Beware of resistance to 2nd-generation integrase inhibitors: A systematic meta-analysis of HIV-1 integrase inhibitors resistance and drug resistance mutations

Objective

Assessing the prevalence of resistance and drug resistance mutations (DRMs) in HIV/AIDS patients towards integrase strand transfer inhibitors (INSTIs), particularly the 2nd-generation INSTIs, provides evidence for rational clinical drug use.

Methods

A systematic search was conducted on five databases to identify relevant literature reporting original data on INSTIs resistance. Meta-analyses, cumulative meta-analyses, subgroup analyses and meta-regression analyses were performed using selected models based on the results of heterogeneity tests.

Results

A total of 81 studies were included in this analysis. The prevalence of pre-treatment drug resistance (PDR) to 1st-generation INSTIs and 2nd-generation INSTIs were 0.41% (95% CI: 0.19%–0.70%) and 0.04% (95% CI: 0.00%–0.13%), respectively; and the prevalence of acquired drug resistance (ADR) were 7.60% (95% CI: 3.54%–12.92%) and 4.93% (95% CI: 1.78%–9.36%), respectively, and ADR showed an increasing and then decreasing time trend. The results of subgroup analyses showed differences in ADR to 2nd-generation INSTIs between regions and economic levels, with the highest ADR of 12.83% (95% CI: 3.24%–27.17%) in the European region. DRMs varied among HIV patients and reduced drug sensitivity to varying degrees.

Conclusion

The prevalence of PDR and DRMs in 2nd-generation INSTIs is currently low, but as the use of DTG-based ART expands, population-level drug resistance monitoring and individual-level genetic testing should be strengthened in order to maximise treatment efficacy. Additionally, attention should be paid to ADR to INSTIs to provide personalised treatments for HIV-infected patients.