Second-line antiretroviral therapy failure and characterization of HIV-1 drug resistance patterns in children in Mali

Abstract

Introduction: In recent years, children born to HIV-infected mothers have been receiving antiretroviral treatment (ART) with limited or no virologic monitoring, which increases the likelihood of development and accumulation of drug resistance mutations, which itself may limit the effectiveness of future ART. The objective of this study was to evaluate the prevalence of resistance mutations in children infected with HIV-1 experiencing virological failure to second-line ART in the Pediatric Department of Gabriel Touré Hospital in Mali.

Methods: Children aged from 5 to 18 infected with HIV-1 on second-line antiretroviral therapy and whose viral load was greater than 1000 copies/mL after observance reinforcement were enrolled. The protease and reverse transcriptase genes were sequenced with ViroSeq^®. The results were interpreted according to the last version of the Stanford algorithm in 2018. The study was approved by the Ethics Committee of the Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies of Bamako (Mali).

Results: Of 216 children, 33 (15.3%) who had a viral load (VL)>1000 copies/mL in second line were recruited and included in the study. The median plasma viral load was 77,000 copies/mL [IQR (28,000-290,000)] and the median CD4 cell count was 310 cells/mm³ [IQR (152-412)]. The median age was 12 years; 48.5% of patients were treated with a combination of stavudine/lamivudine/nevirapine (Triomune^®) for first-line treatment and 60.6% with abacavir/lamivudine/lopinavir/ritonavir for the second-line ART. The median treatment duration was 8.5 years [range, 3-13]. Of the 33 children whose treatment failed, the predominant HIV-1 subtype was CRF02_AG (66.7%). The prevalence of resistance to ART classes was 60.61% (20/33) to nucleoside reverse transcriptase inhibitors (NRTIs), 54.51% (18/33) to nonnucleoside reverse transcriptase inhibitors (NNRTIs), and 51.52% (17/33) to protease inhibitors (PIs). Of the patients studied, 90.9% were exposed to lopinavir/ritonavir (LPV/r) but only 15.2% (5/33) developed resistance to LPV/r.

Conclusions: This study demonstrated that LPV/r remains active in most patients after second-line ART failure. In children whose second-line ART fails, particular attention should be paid to their ART and adherence history when considering the next treatment option.

Keywords: Children; Drug resistance; HIV-1; Second-line ART.