Authors:
Davy-Hyacinthe Gouissi Anguechia, Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaounde, Cameroon
Yagai BOUBA, UniCamillus - Saint Camillus International University of Health Sciences, Rome, Italy
Ezechiel NGOUFACK JANGNI SEMENGUE, Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaounde, Cameroon
Aude KA'E, Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaounde, Cameroon
Roland Ulrich BASSECK WOME, Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaounde, Cameroon
Désiré TAKOU, Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaounde, Cameroon
Collins CHENWI AMBE, National HIV drug resistance working group, Yaoundé, Cameroon
Grace BELOUMOU, Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaounde, Cameroon
Alex Durand NKA, Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaounde, Cameroon
Maria-Mercedes SANTORO, Department of Experimental Medicine, University of Rome “Tor Vergata”, Rome, Italy
Francesca CECCHERINI-SILBERSTEIN, Department of Experimental Medicine, University of Rome “Tor Vergata”, Rome, Italy
Adawaye CHATTE, Project Management Unit, Ministry of Health, N’djamena, Chad
Carla MONTESANO, Department of Experimental Medicine, University of Rome “Tor Vergata”, Rome, Italy
Giulia CAPPELI, LAGET, Centre Hospitalo-Universitaire (CHU), N’djamena, Chad
Vittorio COLIZZI, EUROBIOPARK and UNSECO board for Biotechnology, University of Rome Tor Vergata, Rome, Italy
Alexis NDJOLO, Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaounde, Cameroon
Dora MBANYA, Faculty of Medicine and Biomedical Sciences, University of Yaounde I, Yaounde, Cameroon
Nicaise NDEMBI, National Research Council, Rome, Italy
Carlo-Federico PERNO, Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaounde, Cameroon
Joseph FOKAM, Central Technical Group, National AIDS Control Committee, Yaounde, Cameroon
Background: Dual therapies (DT) combining integrase 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 mutations (DRMs) to prior antiretrovirals may jeopardize the efficacy of DT. We herein describe the predicted efficacy of DT combining INSTIs+2gen-NNRTI following treatment failure among Cameroonian patients.
Methods: A laboratory-based study with 130 patients experiencing virological failure was carried out at the Chantal Biya International Reference Centre (CIRCB), Yaoundé-Cameroon. We genotyped HIV-1 Reverse transcriptase (RT) and integrase (INT) gene by Sanger sequencing and assessed acquired HIV-1 drug resistance (ADR) mutations, in patients failing treatment from February -2019 to December -2023.We characterized the effect of ADR mutations on the predicted susceptibility to dual therapy combining second generation NNRTIs/INSTIs using Stanford HIVdb algorithm. Statical comparison was performed using the chi2-and fisher test.
Results: Of the 130 participants with successful genotypic resistance testing (59.2% female, 38 [27-46] years), DRMs to NNRTIs and INSTIs were found at 92.3% and 1.5%, respectively. Prevailing DRMs were Y181C (32.3%) among 2nd-gen-NNRTIs and R263K (0.7%) among INSTIs. Among 2nd-Gen-NNRTIs, etravirine, doravirine and rilpivirine had 43.85%, 41.54%, and 38.46% preserved efficacy respectively. Among INSTIs, we found 97.69% efficacy for bictegravir/dolutregravir, 96.15% for cabotegravir and 92.31% for elvitegravir/raltegravir. Overall predictive efficacy of DT was lower among participants who failed 1st-en-NNRTI (p<0.001); and etravirine+(dolutegravir or bictegravir) showing the highest score (43.8%).
Conclusion: There are high levels of NNRTIs-RAMs and low-level of INSTI-RAMs among patients failing ART in Cameroon. Consequently, the efficacy of dual therapy combining INSTIs and 2nd-Gen NNRTIs might be suboptimal for most patients with history of ART failure in low- and middle-income countries. Thus, the use of long-acting injectable RPV+CAB in such context should be genotypic-guided for optimal outcomes.
