Landon Myer1,2, Andrew D Redd3,4, Elton Mukonda1, Briana A Lynch3, Tamsin K Phillips1,2, Anna Eisenberg3, Nei-Yuan Hsiao5,6, Adam Capoferri4, Alison Zerbe7, William Clarke8, Maia Lesosky1, Autumn Breaud8, James McIntyre1,9, Daniel Bruno10, Craig Martens10, Elaine J Abrams7,11, Steven J Reynolds3,4. 1. Division of Epidemiology and Biostatistics, University of Cape Town, South Africa. 2. Centre for Infectious Diseases Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, South Africa. 3. Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda. 4. Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland. 5. Division of Medical Virology, Department of Pathology, University of Cape Town, South Africa. 6. National Health Laboratory Services, Groote Schuur Hospital, Cape Town, South Africa. 7. ICAP at Columbia University Mailman School of Public Health, New York, New York. 8. Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland. 9. Anova Health Institute, Johannesburg, South Africa. 10. Genomics Unit, Research Technologies Branch, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, Montana. 11. Vagelos College of Physicians and Surgeons, Columbia University, New York, New York.
Abstract
BACKGROUND: Elevated viral load (VL) early after antiretroviral therapy (ART) initiation appears frequently in pregnant and postpartum women living with human immunodeficiency virus; however the relative contributions of pre-ART drug resistance mutations (DRMs) vs nonadherence in the etiology of elevated VL are unknown. METHODS: Within a cohort of women initiating ART during pregnancy in Cape Town, South Africa, we compared women with elevated VL after initial suppression (cases, n = 80) incidence-density matched to women who maintained suppression over time (controls, n = 87). Groups were compared on pre-ART DRMs and detection of antiretrovirals in stored plasma. RESULTS: The prevalence of pre-ART DRMs was 10% in cases and 5% in controls (adjusted odds ratio [aOR], 1.53 [95% confidence interval {CI}, .4-5.9]); all mutations were to nonnucleoside reverse transcriptase inhibitors. At the time of elevated VL, 19% of cases had antiretrovirals detected in plasma, compared with 87% of controls who were suppressed at a matched time point (aOR, 131.43 [95% CI, 32.8-527.4]). Based on these findings, we estimate that <10% of all elevated VL in the cohort may be attributable to pre-ART DRMs vs >90% attributable to ART nonadherence. CONCLUSIONS: DRMs account for a small proportion of all elevated VL among women occurring in the 12 months after ART initiation during pregnancy in this setting, with nonadherence appearing to drive most episodes of elevated VL. Alongside the drive for access to more robust antiretroviral agents in resource-limited settings, there is an ongoing need for effective strategies to support ART adherence in this patient population.
BACKGROUND: Elevated viral load (VL) early after antiretroviral therapy (ART) initiation appears frequently in pregnant and postpartum women living with human immunodeficiency virus; however the relative contributions of pre-ART drug resistance mutations (DRMs) vs nonadherence in the etiology of elevated VL are unknown. METHODS: Within a cohort of women initiating ART during pregnancy in Cape Town, South Africa, we compared women with elevated VL after initial suppression (cases, n = 80) incidence-density matched to women who maintained suppression over time (controls, n = 87). Groups were compared on pre-ART DRMs and detection of antiretrovirals in stored plasma. RESULTS: The prevalence of pre-ART DRMs was 10% in cases and 5% in controls (adjusted odds ratio [aOR], 1.53 [95% confidence interval {CI}, .4-5.9]); all mutations were to nonnucleoside reverse transcriptase inhibitors. At the time of elevated VL, 19% of cases had antiretrovirals detected in plasma, compared with 87% of controls who were suppressed at a matched time point (aOR, 131.43 [95% CI, 32.8-527.4]). Based on these findings, we estimate that <10% of all elevated VL in the cohort may be attributable to pre-ART DRMs vs >90% attributable to ART nonadherence. CONCLUSIONS: DRMs account for a small proportion of all elevated VL among women occurring in the 12 months after ART initiation during pregnancy in this setting, with nonadherence appearing to drive most episodes of elevated VL. Alongside the drive for access to more robust antiretroviral agents in resource-limited settings, there is an ongoing need for effective strategies to support ART adherence in this patient population.
