Disparities in Dolutegravir Uptake Affecting Females of Reproductive Age With HIV in Low- and Middle-Income Countries After Initial Concerns About Teratogenicity
Authors: Matthew L. Romo, Rena C. Patel, Jessie K. Edwards, John M. Humphrey, Beverly S. Musick, Caitlin Bernard, Mercy W. Maina, Ellen Brazier, Barbara Castelnuovo, Jeremy Penner, Katarzyna Wyka, Sandra Wagner Cardoso, Penh Sun Ly, Cordelia Kunzekwenyika, Claudia P. Cortés, Radoslaw Panczak, Elizabeth A. Kelvin, Kara K. Wools-Kaloustian, Denis Nash, Matthew L. Romo, Jessie K. Edwards, Beverly Musick, Ellen Brazier, Barbara Castelnuovo, Sandra Wagner Cardoso, P.S. Ly, Cordelia Kunzekwenyika, Claudia P. Cortés, Radoslaw Panczak, Elizabeth A. Kelvin, Kara Wools-Kaloustian, Denis Nash, V. Khol, F.J. Zhang, H.X. Zhao, N. Han, M.P. Lee, P.C.K. Li, W. Lam, H.Y. Wong, N. Kumarasamy, C. Ezhilarasi, S. Pujari, K. Joshi, S. Gaikwad, A. Chitalikar, T.P. Merati, D.N. Wirawan, F. Yuliana, E. Yunihastuti, D. Imran, A. Widhani, J. Tanuma, S. Oka, T. Nishijima, J.Y. Choi, S. Na, J.M. Kim, Y.M. Gani, N.B. Rudi, I. Azwa, A. Kamarulzaman, S.F. Syed Omar, S. Ponnampalavanar, R. Ditangco, M.K. Pasayan, M.L. Mationg, Y.J. Chan, W.W. Ku, E. Ke, P.C. Wu, O.T. Ng, P.L. Lim, L.S. Lee, J.K. Ya, A. Avihingsanon, S. Gatechompol, P. Phanuphak, C. Phadungphon, S. Kiertiburanakul, A. Phuphuakrat, L. Chumla, N. Sanmeema, R. Chaiwarith, T. Sirisanthana, J. Praparattanapan, K. Nuket, S. Khuwuwan, P. Kantipong, P. Kambua, K.V. Nguyen, H.V. Bui, D.T.H. Nguyen, D.T. Nguyen, C.D. Do, A.V. Ngo, L.T. Nguyen, A.H. Sohn, J.L. Ross, B. Petersen, M.G. Law, A. Jiamsakul, R. Bijker, D. Rupasinghe, Pedro Cahn, Carina Cesar, Valeria Fink, Omar Sued, Emanuel Dell’Isola, Hector Perez, Jose Valiente, Cleyton Yamamoto, Beatriz Grinsztejn, Valdilea Veloso, Paula Luz, Raquel de Boni, Ruth Friedman, Ronaldo Moreira, Jorge Pinto, Flavia Ferreira, Marcelle Maia, Regina Célia de Menezes Succi, Daisy Maria Machado, Aida de Fátima Barbosa Gouvêa, Marcelo Wolff, Maria Fernanda Rodriguez, Gladys Allendes, Jean William Pape, Vanessa Rouzier, Adias Marcelin, Christian Perodin, Marco Tulio Luque, Denis Padgett, Juan Sierra Madero, Brenda Crabtree Ramirez, Paco Belaunzaran, Yanink Caro Vega, Eduardo Gotuzzo, Fernando Mejia, Gabriela Carriquiry, Catherine C. McGowan, Bryan E. Shepherd, Timothy Sterling, Karu Jayathilake, Anna K. Person, Peter F. Rebeiro, Jessica Castilho, Stephany N. Duda, Fernanda Maruri, Hilary Vansell, Cathy Jenkins, Ahra Kim, Sarah Lotspeich, Nimbona Pélagie, Patrick Gateretse, Jeanine Munezero, Valentin Nitereka, Théodore Niyongabo, Christelle Twizere, Hélène Bukuru, Thierry Nahimana, Elysée Baransaka, Patrice Barasukana, Eugene Kabanda, Martin Manirakiza, François Ndikumwenayo, Jérémie Biziragusenyuka, Ange Marie Michelline Munezero, Denis Nsame Nforniwe, Rogers Ajeh, Marc Lionel Ngamani, Anastase Dzudie, Akindeh Mbuh, Djenabou Amadou, Eric Walter Pefura Yone, Ernestine Kendowo, Catherine Akele, Akili Clever, Faustin Kitetele, Patricia Lelo, Martine Tabala, Cherubin Ekembe, Didine Kaba, Merlin Diafouka, Martin Herbas Ekat, Dominique Mahambou Nsonde, Adolphe Mafoua, Massamba Ndala Christ, Jules Igirimbabazi, Nicole Ayinkamiye, Providance Uwineza, Emmanuel Ndamijimana, Emmanuel Habarurema, Marie Luise Nyiraneza, Marie Louise Nyiransabimana, Liliane Tuyisenge, Christian Shyaka, Catherine Kankindi, Bonheur Uwakijijwe, Marie Grace Ingabire, Jules Ndumuhire, Marie Goretti Nyirabahutu, Fred Muyango, Jean Christophe Bihibindi, Oliver Uwamahoro, Yvette Ndoli, Sabin Nsanzimana, Placidie Mugwaneza, Eric Remera, Esperance Umumararungu, Gallican Nshogoza Rwibasira, Dominique Savio Habimana, Josephine Gasana, Faustin Kanyabwisha, Gallican Kubwimana, Benjamin Muhoza, Athanase Munyaneza, Gad Murenzi, Francoise Musabyimana, Francine Umwiza, Charles Ingabire, Patrick Tuyisenge, Alex M. Butera, Jules Kabahizi, Ephrem Rurangwa, Rosine