Introduction: Extensive use of antiretroviral therapy has remarkably improved the survival rates of people living with HIV. Doravirine (DOR) is a newly-approved antiretroviral belonging to the class of non-nucleoside reverse transcriptase inhibitors. Here, we compared the efficacy and safety of DOR + tenofovir dipivoxil fumarate (TDF)+Lamivudine (3TC)/Emtritabine (FTC) with traditional triple therapies in treatment-naïve HIV-1-positive adults. Methods: Randomized controlled trials involving treatment-naïve HIV-1-positive adults that met inclusion criteria were systematically retrieved and data on the following outcomes extracted: virological suppression, adverse events, severe adverse events, and drug-related adverse events. A Bayesian network meta-analysis was then performed on the data. Results: This study included a total of 39 randomized controlled trials involving 26 antiretroviral therapies and 21,110 HIV1-positive patients. At week 48, relative to the other 25 regimens included in the network of virological suppression, DOR + TDF+3TC/FTC exhibited superiority to some efavirenz, nevirapine, atazanavir, or lopinavir-based regimens, including efavirenz + abacavir+3TC [Odd Ratio (OR) = 0.52, 95% confidence interval (CrI) = 0.35-0.77]. At week 48, the performance of DOR + TDF+3TC/FTC was relatively similar to all other analyzed regimens in terms of adverse events. The DOR + TDF+3TC/FTC regimen performed better in terms of severe adverse events and drug-related adverse events. Conclusion: The network meta-analysis showed that DOR + TDF+3TC/FTC has good efficacy and safety at 48 weeks. Systematic Review Registration: Open Science Framework, https://osf.io/6ybp7.
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.
Introduction: Integrase strand transfer inhibitor (InSTI)-based antiretroviral regimens have become the recommended antiretroviral therapy for people living with HIV (PLWH) who are antiretroviral-naïve or stably antiretroviral-treated. This meta-analysis aimed to systematically review the efficacy and safety of coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) among PLWH. Methods: Randomized controlled trials (RCTs) were included to compare the efficacy and safety between BIC/FTC/TAF and other antiretroviral regimens containing a non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or integrase strand transfer inhibitor plus two nucleos(t)ide reverse transcriptase inhibitors. A Mantel–Haenszel model was used to investigate the combination or interaction of a group of independent studies. I2 was used to determine whether a fixed-effect model or random-effect model was to be used. Results: A total of seven published randomized clinical trials including 3547 participants were analyzed; three studies were conducted in antiretroviral-naïve PLWH and four in stably antiretroviral-treated PLWH. At week 48, the efficacy with BIC/FTC/TAF was not statistically significantly different from that with control regimens [odds ratio (OR) 1.01 (95% CI 0.79, 1.30)]. BIC/FTC/TAF had comparable safety profiles to control regimens: OR for all adverse effects (AEs) was 0.92 (95% CI 0.78, 1.09); OR for any grade 3 or grade 4 AEs was 0.96 (95% CI 0.66, 1.39); and OR for treatment-related AEs was 1.31 (95% CI 0.68, 2.53). Conclusions: This meta-analysis of published randomized clinical trials of antiretroviral-naïve and stably antiretroviral-treated PLWH suggests that BIC/FTC/TAF is as safe and efficacious as are its comparators at week 48. The interstudy differences in selected populations and control regimens may lead to the high heterogeneity of the meta-analysis.
In this study, we aim to explore the effects on lipids of integrase strand transfer inhibitors (INSTIs) in naïve and switch randomised controlled trials, and compare them with protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). We reviewed phase 3/4 randomised clinical trials in the Cochrane and PubMed databases that compare an INSTI with a boosted PI, an NNRTI, or another INSTI plus one or two nucleoside/nucleotide reverse transcriptase inhibitors (NtRTIs) in naïve patients and switching strategies in HIV-infected patients. We reported the baseline plasma concentration of total cholesterol (TC), low and high-density lipoprotein cholesterol (LDL-c, HDL-c), triglycerides (TG), and the TC/HDL-c ratio, as well as the change at weeks 48 and 96, when available. In naïve HIV-infected patients, raltegravir (RAL) and dolutegravir (DTG) have a more favourable lipid profile compared with NNRTI and boosted PI. Elvitegravir (EVG/c) has a superior lipid profile compared with efavirenz and is similar to that observed with ritonavir-boosted atazanavir except in TG, which increases less with EVG/c. In naïve patients, RAL, DTG, and bictegravir (BIC) produce a similar, slight increase in lipids. In switching trials, the regimen change based on a boosted PI or efavirenz to RAL, DTG, or BIC is associated with clinically significant decreases in lipids that are minor when the change is executed on EVG/c. No changes were observed in lipids by switching trials between INSTIs. In summary, RAL, DTG, and BIC have superior lipid profiles compared with boosted-PI, efavirenz, and EVG/c, in studies conducted in naïve participants, and they are associated with a clinically significant decrease in lipoproteins by switching studies.
