Mocroft, A, Munroe, D, Norton, M, Palmer, RC, Pett, SL, Phillips, A, Pillay, D, Porter, D, Price, RW, Proschan, M, Rappoport, C, Reiss, P, Renjifo, B, Robertson, K, Rockstroh, J, Rodriguez, G, Rooney, JF, Ross, MJ, Schechter, M, Schwarze, S, Seekins, D, Sharma, S, Snowden, W, Telenti, A, Tryon, J, van Wyk, J, Vjecha, MJ, Wright, E, Lundgren, J, Babiker, A, Gordin, F, Emery, S, Fätkenheuer, G, Molina, JM, Wood, R, Neaton, JD, Agan, BK, Alston-Smith, B, Arenas-Pinto, A, Arribas, JR, Baker, JV, Baxter, J, Belloso, WH, Brekke, K, Brew, B, Brobst, SW, Burman, W, Carey, C, Clark, R, Cooper, DA, Davey, RT, De La Rosa, G, Denning, ET, Dolan, M, Dore, G, Duprez, D, Emanuel, E, Grady, C, Grund, B, Hirschel, B, Hoen, B, Hudson, F, Johnson, MA, Kambili, C, Klingman, K, Kunisaki, KM, Landay, A, Ledergerber, B, Lehrman, SN, Martinez, A, Meger, S, Misar, K, Mitsuyasu, RT, Mocroft, A, Munroe, D, Norton, M, Palmer, RC, Pett, SL, Phillips, A, Pillay, D, Porter, D, Price, RW, Proschan, M, Rappoport, C, Reiss, P, Renjifo, B, Robertson, K, Rockstroh, J, Rodriguez, G, Rooney, JF, Ross, MJ, Schechter, M, Schwarze, S, Seekins, D, Sharma, S, Snowden, W, Telenti, A, Tryon, J, van Wyk, J, Vjecha, MJ, and Wright, E

Published
2015

11. Pharmacokinetics of lamivudine, abacavir and zidovudine administered twice daily as syrups versus scored tablets in HIV-1-infected Ugandan children

Author

Gitta, P.K., Kendall, L., Musiime, V., Adkison, K., Kekitiinwa, A.A., Ferrier, A., Opilo, O., Lou, Y., Bwakura-Dangarembi, M.F., Nahirya-Ntege, P., Bakeera-Kitaka, S., Ssenyonga, M., Snowden, W., Burger, D., Walker, A.S., and Gibb, D.

Subjects
Abacavir -- Dosage and administration -- Testing, Pharmacokinetics -- Evaluation, Lamivudine -- Dosage and administration -- Testing, Zidovudine -- Dosage and administration -- Testing, HIV infection in children -- Drug therapy, Health
Abstract

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK, Purpose of the study Currently there is an effort to develop simple, more convenient antiretroviral regimens for children to reduce costs and promote adherence. We report the plasma pharmacokinetics (PK) [...]

Published
2010
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12. Pharmacokinetic study of once-daily versus twice-daily abacavir and lamivudine in HIV type-1-infected children aged 3-< 36 months

Author

Paediatric European Network for Treatment of AIDS including Jacqz Aigrain, E, Harrison, L, Zhao, W, Compagnucci, A, Castro, H, Farrelly, L, Saidi, Y, Hamadache, D, Welch, S, Wintergerst, U, Forcat, S, Hadjou, G, Firtion, G, Snowden, W, Giaquinto, C, Gibb, D, Burger, D, Aboulker, Jp, Brothers, C, Gibb, Dm, Jacqz Aigrain, E, Snowdon, W, Lyall, H, Pharo, C, Le Provost, M, Saïdi, Y, Adkison, K, Song, I, Thoofer, N, Yeo, J, Clayden, P, Cressey, Tr, Khoo, S, Tréluyer, Jm, Babiker, A, Bohlin, Ab, Butler, K, Castelli Gattinara, G, Darbyshire, J, Debré, M, Faye, A, de Groot, R, della Negra, M, Duicelescu, D, Grosch Wörner, I, Kind, C, Lallemant, M, Levy, J, Marczynska, M, Peña, Mj, Nadal, D, Niehues, T, Peckham, C, Amador, Jt, Rosado, L, Rudin, C, Scherpbier, H, Sharland, M, Stevanovic, M, Tovo, Pier Angelo, Tudor Williams, G, Valerius, N, Walker, As, and Wintergerst, U.

