# HIV-1 genetic diversity and pretreatment drug resistance survey prior to dolutegravir introduction in Senegal

## TL;DR

This study found intermediate levels of drug resistance in HIV patients in Senegal before new treatments were introduced, suggesting a need for updated therapy approaches.

## Contribution

The study provides a nationwide survey of pretreatment drug resistance in Senegal, revealing regional disparities and supporting a shift to dolutegravir-based regimens.

## Key findings

- 10.7% of sequenced samples harbored surveillance drug resistance mutations (SDRMs) with significant regional variation.
- NNRTI resistance was highest in the Southeast (20.8%), and K103N was the most frequent mutation conferring resistance to efavirenz and nevirapine.
- Findings support transitioning from NNRTI-based regimens to dolutegravir-based therapy due to observed resistance patterns.

## Abstract

•Intermediate prevalence of non-nucleoside reverse transcriptase inhibitor drug resistance in HIV-1 patients prior to TLD introduction in Senegal.•Regional disparities in surveillance drug resistance mutation rates in Senegal highlighted the importance of tailored approaches.•There is a need to support the transition to a non-nucleoside reverse transcriptase inhibitor-free-based regimen, such as dolutegravir-based therapy.

Intermediate prevalence of non-nucleoside reverse transcriptase inhibitor drug resistance in HIV-1 patients prior to TLD introduction in Senegal.

Regional disparities in surveillance drug resistance mutation rates in Senegal highlighted the importance of tailored approaches.

There is a need to support the transition to a non-nucleoside reverse transcriptase inhibitor-free-based regimen, such as dolutegravir-based therapy.

This study aimed to document the prevalence of pretreatment drug resistance in antiretroviral therapy-naïve patients in Senegal, describe mutation profiles, and evaluate their potential impact on future therapy.

A pretreatment drug resistance survey was carried out in 35 sites throughout the country between 2017 and 2018 using dried blood spots and whole blood samples. Amplification and sequencing were performed on the partial reverse transcriptase (RT) gene using the Agence Nationale de Recherches sur le Sida et les hépatitis virales (ANRS: French National Agency for Research on acquired immunodeficiency syndrome [AIDS] and Viral Hepatitis)/AC11 method at the HIV National Reference Laboratory. Surveillance drug resistance mutations (SDRM) were analyzed using the Calibrated Population Resistance v8.1, and the proportion of SDRM was evaluated after grouping sites by geographical areas.

A total of 237 samples from different patients were analyzed, and 131 (55.3%) were successfully amplified and sequenced. Among these, 14 (10.7%) harbored SDRM with significant variability across regions. For nucleoside reverse transcriptase inhibitors (NRTI), the SDRM rate was highest in Dakar (9.1%), followed by the Southwest (5.3%) and the Southeast (4.2%). For non-NRTIs (NNRTIs), the highest rate was observed in the Southeast (20.8%), followed by Dakar (13.6%), the Midwest (8.3%), and the Southwest (3.6%). Among NRTIs, the most frequent mutation was M184V (3/6), conferring high-level resistance to lamivudine and emtricitabine, and K103N (11/12) among NNRTIs, conferring resistance to efavirenz and nevirapine. Notably, four sequences harbored SDRMs for both NRTI and NNRTI, reflecting overlapping resistance in some patients. The higher prevalence of NNRTI resistance is consistent with the lower genetic barrier of these drugs compared to NRTIs, which may facilitate the emergence of pretreatment drug resistance.

Through a quasi-national survey, an intermediate level of NNRTI resistance was observed, with regional disparities in Senegal. These findings highlight the limitations of NNRTI-based first-line regimens in Senegal and support the transition to other antiretroviral therapy regimens, such as dolutegravir-based therapy in newly infected individuals as well as in treated patients.