Authors: Jean B Nachega; Nadia A Sam-Agudu; Lynne M Mofenson; Mauro Schechter; John W Mellors Journal: Clin Infect Dis Date: 2018-05-02 Impact factor: 9.079
Authors: Cassidy E Henegar; Daniel J Westreich; Mhairi Maskew; William C Miller; M Alan Brookhart; Annelies Van Rie Journal: J Acquir Immune Defic Syndr Date: 2015-04-01 Impact factor: 3.731
Authors: Christopher J Hoffmann; Silvia Cohn; Fildah Mashabela; Jennifer D Hoffmann; Helen McIlleron; Paolo Denti; David W Haas; Kelly E Dooley; Neil A Martinson; Richard E Chaisson Journal: J Acquir Immune Defic Syndr Date: 2016-01-01 Impact factor: 3.731
Authors: Joëlla W Adams; Kathleen A Brady; Yvonne L Michael; Baligh R Yehia; Florence M Momplaisir Journal: Clin Infect Dis Date: 2015-08-11 Impact factor: 9.079
Authors: T Sonia Boender; Bernice M Hoenderboom; Kim C E Sigaloff; Raph L Hamers; Maureen Wellington; Tinei Shamu; Margaret Siwale; Eman E F Labib Maksimos; Immaculate Nankya; Cissy M Kityo; Titilope A Adeyemo; Alani Sulaimon Akanmu; Kishor Mandaliya; Mariette E Botes; Pascale Ondoa; Tobias F Rinke de Wit Journal: Clin Infect Dis Date: 2015-08-03 Impact factor: 9.079
Authors: Jessica E Haberer; Lora Sabin; K Rivet Amico; Catherine Orrell; Omar Galárraga; Alexander C Tsai; Rachel C Vreeman; Ira Wilson; Nadia A Sam-Agudu; Terrence F Blaschke; Bernard Vrijens; Claude A Mellins; Robert H Remien; Sheri D Weiser; Elizabeth Lowenthal; Michael J Stirratt; Papa Salif Sow; Bruce Thomas; Nathan Ford; Edward Mills; Richard Lester; Jean B Nachega; Bosco Mwebesa Bwana; Fred Ssewamala; Lawrence Mbuagbaw; Paula Munderi; Elvin Geng; David R Bangsberg Journal: J Int AIDS Soc Date: 2017-03-22 Impact factor: 5.396
Authors: Pamela M Murnane; James Ayieko; Eric Vittinghoff; Monica Gandhi; Chaplain Katumbi; Beteniko Milala; Catherine Nakaye; Peter Kanda; Dhayendre Moodley; Mandisa E Nyati; Amy J Loftis; Mary G Fowler; Pat Flynn; Judith S Currier; Craig R Cohen Journal: J Acquir Immune Defic Syndr Date: 2021-12-15 Impact factor: 3.771
Authors: Jane Kabami; Laura B Balzer; Hachem Saddiki; James Ayieko; Dalsone Kwarisiima; Mucunguzi Atukunda; Edwin D Charlebois; Tamara D Clark; Catherine A Koss; Theodore Ruel; Elizabeth A Bukusi; Craig R Cohen; Phillipa Musoke; Maya L Petersen; Diane V Havlir; Moses R Kamya; Gabriel Chamie Journal: AIDS Date: 2020-07-15 Impact factor: 4.632
Authors: Megan Landes; Monique van Lettow; Joep J van Oosterhout; Erik Schouten; Andrew Auld; Thokozani Kalua; Andreas Jahn; Beth A Tippett Barr Journal: PLoS One Date: 2021-03-12 Impact factor: 3.240
Authors: Monique van Lettow; Beth A Tippett Barr; Joep J van Oosterhout; Erik Schouten; Andreas Jahn; Thokozani Kalua; Andrew Auld; Rose Nyirenda; Nellie Wadonda; Evelyn Kim; Megan Landes Journal: HIV Med Date: 2021-12-30 Impact factor: 3.094
Authors: John M Humphrey; Julia Songok; Susan Ofner; Beverly Musick; Marsha Alera; Bett Kipchumba; Megan S McHenry; James G Carlucci; Jun Park; Winfred Mwangi; Constantin Yiannoutsos; Giorgos Bakoyannis; Kara Wools-Kaloustian Journal: AIDS Behav Date: 2022-04-25
Authors: Lufuno G Mavhandu-Ramarumo; Lisa A M Tambe; Nontokozo D Matume; David Katerere; Pascal O Bessong Journal: South Afr J HIV Med Date: 2021-04-08 Impact factor: 2.744