Figure 1.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Flow Chart.
PubMed/MEDLINE, Embase, and Cochrane databases were searched to identify randomized controlled trials evaluating efficacy and/or safety of ATV/r, DRV/r, DTG, EFV, EVG/c, LPV/r, RAL, or RPV in treatment-naive HIV-1–infected patients. Records were screened by independent researchers, who selected study titles and abstracts for full text review. Following several rounds of exclusion based on multiple criteria, 31 trials and publications were selected for subsequent analysis. *Additional records were identified via ClinicalTrials.gov, the Food and Drug Administration (FDA), scientific discussions of the European Medicines Agency (EMA)/European Public Assessment Reports (EPAR), and third-agent package inserts. Each of these were found to be included in initial search records and noted as such. †Reasons for exclusion at time of full text review: non-randomized trial; Phase 1/Phase 2 trials; patient population age <13 years; outcomes not of interest; trial duration <12 weeks; and out-of-network comparator. ‡34 publications were matches to ClinicalTrials.gov registry results (NCTs) to ensure comprehensive extraction of all available data pertaining to outcomes of interest.
Figure 2.
Network of treatment comparisons contained within the identified clinical trials.
The major classes of third agents studied in the selected trials are indicated along the perimeter of the figure: NNRTIs, green; integrase inhibitors and PIs, purple; connectors, yellow. Black lines connecting each of the treatments of interest (red dots) represent a publication or clinical trial containing those two agents. Connector agents are drugs identified in 2 or more trials, and which were compared to 2 or more treatments of interest; connector agents are also members of the PI class. ATV = atazanavir; ATV/r = ritonavir-boosted atazanavir; DTG = dolutegravir; DRV/r = ritonavir-boosted darunavir; EFV = efavirenz; EVG/c = cobicistat-boosted elvitegravir; FPV/r = ritonavir-boosted fosamprenavir; LPV/r = lopinavir-boosted ritonavir; NFV = nelfinavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; RAL = raltegravir; RPV = rilpivirine; SQV/r = ritonavir-boosted saquinavir.
Figure 3.
Comparison of immunologic endpoints with dolutegravir versus third agents of interest.
(A) Odds ratio [95% CrI] for virologic suppression (HIV RNA<50 c/mL) of DTG compared with other third agents. Odds ratio values greater than 1 indicate the comparison favors DTG; CrI intervals that do not contain 1 are considered statistically significant. (B) Mean [95% CrI] CD4+ cell increase with dolutegravir versus third agents of interest. Crls of mean differences that do not contain 0 are considered statistically significant. ATV = atazanavir; ATV/r = ritonavir-boosted atazanavir; Crl = credible interval; DTG = dolutegravir; DRV/r = ritonavir-boosted darunavir; EFV = efavirenz; EVG/c = cobicistat-boosted elvitegravir; FPV/r = ritonavir-boosted fosamprenavir; LPV/r = lopinavir-boosted ritonavir; NFV = nelfinavir; RAL = raltegravir; RPV = rilpivirine; SQV/r = ritonavir-boosted saquinavir. *Indicates statistically significant comparison.
Table 1.
Estimated probability of virologic suppression and absolute CD4+ cell count change from baseline.
Figure 4.
Relative changes in cholesterol and triglyceride parameters for dolutegravir versus third agents of interest.
Mean changes (mg/dL [95% Crl] in lipid levels with DTG compared with other third agents are shown for (A) total cholesterol (TC), (B) HDL cholesterol, (C) LDL cholesterol, and (D) triglycerides. In all cases, Crls of mean differences that do not include 0 are considered statistically significant. ATV = atazanavir; ATV/r = ritonavir-boosted atazanavir; DTG = dolutegravir; DRV/r = ritonavir-boosted darunavir; EFV = efavirenz; EVG/c = cobicistat-boosted elvitegravir; FPV/r = ritonavir-boosted fosamprenavir; HDL = high-density lipoprotein; LDL = low-density lipoprotein; LPV/r = lopinavir-boosted ritonavir; NFV = nelfinavir; RAL = raltegravir; RPV = rilpivirine; SQV/r = ritonavir-boosted saquinavir; TC = total cholesterol. *Indicates statistically significant comparison.
Table 2.
Mean odds ratio (95% CrI) of AEs and discontinuation due to AEs.
Table 3.
Difference (95% CrI) between direct clinical trial data and indirect model estimates.