Introduction: The extensive utilisation of antiretroviral therapy has greatly improved the survival rates of those infected with human immunodeficiency virus (HIV). The objective of this study was to compare 3-drug regimens containing non-nucleoside reverse transcriptase inhibitor with 3-drug regimens containing integrase inhibitor (INI) regarding efficacy and safety in treatment-naive HIV-1-infected adults at 48 and 96 weeks, respectively. Methods: This study was a network meta-analysis using a Bayesian methodology. On January 8, 2020, we searched databases and other sources for randomized controlled trials conducted in treatment-naive HIV-1 adults and compared multiple 3-drug antiretroviral regimens containing INI, efavirenz (EFV), or rilpivirine (RPV). We extracted data on the following outcomes: virologic suppression, CD4+ cell recovery, discontinuations, deaths, adverse events, serious adverse events, deaths related to study drugs, and drug-related adverse events. We conducted calculations within a Bayesian framework using R software. Results: The network contained 15 randomized controlled trials including 9,745 patients. For efficacy outcomes, regimens containing INI, especially dolutegravir (DTG), were generally superior to other regimens. For virologic suppression at 48 weeks, odds ratios (95% credible intervals) were 0.6 (0.43, 0.82) for EFV+ tenofovir disoproxil fumarate (TDF)+emtricitabine (FTC) versus DTG+ abacavir+ lamivudine (3TC) and 0.52 (0.36, 0.75) for EFV+TDF+FTC vs. DTG+TDF+FTC/3TC. For safety outcomes, regimens containing INI tended to be safer relative to regimens without INI. Outcomes associated with death were unsuitable for network meta-analysis due to low event rates. Conclusion: 3-drug regimens containing INI demonstrate better efficacy and safety than those containing RPV or EFV.
Integrase strand transfer inhibitors (INSTIs) are the most recent class of antiretroviral drugs with potent and durable antiviral activity used to treat human immunodeficiency virus type 1 (HIV-1) infection. However, the development of drug resistance increases the risk of treatment failure, disease progression and mortality. A better understanding of drug efficacy and resistance against INSTIs is crucial for their efficient use and the development of new antiretrovirals. We performed meta-analyses of studies reporting efficacy and resistance data on INSTI use in HIV-infected patients. Odds ratios (ORs) of efficacy outcome data favoring INSTI use in different clinical settings demonstrated that compared with drugs of other classes, INSTIs have higher efficacy. For combination antiretroviral treatment (cART)-naïve patients and viral suppressed patients that switched to INSTI-based therapy, the ORs were 1.484 (95% CI, 1.229-1.790) and 1.341 (95% CI, 0.913-1.971), respectively. ORs of resistance data indicated decreased treatment-emergent resistance development to dolutegravir (DTG) upon virologic failure than to non-INSTIs (OR = 0.081, 95% CI, 0.004-1.849), whereas the opposite was observed for raltegravir (RAL; OR = 3.137, 95% CI, 1.827-5.385) and elvitegravir (EVG; OR = 1.886, 95% CI, 0.569-6.252). Pooled analysis of resistance data indicated that development of resistance to DTG and bictegravir (BIC) was rare, while EVG and RAL had low genetic barriers to resistance and that the intensive cross-resistance between them limits INSTI efficiency. Efficient means of monitoring emergence of resistance to INSTIs and development of drugs with high genetic barriers are clear paths for future research.
Introduction: Extensive use of antiretroviral therapy has remarkably improved the survival rates of people living with HIV. Doravirine (DOR) is a newly-approved antiretroviral belonging to the class of non-nucleoside reverse transcriptase inhibitors. Here, we compared the efficacy and safety of DOR + tenofovir dipivoxil fumarate (TDF)+Lamivudine (3TC)/Emtritabine (FTC) with traditional triple therapies in treatment-naïve HIV-1-positive adults. Methods: Randomized controlled trials involving treatment-naïve HIV-1-positive adults that met inclusion criteria were systematically retrieved and data on the following outcomes extracted: virological suppression, adverse events, severe adverse events, and drug-related adverse events. A Bayesian network meta-analysis was then performed on the data. Results: This study included a total of 39 randomized controlled trials involving 26 antiretroviral therapies and 21,110 HIV1-positive patients. At week 48, relative to the other 25 regimens included in the network of virological suppression, DOR + TDF+3TC/FTC exhibited superiority to some efavirenz, nevirapine, atazanavir, or lopinavir-based regimens, including efavirenz + abacavir+3TC [Odd Ratio (OR) = 0.52, 95% confidence interval (CrI) = 0.35-0.77]. At week 48, the performance of DOR + TDF+3TC/FTC was relatively similar to all other analyzed regimens in terms of adverse events. The DOR + TDF+3TC/FTC regimen performed better in terms of severe adverse events and drug-related adverse events. Conclusion: The network meta-analysis showed that DOR + TDF+3TC/FTC has good efficacy and safety at 48 weeks. Systematic Review Registration: Open Science Framework, https://osf.io/6ybp7.