Subjects
Infectious diseases and international health [NCEBP 13], Human immunodeficiency virus (HIV), HIV Infections, Pharmacology, medicine.disease_cause, 030226 pharmacology & pharmacy, Gastroenterology, 0302 clinical medicine, Abacavir, Pharmacology (medical), 030212 general & internal medicine, Viral, Child, Preschool, Drug Administration Schedule, Drug Therapy, Combination, HIV-1, Humans, Infant, RNA, Viral, Treatment Outcome, Anti-HIV Agents, Dideoxynucleosides, Lamivudine, Reverse Transcriptase Inhibitors, Infectious Diseases, Medicine (all), Child, 3. Good health, Combination, Viral load, medicine.drug, medicine.medical_specialty, Bioequivalence, Article, Invasive mycoses and compromised host [N4i 2], 03 medical and health sciences, Pharmacokinetics, Drug Therapy, Internal medicine, medicine, Dosing, Preschool, business.industry, Poverty-related infectious diseases [N4i 3], Confidence interval, RNA, business
Abstract

Background Once-daily dosing of abacavir and lamivudine has been approved for adults, but paediatric data are insufficient. We conducted a pharmacokinetic study of once-daily and twice-daily abacavir and lamivudine in children aged 3–Methods Children with stable HIV type-1 (HIV-1) RNA levels after 12 weeks treatment with twice-daily abacavir (8 mg/kg) with or without lamivudine (4 mg/kg) underwent plasma pharmacokinetic sampling. Children then switched to once-daily abacavir (16 mg/kg) with or without lamivudine (8 mg/kg), and sampling was repeated 4 weeks later. The area under the plasma concentration– time curve over 24 h (AUC0–24) and the maximum concentration (Cmax) were compared using geometric mean ratios (GMRs); 90% confidence intervals (CIs) within the range of 0.80–1.25 were considered bioequivalent. Results A total of 18 children (4, 6 and 8 in the 3–0–24, once-daily versus twice-daily, was 1.07 (90% CI 0.92–1.23) for abacavir and 0.91 (90% CI 0.79–1.06) for lamivudine. Cmax almost doubled on once-daily versus twice-daily dosing: abacavir and lamivudine GMRs were 2.04 (90% CI 1.73–2.42) and 1.78 (90% CI 1.52–2.09), respectively. At baseline, 12, 24 and 48 weeks, 89%, 94%, 100% and 89% of children had HIV-1 RNAConclusions Bioequivalence was demonstrated on AUC0–24 between twice-daily and once-daily abacavir; very similar AUC0–24 values were seen for twice-daily and once-daily lamivudine. Given that viral load suppression rates were maintained, these data suggest that once-daily abacavir and lamivudine might be an option for children aged 3–

Published
2010

13. Pharmacokinetics of antiretroviral drug varies with formulation in the target population of children with HIV-1.

Author

Kasirye, P., Kendall, L., Adkison, K.K., Tumusiime, C., Ssenyonga, M., Bakeera-Kitaka, S., Nahirya-Ntege, P., Mhute, T., Kekitiinwa, A., Snowden, W., Burger, D.M., Gibb, D.M., Walker, A.S., Kasirye, P., Kendall, L., Adkison, K.K., Tumusiime, C., Ssenyonga, M., Bakeera-Kitaka, S., Nahirya-Ntege, P., Mhute, T., Kekitiinwa, A., Snowden, W., Burger, D.M., Gibb, D.M., and Walker, A.S.

