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  • PA-824 Impact of multi-class antiretroviral drug resistant variants on newly approved antiretroviral therapy (ART) among people living with HIV in Botswana

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PA-824 Impact of multi-class antiretroviral drug resistant variants on newly approved antiretroviral therapy (ART) among people living with HIV in Botswana
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  1. Nokuthula Sibusiso Ndlovu1,2,
  2. Ontlametse Thato Bareng1,3,
  3. Kaelo Seatla1,4,
  4. Wonderful Tatenda Choga1,
  5. Kedumetse Seru1,
  6. David Nkwe2,
  7. Vlad Novitsky1,5,
  8. Sikhulile Moyo1,5,
  9. Simani Gaseitsiwe1,5
  1. 1Botswana Harvard AIDS Institute Partnership, Botswana
  2. 2Department of Biological Sciences and Biotechnology, Botswana International University of Science and Technology, Botswana
  3. 3Department of Medical Sciences, School of Allied Health Professions, University of Botswana, Botswana
  4. 4Careena Centre for Health, Botswana
  5. 5Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, USA

Abstract

Background To evaluate for potential alternative antiretroviral therapy (ART) among people living with HIV(PLWH) who have multi-drug resistance (MDR) variants, we determined resistance to second-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs): Doravirine (DOR), Etravirine (ETR) and Rilpivirine (RPV), and entry inhibitors: Maraviroc (MVC), Enfuvirtide (T20) and Fostemsavir (FTR).

Methods A total of 7473 HIV sequences were analysed, MDR was defined as resistance to ≥2 drug classes. The Stanford HIV drug resistance database was used for determining DOR-, ETR- and RPV-resistance. MVC-resistance was determined by evaluating for CXCR4 coreceptor usage using geno2pheno and WebPSSM. FTR-resistance was evaluated using previously reported FTR-resistance mutations. T20-resistance was determined according to the 2022 IAS resistance mutations update. Predictors of MDR were determined using the univariate and multivariate logistic regression hazard models.

Results The prevalence of PLWH with MDR was 682/7473 (9.1%: 95% CI; 8.3–9.6). Within the MDR group, resistance to the four drug classes was as follows: NNRTIs (84.6%), NRTIs (83.9%), PIs (55.3%) and INSTIs (6%). High prevalence of resistance to second generation NNRTIs was observed within MDR group: RPV (79.3%), ETR (63.6%) and DOR (67.1%). Within entry inhibitors, 7.9% (31/391) CXCR4 coreceptor usage was observed, indicating low prevalence of MVC-resistance. A total of 113/626 (18.1%) MDR individuals presented FTR-resistance. T20-resistance was observed in 313/623 (50.2%) of MDR individuals. ART experience, virologic failure at VL> 400 copies/mL and being male were significantly associated with developing MDR.

Conclusion The study reports high prevalence of resistance to second generation NNRTIs and T20 in individuals with MDR HIV variants which reduces their potential use as alternative therapy for this group of PLWH. In contrast, low prevalence of FTR-and MVC-resistance allows for their potential use although we suggest genotypic testing prior to use of these drugs to avoid selection of ineffective ARV regimens.

https://doi.org/10.1136/bmjgh-2023-EDC.313

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