Claudia Hawkins1, Nzovu Ulenga2, Enju Liu3, Said Aboud4, Ferdinand Mugusi4, Guerino Chalamilla5, David Sando5, Eric Aris5, Deborah Carpenter6, Wafaie Fawzi7. 1. Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA c-hawkins@md.northwestern.edu. 2. Management and Development for Health, Dar es Salaam, Tanzania Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA. 3. Departments of Nutrition, Epidemiology, Biostatistics, and Global Health and Population, Harvard School of Public Health, Boston, MA, USA. 4. Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania. 5. Management and Development for Health, Dar es Salaam, Tanzania. 6. Centers for Disease Control and Prevention, Dar es Salaam, Tanzania. 7. Department of Global Health and Population, Harvard School of Public Health, Boston, MA, USA.
Abstract
OBJECTIVES: There are few data on ART failure rates and drug resistance from Tanzania, where there is a wide diversity of non-B HIV subtypes. We assessed rates and predictors of virological failure in HIV-infected Tanzanians and describe drug resistance patterns in a subgroup of these patients. METHODS: ART-naive, HIV-1-infected adults enrolled in a randomized controlled trial between November 2006 and 2008 and on ≥24 weeks of first-line NNRTI-containing ART were included. Population-based genotyping of HIV-1 protease and reverse transcriptase was performed on stored plasma from patients with virological failure (viral load >1000 copies/mL at ≥24 weeks of ART) and at baseline, where available. RESULTS: A total of 2403 patients [median (IQR) age 37 (32-43) years; 70% female] were studied. The median (IQR) baseline CD4+ T cell count was 128 (62-190) cells/μL. Predominant HIV subtypes were A, C and D (92.2%). The overall rate of virological failure was 14.9% (95% CI 13.2%-16.1%). In adjusted analyses, significant predictors of virological failure were lower CD4+ T cell count (P = 0.01) and non-adherence to ART (P < 0.01). Drug resistance mutations were present in 87/115 samples (75.7%); the most common were M184V/I (52.2%) and K103N (35%). Thymidine analogue mutations were uncommon (5.2%). The prevalence of mutations in 45 samples pre-ART was 22%. CONCLUSIONS: High levels of early ART failure and drug resistance were observed among Tanzanian HIV-1-infected adults enrolled in a well-monitored study. Initiating treatment early and ensuring optimal adherence are vital for the success and durability of first-line ART in these settings.
OBJECTIVES: There are few data on ART failure rates and drug resistance from Tanzania, where there is a wide diversity of non-B HIV subtypes. We assessed rates and predictors of virological failure in HIV-infected Tanzanians and describe drug resistance patterns in a subgroup of these patients. METHODS: ART-naive, HIV-1-infected adults enrolled in a randomized controlled trial between November 2006 and 2008 and on ≥24 weeks of first-line NNRTI-containing ART were included. Population-based genotyping of HIV-1 protease and reverse transcriptase was performed on stored plasma from patients with virological failure (viral load >1000 copies/mL at ≥24 weeks of ART) and at baseline, where available. RESULTS: A total of 2403 patients [median (IQR) age 37 (32-43) years; 70% female] were studied. The median (IQR) baseline CD4+ T cell count was 128 (62-190) cells/μL. Predominant HIV subtypes were A, C and D (92.2%). The overall rate of virological failure was 14.9% (95% CI 13.2%-16.1%). In adjusted analyses, significant predictors of virological failure were lower CD4+ T cell count (P = 0.01) and non-adherence to ART (P < 0.01). Drug resistance mutations were present in 87/115 samples (75.7%); the most common were M184V/I (52.2%) and K103N (35%). Thymidine analogue mutations were uncommon (5.2%). The prevalence of mutations in 45 samples pre-ART was 22%. CONCLUSIONS: High levels of early ART failure and drug resistance were observed among Tanzanian HIV-1-infected adults enrolled in a well-monitored study. Initiating treatment early and ensuring optimal adherence are vital for the success and durability of first-line ART in these settings.
