Mapping the Gut Microbiota Composition in the Context of Raltegravir, Dolutegravir, and Bictegravir—A Scoping Review
Abstract
1. Introduction
1.1. Development and Characteristics of Antiretroviral Therapy
1.2. Integrase Strand Transfer Inhibitors
1.3. The Role of Gut Microbiota in Chronic Inflammation Among PLWH
1.4. Aims of the Scoping Review
- To map alterations in the gut microbiota of PLWH receiving specific INSTI-based therapy in comparison to those undergoing NNRTI or PI-based regimens.
- To assess differences in gut microbiota composition between PLWH treated with dolutegravir-based regimens and those receiving bictegravir-based therapy.
2. Materials and Methods
3. Results
3.1. Study Selection Process
3.2. Specific INSTI Related Changes in the Gut Microbiota
Study Title | Author | Publication Year | Participants | INSTI-Mediated Alpha Diversity Changes | INSTI-Mediated Beta Diversity Changes | INSTI-Mediated Changes in Microbiome Composition | Stool Sample Analysis | INSTI-Mediated Change on Translocation or Inflammation Markers |
---|---|---|---|---|---|---|---|---|
Gut microbiota alterations after switching from a protease inhibitor or efavirenz to raltegravir in a randomized, controlled study [63] | Hanttu et al. | 2023 | PLWH on either efavirenz or PI (n = 41) vs. 24 weeks after switch to raltegravir (n = 19) vs. negative controls (n = 10) | Raltegravir treatment approximated the alpha diversity of HIV-seronegative individuals | - | Raltegravir:
| 16S rRNA sequencing | No changes |
Differential effects of antiretrovirals on microbial translocation and gut microbiota composition of HIV-infected patients [64] | Villanueva-Millán et al. | 2017 | PLWH on either NNRI (n = 22) or PI (n = 15) or raltegravir (n = 8) vs. ART-naïve (n = 5) and negative controls (n = 21) | Raltegravir treatment approximated the alpha diversity of HIV-seronegative individuals | - | Raltegravir:
| 16S rDNA pyrosequencing | Raltegravir
|
Lower Pretreatment Gut Integrity Is Independently Associated With Fat Gain on Antiretroviral Therapy [65] | El Kamari et al. | 2018 | PLWH randomized to raltegravir (n = 82), darunavir/ritonavir (n = 82), and atazanavir/ritonavir (n = 67) therapies | - | - | - | - | Raltegravir
|
Changes in Inflammation and Immune Activation With Atazanavir-, Raltegravir-, Darunavir-Based Initial Antiviral Therapy: ACTG 5260s [66] | Kelesidis et al. | 2015 | PLWH randomized to raltegravir (n = 106), darunavir/ritonavir (n = 113), and atazanavir/ritonavir (n = 109) therapies | - | - | - | - | Raltegravir
|
Exploring the interplay between antiretroviral therapy and the gut-oral microbiome axis in people living with HIV [67] | Narayanan et al. | 2023 | [INSTI (bictegravir vs. dolutegravir) vs. NNRTI vs. PI] (n = 69) vs. [negative controls] (n = 80) | Dolutegravir:
| Dolutegravir:
| Bictegravir:
| 16S rRNA sequencing | - |
Comparative Effects of Efavirenz and Dolutegravir on Metabolomic and Inflammatory Profiles, and Platelet Activation of People Living with HIV: A Pilot Study [68] | Roux et al. | 2024 | Efavirenz (n = 9) vs. 6 months after dolutegravir switch (n = 9) vs. negative controls (n = 20) | - | - | - | 16S rRNA sequencing | Dolutegravir:
|
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ART | Antiretroviral therapy |
BMI | Body mass index |
CCR5 | C-C chemokine receptor type 5 |
CRP | C-reactive protein |
DNA | Deoxyribonucleic acid |
GALT | Gut-associated lymphoid tissue |
G-CSF | Granulocyte colony-stimulating factor |
GlycA | Glycoprotein acetylation |
GM-CSF | Granulocyte macrophage colony-stimulating factor |
HIV | Human immunodeficiency virus |
I-BABP | Ileal bile acid-binding protein |
ICAM-1 | Intercellular adhesion molecule 1 |
I-FABP | Intestinal fatty acid-binding protein |
IL-6 | Iinterleukin-6 |
INSTI | Integrase strand transfer inhibitor |
LPS | Lipopolysaccharide |
MeSH | Medical Subject Headings |
NCD | Noncommunicable disease |
NRTI | Nucleoside reverse transcriptase inhibitor |
NNRTI | Non-nucleoside reverse transcriptase inhibitor |
PDGF-BB | Platelet derived growth factor subunit B |
PI | Protease inhibitor |
PLWH | People living with HIV |
PRISMA | Preferred Reporting Items for Systematic Reviews and Meta-Analyses |
PRISMA-ScR | PRISMA for Scoping Reviews |
RANTES | Regulated on activation, normal T-cell expressed and secreted |
RNA | Ribonucleic acid |
rRNA | Ribosomal ribonucleic acid |
sCD14 | Soluble cluster of differentiation 14 |
sCD40 | Soluble cluster of differentiation 40 |
sCD163 | Soluble cluster of differentiation 163 |
SCFA | Short-chain fatty acid |
sIL-2r | Soluble interleukin-2 receptor |
WHO | World Health Organization |
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Inclusion criteria | |||
Studies published in English were included if they belonged to one of the following categories: case-control studies, cohort studies, single-arm trials, ort randomized controlled trials. | |||
Population | Intervention | Comparator | |
PICO 1 | Adults diagnosed with HIV infection confirmed by serological tests | PLWH receiving INSTI-based therapy | PLWH receiving NNRTI/PI-based therapy |
PICO 2 | Adults diagnosed with HIV infection confirmed by serological tests | PLWH receiving dolutegravir-based therapy | PLWH receiving bictegravir-based therapy |
Exclusion criteria | |||
The following types of publications were excluded: reviews, case series, case reports, clinical guidelines, conference abstracts, letters, preprints, and editorials. |
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© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Gáspár, Z.; Lakatos, B. Mapping the Gut Microbiota Composition in the Context of Raltegravir, Dolutegravir, and Bictegravir—A Scoping Review. Int. J. Mol. Sci. 2025, 26, 6366. https://doi.org/10.3390/ijms26136366
Gáspár Z, Lakatos B. Mapping the Gut Microbiota Composition in the Context of Raltegravir, Dolutegravir, and Bictegravir—A Scoping Review. International Journal of Molecular Sciences. 2025; 26(13):6366. https://doi.org/10.3390/ijms26136366
Chicago/Turabian StyleGáspár, Zsófia, and Botond Lakatos. 2025. "Mapping the Gut Microbiota Composition in the Context of Raltegravir, Dolutegravir, and Bictegravir—A Scoping Review" International Journal of Molecular Sciences 26, no. 13: 6366. https://doi.org/10.3390/ijms26136366
APA StyleGáspár, Z., & Lakatos, B. (2025). Mapping the Gut Microbiota Composition in the Context of Raltegravir, Dolutegravir, and Bictegravir—A Scoping Review. International Journal of Molecular Sciences, 26(13), 6366. https://doi.org/10.3390/ijms26136366