Abstract

1 februari 2012, Item does not contain fulltext, The bioequivalence of formulations is usually evaluated in healthy adult volunteers. In our study in 19 HIV-1-infected Ugandan children (1.8-4 years of age, weight 12 to <15 kg) receiving zidovudine, lamivudine, and abacavir solutions twice a day for >/=24 weeks, the use of scored tablets allowed comparison of plasma pharmacokinetics of oral solutions vs. tablets. Samples were collected 0, 1, 2, 4, 6, 8, and 12 h after each child's last morning dose of oral solution before changing to scored tablets of Combivir (coformulated zidovudine + lamivudine) and abacavir; this was repeated 4 weeks later. Dose-normalized area under curve (AUC)(0-12) and peak concentration (C(max)) for the tablet formulation were bioequivalent with those of the oral solution with respect to zidovudine and abacavir (e.g., dose-normalized geometric mean ratio (dnGMR) (tablet:solution) for zidovudine and abacavir AUC(0-12) were 1.01 (90% confidence interval (CI) 0.87-1.18) and 0.96 (0.83-1.12), respectively). However, lamivudine exposure was ~55% higher with the tablet formulation (AUC(0-12) dnGMR = 1.58 (1.37-1.81), C(max) dnGMR = 1.55 (1.33-1.81)). Although the clinical relevance of this finding is unclear, it highlights the impact of the formulation and the importance of conducting bioequivalence studies in target pediatric populations.

Published
2012

14. Pharmacokinetic study of once-daily versus twice-daily abacavir and lamivudine in HIV type-1-infected children aged 3-<36 months.

Author

Jacqz-Aigrain, E., Harrison, L., Zhao, W., Compagnucci, A., Castro, H., Farrelly, L., Saidi, Y., Hamadache, D., Welch, S., Wintergerst, U., Forcat, S., Hadjou, G., Firtion, G., Snowden, W., Giaquinto, C., Gibb, D., Burger, D.M., Aboulker, J.P., Brothers, C., et al., Jacqz-Aigrain, E., Harrison, L., Zhao, W., Compagnucci, A., Castro, H., Farrelly, L., Saidi, Y., Hamadache, D., Welch, S., Wintergerst, U., Forcat, S., Hadjou, G., Firtion, G., Snowden, W., Giaquinto, C., Gibb, D., Burger, D.M., Aboulker, J.P., Brothers, C., and et al.

Abstract

Contains fulltext : 89764.pdf (publisher's version ) (Closed access)

Published
2010

15. 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

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, Walker, A Sarah, 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, Mulima, D, 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, Abunyang, S, 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, Hakim, J, Kangewende, A, Lakhi, S, Luyirika, E, Miiro, F, Mwamba, P, Mugyenyi, P, Ojoo, S, Paton, N, Phiri, S, van Oosterhout, J, Siika, A, Walker, S, 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, and Villacian, J

Abstract

Cross-resistance after first-line antiretroviral therapy (ART) failure is expected to impair activity of nucleoside reverse-transcriptase inhibitors (NRTIs) in second-line therapy for patients with HIV, but evidence for the effect of cross-resistance on virological outcomes is limited. We aimed to assess the association between the activity, predicted by resistance testing, of the NRTIs used in second-line therapy and treatment outcomes for patients infected with HIV.

Published
2017
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17. Maternal or Infant Antiretroviral Drugs to Reduce HIV-1 Transmission

Author

Shapiro, R. L., primary, Hughes, M. D., additional, Ogwu, A., additional, Kitch, D., additional, Lockman, S., additional, Moffat, C., additional, Makhema, J., additional, Moyo, S., additional, Thior, I., additional, McIntosh, K., additional, van Widenfelt, E., additional, Leidner, J., additional, Powis, K., additional, Asmelash, A., additional, Tumbare, E., additional, Zwerski, S., additional, Sharma, U., additional, Handelsman, E., additional, Mburu, K., additional, Jayeoba, O., additional, Moko, E., additional, Souda, S., additional, Lubega, E., additional, Akhtar, M., additional, Wester, C., additional, Tuomola, R., additional, Snowden, W., additional, Martinez-Tristani, M., additional, Mazhani, L., additional, and Essex, M., additional

Published
2010
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23. Resistance to the HIV Protease Inhibitor Amprenavir In Vitro and in Clinical Studies: A Review.

Author

Tisdale, M., Myers, R., Randall, S., Maguire, M., Ait-Khaled, M., Elston, R., and Snowden, W.