Authors: D B Fofana; C Soulié; A Baldé; S Lambert-Niclot; M Sylla; Z Ait-Arkoub; F Diallo; B Sangaré; M Cissé; I A Maïga; S Fourati; O Koita; V Calvez; A G Marcelin; A I Maïga Journal: J Antimicrob Chemother Date: 2014-05-22 Impact factor: 5.790
Authors: Jonathan Z Li; Roger Paredes; Heather J Ribaudo; Evguenia S Svarovskaia; Michael J Kozal; Katherine H Hullsiek; Michael D Miller; David R Bangsberg; Daniel R Kuritzkes Journal: AIDS Date: 2012-01-14 Impact factor: 4.177
Authors: Vincent C Marconi; Baohua Wu; Jane Hampton; Claudia E Ordóñez; Brent A Johnson; Dinesh Singh; Sally John; Michelle Gordon; Anna Hare; Richard Murphy; Jean Nachega; Daniel R Kuritzkes; Carlos del Rio; Henry Sunpath Journal: AIDS Patient Care STDS Date: 2013-12 Impact factor: 5.078
Authors: Sheila Isanaka; Ferdinand Mugusi; Claudia Hawkins; Donna Spiegelman; James Okuma; Said Aboud; Chalamilla Guerino; Wafaie W Fawzi Journal: JAMA Date: 2012-10-17 Impact factor: 56.272
Authors: Pierre De Beaudrap; Moussa Thiam; Assane Diouf; Coumba Toure-Kane; Ndèye F Ngom-Guèye; Nicole Vidal; Souleymane Mboup; Ibrahim Ndoye; Papa S Sow; Eric Delaporte Journal: J Acquir Immune Defic Syndr Date: 2013-04-01 Impact factor: 3.731
Authors: Mireia Arnedo; Elena Alonso; Nell Eisenberg; Laura Ibáñez; Cecilia Ferreyra; Angels Jaén; Laurence Flevaud; Samuel Khamadi; Paul Roddy; Jose Maria Gatell; David Dalmau Journal: PLoS One Date: 2012-12-06 Impact factor: 3.240
Authors: Nicholas I Nii-Trebi; Shiro Ibe; Jacob S Barnor; Koichi Ishikawa; James A M Brandful; Sampson B Ofori; Shoji Yamaoka; William K Ampofo; Wataru Sugiura Journal: PLoS One Date: 2013-08-19 Impact factor: 3.240
Authors: Daniel W Gunda; Semvua B Kilonzo; Tarcisius Mtaki; Desderius M Bernard; Samwel E Kalluvya; Elichilia R Shao Journal: BMC Infect Dis Date: 2019-03-07 Impact factor: 3.090
Authors: Bernhard Kerschberger; Michael Schomaker; Kiran Jobanputra; Serge M Kabore; Roger Teck; Edwin Mabhena; Simangele Mthethwa-Hleza; Barbara Rusch; Iza Ciglenecki; Andrew Boulle Journal: J Int AIDS Soc Date: 2020-03 Impact factor: 5.396
Authors: Allan Buzibye; Joseph Musaazi; Amrei von Braun; Sarah Nanzigu; Christine Sekaggya-Wiltshire; Andrew Kambugu; Jan Fehr; Mohammed Lamorde; Ursula Gutteck; Daniel Muller; Stefanie Sowinski; Steven J Reynolds; Barbara Castelnuovo Journal: AIDS Res Ther Date: 2019-12-06 Impact factor: 2.250
Authors: Rahel E Bircher; Alex J Ntamatungiro; Tracy R Glass; Dorcas Mnzava; Amina Nyuri; Herry Mapesi; Daniel H Paris; Manuel Battegay; Thomas Klimkait; Maja Weisser Journal: PLoS One Date: 2020-01-13 Impact factor: 3.240
Authors: Shimba Henerico; Sello Given Mikasi; Samuel Elias Kalluvya; Jan M Brauner; Seif Abdul; Eric Lyimo; Bernard Desderius; Klaus Korn; Gert van Zyl; Graeme Brendon Jacobs; Wolfgang Preiser; Christa Kasang Journal: J Antimicrob Chemother Date: 2022-02-02 Impact factor: 5.790