HIV protease resistance mutations in patients receiving second-line antiretroviral therapy in Libreville, Gabon

Introduction In 2022, the WHO reported that 29.8 million people around the world were living with HIV (PLHIV) and receiving antiretroviral treatment (ART), including 25‌ 375 people in Gabon (54% of all those living with HIV in the country).

The literature reports a frequency of therapeutic failure with first-line antiretrovirals (ARVs) of between 20% and 82%.

Unfortunately, data relating to the failure of second-line ARVs are scarce in Gabon.

This study aims to determine the profiles of HIV drug resistance mutations related to protease inhibitors in Gabon.

Methodology Plasma from 84 PLHIV receiving ARVs was collected from 2019 to 2021, followed by RNA extraction, amplification, and sequencing of the protease gene.

ARV resistance profiles were generated using the Stanford interpretation algorithm version 8.9-1 ( https://hivdb.stanford.edu ) and statistical analyses were performed using EpiInfo software version 7.2.1.0 (CDC, USA).

Results Of 84 HIV plasma samples collected from 45 men and 39 women, 342 mutations were detected.

Of these, 43.3% (148/342) were associated with nucleoside reverse transcriptase inhibitors (NRTIs), 30.4% (104/342) with non-nucleoside reverse transcriptase inhibitors (NNRTIs), and 26.3% (90/342) with protease inhibitors (PIs).

Most NRTI mutations were associated with thymidine analogues (TAMs) (50.7%; 75/148), including T215F/V (14.9%; 22/148), D67DN/E/G/N/T (10.1%; 15/148), M41L (9.5%; 14/148), and K70E/KN/S/R (9.5%; 14/148).

Resistance mutations related to non-TAM NRTIs (33.1%; 49/148) were M184V (29.1%; 43/148), and L74I/V (8.1%; 12/148).

NNRTI mutations were predominantly K103N/S (32.7%; 34/104), V108I (10.6%; 11/104), A98G (10.6%; 11/104), and P225H (9.6%; 10/104).

Minor mutations associated with PIs (60.0%; 54/90) were predominantly K20I (15.6%; 14/90) and L10F/I/V (14.5%; 13/90).

The major mutations associated with PIs (40.0%; 36/90) were M41L (12.2%; 11/90), I84V (6.7%; 06/90), and V82A (6.7%; 06/90).

The four most prescribed therapeutic regimens were TDF + 3TC + LPV/r (20.3%; 17/84), ABC + DDI + LPV/r (17.9%; 15/84), TDF + FTC + LPV/r (11.9%; 10/84), and ABC + 3TC + LPV/r (11.9%; 10/84).

Conclusion This study revealed that HIV drug resistance mutations are common in Gabon.

The major mutations associated with PIs were M41L, I84V, and V82A.

There is a need for access to new NRTIs, NNRTIs, and PIs for a better therapeutic management of PLHIV in Gabon.