Subjects
PROTEOLYTIC enzymes, HIV infections
Abstract

Amprenavir (APV) is a highly active and selective HIV protease inhibitor (PI) that is used for the treatment of HIV infection in adults and children. In this review we present data from extensive resistance studies undertaken during the development of amprenavir. These include in vitro and clinical studies where the phenotype and genotype of HIV protease was determined after treatment with amprenavir either as the single PI [alone or with nucleoside reverse transcriptase inhibitors (NRTIs)] or in combination with other PIs. In addition, cross-resistance with other PIs has been examined to help position use of amprenavir in the clinic. The key signature amino acid substitution associated with amprenavir resistance that was identified from in vitro and subsequent in vivo studies was isoleucine to valine at position 50 (I50V) in HIV protease. This was a new mutation not observed as a natural variant or in PI-experienced patients. Additional mutations including M46I/L and I47V were required to produce high level resistance. Cross-resistance was limited and observed only with ritonavir. In amprenavir/zidovudine/lamivudine combination therapy in PI-naive and lamivudine-naive patients, therapy failure is associated frequently with the reverse transcriptase M184V mutation, and not with amprenavir resistance. However, when amprenavir was added to NRTI therapy in NRTI-experienced and PI-naive patients where treatment was compromised by baseline NRTI resistance, failure was more frequently associated with the development of amprenavir resistance. From these studies, four pathways of amprenavir resistance were identified, with the I50V pathway associated with the highest levels of resistance. Alternative pathways to amprenavir resistance involved key substitutions, either V32I + I47V, or I54L/M, or more rarely I84V. Limited cross-resistance was observed to other PIs with each of these genetic mechanisms. Similarly, in PI-experienced patients, cross-resistance to amprenavir is markedly lower than for the other four approved PIs. Markers of cross-resistance to amprenavir include the above mutations but not L90M or V82A/T/Y as observed for other PIs. These data suggest that amprenavir may have an important part to play in rescue therapy regimens. In combination with other PIs, resistance development may be suppressed and key signature mutations, such as I50V (amprenavir), D30N (nelfinavir) and V82A/T/Y (ritonavir, indinavir) have not been observed in vitro. In addition, passage with saquinavir may resensitise amprenavir-resistant variants to amprenavir. Hypersensitivity to amprenavir has been reported for N88S variants occasionally observed after nelfinavir therapy. Differences in the resistance profile of amprenavir from that of other PIs suggest that amprenavir may add value to HIV combination therapy, particularly in PI combinations and in rescue therapy. [ABSTRACT FROM AUTHOR]

Published
2000
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24. Routine versus clinically driven laboratory monitoring of HIV antiretroviral therapy in Africa (DART): a randomised non-inferiority trial

