CAM-HERO ABSTRACTS 2022

HIV RESISTANCE TO 2nd GENERATION NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS AMONG PATIENTS FAILING THERAPY
Authors:
Davy Hyacinthe ANGUECHIA GOUISSI, Faculty of Medicine and Biomedical Sciences, University of Yaounde I, Yaounde, Cameroon;
Joseph FOKAM, Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaounde, Cameroon;
Desire TAKOU, Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaounde, Cameroon;
Ezechiel Ngoufack JAGNI SEMENGUE, Department of Experimental Medicine, University of Rome “Tor Vergata”, Rome, Italy
Collins Chenwi, Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaounde, Cameroon;
Grace BELOUMOU, Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaounde, Cameroon;
Sandrine DJUPSA, Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaounde, Cameroon;
Vittorio COLIZZI, Evangelical University of Cameroon, Bandjoun, Cameroon.
Carlo-Federico PERNO, Bambino Gesu Hospital, Rome, Italy;
Alexis NDJOLO, Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaounde, Cameroon;
Abstract ID: 95
Event: CAM-HERO 2022
Category: Clinical Science
Presenter Name: Davy Hyacinthe ANGUECHIA GOUISSI
Presenter Preference: Oral
Keywords: 2Gen-NNRTI, Cameroon., HIV drug resistance

Background:Etravirine (ETR), rilpivirine (RPV) and doravirine (DOR) are second generation (2Gen) non-nucleoside reverse transcriptase inhibitors (NNRTI) approved for the treatment of HIV-1 infection. In Africa, there are limited data on the resistance profile of 2Gen-NNRTI.This study aimed to evaluate 2Gen-NNRTI resistance and their susceptibility in patients failing antiretroviral treatment (ART) in Cameroon.

Methods: A cross-sectional study was conducted from 2020-2021 among 340 patients failing ART, received at the Chantal Biya International Reference Centre, Yaoundé-Cameroon. Treatment history and immuno-virological data were obtained from patients’ files. Genotypic resistance testing was interpreted using Stanford HIVdb v8.7. The following variants were considered as resistance mutations to 2Gen-NNRTI: Y181CIV, Y188LC, V106AMI, M230L, K101EP, L234I, G190ASEQ, L100I. The penalty scores of drug resistance were ≥60(high-resistance);30–59(intermediate-resistance); <30(susceptible). Acceptable threshold for potential drug-efficacy was set at >50% at population-level.

Results: A total of 340 patients were enrolled, of which 230 were failing first-line (1Gen-NNRTI based) and 110 second-line (protease-inhibitors) regimens. Median [IQR] CD4 and viremia were respectively 184 [60–332] cells/μl and 82,374 [21,817–289,907] copies/ml; ART-duration was 18 [10–27] months. Overall rate of resistance to 2Gen-NNRTI was 79.70% [71.30–87.02], similar between first- vs second-lines. Prevailing mutations were: Y181C(23.52%), G190A(17.64%) and P225H (13.53%). Drug susceptibility rate was 52.05%(ETR);43.23% (RPV), 36.17%(DOR).Following susceptibility profile, patients failing on EFV-based regimens were more susceptible to 2Gen-NNRTI (OR=0.42;95%CI:[0.24–0.74]; p=0.003), while those failing after receiving EFV and NVP were less susceptible to 2Gen-NNRTI (OR=4.4; 95%CI:[1.16–14.81]; p=0.02). Low viremia (≤4log10) was associated with susceptibility to 2Gen-NNRTI (OR=0.22; 95%CI:[0.12–0.41]; p<0.0001).CRF02_AG was the prevailing subtype(58.53%), followed by A1 (11.47%), G (7.35%);without any significant effect on 2Gen-NNRTI susceptibility (CRF02_AG vs non-AG; p=0.8).

Conclusion: After ART-failure in Cameroon , there is a high-level of cross-resistance to 2Gen-NNRTI. However, etravirine retains residual efficacy in half of the population. Thus, after ART-failure in African patients, the use of etravirine as 2Gen-NNRTI is possible, pending genotypic profiling.