Tenofovir and Doravirine Are Potential Reverse-Transcriptase Analogs in Combination with the New Reverse-Transcriptase Translocation Inhibitor (Islatravir) Among Treatment-Experienced Patients in Cameroon: Designing Future Treatment Strategies for Low- and Middle-Income Countries
Islatravir (ISL) is a novel antiretroviral that inhibits HIV-1 reverse transcriptase translocation. The M184V mutation, known to reduce ISL’s viral susceptibility in vitro, could arise from prolonged exposure to nucleoside reverse transcriptase inhibitors (NRTI) (3TC). This study evaluated the predi...
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| author | Alex Durand Nka Yagai Bouba Wilfried Rooker Tsapi Lontsi Davy-Hyacinte Gouissi Anguechia Georges Teto Aude christelle Ka’e Ezechiel Ngoufack Jagni Semengue Collins Ambe Chenwi Désiré Takou Lum Forgwei Tatiana Anim-Keng Tekoh Aurelie Minelle Kengni Ngueko Bernadette Bomgning Fokou Jeremiah Efakika Gabisa Michel Carlos Tommo Tchouaket Willy Leroi TognaPabo Derrick Tambe Ayuk Ngwese Jacky Njiki Bikoi Daniele Armenia Vittorio Colizzi Marcel Yotebieng Nicaise Ndembi Maria-Mercedes Santoro Francesca Ceccherini-Silberstein Carlo-Federico Perno Alexis Ndjolo Joseph Fokam |
| author_facet | Alex Durand Nka Yagai Bouba Wilfried Rooker Tsapi Lontsi Davy-Hyacinte Gouissi Anguechia Georges Teto Aude christelle Ka’e Ezechiel Ngoufack Jagni Semengue Collins Ambe Chenwi Désiré Takou Lum Forgwei Tatiana Anim-Keng Tekoh Aurelie Minelle Kengni Ngueko Bernadette Bomgning Fokou Jeremiah Efakika Gabisa Michel Carlos Tommo Tchouaket Willy Leroi TognaPabo Derrick Tambe Ayuk Ngwese Jacky Njiki Bikoi Daniele Armenia Vittorio Colizzi Marcel Yotebieng Nicaise Ndembi Maria-Mercedes Santoro Francesca Ceccherini-Silberstein Carlo-Federico Perno Alexis Ndjolo Joseph Fokam |
| author_sort | Alex Durand Nka |
| collection | DOAJ |
| description | Islatravir (ISL) is a novel antiretroviral that inhibits HIV-1 reverse transcriptase translocation. The M184V mutation, known to reduce ISL’s viral susceptibility in vitro, could arise from prolonged exposure to nucleoside reverse transcriptase inhibitors (NRTI) (3TC). This study evaluated the predictive efficacy of ISL and identified potentially active antiretrovirals in combination among treatment-experienced patients in Cameroon, where NRTIs (3TC) have been the backbone of ART for decades now. Although ISL is a long-acting antiretroviral, it will provide other therapeutic options in combination with other reverse transcriptase inhibitors that remain effective. We analyzed 1170 HIV-1 sequences from patients failing first-, second-, and third-line ART using the CIRCB Antiviral Resistance Evaluation (CIRCB-CARE) database. Drug resistance mutations (DRMs) were interpreted using Stanford HIVdb.v9, and covariation patterns between M184V and major NRTI/NNRTI DRMs were assessed. The study population, with a median age of 40 years, showed a high prevalence of resistance to NRTIs (77.4%) and NNRTIs (49.2%). The most frequent NRTI DRMs were M184V/I (83.3%), M41L (25.0%), and T215FY (36.8%), while common NNRTI DRMs included K103NS (53.3%), Y181CIV (27.7%), and G190ASE (22.2%). In first-line ART failure, M184V significantly covaried with K70R, L74I, and M41L for NRTIs and K103N and G190A for NNRTIs. In second-line failure, the covariation with M184V extended to T215Y, M41L, and D67N for NRTIs and G190A, K103N, and K103S for NNRTIs. No significant covariation with M184V was observed in third-line treatment failures. Based on these covariations and on the effect of these mutations on available anti-HIV drugs, TDF (partial efficacy) and Doravirine (fully active) were identified as potentially suitable candidates in combination with ISL among patients failing the first, second, and third lines, and could serve as a valuable therapeutic option in LMICs facing similar treatment challenges. |
| format | Article |
| id | doaj-art-f8c6acf70bd640c082f3dee22aa824d3 |
| institution | Kabale University |