Author

DART Trial Team, Mugyenyi, P, Walker, AS, Hakim, J, Munderi, P, Gibb, DM, Kityo, C, Reid, A, Grosskurth, H, Darbyshire, JH, Ssali, F, Bray, D, Katabira, E, Babiker, AG, Gilks, CF, Kabuye, G, Nsibambi, D, Kasirye, R, Zalwango, E, Nakazibwe, M, Kikaire, B, Nassuna, G, Massa, R, Fadhiru, K, Namyalo, M, Zalwango, A, Generous, L, Khauka, P, Rutikarayo, N, Nakahima, W, Mugisha, A, Todd, J, Levin, J, Muyingo, S, Ruberantwari, A, Kaleebu, P, Yirrell, D, Ndembi, N, Lyagoba, F, Hughes, P, Aber, M, Lara, A Medina, Foster, S, Amurwon, J, Wakholi, B Nyanzi, Whitworth, J, Wangati, K, Amuron, B, Kajungu, D, Nakiyingi, J, Omony, W, Tumukunde, D, Otim, T, Kabanda, J, Musana, H, Akao, J, Kyomugisha, H, Byamukama, A, Sabiiti, J, Komugyena, J, Wavamunno, P, Mukiibi, S, Drasiku, A, Byaruhanga, R, Labeja, O, Katundu, P, Tugume, S, Awio, P, Namazzi, A, Bakeinyaga, GT, Katabira, H, Abaine, D, Tukamushaba, J, Anywar, W, Ojiambo, W, Angweng, E, Murungi, S, Haguma, W, Atwiine, S, Kigozi, J, Namale, L, Mukose, A, Mulindwa, G, Atwiine, D, Muhwezi, A, Nimwesiga, E, Barungi, G, Takubwa, J, Mwebesa, D, Kagina, G, Mulindwa, M, Ahimbisibwe, F, Mwesigwa, P, Akuma, S, Zawedde, C, Nyiraguhirwa, D, Tumusiime, C, Bagaya, L, Namara, W, Karungi, J, Kankunda, R, Enzama, R, Latif, A, Robertson, V, Chidziva, E, Bulaya-Tembo, R, Musoro, G, Taziwa, F, Chimbetete, C, Chakonza, L, Mawora, A, Muvirimi, C, Tinago, G, Svovanapasis, P, Simango, M, Chirema, O, Machingura, J, Mutsai, S, Phiri, M, Bafana, T, Chirara, M, Muchabaiwa, L, Muzambi, M, Mutowo, J, Chivhunga, T, Chigwedere, E, Pascoe, M, Warambwa, C, Zengeza, E, Mapinge, F, Makota, S, Jamu, A, Ngorima, N, Chirairo, H, Chitsungo, S, Chimanzi, J, Maweni, C, Warara, R, Matongo, M, Mudzingwa, S, Jangano, M, Moyo, K, Vere, L, Mdege, N, Machingura, I, Ronald, A, Kambungu, A, Lutwama, F, Mambule, I, Nanfuka, A, Walusimbi, J, Nabankema, E, Nalumenya, R, Namuli, T, Kulume, R, Namata, I, Nyachwo, L, Florence, A, Kusiima, A, Lubwama, E, Nairuba, R, Oketta, F, Buluma, E, Waita, R, Ojiambo, H, Sadik, F, Wanyama, J, Nabongo, P, Oyugi, J, Sematala, F, Muganzi, A, Twijukye, C, Byakwaga, H, Ochai, R, Muhweezi, D, Coutinho, A, Etukoit, B, Gilks, C, Boocock, K, Puddephatt, C, Grundy, C, Bohannon, J, Winogron, D, Burke, A, Babiker, A, Wilkes, H, Rauchenberger, M, Sheehan, S, Spencer-Drake, C, Taylor, K, Spyer, M, Ferrier, A, Naidoo, B, Dunn, D, Goodall, R, Peto, L, Nanfuka, R, Mufuka-Kapuya, C, Pillay, D, McCormick, A, Weller, I, Bahendeka, S, Bassett, M, Wapakhabulo, A Chogo, Gazzard, B, Mapuchere, C, Mugurungi, O, Burke, C, Jones, S, Newland, C, Pearce, G, Rahim, S, Rooney, J, Smith, M, Snowden, W, Steens, J-M, Breckenridge, A, McLaren, A, Hill, C, Matenga, J, Pozniak, A, Serwadda, D, Peto, T, Palfreeman, A, and Borok, M

Subjects
Male, Neutrophils, HIV Infections, law.invention, Hemoglobins, Randomized controlled trial, law, Medicine, Urea, HIV-Associated Lipodystrophy Syndrome, Hazard ratio, Lamivudine, Anemia, General Medicine, Middle Aged, Viral Load, Anti-Retroviral Agents, Creatinine, Disease Progression, RNA, Viral, Female, Drug Monitoring, Zidovudine, medicine.drug, Glomerular Filtration Rate, Adult, medicine.medical_specialty, Neutropenia, Adolescent, Organophosphonates, Acquired immunodeficiency syndrome (AIDS), Internal medicine, Fast track — Articles, Humans, Nevirapine, Adverse effect, Tenofovir, Aged, Intention-to-treat analysis, business.industry, Adenine, medicine.disease, Dideoxynucleosides, CD4 Lymphocyte Count, Clinical trial, Clinical research, Immunology, Africa, HIV-1, business
Abstract

