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
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
Affiliations
Alex Durand Nka
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon
Yagai Bouba
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon
Wilfried Rooker Tsapi Lontsi
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon
Davy-Hyacinte Gouissi Anguechia
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon
Georges Teto
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon
Aude christelle Ka’e
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon
Ezechiel Ngoufack Jagni Semengue
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon
Collins Ambe Chenwi
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon
Désiré Takou
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon
Lum Forgwei
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon
Tatiana Anim-Keng Tekoh
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon
Aurelie Minelle Kengni Ngueko
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon
Bernadette Bomgning Fokou
Department of Immunology, Molecular Medicine and Applied Biotechnology, University of Rome Tor Vergata, 00133 Rome, Italy
Jeremiah Efakika Gabisa
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon
Michel Carlos Tommo Tchouaket
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon
Willy Leroi TognaPabo
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon
Derrick Tambe Ayuk Ngwese
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon
Jacky Njiki Bikoi
Department of Microbiology, Faculty of Science, University of Yaoundé 1, Yaoundé P.O. Box 337, Cameroon
Daniele Armenia
Faculty of Medicine, UniCamillus-Saint Camillus International University of Health Sciences, 00131 Rome, Italy
Vittorio Colizzi
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon
Marcel Yotebieng
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Nicaise Ndembi
Africa Centres for Disease Control and Prevention, Addis Ababa P.O. Box 3243, Ethiopia
Maria-Mercedes Santoro
Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
Francesca Ceccherini-Silberstein
Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
Carlo-Federico Perno
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon
Alexis Ndjolo
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon
Joseph Fokam
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon
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.
