Evaluation of Circulating and Archived HIV-1 Integrase Drug-Resistance Variants among Patients on Third-Line ART in Cameroon: Implications for Dolutegravir-Containing Regimens in Resource-Limited Settings
ABSTRACT To ensure the long-term efficacy of dolutegravir (DTG), we evaluated the genotypic profile in viral reservoirs among patients on third-line (3L) antiretroviral therapy (ART) in Cameroon, according to prior exposure to raltegravir (RAL). A facility-based study was conducted from May through...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-12-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.03420-22 |
| _version_ | 1797979663144845312 |
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| author | Joseph Fokam Ezechiel Ngoufack Jagni Semengue Evariste Molimbou Naomi-Karell Etame Maria Mercedes Santoro Désiré Takou Leonella Mossiang Alain Patrice Meledie Collins Ambe Chenwi Bouba Yagai Alex Durand Nka Beatrice Dambaya Georges Teto Aude Christelle Ka’e Grâce Angong Beloumou Sandrine Claire Djupsa Ndjeyep Nadine Fainguem Aissatou Abba Aurelie Minelle Ngueko Kengni Michel Carlos Tommo Tchouaket Nounouce Pamen Bouba Serge-Clotaire Billong Rina Djubgang Edith Temgoua Saounde Samuel Martin Sosso Charles Kouanfack Anne-Cecile Zoung-Kanyi Bissek Emmanuel Eben-Moussi Vittorio Colizzi Carlo-Federico Perno Francesca Ceccherini-Silberstein Alexis Ndjolo |
| author_facet | Joseph Fokam Ezechiel Ngoufack Jagni Semengue Evariste Molimbou Naomi-Karell Etame Maria Mercedes Santoro Désiré Takou Leonella Mossiang Alain Patrice Meledie Collins Ambe Chenwi Bouba Yagai Alex Durand Nka Beatrice Dambaya Georges Teto Aude Christelle Ka’e Grâce Angong Beloumou Sandrine Claire Djupsa Ndjeyep Nadine Fainguem Aissatou Abba Aurelie Minelle Ngueko Kengni Michel Carlos Tommo Tchouaket Nounouce Pamen Bouba Serge-Clotaire Billong Rina Djubgang Edith Temgoua Saounde Samuel Martin Sosso Charles Kouanfack Anne-Cecile Zoung-Kanyi Bissek Emmanuel Eben-Moussi Vittorio Colizzi Carlo-Federico Perno Francesca Ceccherini-Silberstein Alexis Ndjolo |
| author_sort | Joseph Fokam |
| collection | DOAJ |
| description | ABSTRACT To ensure the long-term efficacy of dolutegravir (DTG), we evaluated the genotypic profile in viral reservoirs among patients on third-line (3L) antiretroviral therapy (ART) in Cameroon, according to prior exposure to raltegravir (RAL). A facility-based study was conducted from May through December 2021 among patients on 3L ART from HIV treatment centers in Yaoundé and Douala. Viral load was measured, and genotyping was performed on plasma RNA and proviral DNA. HIV-1 drug resistance mutations were interpreted using HIVdb.v9.1 and phylogeny analysis was performed using MEGA.v7, with P < 0.05 considered significant. Of the 12,093 patients on ART, 53 fully met our inclusion criteria. The median (IQR) age was 51 years (40 to 55 years), and the male/female ratio was 4/5. The median duration on integrase strand-transfer inhibitors (INSTI)-containing regimens was 18 months (12 to 32 months), and 15.09% (8/53) were exposed to RAL. The most administered 3L ART was TDF+3TC+DTG+DRV/r (33.96%, 18/53). Only 5.66% (3/53) had unsuppressed viremia (>1000 copies/mL). Resistance testing in proviral DNA was successful for 18/22 participants and revealed 1/18 patients (5.56%, in the RAL-arm) with archived mutations at major resistance positions (G140R and G163R). Five subtypes were identified, CRF02_AG (12/18), CRF22_01AE (3/18), A1 (1/18), G (1/18), and F2 (1/18). In Cameroon, 3L-experienced patients had a good virological response with a low level of archived mutations in the integrase. This finding underscored the use of DTG-containing ART for heavily treated patients in similar programmatic settings. However, patients with prior exposure to RAL should be closely monitored following a stratified or personalized approach to mitigate risks of INSTI-resistance, alongside pharmacovigilance. IMPORTANCE We described the analysis of the genotypes of the population within third-line antiviral therapy in Cameroon, with a focus on defining the effects of prior raltegravir (RAL) treatment and resistance mutations for current dolutegravir (DTG) treatment. While supporting the current transition to DTG-containing ART in resource-limited settings toward the achievement of the UNAIDS’ goal of HIV elimination by 2030, our findings suggested that RAL-exposed patients may need a specific monitoring approach either in a stratified or personalized model of third-line ART to ensure the long-term success of DTG-containing regimens. |
| first_indexed | 2024-04-11T05:42:29Z |
