Pierre de Truchis1,2,3, Minh Patrick Lê4, Mamane Daou2,5, Boubacar Madougou2,5, Yacouba Nouhou6, Sahada Moussa Saley5, Achirou Sani5, Eric Adehossi5, Elisabeth Rouveix7,2,3, Mamadou Saidou8, Gilles Peytavin4, Constance Delaugerre9. 1. Hôpitaux Universitaires Paris IdF-Ouest, APHP, France p.de-truchis@aphp.fr. 2. GIP-ESTHER, Expertise France, Paris, France. 3. Entraide Sante 92, France. 4. Pharmaco-Toxicology Department, Hôpital Bichat - Claude Bernard, APHP, INSERM IAME UMR 1137, Paris, France. 5. Hôpital National de Niamey, Niger. 6. Centre de Traitement Ambulatoire, CTA, Niamey, Niger. 7. Hôpitaux Universitaires Paris IdF-Ouest, APHP, France. 8. Laboratoire National de Virologie, CHU Lamordé, Niamey, Niger. 9. Laboratoire de Virologie-INSERM U941, Hôpital Saint Louis-APHP, Université Paris Diderot, Paris, France.
Abstract
OBJECTIVES: The objectives of this study were to determine the rate of viral success in HIV-infected patients on first-line ART by the assessment of dried blood spot (DBS) viral load (VL) and to assess the performance of DBS sampling for VL measurement, genotypic resistance and antiretroviral concentration determinations. METHODS: HIV-infected patients treated for >1 year with first-line ART in Niamey, Niger were included. VL based on nucleic acid sequence-based amplification (NASBA) assay (limit of quantification <800 copies/mL) was measured on DBS capillary samples. Resistance genotype was assessed for all detectable VLs (limit of detection >100 copies/mL); antiretroviral concentrations were interpreted using standard plasma cut-offs after extrapolation of blood to plasma results. Median (IQR) results are presented. RESULTS: Two hundred and eighteen patients (61% women), aged 41 (34-46) years, with 138 (56-235) CD4 cells/mm3 at baseline were included. After 4 (2-6) years of follow-up under therapy, CD4 gain was +197 (98-372) cells/mm3; 81% had VL <800 copies/mL. Antiretroviral concentrations were adequate in 87% of patients and nevirapine/efavirenz concentrations were related to viral success (P < 0.001). DBS genotypic resistance amplification succeeded in 71% of failing patients: NRTI drug resistance mutations were identified in 73% including resistance to lamivudine/emtricitabine (67%), abacavir (30%) and tenofovir (21%); and NNRTI drug resistance mutations were identified in 82% including resistance to rilpivirine (39%) and etravirine (15%). CONCLUSIONS: This study demonstrated a good response after 4 years of first-line ART in Niger. Adherence was high, according to antiretroviral concentrations, and the majority of failures were explained by selection of drug resistance mutations detected in the DBS genotype. Using DBS might improve the assessment of ART failure in HIV-infected patients in low-income countries.
OBJECTIVES: The objectives of this study were to determine the rate of viral success in HIV-infectedpatients on first-line ART by the assessment of dried blood spot (DBS) viral load (VL) and to assess the performance of DBS sampling for VL measurement, genotypic resistance and antiretroviral concentration determinations. METHODS:HIV-infectedpatients treated for >1 year with first-line ART in Niamey, Niger were included. VL based on nucleic acid sequence-based amplification (NASBA) assay (limit of quantification <800 copies/mL) was measured on DBS capillary samples. Resistance genotype was assessed for all detectable VLs (limit of detection >100 copies/mL); antiretroviral concentrations were interpreted using standard plasma cut-offs after extrapolation of blood to plasma results. Median (IQR) results are presented. RESULTS: Two hundred and eighteen patients (61% women), aged 41 (34-46) years, with 138 (56-235) CD4 cells/mm3 at baseline were included. After 4 (2-6) years of follow-up under therapy, CD4 gain was +197 (98-372) cells/mm3; 81% had VL <800 copies/mL. Antiretroviral concentrations were adequate in 87% of patients and nevirapine/efavirenz concentrations were related to viral success (P < 0.001). DBS genotypic resistance amplification succeeded in 71% of failing patients: NRTI drug resistance mutations were identified in 73% including resistance to lamivudine/emtricitabine (67%), abacavir (30%) and tenofovir (21%); and NNRTI drug resistance mutations were identified in 82% including resistance to rilpivirine (39%) and etravirine (15%). CONCLUSIONS: This study demonstrated a good response after 4 years of first-line ART in Niger. Adherence was high, according to antiretroviral concentrations, and the majority of failures were explained by selection of drug resistance mutations detected in the DBS genotype. Using DBS might improve the assessment of ART failure in HIV-infectedpatients in low-income countries.
Authors: Tanja R Zijp; Zamrotul Izzah; Daan J Touw; Job F M van Boven; Christoffer Åberg; C Tji Gan; Stephan J L Bakker Journal: Drugs Date: 2021-11-01 Impact factor: 9.546