Background: In order to ensure long-term efficacy of dolutegravir (DTG), we evaluated the genotypic profile in viral reservoirs among patients on third line antiretroviral therapy (ART) in Cameroon, according to prior exposure to raltegravir (RAL).
Methods: A facility-based study was conducted from May throughout December 2021, among patients on third line from HIV treatment centres in Yaoundé and Douala. Viral load was measured, and genotyping was performed on plasma-RNA and pro-viral DNA. HIV-1 drug resistance mutations were interpreted using HIVdb.v9.1 and phylogeny was performed using MEGA.v7, with p<0.05 considered significant.
Results: Of the 12,093 patients on ART, 53 fully met our inclusion criteria. Median [IQR] age was 51 [40-55] years and the M/F sex-ratio was 4/5. Median duration on integrase strand-transfer inhibitors (INSTI)-containing regimens was 18 [12-32] months; 15.09% (8/53) were exposed to RAL and the most administered third line was TDF+3TC+DTG+DRV/r (33.96%, 18/53). Only 5.66% (3/53) had unsuppressed viremia (>1000 copies/ml). Resistance testing in pro-viral DNA was successful for 18/22 participants and revealed 1/18 patient (5.56%, in the RAL-arm) with archived mutations at major resistance positions (G140R, G163R). Five subtypes were identified, CRF02_AG (12/18), CRF22_01AE (3/18), A1 (1/18), G (1/18) and F2 (1/18).
Conclusions: In Cameroon, third line experienced patients have a good virological response with low level of archived mutations in the integrase. This finding underscores the use of DTG containing ART for heavily treated patients in similar programmatic settings. However, patients with prior exposure to RAL should be closely monitored following a stratified or personalized approach to mitigate risks of INSTI resistance, alongside pharmacovigilance.