| format | Article |
| id | doaj.art-4eb0af5fbdc64fd6b3d9736ea8d003b6 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-04-11T05:42:29Z |
| publishDate | 2022-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-4eb0af5fbdc64fd6b3d9736ea8d003b62022-12-22T04:42:23ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-12-0110610.1128/spectrum.03420-22Evaluation of Circulating and Archived HIV-1 Integrase Drug-Resistance Variants among Patients on Third-Line ART in Cameroon: Implications for Dolutegravir-Containing Regimens in Resource-Limited SettingsJoseph Fokam0Ezechiel Ngoufack Jagni Semengue1Evariste Molimbou2Naomi-Karell Etame3Maria Mercedes Santoro4Désiré Takou5Leonella Mossiang6Alain Patrice Meledie7Collins Ambe Chenwi8Bouba Yagai9Alex Durand Nka10Beatrice Dambaya11Georges Teto12Aude Christelle Ka’e13Grâce Angong Beloumou14Sandrine Claire Djupsa Ndjeyep15Nadine Fainguem16Aissatou Abba17Aurelie Minelle Ngueko Kengni18Michel Carlos Tommo Tchouaket19Nounouce Pamen Bouba20Serge-Clotaire Billong21Rina Djubgang22Edith Temgoua Saounde23Samuel Martin Sosso24Charles Kouanfack25Anne-Cecile Zoung-Kanyi Bissek26Emmanuel Eben-Moussi27Vittorio Colizzi28Carlo-Federico Perno29Francesca Ceccherini-Silberstein30Alexis Ndjolo31Chantal BIYA International Reference Centre for Research on HIV/AIDS Management and Care, Yaoundé, CamerounChantal BIYA International Reference Centre for Research on HIV/AIDS Management and Care, Yaoundé, CamerounChantal BIYA International Reference Centre for Research on HIV/AIDS Management and Care, Yaoundé, CamerounChantal BIYA International Reference Centre for Research on HIV/AIDS Management and Care, Yaoundé, CamerounUniversity of Rome Tor Vergata, Rome, ItalyChantal BIYA International Reference Centre for Research on HIV/AIDS Management and Care, Yaoundé, CamerounYaoundé Central Hospital, Yaoundé, CamerounDouala General Hospital, Douala, CameroonChantal BIYA International Reference Centre for Research on HIV/AIDS Management and Care, Yaoundé, CamerounChantal BIYA International Reference Centre for Research on HIV/AIDS Management and Care, Yaoundé, CamerounChantal BIYA International Reference Centre for Research on HIV/AIDS Management and Care, Yaoundé, CamerounChantal BIYA International Reference Centre for Research on HIV/AIDS Management and Care, Yaoundé, CamerounChantal BIYA International Reference Centre for Research on HIV/AIDS Management and Care, Yaoundé, CamerounChantal BIYA International Reference Centre for Research on HIV/AIDS Management and Care, Yaoundé, CamerounChantal BIYA International Reference Centre for Research on HIV/AIDS Management and Care, Yaoundé, CamerounChantal BIYA International Reference Centre for Research on HIV/AIDS Management and Care, Yaoundé, CamerounChantal BIYA International Reference Centre for Research on HIV/AIDS Management and Care, Yaoundé, CamerounChantal BIYA International Reference Centre for Research on HIV/AIDS Management and Care, Yaoundé, CamerounChantal BIYA International Reference Centre for Research on HIV/AIDS Management and Care, Yaoundé, CamerounChantal BIYA International Reference Centre for Research on HIV/AIDS Management and Care, Yaoundé, CamerounFaculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, CamerounFaculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, CamerounDirectorate of Pharmacy, Drug and Laboratory, Ministry of Public Health, Yaoundé, CamerounCentral Technical Group, National AIDS Control Committee, Yaoundé, CamerounChantal BIYA International Reference Centre for Research on HIV/AIDS Management and Care, Yaoundé, CamerounYaoundé Central Hospital, Yaoundé, CamerounFaculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, CamerounChantal BIYA International Reference Centre for Research on HIV/AIDS Management and Care, Yaoundé, CamerounChantal BIYA International Reference Centre for Research on HIV/AIDS Management and Care, Yaoundé, CamerounChantal BIYA International Reference Centre for Research on HIV/AIDS Management and Care, Yaoundé, CamerounUniversity of Rome Tor Vergata, Rome, ItalyChantal BIYA International Reference Centre for Research on HIV/AIDS Management and Care, Yaoundé, CamerounABSTRACT To ensure the long-term efficacy of dolutegravir (DTG), we evaluated the genotypic profile in viral reservoirs among patients on third-line (3L) antiretroviral therapy (ART) in Cameroon, according to prior exposure to raltegravir (RAL). A facility-based study was conducted from May through December 2021 among patients on 3L ART from HIV treatment centers in Yaoundé and Douala. Viral load was measured, and genotyping was performed on plasma RNA and proviral