Cargando…

Laboratory Based Surveillance of HIV-1 Acquired Drug Resistance in Cameroon: Implications for Use of Tenofovir-Lamivudine-Dolutegravir (TLD) as Second- or Third-Line Regimens

Increased HIV drug resistance (HIVDR) with antiretroviral therapy (ART) rollout may jeopardize therapeutic options, especially in this era of transition to fixed-dose tenofovir-lamivudine-dolutegravir (TLD). We studied acquired HIVDR (ADR) patterns and describe potentially active drugs after first-...

Descripción completa

Detalles Bibliográficos
Autores principales: Fokam, Joseph, Chenwi, Collins Ambe, Takou, Desire, Santoro, Maria Mercedes, Tala, Valere, Teto, George, Beloumou, Grace, Semengue, Ezechiel Ngoufack Jagni, Dambaya, Beatrice, Djupsa, Sandrine, Kembou, Etienne, Bouba, Nounouce Pamen, Ajeh, Rogers, Cappelli, Giulia, Mbanya, Dora, Colizzi, Vittorio, Ceccherini-Silberstein, Francesca, Perno, Carlo-Federico, Ndjolo, Alexis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10459610/
https://www.ncbi.nlm.nih.gov/pubmed/37632026
http://dx.doi.org/10.3390/v15081683
_version_ 1785097452779470848
author Fokam, Joseph
Chenwi, Collins Ambe
Takou, Desire
Santoro, Maria Mercedes
Tala, Valere
Teto, George
Beloumou, Grace
Semengue, Ezechiel Ngoufack Jagni
Dambaya, Beatrice
Djupsa, Sandrine
Kembou, Etienne
Bouba, Nounouce Pamen
Ajeh, Rogers
Cappelli, Giulia
Mbanya, Dora
Colizzi, Vittorio
Ceccherini-Silberstein, Francesca
Perno, Carlo-Federico
Ndjolo, Alexis
author_facet Fokam, Joseph
Chenwi, Collins Ambe
Takou, Desire
Santoro, Maria Mercedes
Tala, Valere
Teto, George
Beloumou, Grace
Semengue, Ezechiel Ngoufack Jagni
Dambaya, Beatrice
Djupsa, Sandrine
Kembou, Etienne
Bouba, Nounouce Pamen
Ajeh, Rogers
Cappelli, Giulia
Mbanya, Dora
Colizzi, Vittorio
Ceccherini-Silberstein, Francesca
Perno, Carlo-Federico
Ndjolo, Alexis
author_sort Fokam, Joseph
collection PubMed
description Increased HIV drug resistance (HIVDR) with antiretroviral therapy (ART) rollout may jeopardize therapeutic options, especially in this era of transition to fixed-dose tenofovir-lamivudine-dolutegravir (TLD). We studied acquired HIVDR (ADR) patterns and describe potentially active drugs after first- and second-line failure in resource-limited settings (RLS) like Cameroon. A laboratory-based study with 759 patients (≥15 years) experiencing virological failure was carried out at the Chantal Biya International Reference Centre (CIRCB), Yaoundé, Cameroon. Socio-demographic, therapeutic and immunovirological data from patient records were analysed according to HIV-1 genotypic profiles. Median (IQR) ART-duration was 63 (50–308) months. Median CD4 and viremia were 153 (IQR:50–308) cells/mm(3) and 138,666 (IQR:28,979–533,066) copies/mL, respectively. Overall ADR was high (93.4% first-line; 92.9%-second-line). TDF, potentially active in 35.7% of participants after first-line and 45.1% after second-line, suggested sub-optimal TLD-efficacy in second-line (64.3%) and third-line (54.9%). All PI/r preserved high efficacy after first-line failure while only DRV/r preserved high-level efficacy (87.9%) after second-line failure. In this resource-limited setting (RLS), ADR is high in ART-failing patients. PI/r strategies remain potent backbones for second-line ART, while only DRV/r remains very potent despite second-line failure. Though TLD use would be preferable, blind use for second- and third-line regimens may be sub-optimal (functional monotherapy with dolutegravir) with high risk of further failure, thus suggesting strategies for selective ART switch to TLD in failing patients in RLS.