Feza, Eugenie Mukashyaka, Chantal Benekigeri, Jacqueline Musaninyange, Adebola Adedimeji, Kathryn Anastos, Madeline Dilorenzo, Lynn Murchison, Jonathan Ross, Marcel Yotebieng, Diane Addison, Heidi Jones, Sarah Kulkarni, Olga Tymejczyk, Batya Elul, Xiatao Cai, Allan Dong, Don Hoover, Hae-Young Kim, Chunshan Li, Qiuhu Shi, Kathryn Lancaster, Mark Kuniholm, Andrew Edmonds, Angela Parcesepe, Olivia Keiser, Stephany Duda, April Kimmel, L. Diero, S. Ayaya, E. Sang, E. Bukusi, Edwin Mulwa, George Nyanaro, Charles Kasozi, Mathew Ssemakadde, Mwebesa Bosco Bwana, Winnie Muyindike, Helen Byakwaga, Michael Kanyesigye, Aggrey Semeere, John Michael Matovu, Fred Nalugoda, Francis X. Wasswa, Paul Kazyoba, Mary Mayige, Rita Elias Lyamuya, Francis Mayanga, Kapella Ngonyani, Jerome Lwali, Mark Urassa, Charles Nyaga, Richard Machemba, Constantin Yiannoutsos, Batya Elul, Rachel Vreeman, Jennifer Syvertsen, Rami Kantor, Jeffrey Martin, Megan Wenger, Craig Cohen, Jayne Kulzer, Gary Maartens, Carolyn Bolton, Robin Wood, Nosisa Sipambo, Frank Tanser, Andrew Boulle, Geoffrey Fatti, Safari Mbewe, Elvira Singh, Cleophas Chimbetete, Karl Technau, Brian Eley, Josephine Muhairwe, Idivino Rafael, Matthew P. Fox, Hans Prozesky, Nina Anderegg, Marie Ballif, Cam Ha Dao Ostinelli, Matthias Egger, Lukas Fenner, Andreas Haas, Stefanie Hossmann, Eliane Rohner, Julien Riou, Veronika Skrivankova, Lilian Smith, Katayoun Taghavi, Per von Groote, Gilles Wandeler, Elizabeth Zaniewski, Kathrin Zürcher, Kim Anderson, Andrew Boulle, Morna Cornell, Mary-Ann Davies, Victoria Iyun, Leigh Johnson, Reshma Kassanjee, Kathleen Kehoe, Mmamapudi Kubjane, Nicola Maxwell, Patience Nyakato, Gem Patten, Mpho Tlali, Priscilla Tsondai, Renee de Waal
Journal: Annals of Internal Medicine (2021)

Background: The transition to dolutegravir-containing antiretroviral therapy (ART) in low- and middle-income countries (LMICs) was complicated by an initial safety signal in May 2018 suggesting that exposure to dolutegravir at conception was possibly associated with infant neural tube defects. On the basis of additional evidence, in July 2019, the World Health Organization recommended dolutegravir for all adults and adolescents living with HIV. Objective: To describe dolutegravir uptake and disparities by sex and age group in LMICs. Design: Observational cohort study. Setting: 87 sites that began using dolutegravir in 11 LMICs in the Asia-Pacific; Caribbean, Central and South America network for HIV epidemiology (CCASAnet); and sub-Saharan African regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. Patients: 134 672 patients aged 16 years or older who received HIV care from January 2017 through March 2020. Measurements: Sex, age group, and dolutegravir uptake (that is, newly initiating ART with dolutegravir or switching to dolutegravir from another regimen). Results: Differences in dolutegravir uptake among females of reproductive age (16 to 49 years) emerged after the safety signal. By the end of follow-up, the cumulative incidence of dolutegravir uptake among females 16 to 49 years old was 29.4% (95% CI, 29.0% to 29.7%) compared with 57.7% (CI, 57.2% to 58.3%) among males 16 to 49 years old. This disparity was greater in countries that began implementing dolutegravir before the safety signal and initially had highly restrictive policies versus countries with a later rollout. Dolutegravir uptake was similar among females and males aged 50 years or older. Limitation: Follow-up was limited to 6 to 8 months after international guidelines recommended expanding access to dolutegravir. Conclusion: Substantial disparities in dolutegravir uptake affecting females of reproductive age through early 2020 are documented. Although this disparity was anticipated because of country-level restrictions on access, the results highlight its extent and initial persistence. Primary Funding Source: National Institutes of Health.