BACKGROUND: HIV antiretroviral therapy (ART) is often managed without routine laboratory monitoring in Africa; however, the effect of this approach is unknown. This trial investigated whether routine toxicity and efficacy monitoring of HIV-infected patients receiving ART had an important long-term effect on clinical outcomes in Africa. METHODS: In this open, non-inferiority trial in three centres in Uganda and one in Zimbabwe, 3321 symptomatic, ART-naive, HIV-infected adults with CD4 counts less than 200 cells per microL starting ART were randomly assigned to laboratory and clinical monitoring (LCM; n=1659) or clinically driven monitoring (CDM; n=1662) by a computer-generated list. Haematology, biochemistry, and CD4-cell counts were done every 12 weeks. In the LCM group, results were available to clinicians; in the CDM group, results (apart from CD4-cell count) could be requested if clinically indicated and grade 4 toxicities were available. Participants switched to second-line ART after new or recurrent WHO stage 4 events in both groups, or CD4 count less than 100 cells per microL (LCM only). Co-primary endpoints were new WHO stage 4 HIV events or death, and serious adverse events. Non-inferiority was defined as the upper 95% confidence limit for the hazard ratio (HR) for new WHO stage 4 events or death being no greater than 1.18. Analyses were by intention to treat. This study is registered, number ISRCTN13968779. FINDINGS: Two participants assigned to CDM and three to LCM were excluded from analyses. 5-year survival was 87% (95% CI 85-88) in the CDM group and 90% (88-91) in the LCM group, and 122 (7%) and 112 (7%) participants, respectively, were lost to follow-up over median 4.9 years' follow-up. 459 (28%) participants receiving CDM versus 356 (21%) LCM had a new WHO stage 4 event or died (6.94 [95% CI 6.33-7.60] vs 5.24 [4.72-5.81] per 100 person-years; absolute difference 1.70 per 100 person-years [0.87-2.54]; HR 1.31 [1.14-1.51]; p=0.0001). Differences in disease progression occurred from the third year on ART, whereas higher rates of switch to second-line treatment occurred in LCM from the second year. 283 (17%) participants receiving CDM versus 260 (16%) LCM had a new serious adverse event (HR 1.12 [0.94-1.32]; p=0.19), with anaemia the most common (76 vs 61 cases). INTERPRETATION: ART can be delivered safely without routine laboratory monitoring for toxic effects, but differences in disease progression suggest a role for monitoring of CD4-cell count from the second year of ART to guide the switch to second-line treatment. FUNDING: UK Medical Research Council, the UK Department for International Development, the Rockefeller Foundation, GlaxoSmithKline, Gilead Sciences, Boehringer-Ingelheim, and Abbott Laboratories.

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25. A Comparative Study of the in vitroand in vivoAntiviral Activities of Acyclovir and Penciclovir

Author

Ertl, P., Snowden, W., Lowe, D., Miller, W., Collins, P., and Littler, E.

Abstract

The antiviral properties of the compounds acyclovir (ACV) and penciclovir (PCV) have been compared in a number of in vitroand in vivoassays. In vitro, both compounds had good activity against herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV), although ACV showed statistically significant superiority. In addition, ACV had greater activity against herpes simplex virus type 2 (HSV-2), human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV). We examined the effect of time of addition and removal of ACV and PCV under a variety of conditions and found similar results with the two compounds under most conditions. However, at a high multiplicity of infection, when all of the cells would be expected to be synchronously expressing large amounts of the viral thymidine kinase, short exposures to PCV appeared to be superior to similar exposures to ACV. In the HSV-1 zosteriform mouse model there was no significant difference between the activities of ACV and PCV, or its prodrug famciclovir (FCV), in once- or twice-daily treatment. The possible significance of these results and those previously reported on the activity of the compounds in humans is discussed.

Published
1995
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27. Synthesis and Anti-Herpes Virus Activity of 2‘-Deoxy-4‘-thiopyrimidine Nucleosides

Author

Rahim, S. G., Trivedi, N., Bogunovic-Batchelor, V., M., Hardy, G. W., Mills, G., Selway, J. W. T., Snowden, W., Littler, E., Coe, P. L., Basnak, I., Whale, R. F., and Walker, R. T.

Abstract

A series of 5-substituted 2‘-deoxy-4‘-thiopyrimidine nucleosides was synthesized and evaluated as potential antiviral agents. A number of analogues such as 2‘-deoxy-5-propyl-4‘-thiouridine (3ii), 2‘-deoxy-5-isopropyl-4‘-thiouridine (3iii), 5-cyclopropyl-2‘-deoxy-4‘-thiouridine (3iv), 2‘-deoxy-4‘-thio-5-vinyluridine (3viii), and 5-(2-chloroethyl)-2‘-deoxy-4‘-thiouridine (3xx) were found to be highly active against herpes simplex virus type-1 (HSV-1) and varicella zoster virus (VZV) in vitro with no significant cytotoxicity. The compound with the broadest spectrum of activity was 2‘-deoxy-5-ethyl-4‘-thiouridine (3i) which showed significant activity against HSV-1, HSV-2, and VZV.