format Online
Article
Text
id pubmed-10459610
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-104596102023-08-27 Laboratory Based Surveillance of HIV-1 Acquired Drug Resistance in Cameroon: Implications for Use of Tenofovir-Lamivudine-Dolutegravir (TLD) as Second- or Third-Line Regimens Fokam, Joseph Chenwi, Collins Ambe Takou, Desire Santoro, Maria Mercedes Tala, Valere Teto, George Beloumou, Grace Semengue, Ezechiel Ngoufack Jagni Dambaya, Beatrice Djupsa, Sandrine Kembou, Etienne Bouba, Nounouce Pamen Ajeh, Rogers Cappelli, Giulia Mbanya, Dora Colizzi, Vittorio Ceccherini-Silberstein, Francesca Perno, Carlo-Federico Ndjolo, Alexis Viruses Article Increased HIV drug resistance (HIVDR) with antiretroviral therapy (ART) rollout may jeopardize therapeutic options, especially in this era of transition to fixed-dose tenofovir-lamivudine-dolutegravir (TLD). We studied acquired HIVDR (ADR) patterns and describe potentially active drugs after first- and second-line failure in resource-limited settings (RLS) like Cameroon. A laboratory-based study with 759 patients (≥15 years) experiencing virological failure was carried out at the Chantal Biya International Reference Centre (CIRCB), Yaoundé, Cameroon. Socio-demographic, therapeutic and immunovirological data from patient records were analysed according to HIV-1 genotypic profiles. Median (IQR) ART-duration was 63 (50–308) months. Median CD4 and viremia were 153 (IQR:50–308) cells/mm(3) and 138,666 (IQR:28,979–533,066) copies/mL, respectively. Overall ADR was high (93.4% first-line; 92.9%-second-line). TDF, potentially active in 35.7% of participants after first-line and 45.1% after second-line, suggested sub-optimal TLD-efficacy in second-line (64.3%) and third-line (54.9%). All PI/r preserved high efficacy after first-line failure while only DRV/r preserved high-level efficacy (87.9%) after second-line failure. In this resource-limited setting (RLS), ADR is high in ART-failing patients. PI/r strategies remain potent backbones for second-line ART, while only DRV/r remains very potent despite second-line failure. Though TLD use would be preferable, blind use for second- and third-line regimens may be sub-optimal (functional monotherapy with dolutegravir) with high risk of further failure, thus suggesting strategies for selective ART switch to TLD in failing patients in RLS. MDPI 2023-08-02 /pmc/articles/PMC10459610/ /pubmed/37632026 http://dx.doi.org/10.3390/v15081683 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fokam, Joseph
Chenwi, Collins Ambe
Takou, Desire
Santoro, Maria Mercedes
Tala, Valere
Teto, George
Beloumou, Grace
Semengue, Ezechiel Ngoufack Jagni
Dambaya, Beatrice
Djupsa, Sandrine
Kembou, Etienne
Bouba, Nounouce Pamen
Ajeh, Rogers
Cappelli, Giulia
Mbanya, Dora
Colizzi, Vittorio
Ceccherini-Silberstein, Francesca
Perno, Carlo-Federico
Ndjolo, Alexis
Laboratory Based Surveillance of HIV-1 Acquired Drug Resistance in Cameroon: Implications for Use of Tenofovir-Lamivudine-Dolutegravir (TLD) as Second- or Third-Line Regimens
title Laboratory Based Surveillance of HIV-1 Acquired Drug Resistance in Cameroon: Implications for Use of Tenofovir-Lamivudine-Dolutegravir (TLD) as Second- or Third-Line Regimens
title_full Laboratory Based Surveillance of HIV-1 Acquired Drug Resistance in Cameroon: Implications for Use of Tenofovir-Lamivudine-Dolutegravir (TLD) as Second- or Third-Line Regimens
title_fullStr Laboratory Based Surveillance of HIV-1 Acquired Drug Resistance in Cameroon: Implications for Use of Tenofovir-Lamivudine-Dolutegravir (TLD) as Second- or Third-Line Regimens
title_full_unstemmed Laboratory Based Surveillance of HIV-1 Acquired Drug Resistance in Cameroon: Implications for Use of Tenofovir-Lamivudine-Dolutegravir (TLD) as Second- or Third-Line Regimens