| issn | 1999-4915 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Viruses |
| spelling | doaj-art-f8c6acf70bd640c082f3dee22aa824d32025-01-24T13:52:28ZengMDPI AGViruses1999-49152025-01-011716910.3390/v17010069Tenofovir and Doravirine Are Potential Reverse-Transcriptase Analogs in Combination with the New Reverse-Transcriptase Translocation Inhibitor (Islatravir) Among Treatment-Experienced Patients in Cameroon: Designing Future Treatment Strategies for Low- and Middle-Income CountriesAlex Durand Nka0Yagai Bouba1Wilfried Rooker Tsapi Lontsi2Davy-Hyacinte Gouissi Anguechia3Georges Teto4Aude christelle Ka’e5Ezechiel Ngoufack Jagni Semengue6Collins Ambe Chenwi7Désiré Takou8Lum Forgwei9Tatiana Anim-Keng Tekoh10Aurelie Minelle Kengni Ngueko11Bernadette Bomgning Fokou12Jeremiah Efakika Gabisa13Michel Carlos Tommo Tchouaket14Willy Leroi TognaPabo15Derrick Tambe Ayuk Ngwese16Jacky Njiki Bikoi17Daniele Armenia18Vittorio Colizzi19Marcel Yotebieng20Nicaise Ndembi21Maria-Mercedes Santoro22Francesca Ceccherini-Silberstein23Carlo-Federico Perno24Alexis Ndjolo25Joseph Fokam26Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, CameroonChantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, CameroonChantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, CameroonChantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, CameroonChantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, CameroonChantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, CameroonChantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, CameroonChantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, CameroonChantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, CameroonChantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, CameroonChantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, CameroonChantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, CameroonDepartment of Immunology, Molecular Medicine and Applied Biotechnology, University of Rome Tor Vergata, 00133 Rome, ItalyChantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, CameroonChantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, CameroonChantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, CameroonChantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, CameroonDepartment of Microbiology, Faculty of Science, University of Yaoundé 1, Yaoundé P.O. Box 337, CameroonFaculty of Medicine, UniCamillus-Saint Camillus International University of Health Sciences, 00131 Rome, ItalyChantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, CameroonDepartment of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USAAfrica Centres for Disease Control and Prevention, Addis Ababa P.O. Box 3243, EthiopiaDepartment of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, ItalyChantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, CameroonChantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, CameroonChantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, CameroonIslatravir (ISL) is a novel antiretroviral that inhibits HIV-1 reverse transcriptase translocation. The M184V mutation, known to reduce ISL’s viral susceptibility in vitro, could arise from prolonged exposure to nucleoside reverse transcriptase inhibitors (NRTI) (3TC). This study evaluated the predictive efficacy of ISL and identified potentially active antiretrovirals in combination among treatment-experienced patients in Cameroon, where NRTIs (3TC) have been the backbone of ART for decades now. Although ISL is a long-acting antiretroviral, it will provide other therapeutic options in combination with other reverse transcriptase inhibitors that remain effective. We analyzed 1170 HIV-1 sequences from patients failing first-, second-, and third-line ART using the CIRCB Antiviral Resistance Evaluation (CIRCB-CARE) database. Drug resistance mutations (DRMs) were interpreted using Stanford HIVdb.v9, and covariation patterns between M184V and major NRTI/NNRTI DRMs were assessed. The study