Nadine Bachmann1,2, Amrei von Braun1,3, Niklaus D Labhardt4,5,6, Claus Kadelka1,2, Huldrych F Günthard1,2, Christine Sekaggya-Wiltshire3, Barbara Castelnuovo3, Andrew Kambugu3, Thabo I Lejone7, Jürg Böni2, Sabine Yerly8, Matthieu Perreau9, Thomas Klimkait5, Roger D Kouyos1,2, Jan Fehr1,10. 1. Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. 2. Institute of Medical Virology, University of Zurich, Zurich, Switzerland. 3. Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda. 4. Swiss Tropical and Public Health Institute, Basel, Switzerland. 5. University of Basel, Basel, Switzerland. 6. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland. 7. SolidarMed, Swiss Organization for Health in Africa, Butha-Buthe, Lesotho. 8. Laboratory of Virology, University Hospital Geneva, University of Geneva, Geneva, Switzerland. 9. Division of Immunology and Allergy, CHUV, Lausanne, Switzerland. 10. Department of Public Health at Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
Abstract
Objectives: Emerging resistance to antiretroviral drugs may jeopardize the achievements of improved access to ART. We compared the prevalence of different resistance mutations in HIV-infected adults with virological failure in a cohort with regular routine viral load (VL) monitoring (Switzerland) and cohorts with limited access to VL testing (Uganda and Lesotho). Methods: We considered individuals who had genotypic resistance testing (GRT) upon virological failure (≥1000 copies/mL) and were on ART consisting of at least one NNRTI and two NRTIs. From Lesotho, individuals with two subsequent VLs ≥1000 copies/mL despite enhanced adherence counselling (n = 58) were included in the analysis. From Uganda, individuals with a single VL ≥1000 copies/mL (n = 120) were included in the analysis. From the Swiss HIV Cohort Study (SHCS), a population without history of monotherapy or dual therapy with the first GRT upon virological failure (n = 61) was selected. Results: We found that 50.8% of individuals in the SHCS, 72.5% in Uganda and 81.0% in Lesotho harboured HIV with high-level resistance to at least two drugs from their current regimen. Stanford resistance scores were higher in Uganda compared with Switzerland for all drugs used in first-line treatment except zidovudine and tenofovir (P < 0.01) and higher in Lesotho compared with Uganda for all drugs used in first-line treatment except zidovudine (P < 0.01). Conclusions: Frequent VL monitoring and possibly pretreatment GRT as done in the SHCS pays off by low levels of resistance even when treatment failure occurs. The high-level resistance patterns in Lesotho compared with Uganda could reflect a selection of strains with multiple resistance during enhanced adherence counselling.
Objectives: Emerging resistance to antiretroviral drugs may jeopardize the achievements of improved access to ART. We compared the prevalence of different resistance mutations in HIV-infected adults with virological failure in a cohort with regular routine viral load (VL) monitoring (Switzerland) and cohorts with limited access to VL testing (Uganda and Lesotho). Methods: We considered individuals who had genotypic resistance testing (GRT) upon virological failure (≥1000 copies/mL) and were on ART consisting of at least one NNRTI and two NRTIs. From Lesotho, individuals with two subsequent VLs ≥1000 copies/mL despite enhanced adherence counselling (n = 58) were included in the analysis. From Uganda, individuals with a single VL ≥1000 copies/mL (n = 120) were included in the analysis. From the Swiss HIV Cohort Study (SHCS), a population without history of monotherapy or dual therapy with the first GRT upon virological failure (n = 61) was selected. Results: We found that 50.8% of individuals in the SHCS, 72.5% in Uganda and 81.0% in Lesotho harboured HIV with high-level resistance to at least two drugs from their current regimen. Stanford resistance scores were higher in Uganda compared with Switzerland for all drugs used in first-line treatment except zidovudine and tenofovir (P < 0.01) and higher in Lesotho compared with Uganda for all drugs used in first-line treatment except zidovudine (P < 0.01). Conclusions: Frequent VL monitoring and possibly pretreatment GRT as done in the SHCS pays off by low levels of resistance even when treatment failure occurs. The high-level resistance patterns in Lesotho compared with Uganda could reflect a selection of strains with multiple resistance during enhanced adherence counselling.
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