Temporal shifts in antiretroviral therapy regimens and metabolic outcomes in people living with HIV: A systematic review and meta-analysis.

INTRODUCTION

Antiretroviral therapy (ART) for people living with HIV has led to dramatically reduced mortality and improved life expectancy. This achievement is accompanied by a higher risk for metabolic and other non-communicable diseases. The role and contribution of various ART regimens to adverse metabolic outcomes are not fully understood. We aimed to systematically evaluate the risk of metabolic outcomes associated with ART and to describe temporal trends in these risks across the modern ART era.

METHODS

Following our prespecified, registered protocol, we conducted a systematic review and meta-analysis of non-randomized observational studies, comparing ART-treated and ART-naïve adult people living with HIV and report the metabolic outcomes of interest. We extracted ART regimen combinations and metabolic outcomes and calculated pooled odds ratios (ORs) with 95% confidence intervals (95% CI) using a random-effects model. Temporal patterns were summarized by publication year and year of ART rollout.

RESULTS

We identified 6827 studies, in which 39 studies were eligible for analysis with information from 24 632 people living with HIV. Nucleoside reverse transcriptase inhibitors (NRTIs) were present throughout the review period. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) predominated from the early 2000s to 2014, while protease inhibitors (PIs) dominated 1998-2014. Integrase strand transfer inhibitors (INSTIs) appeared from 2016 onwards. ART-treated adult people living with HIV had higher odds for metabolic syndrome (OR = 2.16, 95% CI = 1.33-3.52), while no statistically significant association was observed for type 2 diabetes mellitus (T2DM) (OR = 1.37, 95% CI = 0.65-2.90).

DISCUSSION: Metabolic burden associated with modern HIV treatment shifted from lipid abnormalities to weight- and glucose-related outcomes. Meta-analysis results showed that ART-treated adults had nearly twice the odds of metabolic syndrome compared with ART-naïve adults. In contrast, our meta-analytic evidence did not demonstrate a statistically significant association between ART use and the odds of developing T2DM. Findings should be interpreted with caution given potential confounding by disease stage, access to healthcare and survivorship bias.

CONCLUSIONS

ART regimens and their metabolic outcomes have shifted over time. ART-treated adult people living with HIV had higher odds of metabolic syndrome than their ART-naïve peers. Given heterogeneity and residual confounding, robust, long-term studies would be needed to refine regimen-specific risks.