title_short Laboratory Based Surveillance of HIV-1 Acquired Drug Resistance in Cameroon: Implications for Use of Tenofovir-Lamivudine-Dolutegravir (TLD) as Second- or Third-Line Regimens
title_sort laboratory based surveillance of hiv-1 acquired drug resistance in cameroon: implications for use of tenofovir-lamivudine-dolutegravir (tld) as second- or third-line regimens
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10459610/
https://www.ncbi.nlm.nih.gov/pubmed/37632026
http://dx.doi.org/10.3390/v15081683
work_keys_str_mv AT fokamjoseph laboratorybasedsurveillanceofhiv1acquireddrugresistanceincameroonimplicationsforuseoftenofovirlamivudinedolutegravirtldassecondorthirdlineregimens
AT chenwicollinsambe laboratorybasedsurveillanceofhiv1acquireddrugresistanceincameroonimplicationsforuseoftenofovirlamivudinedolutegravirtldassecondorthirdlineregimens
AT takoudesire laboratorybasedsurveillanceofhiv1acquireddrugresistanceincameroonimplicationsforuseoftenofovirlamivudinedolutegravirtldassecondorthirdlineregimens
AT santoromariamercedes laboratorybasedsurveillanceofhiv1acquireddrugresistanceincameroonimplicationsforuseoftenofovirlamivudinedolutegravirtldassecondorthirdlineregimens
AT talavalere laboratorybasedsurveillanceofhiv1acquireddrugresistanceincameroonimplicationsforuseoftenofovirlamivudinedolutegravirtldassecondorthirdlineregimens
AT tetogeorge laboratorybasedsurveillanceofhiv1acquireddrugresistanceincameroonimplicationsforuseoftenofovirlamivudinedolutegravirtldassecondorthirdlineregimens
AT beloumougrace laboratorybasedsurveillanceofhiv1acquireddrugresistanceincameroonimplicationsforuseoftenofovirlamivudinedolutegravirtldassecondorthirdlineregimens
AT semengueezechielngoufackjagni laboratorybasedsurveillanceofhiv1acquireddrugresistanceincameroonimplicationsforuseoftenofovirlamivudinedolutegravirtldassecondorthirdlineregimens
AT dambayabeatrice laboratorybasedsurveillanceofhiv1acquireddrugresistanceincameroonimplicationsforuseoftenofovirlamivudinedolutegravirtldassecondorthirdlineregimens
AT djupsasandrine laboratorybasedsurveillanceofhiv1acquireddrugresistanceincameroonimplicationsforuseoftenofovirlamivudinedolutegravirtldassecondorthirdlineregimens
AT kembouetienne laboratorybasedsurveillanceofhiv1acquireddrugresistanceincameroonimplicationsforuseoftenofovirlamivudinedolutegravirtldassecondorthirdlineregimens
AT boubanounoucepamen laboratorybasedsurveillanceofhiv1acquireddrugresistanceincameroonimplicationsforuseoftenofovirlamivudinedolutegravirtldassecondorthirdlineregimens
AT ajehrogers laboratorybasedsurveillanceofhiv1acquireddrugresistanceincameroonimplicationsforuseoftenofovirlamivudinedolutegravirtldassecondorthirdlineregimens
AT cappelligiulia laboratorybasedsurveillanceofhiv1acquireddrugresistanceincameroonimplicationsforuseoftenofovirlamivudinedolutegravirtldassecondorthirdlineregimens
AT mbanyadora laboratorybasedsurveillanceofhiv1acquireddrugresistanceincameroonimplicationsforuseoftenofovirlamivudinedolutegravirtldassecondorthirdlineregimens
AT colizzivittorio laboratorybasedsurveillanceofhiv1acquireddrugresistanceincameroonimplicationsforuseoftenofovirlamivudinedolutegravirtldassecondorthirdlineregimens
AT ceccherinisilbersteinfrancesca laboratorybasedsurveillanceofhiv1acquireddrugresistanceincameroonimplicationsforuseoftenofovirlamivudinedolutegravirtldassecondorthirdlineregimens
AT pernocarlofederico laboratorybasedsurveillanceofhiv1acquireddrugresistanceincameroonimplicationsforuseoftenofovirlamivudinedolutegravirtldassecondorthirdlineregimens
AT ndjoloalexis laboratorybasedsurveillanceofhiv1acquireddrugresistanceincameroonimplicationsforuseoftenofovirlamivudinedolutegravirtldassecondorthirdlineregimens