The effect of protease inhibitors-based antiretroviral therapy on serum/plasma interleukin-6 levels among PLHIV: a systematic review and meta-analysis.

Recommended treatment regimen for human immune deficiency virus (HIV) infection includes protease inhibitors/ritonavir (PIs/r) combined with two-nucleoside reverse-transcriptase inhibitors (2NRTIs), which enable to achieve and maintain viral suppression, restore, and preserve immune function. However, there were inconsistent findings on the levels of interleukin-6 (IL-6) levels. Systematic review and meta-analysis were performed to quantify the pooled effects of PIs/r-based antiretroviral therapy (ART) on serum/plasma IL-6 levels in people living with the HIV (PLHIV). PubMed, Web of Science, and Embase were searched from the earliest record to November 4, 2020. Data analysis was conducted on Stata version 16 and Review Manager 5.3. A random-effect model was used to compute a pooled effect size and weighted mean difference (WMD) was considered the summary effect size. Heterogeneity between studies was estimated by Cochrane's Q test (χ2 test) and I2 statistic and subgroup analysis were performed to explore the source of heterogeneity. Initial search identified 3098 records and 5 studies (7 trials) met inclusion criteria. The pooled mean difference in serum/plasma IL-6 levels from baseline to follow-up was 0.534 pg/ml (95% confidence interval: -0.012, 1.08, P = 0.05, I2 = 76.4%). In subgroup analysis, there was a significant association between increased serum/plasma IL-6 levels and age group ≥ 35 years old, baseline CD4+ counts < 350 cell/mm3 , and mean viral load ≥ 4.5 log10 copies/ml. We found that serum/plasma IL-6 levels increased after combined ART among treatment-naïve individuals who initiated a successful combination of PIs/r with 2NRTIs. This result also highlights the need to monitor serum/plasma IL-6 levels during antiviral therapy, which may aid in the effective future treatment of systemic inflammation and related disorders following elevated IL-6 levels.

The Effect of Probiotics, Prebiotics, and Synbiotics on CD4 Counts in HIV-Infected Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Probiotics as a potential adjuvant therapy may improve the restoration of the intestinal CD4+ T-cell population in HIV-infected patients, whereas findings from clinical trials are inconsistent. This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to quantify the effects of probiotic, prebiotic, and synbiotic supplementation on CD4 counts in HIV-infected patients. METHODS: We searched PubMed, Embase, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials for relevant articles published up to March 20, 2020. Two authors independently performed the study selection, data extraction, and risk of bias assessment. Data were pooled by using the random effects model, and weighted mean difference (WMD) was considered the summary effect size. Publication bias was evaluated by a funnel plot and Egger's test. RESULTS: The search strategy identified 1712 citations. After screening, a total of 16 RCTs with 19 trials were included in the meta-analysis. Pooling of the extracted data indicated no significant difference between the probiotics/prebiotics/synbiotics and placebo groups on CD4 counts (WMD = 3.86, 95% confidence interval (CI) -24.72 to 32.45, P = 0.791). In subgroup analysis, a significant increase in CD4 counts was found in the study with high risk of bias (WMD = 188, 95% CI 108.74 to 227.26, P ≤ 0.001). Egger's test showed no evidence of significant publication bias (P = 0.936). CONCLUSIONS: In summary, the evidence for the efficacy of probiotics, prebiotics, and synbiotics in improving HIV-infected patients' CD4 counts as presented in currently published RCTs is insufficient. Therefore, further comprehensive studies are needed to reveal the exact effect of probiotics, prebiotics, and synbiotics on CD4+ cell counts.