Predictive Efficacy of Dual Therapies Combining Integrase Strand Transfer Inhibitors with Second-Generation Non-Nucleoside Reverse Transcriptase Inhibitors Following HIV-1 Treatment Failure in Cameroon: Implications for the Use of a Long-Acting Therapeutic Strategy in Low- and Middle-Income Countries
Davy-Hyacinthe Gouissi Anguechia,
Yagai Bouba,
Ezechiel Ngoufack Jagni Semengue,
Aude Christelle Ka’e,
Désiré Takou,
Collins Ambe Chenwi,
Grace Beloumou,
Alex Durand Nka,
Ulrich Roland Basseck Wome,
Maria Mercedes Santoro,
Francesca Ceccherini-Silberstein,
Adawaye Chatté,
Carla Montesano,
Giulia Cappelli,
Vittorio Colizzi,
Alexis Ndjolo,
Dora Mbanya,
Nicaise Ndembi,
Carlo-Federico Perno,
Joseph Fokam
Affiliations
Davy-Hyacinthe Gouissi Anguechia
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
Ezechiel Ngoufack Jagni Semengue
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
Désiré Takou
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
Grace Beloumou
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon
Alex Durand Nka
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon
Ulrich Roland Basseck Wome
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon
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
Adawaye Chatté
Project Management Unit, Ministry of Health, N’djamena P.O. Box 548, Chad
Carla Montesano
Department of Biology, University of Rome “Tor Vergata”, 00133 Rome, Italy
Giulia Cappelli
National Research Council, 00185 Rome, Italy
Vittorio Colizzi
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
Dora Mbanya
Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé P.O. Box 337, Cameroon
Nicaise Ndembi
Africa Centres for Disease Control and Prevention, Addis Ababa P.O. Box 3243, Ethiopia
Carlo-Federico Perno
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
Dual therapies (DT) combining integrase strand transfer inhibitors (INSTIs) with second-generation non-nucleoside reverse transcriptase inhibitors (2nd-Gen-NNRTIs) offer new possibilities for HIV treatment to improve adherence. However, drug resistance associated mutations (RAMs) to prior antiretrovirals may jeopardize the efficacy of DT. We herein describe the predicted efficacy of DT combining INSTIs + 2nd-Gen-NNRTI following treatment failure among Cameroonian patients. We genotyped the HIV-1 pol gene using Sanger sequencing and assessed acquired RAMs to NNRTIs and INSTIs in patients failing treatment from March 2019 to December 2023. Drug susceptibility was interpreted using Stanford HIVdb v9.5, and statistical analyses were performed using SPSS v22. Of 130 successfully genotyped participants (median age (IQR): 38 (27–46) years; 59.2% female), 92.3% had RAMs to NNRTIs and 1.5% to INSTIs. Prevailing RAMs were Y181C (32.3%) among NNRTIs and R263K (0.7%) among INSTIs. Among 2nd-Gen-NNRTIs, etravirine, doravirine and rilpivirine had 43.85%, 41.54% and 38.46% genotypic sensitivity, respectively. Among INSTIs, we found 97.69% efficacy for dolutegravir/bictegravir, 96.15% for cabotegravir and 92.31% for elvitegravir/raltegravir. The overall predictive efficacy of DT was lower among participants who failed 1st-Gen-NNRTI (p < 0.001); with etravirine + dolutegravir/bictegravir combination showing the highest score (43.8%). Conclusively, DT combining INSTIs + 2nd-Gen-NNRTIs might be suboptimal in the context of previous ART failure, especially with NNRTI-based treatment in low- and middle-income countries. The general data clearly indicate that without resistance testing, it is nearly impossible to use long-acting dual therapies in previously failing patients.
