Meta AnalysisID 4020
HIV-1 Gag基因突变、治疗反应及对蛋白酶抑制剂耐药：一项系统评价与Meta分析方案
CRD42019114851
What is the implication of the HIV-1 gag gene mutations in resistance to protease inhibitors, and how does the replicative capacity of HIV-1 vary with different HIV-1 gag mutations and HIV viral subtypes in order to clar
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Meta-analysis: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final meta_analysis record.
- Meta Analysis Id
- 4020
- Evidence Id
- 12578
- Core Evidence Id
- 12578
- Source Meta Analysis Id
- 3978
- Herb2 Meta Analysis Id
- HBMA003978
- Crd Id
- CRD42019114851
- Title
- HIV-1 Gag gene mutations, treatment response and drug resistance to protease inhibitors: a systematic review and meta-analysis protocol
- Review Question
- What is the implication of the HIV-1 gag gene mutations in resistance to protease inhibitors, and how does the replicative capacity of HIV-1 vary with different HIV-1 gag mutations and HIV viral subtypes in order to clarify the role of mutations in the gag gene that may cause resistance?
- Study Type Included
- We will include randomized and non-randomized trials, cohort and cross-sectional studies evaluating HIV-1 Gag gene mutations and protease resistance associated mutations.
- Condition Being Studied
- Many HIV patients have access to combined antiretroviral therapy (ART). Antiretroviral therapy generally works well to keep the virus suppressed and the patient healthy when the patient has good adherence . However, the treatment only works as long as the virus is not resistant to the drugs used. When the first antiretrovirals were commercialized in the 1980s, drug resistance was a definite result for all patients and the duration of successful treatment was limited. Nowadays, some patients are treated for many years without any resistance problem, while for others, drug resistance is a serious threat to their health.Studies have shown that mutations in the HIV-1 Gag gene confer resistance to protease inhibitors. However, the clinical implications remain controversial and most current genotyping algorithms only take into account the protease gene to evaluate resistance to protease inhibitors. We propose a systematic review to describe the potential role of HIV-1 gag gene in protease inhibitor resistance, to characterize the gag gene resistance mutations in covariance with mutations of the protease and their possible interactions.
- Participant
- We will include studies including HIV-positive people on protease inhibitors treatment failure, including men and women without age restrictions. Cases of co-infection or opportunistic illness will not be excluded. Studies on patients with HIV-2 will be excluded and in the case where the type of HIV is not specified, we will consider subtype 1. We will exclude studies of antiretroviral therapy taken by participants not notified and the combined data of mutations of the gag gene and protease are not provided.
- Animal
- Human Disease Modelled
- Intervention
- Protease inhibitors based regimens will be our intervention of interest. Studies focusing on patients under Atazanavir (ATV/r), Lopinavir (LPV/r) or Darunavir (DVR/r) based regimens will be considered as our first group of interest. Our second group of interest will be made up of studies on patients under PI-sparing regimens. Finally, studies on naïve patients will serve as control group.
- Comparator Control
- Given that studies onHIV-1 Gag gene mutations and protease resistance associated mutationswill be the only ones included, genotypic profiles of both the Gag gene and the protease region will serve as comparators. Also, given the wide genetic variability of HIV-1, viral subtypes (and especially B vs. non B) may serve as comparators as well.
- Main Outcome
- Primary outcomes will be the “prevalence of Gag mutations” and the “prevalence of PI/r resistance associated mutations”. Secondary outcomes will be the “rate of treatment failure” and the distribution of Gag mutations according to subtypes. HIV-1 Gag gene mutations will be consideredasnon-polymorphic mutations (< 5% occurrence) according to gene portion (cleavage and non-cleavage sites). PI/r resistance associated mutations will be considered as defined by Stanford HIVdb list( https://hivdb.stanford.edu/hivdb/by-mutations/) and the 2019-International AIDS Society drug resistance list .Treatment failure here refers to an unsuppressed viral load (≥1000 copies/ml) for people under antiretrovirals. Measures of effect Data will be analyzed using the ‘meta’ and ‘metafor’ packages of the R statistical software (V.3.4.4, R Foundation for Statistical Computing, Vienna, Austria).A descriptive analysis of study characteristics will be undertaken to explore the heterogeneity of the studies. Summary statistics will then be used to describe study outcomes, including means or medians, and frequencies. Proportions with exact binomial 95% confidence intervals (95% CI) will be calculated for each outcome and presented in forest plots.Heterogeneity will be evaluated by the χ² test on Cochran’s Q statistic, which will be quantified by H and I² values. The I² statistic estimates the percentage of total variation across studies due to true between-study differences rather than chance. In general, I² values greater than 60%–70% indicate the presence of substantial heterogeneity.In the case of substantial heterogeneity, subgroup and meta-regression analyses will be used to investigate sources of heterogeneity. Univariable and multivariable meta-regression will be used to test for an effect of PI/r regimen and viral subtype on Gag gene non polymorphic mutations. We will use the GRADE approach to rate the certainty of evidences as “high”, “moderate”, “low” and “very low.
- Outcome Measure
- Additional Outcome
- None. Measures of effect Not applicable.
- Study Method
- Meta-analysis, Narrative synthesis, Systematic review
- Keyword
- Genes, gag; HIV Protease; HIV-1; Humans; Mutation; Protease Inhibitors; gag Gene Products, Human Immunodeficiency Virus
- Contact
- Alex Durand Nka [email protected]
- Organisational Affiliation
- Not affiliated to any organisation
- Funding Source
- Chantal Biya International Reference Center for research on HIV/AIDS Prevention and Management
- Other Selection Criteria
- Final Publication
- Same Topic Review
- Published Protocol
- Review Type
- Language
- English
- Country
- Brazil, Cameroon, England, France
- Review Stage
- Review Ongoing
- First Submission Date
- 2019-02-07
- Registration Date
- 2019-04-09
- Anticipated Start Date
- 2020-12-01
- Anticipated Completion Date
- 2021-02-02
- Title Cn
- HIV-1 Gag基因突变、治疗反应及对蛋白酶抑制剂耐药：一项系统评价与Meta分析方案
- Title En
- HIV-1 Gag gene mutations, treatment response and drug resistance to protease inhibitors: a systematic review and meta-analysis protocol
- Bilingual Status
- complete