Integrase inhibitors versus efavirenz combination antiretroviral therapies for TB/HIV coinfection: a meta-analysis of randomized controlled trials.

BACKGROUND: Integrase inhibitors (INIs)-based antiretroviral therapies (ART) are more recommended than efavirenz (EFV)-based ART for people living with HIV/AIDS (PLWHA). Yet, the advantage of integrase inhibitors in treating TB/HIV coinfection is uncertain. Therefore, the objective of this systematic review is to evaluate the effects and safety of INIs- versus EFV-based ART in TB/HIV coinfection, and demonstrate the feasibility of the regimens. METHODS: Four electronic databases were systematically searched through September 2020. Fixed-effects models were used to calculate pooled effect size for all outcomes. The primary outcomes were virologic suppression and bacteriology suppression for INIs- versus EFV-based ART. Secondary outcomes included CD4+ cell counts change from baseline, adherence and safety. RESULTS: Three trials (including 672 TB/HIV patients) were eligible. ART combining INIs and EFV had similar effects for all outcomes, with none of the point estimates argued against the INIs-based ART on TB/HIV patients. Compared to EFV-based ART as the reference group, the RR was 0.94 (95% CI 0.85 to 1.05) for virologic suppression, 1.00 (95% CI 0.95 to 1.05) for bacteriology suppression, 0.98 (95% CI 0.95 to 1.01) for adherence. The mean difference in CD4+ cell counts increase between the two groups was 14.23 cells/µl (95% CI 0- 6.40 to 34.86). With regard to safety (adverse events, drug-related adverse events, discontinuation for drugs, grade 3-4 adverse events, IRIS (grade 3-4), and death), INIs-based regimen was broadly similar to EFV-based regimens. The analytical results in all sub-analyses of raltegravir- (RAL) and dolutegravir (DTG) -based ART were valid. CONCLUSION: This meta-analysis demonstrates similar efficacy and safety of INIs-based ART compared with EFV-based ART. This finding supports INIs-based ART as a first-line treatment in TB/HIV patients. The conclusions presented here still await further validation owing to insufficient data.

Baricitinib induces LDL-C and HDL-C increases in rheumatoid arthritis: a meta-analysis of randomized controlled trials.

BACKGROUND: Baricitinib, an oral-administrated selective inhibitor of the JAK1 and JAK2, is recently approved for rheumatoid arthritis (RA) treatment. With the aim to provide some insights on the clinical safety, the current study mainly focused on the effect of baricitinib on low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels and cardiovascular risk. METHODS: The net change scores [least squares mean (LSM) and mean change] of LDL-C and HDL-C levels from baseline with the comparison of baricitinib versus placebo were pooled, respectively. Risk rations (RR) of major cardiovascular events (MACEs) and differences of cardiovascular risk scores at the end of treatment across groups were compared. RESULTS: Six trials with randomized 3552 patients were finally included in summary analysis. Results showed that baricitinib significantly increased LDL-C levels, the net mean change was 13.15 mg/dl with 95% CI 8.89~17.42 (I2 = 0) and the net LSM was 11.94 mg/dl with 95% CI 7.52~16.37 (I2 = 84%). HDL-C also increased obviously with the net LSM change was 7.19 mg/dl (95% CI, 6.05~8.33, I2 = 47%) and net mean change was 5.40 mg/dl (95% CI, 3.07~7.74, I2 = 10%). Subgroup and meta-regression analysis demonstrated baricitinib induced LDL-C and HDL-C increases in a dose-response manner. However, both the pooled RRs of MACEs and differences of cardiovascular risk scores were not statistically significant across groups. CONCLUSION: This study confirmed that baricitinib induced a stable dose-response increase in LDL-C and HDL-C levels. Since the causality association between altered lipids and cardiovascular risk was not identified yet, this issue cannot be completely dismissed. Future research is needed to fully dissect the implications of these lipid changes.

Efficacy and Safety of Triple versus Dolutegravir-based Dual Therapy in Patients with HIV-1 Infection: A Meta-analysis of Randomized Controlled Trials.

A new strategy of simplification therapy shown the unique benefits in clinical treatment, by reducing pill burden and avoid drug exposure. To provide more evidence for the strategy, we compared the efficacy and safety of dolutegravir (DTG)-containing simplified dual combination antiretroviral therapy (cART) and traditional triple cART for people living with HIV/AIDS. The meta-analysis of randomized controlled trials compared DTG-containing dual therapy with triple cART. The primary outcome was virologic suppression. The secondary outcomes included CD4T cell recovery, lipids change from baseline, and adverse events (AEs). A total of 7 studies, 4852 patients were eligible, 2423 (49.9%) received DTG-based simplified dual cART, and 2429 (50.1%) received triple cART. The viral suppression rate was 94.7% at 24 weeks, 93.0% at 48 weeks, and 96.6% at 96 weeks in dual cART. The viral suppression rate of dual cART was non-inferior to triple cART at 24 weeks (risk difference [RD], -0.00; 95% confidence interval [CI] -0.02-0.01), at 48 weeks (RD, -0.01; 95% CI -0.02-0.01), and at 96 weeks (RD, -0.01; 95% CI -0.02-0.00). Sub-analysis results were consistent with the overall results. With regard to other outcomes (CD4T counts, lipids, any AEs, and AEs grade ≥ 3), there was no significant statistical difference between the two regimens. DTG-based simplified dual cART was non-inferior to triple cART in terms of efficacy and safety. This finding provides strong support for current consensus guidelines recommended the dual regimen as first-line treatment.