population, with a median age of 40 years, showed a high prevalence of resistance to NRTIs (77.4%) and NNRTIs (49.2%). The most frequent NRTI DRMs were M184V/I (83.3%), M41L (25.0%), and T215FY (36.8%), while common NNRTI DRMs included K103NS (53.3%), Y181CIV (27.7%), and G190ASE (22.2%). In first-line ART failure, M184V significantly covaried with K70R, L74I, and M41L for NRTIs and K103N and G190A for NNRTIs. In second-line failure, the covariation with M184V extended to T215Y, M41L, and D67N for NRTIs and G190A, K103N, and K103S for NNRTIs. No significant covariation with M184V was observed in third-line treatment failures. Based on these covariations and on the effect of these mutations on available anti-HIV drugs, TDF (partial efficacy) and Doravirine (fully active) were identified as potentially suitable candidates in combination with ISL among patients failing the first, second, and third lines, and could serve as a valuable therapeutic option in LMICs facing similar treatment challenges.https://www.mdpi.com/1999-4915/17/1/69HIVIslatravirtreatment-experienced patientsCameroon |
| spellingShingle | Alex Durand Nka Yagai Bouba Wilfried Rooker Tsapi Lontsi Davy-Hyacinte Gouissi Anguechia Georges Teto Aude christelle Ka’e Ezechiel Ngoufack Jagni Semengue Collins Ambe Chenwi Désiré Takou Lum Forgwei Tatiana Anim-Keng Tekoh Aurelie Minelle Kengni Ngueko Bernadette Bomgning Fokou Jeremiah Efakika Gabisa Michel Carlos Tommo Tchouaket Willy Leroi TognaPabo Derrick Tambe Ayuk Ngwese Jacky Njiki Bikoi Daniele Armenia Vittorio Colizzi Marcel Yotebieng Nicaise Ndembi Maria-Mercedes Santoro Francesca Ceccherini-Silberstein Carlo-Federico Perno Alexis Ndjolo Joseph Fokam Tenofovir and Doravirine Are Potential Reverse-Transcriptase Analogs in Combination with the New Reverse-Transcriptase Translocation Inhibitor (Islatravir) Among Treatment-Experienced Patients in Cameroon: Designing Future Treatment Strategies for Low- and Middle-Income Countries Viruses HIV Islatravir treatment-experienced patients Cameroon |
| title | Tenofovir and Doravirine Are Potential Reverse-Transcriptase Analogs in Combination with the New Reverse-Transcriptase Translocation Inhibitor (Islatravir) Among Treatment-Experienced Patients in Cameroon: Designing Future Treatment Strategies for Low- and Middle-Income Countries |
| title_full | Tenofovir and Doravirine Are Potential Reverse-Transcriptase Analogs in Combination with the New Reverse-Transcriptase Translocation Inhibitor (Islatravir) Among Treatment-Experienced Patients in Cameroon: Designing Future Treatment Strategies for Low- and Middle-Income Countries |
| title_fullStr | Tenofovir and Doravirine Are Potential Reverse-Transcriptase Analogs in Combination with the New Reverse-Transcriptase Translocation Inhibitor (Islatravir) Among Treatment-Experienced Patients in Cameroon: Designing Future Treatment Strategies for Low- and Middle-Income Countries |
| title_full_unstemmed | Tenofovir and Doravirine Are Potential Reverse-Transcriptase Analogs in Combination with the New Reverse-Transcriptase Translocation Inhibitor (Islatravir) Among Treatment-Experienced Patients in Cameroon: Designing Future Treatment Strategies for Low- and Middle-Income Countries |
| title_short | Tenofovir and Doravirine Are Potential Reverse-Transcriptase Analogs in Combination with the New Reverse-Transcriptase Translocation Inhibitor (Islatravir) Among Treatment-Experienced Patients in Cameroon: Designing Future Treatment Strategies for Low- and Middle-Income Countries |
| title_sort | tenofovir and doravirine are potential reverse transcriptase analogs in combination with the new reverse transcriptase translocation inhibitor islatravir among treatment experienced patients in cameroon designing future treatment strategies for low and middle income countries |
| topic | HIV Islatravir treatment-experienced patients Cameroon |
| url | https://www.mdpi.com/1999-4915/17/1/69 |
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