Published
1996

29. Impact of second-line antiretroviral regimens on lipid profiles in an African setting: The DART trial sub-study

Author

Gomo, Z. A. R., Hakim, J. G., Walker, S. A., Tinago, W., Mandozana, G., Kityo, C., Munderi, P., Katabira, E., Reid, A., Gibb, D. M., Gilks, C. F., Grosskurth, H., Kabuye, G., Nsibambi, D., Kasirye, R., Zalwango, E., Nakazibwe, M., Kikaire, B., Nassuna, G., Massa, R., Fadhiru, K., Namyalo, M., Zalwango, A., Generous, L., Khauka, P., Rutikarayo, N., Nakahima, W., Mugisha, A., Todd, J., Levin, J., Muyingo, S., Ruberantwari, A., Kaleebu, P., Yirrell, D., Ndembi, N., Lyagoba, F., Hughes, P., Aber, M., Lara, A. M., Medina, A., Foster, S., Amurwon, J., Wakholi, B. N., Nyanzi, B., Wangati, K., Amuron, B., Kajungu, D., Nakiyingi, J., Omony, W., Mugyenyi, P., Ssali, F., Tumukunde, D., Otim, T., Kabanda, J., Musana, H., Akao, J., Kyomugisha, H., Byamukama, A., Sabiiti, J., Komugyena, J., Wavamunno, P., Mukiibi, S., Drasiku, A., Byaruhanga, R., Labeja, O., Katundu, P., Tugume, S., Awio, P., Namazzi, A., Bakeinyaga, G. T., Abaine, D., Tukamushaba, J., Anywar, W., Ojiambo, W., Angweng, E., Murungi, S., Haguma, W., Atwiine, S., Kigozi, J., Namale, L., Mukose, A., Mulindwa, G., Atwiine, D., Muhwezi, A., Nimwesiga, E., Barungi, G., Takubwa, J., Mwebesa, D., Kagina, G., Mulindwa, M., Ahimbisibwe, F., Mwesigwa, P., Akuma, S., Zawedde, C., Nyiraguhirwa, D., Tumusiime, C., Bagaya, L., Namara, W., Karungi, J., Kankunda, R., Enzama, R., Latif, A., Robertson, V., Chidziva, E., Bulaya-Tembo, R., Musoro, G., Taziwa, F., Chimbetete, C., Chakonza, L., Mawora, A., Muvirimi, C., Svovanapasis, P., Simango, M., Chirema, O., Machingura, J., Mutsai, S., Phiri, M., Bafana, T., Chirara, M., Muchabaiwa, L., Muzambi, M., Chigwedere, E., Pascoe, M., Warambwa, C., Zengeza, E., Mapinge, F., Makota, S., Jamu, A., Ngorima, N., Chirairo, H., Chitsungo, S., Chimanzi, J., Maweni, C., Warara, R., Matongo, M., Mudzingwa, S., Jangano, M., Moyo, K., Vere, L., Machingura, I., Ronald, A., Kambungu, A., Lutwama, F., Mambule, I., Nanfuka, A., Walusimbi, J., Nabankema, E., Nalumenya, R., Namuli, T., Kulume, R., Namata, I., Nyachwo, L., Florence, A., Kusiima, A., Lubwama, E., Nairuba, R., Oketta, F., Buluma, E., Waita, R., Ojiambo, H., Sadik, F., Wanyama, J., Nabongo, P., Oyugi, J., Sematala, F., Muganzi, A., Twijukye, C., Byakwaga, H., Ochai, R., Muhweezi, D., Coutinho, A., Etukoit, B., Boocock, K., Puddephatt, C., Grundy, C., Bohannon, J., Winogron, D., Darbyshire, J., Burke, A., Bray, D., Babiker, A., Wilkes, H., Rauchenberger, M., Sheehan, S., Spencer-Drake, C., Taylor, K., Spyer, M., Ferrier, A., Naidoo, B., Dunn, D., Ruth Goodall, Nanfuka, R., Mufuka-Kapuya, C., Pillay, D., Goodall, R., Kapaata, A., Katuramur, M., Magala, R., Magambo, B., Mataruka, K., Mccormick, A., Mugarura, L., Musunga, T., Nabankkema, M., Nkalubo, J., Nkurunziza, P., Parry, C., Weller, I., Bahendeka, S., Bassett, M., Chogo Wapakhabulo, A., Gazzard, B., Mapuchere, C., Mugurungi, O., Burke, C., Distel, M., Jones, S., Loeliger, E., Naidoo, P., Newland, C., Pearce, G., Rahim, S., Rooney, J., Smith, M., Snowden, W., Steens, J. -M, Breckenridge, A., Mclaren, A., Hill, C., Matenga, J., Pozniak, A., Serwadda, D., Peto, T., Palfreeman, A., and Borok, M.

30. Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings

Author

Firnhaber, C., Torres, M., Santos, B., Webb, N., Mildvan, D., Nair, A., Hoffman, I., McGregor, D., Chariyalertsak, S., Stroberg, T., Martinez, A.I., Infante, R., Para, M.F., Hurley, C., Marcus, C.J., Poongulali, S., Eshleman, S., Andrade, A., Lira, R.A., Tashima, K.T., Lawrence, J., Cohen, M., Swann, E., Noel-Connor, J., Steele, J., Mitsuyasu, R.T., Lalloo, U., Cu-Uvin, S., Riviere, C., Amod, F., Shugarts, D.L., Descallar, R.S., Klingman, K.L., Gormley, J., Corales, R., Luque, A., Smeaton, L.M., Currier, J.S., Said, F., Haas, D.W., Campbell, T.B., Dhayarkar, S., Celentano, D., Sanne, I., Tabet, S., Jain, M., Daar, E.S., Kumwenda, N., Revuelta, M., Kayoyo, V., Feinberg, J., Taha, T., Chilongozi, D., Kazembe, P., Cardoso, S.W., Martinson, F., Berendes, S., Faesen, S., Schooley, R.T., Flanigan, T., Bischofberger, N., Walawander, A., Kumwenda, J., Supparatpinyo, K., Lama, J.R., Pappa, K.A., Klebert, M.K., Severe, P., Berthaud, V., Solomon, S., Petersen, T., la Rosa, A., Frarey, L., Cheng, A., van der Horst, C., Barnett, R.L., Sharma, J., Putnam, B., Fiscus, S.A., Chen, Y., Gaikwad, A., Brizz, B., Chisada, A., Cox, G.M., Uy, J., Adams, M., Moran, L., Bailey, V.L., Rooney, J.F., Snowden, W., Pollard, R.B., Wulfsohn, M., Mayer, K., Gettinger, N., Watson, K.J., Sha, B.E., Ray, M.G., Hakim, J.G., Palmer, M., Kim, G.-Y., Basler, C., Lopez-Detres, L., Samaneka, W.P., Bollinger, R.C., Delph, Y., Wanke, C., Bryson, Y., Faria, D.L., Mogridge, C., Taiwo, B., Nielsen, K., Forcht, J., Winters, M.A., de Gruttola, V., Tebas, P., Lopez, R., Ntshele, S., Asmuth, D., Godbole, S., Patterson, H., Flexner, C., Eron, J., Collier, A.C., Ramratnam, B., Tripathy, S., Jaffe, H., Balfour, H.H., Zifchak, L., Kumarasamy, N., Haas, D.H., Fritsche, J.M., Currin, D., Grinsztejn, B., Mngqibisa, R., Gangakhedkar, R.R., Gallant, J.E., Martin, J.C., Safren, S., Silberman, M., Mullan, B., Geiseler, P.J., Joglekar, A.A., Cespedes, M., Kanyama, C., Gulick, R.M., Burke, K., Maponga, C., Loeliger, E., Hosseinipour, M.C., Baer, J., OBrien, W.A., Melo, M., Pendame, R.B., Hammer, S.M., Sanchez, J., and Sirisanthana, T.

Subjects
virus diseases, 3. Good health
Abstract

Background:Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.Methods and Findings:1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure.An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; p

39. At Rest.

Author

SNOWDEN, W. H.

Published
1902

45. LIBERTY.

Author

SNOWDEN, W. H.

Published
1886

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