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UBC Theses and Dissertations

Comparative efficacy and safety of first-line treatments for HIV patients for clinical guideline development and the impact of individual patient data Kanters, Steve


Since 2008, efavirenz+tenofovir+emtricitabine (EFV+TDF+XTC) has been the preferred first-line antiretroviral therapy (ART) regimen for treating HIV throughout most countries. With an expanding choice of ART, should a newer treatment be preferred? The therapeutic landscape was assessed for efficacy, safety and tolerability through a systematic literature review (SLR) and network meta-analysis (NMA). Data were analyzed using aggregate data (AgD) from publications for each population of interest. Ninety eligible trials were identified in the principal SLR and 65 were included in analyses. There was high certainty that dolutegravir (DTG) was superior to EFV with respect to viral suppression, change in CD4 cell counts, discontinuation, and adverse events. DTG and EFV were comparable among TB-HIV co-infected patients. Among pregnant women initiating DTG, there appeared to be fewer adverse events than with EFV. To determine whether the inclusion of individual patient data (IPD) would impact decision-making and to explore the impact of integrating IPD in varying ways, the SLR and NMA were expanded through the addition of IPD obtained for three critical trials: SINGLE, FLAMINGO and SPRING-2. Use of IPD did not alter the conclusions. In the few cases where IPD-based analyses were selected, the impact on estimates did not meaningfully impact their utility towards the development of clinical guidelines. A simulation study was conducted to determine how network size, density, proportion of IPD, and nature of effect-modification could predict impact of IPD on NMA results. The inclusion of IPD may be most impactful among small and/or sparse networks of evidence. Having a higher proportion of treatment comparisons with IPD also improves the NMA estimates, particularly among larger networks of evidences. Similarly, these simulations suggested while inclusion of IPD led to improvements with respect to both bias and precision of estimates, these improvements decreased within larger and more dense networks – such as those used in the HIV analyses. In conclusion, the findings support the use of DTG+TDF+XTC as the preferred first-line regimen, supporting the change in HIV guidelines by the World Health Organization in late 2018. The analyses provide important insights into the types of networks where IPD would influence results of NMA.

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