Factors Associated With Virological Non-suppression in Treatment-experienced HIV+ Patients in Kenya: a Populationwide Study

Abstract

Background: Virologic failure is an important public health problem threatening the milestones achieved in HIV (Human Immunodeficiency Virus) care and attributed to drug resistance emergence. This study investigated the factors associated with viral load non-suppression (VLNS) in treatment-experienced patients and factors associated with HIV drug-resistant mutations (HIVDRMs) in patients having Nucleoside Reverse Transcriptase Inhibitor (NRTI) and Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI) drug related mutations. The interactions of NNRTIs with mutant HIV-1 Reverse Transcriptase (RT) were also studied. Methods: This was a cross-sectional analytical study conducted on routinely collected data between 2015 to 2022 obtained from the National AIDS and STIs Control Program (NASCOP) database. Multivariable logistic and Poisson regression were used to determine the factors associated with VLNS and HIVDRMs respectively. Molecular docking was performed on Auto Dock Vina. Results: Increased odds of VLNS during multivariable logistic regression were associated with sex: male (aOR=1.33[95%CI: 1.32-1.34], P<0.001), age:13-19 (aOR=2.11 [95%CI: 2.09-2.14], P<0.001) and PI-based regimen (aOR=1.28[95%CI:1.27-1.29], P<0.001). Decreased odds of VLNS were associated with INSTI-based regimen (aOR=0.46[95%CI: 0.45-0.46], P<0.001). Multivariable Poisson regression showed that sex: male (aIRR=2.67[95%CI:1.47-4.84, P=0.001]), regimen: TDF+3TC+DTG (aIRR=0.59[95%CI: 0.39-0.91, P=0.016]), AZT+3TC+NVP (aIRR=1.82 [95%CI: 1.11 -2.99], P=0.018), and TDF+3TC+ATVr (aIRR=1.93 [95%CI: 1.02- 3.64], P=0.043) were significantly associated with HIVDRMs. Molecular docking revealed that the free energy of binding of nevirapine (27.2 kcalmol-1) and efavirenz (21.7kcalmol-1) on the mutant HIV-1 RT was higher than in the wild-type (WT) HIV-1 RT. Conclusions and Recommendations: Levels of VLNS have decreased gradually over the years. Sex, age, treatment duration, cART regimen and some counties were significantly associated with VLNS. It is therefore imperative to set up and maintain follow up targeted intervention programs to achieve the Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95-95 goals. Additionally, the disproportionate levels of VLNS at the county level demand setting up a risk assessment tool to enable equitable allocation of resources pertaining to HIV care and management.