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  • PA-351 HIV-1 genotypic susceptibility to second generation non-nucleoside reverse transcriptase inhibitors among patients failing antiretroviral therapy in Cameroon: implication for the long-acting therapies in Africa

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PA-351 HIV-1 genotypic susceptibility to second generation non-nucleoside reverse transcriptase inhibitors among patients failing antiretroviral therapy in Cameroon: implication for the long-acting therapies in Africa
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  1. Davy-hyacinthe Gouissi Anguechia1,2,
  2. Joseph Fokam1,2,3,
  3. Desire Takou1,
  4. Ezechiel Ngoufack Jagni Semengue1,4,5,
  5. Collins Chenwi1,
  6. Grace Beloumou1,
  7. Sandrine Djupsa1,
  8. Beatrice Dambaya1,
  9. George Teto1,
  10. Vittorio Colizzi1,4,
  11. Carlo-Federico Perno6,
  12. Alexis Ndjolo1,2
  1. 1Chantal Biya International Reference Centre For Research On Hiv/aids Prevention And Management (CIRCB), Cameroon
  2. 2Faculty of Medicine and Biomedical Sciences, University of Yaounde, Cameroon
  3. 3University of Buea, Faculty of health sciences, Cameroon
  4. 4Department of Experimental Medicine, University of Rome “Tor Vergata”, Italy
  5. 5Evangelical University of Cameroon, Cameroon
  6. 6Bambino Gesu Hospital, Italy

Abstract

Background Long-acting therapies combining second generation non-nucleoside reverse transcriptase inhibitors (2Gen-NNRTI) with integrase inhibitor (INSTIs) such as cabotegravir, have demonstrated potent activity in treatment-experienced HIV-infected patients. In our context it has already been shown that less than 1% of patients are resistant to INSTI. However, there is not data on cross-resistance events between first (EFV and NVP) and 2Gen-NNRTI (Etravirine, Rilpivirine,Doravirine). This study aimed to evaluate 2Gen-NNRTI resistance and their susceptibility in patients failing antiretroviral treatment (ART) in Cameroon.

Methods An observational study was conducted at the Chantal BIYA International Reference Centre among patients failing ART from 2020–2023. Genotypic resistance testing was interpreted using Stanford HIVdb; 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 670 patients were enrolled including 366 failing first-line (1stGen-NNRTI based) and 304 second-line (protease-inhibitors) regimens. Median viremia was 54889 [9,867–231,470] copies/ml and ART-duration was 17[15–25] months. Prevailing 2Gen-NNRTI mutations were: Y181C (22.24;149/670%) and G190A (18%;120/670). Overall rate of resistance to NNRTI was 88.81% [ with 91% (334/366) failing first-line and 85% (261/304) failing second-line; p=0.03]. Drug susceptibility was 54.93% (Etravirine); 46.87% (Rilpivirine), 40.60% (Doravirine). Following susceptibility profile, patients failing on Efavirenz-based regimens were more susceptible to 2Gen-NNRTI (OR=0.42[0.21–0.84]; p=0.004), while those failing after receiving EFV and NVP were less-susceptible to 2Gen-NNRTI (OR=4.4[1.16–14.81]; p=0.02). CRF02_AG was the prevailing subtype (68.31%), without any significant effect on any 2Gen-NNRTI susceptibility.

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. Etravirine represents the most suitable 2NNRTI for combination with INSTI as part of long-acting ART, pending a stratified approach to identify eligible patients in RLS.

https://doi.org/10.1136/bmjgh-2023-EDC.167

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