DNA. HIV-1 drug resistance mutations were interpreted using HIVdb.v9.1 and phylogeny analysis was performed using MEGA.v7, with P < 0.05 considered significant. Of the 12,093 patients on ART, 53 fully met our inclusion criteria. The median (IQR) age was 51 years (40 to 55 years), and the male/female ratio was 4/5. The median duration on integrase strand-transfer inhibitors (INSTI)-containing regimens was 18 months (12 to 32 months), and 15.09% (8/53) were exposed to RAL. The most administered 3L ART was TDF+3TC+DTG+DRV/r (33.96%, 18/53). Only 5.66% (3/53) had unsuppressed viremia (>1000 copies/mL). Resistance testing in proviral DNA was successful for 18/22 participants and revealed 1/18 patients (5.56%, in the RAL-arm) with archived mutations at major resistance positions (G140R and G163R). Five subtypes were identified, CRF02_AG (12/18), CRF22_01AE (3/18), A1 (1/18), G (1/18), and F2 (1/18). In Cameroon, 3L-experienced patients had a good virological response with a low level of archived mutations in the integrase. This finding underscored the use of DTG-containing ART for heavily treated patients in similar programmatic settings. However, patients with prior exposure to RAL should be closely monitored following a stratified or personalized approach to mitigate risks of INSTI-resistance, alongside pharmacovigilance. IMPORTANCE We described the analysis of the genotypes of the population within third-line antiviral therapy in Cameroon, with a focus on defining the effects of prior raltegravir (RAL) treatment and resistance mutations for current dolutegravir (DTG) treatment. While supporting the current transition to DTG-containing ART in resource-limited settings toward the achievement of the UNAIDS’ goal of HIV elimination by 2030, our findings suggested that RAL-exposed patients may need a specific monitoring approach either in a stratified or personalized model of third-line ART to ensure the long-term success of DTG-containing regimens.https://journals.asm.org/doi/10.1128/spectrum.03420-22archived resistancethird-line ARTdolutegravirraltegravirCameroonHIV-1 |
| spellingShingle | Joseph Fokam Ezechiel Ngoufack Jagni Semengue Evariste Molimbou Naomi-Karell Etame Maria Mercedes Santoro Désiré Takou Leonella Mossiang Alain Patrice Meledie Collins Ambe Chenwi Bouba Yagai Alex Durand Nka Beatrice Dambaya Georges Teto Aude Christelle Ka’e Grâce Angong Beloumou Sandrine Claire Djupsa Ndjeyep Nadine Fainguem Aissatou Abba Aurelie Minelle Ngueko Kengni Michel Carlos Tommo Tchouaket Nounouce Pamen Bouba Serge-Clotaire Billong Rina Djubgang Edith Temgoua Saounde Samuel Martin Sosso Charles Kouanfack Anne-Cecile Zoung-Kanyi Bissek Emmanuel Eben-Moussi Vittorio Colizzi Carlo-Federico Perno Francesca Ceccherini-Silberstein Alexis Ndjolo Evaluation of Circulating and Archived HIV-1 Integrase Drug-Resistance Variants among Patients on Third-Line ART in Cameroon: Implications for Dolutegravir-Containing Regimens in Resource-Limited Settings Microbiology Spectrum archived resistance third-line ART dolutegravir raltegravir Cameroon HIV-1 |
| title | Evaluation of Circulating and Archived HIV-1 Integrase Drug-Resistance Variants among Patients on Third-Line ART in Cameroon: Implications for Dolutegravir-Containing Regimens in Resource-Limited Settings |
| title_full | Evaluation of Circulating and Archived HIV-1 Integrase Drug-Resistance Variants among Patients on Third-Line ART in Cameroon: Implications for Dolutegravir-Containing Regimens in Resource-Limited Settings |
| title_fullStr | Evaluation of Circulating and Archived HIV-1 Integrase Drug-Resistance Variants among Patients on Third-Line ART in Cameroon: Implications for Dolutegravir-Containing Regimens in Resource-Limited Settings |
| title_full_unstemmed | Evaluation of Circulating and Archived HIV-1 Integrase Drug-Resistance Variants among Patients on Third-Line ART in Cameroon: Implications for Dolutegravir-Containing Regimens in Resource-Limited Settings |
| title_short | Evaluation of Circulating and Archived HIV-1 Integrase Drug-Resistance Variants among Patients on Third-Line ART in Cameroon: Implications for Dolutegravir-Containing Regimens in Resource-Limited Settings |
| title_sort | evaluation of circulating and archived hiv 1 integrase drug resistance variants among patients on third line art in cameroon implications for dolutegravir containing regimens in resource limited settings |
| topic | archived resistance third-line ART dolutegravir raltegravir Cameroon HIV-1 |
| url | https://journals.asm.org/doi/10.1128/spectrum.03420-22 |
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