Evidence map›Paper›PMID 42165254›Full record

SynthesisHIV medicine2026

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

Melani Ratih Mahanani, Myo Chit, Sophie Mohr, Elisenda Cama I Gibernau, Svetlana Hetjens, Volker Winkler, Hans-Michael Steffen, Florian Neuhann

Abstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in HIV medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Melani Ratih MahananiHeidelberg Institute of Global Health, Heidelberg University Hospital, Heidelberg, Germany.ORCID https://orcid.org/0000-0003-3391-934X
Myo ChitHeidelberg Institute of Global Health, Heidelberg University Hospital, Heidelberg, Germany.ORCID https://orcid.org/0009-0004-8711-8008
Sophie MohrHeidelberg Institute of Global Health, Heidelberg University Hospital, Heidelberg, Germany.ORCID https://orcid.org/0009-0008-9775-6504
Elisenda Cama I GibernauHeidelberg Institute of Global Health, Heidelberg University Hospital, Heidelberg, Germany.
Svetlana HetjensDepartment of Medical Statistics and Biomathematics, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Volker Winkler *Heidelberg Institute of Global Health, Heidelberg University Hospital, Heidelberg, Germany.ORCID https://orcid.org/0000-0002-9974-1145
Hans-Michael SteffenDepartment of Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Florian NeuhannHeidelberg Institute of Global Health, Heidelberg University Hospital, Heidelberg, Germany.ORCID https://orcid.org/0000-0001-5944-1597

Funding

German Federal Ministry of Research, Technology and Space (BMFTR) 01KA2403
6 · The paper itself

Abstract

introductionAntiretroviral 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.

methodsFollowing 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.

resultsWe 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.

conclusionsART 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.

Indexed as

Anti-HIV AgentsAntiretroviral Therapy, Highly ActiveHIV InfectionsAdultHumansAnti-HIV Agentsanti‐HIV agentsHIVmetabolic outcomemetabolic syndrometype 2 diabetes mellitus

Identifiers

PMID42165254
PMCPMC13547439

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.