Systematic review to determine the prevalence of transmitted drug resistance mutations to rilpivirine in HIV-infected treatment-naive persons

Abstract

Background: Transmitted drug resistance to antiretrovirals in HIV-1-infected individuals is rising in some regions and could compromise the effectiveness of first-line treatment. It is important to understand the prevalence of resistance to rilpivirine to inform treatment provision.

Methods: A PUBMED/EMBASE search identified analyses of transmitted genotypic resistance to specific non-nucleoside reverse transcriptase inhibitor mutations worldwide. Patients were to be HIV-1-infected and antiretroviral-naive. Rilpivirine mutations assessed were: L100I, K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C and M230I/L. Additionally, frequency of resistance mutations were extracted and pooled by HIV subtype from the Stanford HIV drug resistance database.

Results: 138 eligible articles from 65 countries were identified (n=64,466). Among these 64,466 samples, 7 of the 9 genotypic rilpivirine mutations had a prevalence <0.1%. Two mutations were more prevalent: E138A/G/K/Q/R (0.7%, 95% CI 0.2, 1.3) and Y181C/I/V (0.3%, 95% CI 0.2, 0.4). Prevalence of E138 rilpivirine-related mutations varied between regions: highest in Latin America/Caribbean (3.6%, 95% CI 1.0, 7.6) and in Europe (3.2%, 95% CI 0.7, 6.9). Pooled results from the Stanford database (n=52,680) correlated with these findings indicating a low prevalence of 8/9 rilpivirine mutations (<0.1%), except for E138A/G/K/Q/R (2.9%, 95% CI 1.8, 4.4). Prevalence of the mutations at E138 varied significantly by HIV subtype and was highest for subtype-C (6.1%), subtype-F (5.1%) and subtype-A (3.3%).

Conclusions: The prevalence of most transmitted rilpivirine-related HIV mutations is generally low in treatment-naive HIV-1-infected individuals (<0.1%). The prevalence of E138A/G/K/Q/R mutations is higher (0.7%) and varies according to geographical region and HIV subtype.