Hiv-1 Gag Gene Mutations, Treatment Response and Drug Resistance to Protease Inhibitors: A Systematic Review and Meta-analysis Protocol

Background: Some mutations in the HIV-1 Gag gene are known to confer resistance to ritonavir-boosted protease inhibitors (PI/r), but their clinical implications remain controversial and most genotyping algorithms only consider the protease gene to evaluate resistance to PI/r. Thus, a thorough analysis of existing findings would provide a better understanding on the role of HIV-1 Gag gene on the resistance to PI/r, by characterizing genotypic co-variations between Gag -mutations/polymorphisms and mutations of the protease region. Methods: : We will include randomized and non-randomized trials, cohort and cross-sectional studies published in English and French (from 2012 onwards), and relevant conference reports on PI/r HIV-1 Gag gene resistance associated mutations. Hand searching of the reference lists of relevant reviews will be conducted and we will also look for the aforementioned conference abstracts. PUBMED, EMBASE, CENTRAL, CINAHL databases will be used to conduct the searches. We will include studies of adults and/or children exposed to PI/r based therapies; and we will exclude studies of patients with specific co-morbidities such as tuberculosis or opportunistic infections. Primary outcomes will be “the rate of viral suppression”, “the proportion of patients with immune recovery” and “the level of drug resistance” on protease PI/r-based regimens. Secondary outcomes will be “HIV-1 Gag gene non polymorphic mutations according to PI/r based-regimens” and “viral subtypes/recombinants”. Two reviewers will independently screen titles and abstracts, assess the full texts for eligibility and extract data. If data permits, random effects models will be used where appropriate. Subgroup and additional analyses will be conducted to explore the potential sources of heterogeneity. Discussion: This study will help to better understand the implications of the Gag gene mutations ofPI/r-based ART response for HIV positive individuals, for a potential consideration in algorithms interpreting HIV drug resistance for clinical management. Prospero registration number: CRD42019114851