Review of integrase strand transfer inhibitors for the treatment of human immunodeficiency virus infection

Mohamed, Abdilahi; Kalabalik, Julie; Sharma, Roopali

doi:10.1586/14787210.2015.1075393

Cited by 36 publications

(28 citation statements)

References 80 publications

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“…14,15 With the introduction of INSTI-based single-pill combination ART regimens, such as fixed-dose dolutegravir/abacavir/lamivudine (DTG/ABC/3TC), patients have a new option to replace older non-nucleoside reverse transcriptase inhibitor (NNRTI)-based or protease inhibitor (PI)-based regimens causing adverse CNS, metabolic, or other side-effects. Recently, clinicians at the Vanderbilt Comprehensive Care Clinic, a large, urban HIV clinic, noted substantial weight gain in several patients with long-term viral suppression who switched from daily, fixed-dose efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC) to daily fixed-dose DTG/ABC/3TC.…”

Section: Introductionmentioning

confidence: 99%

Brief Report: Weight Gain in Persons With HIV Switched From Efavirenz-Based to Integrase Strand Transfer Inhibitor–Based Regimens

Norwood

Turner

Bofill

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

230

149

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Background With the introduction of integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART), persons living with HIV have a potent new treatment option. Recently, providers at our large treatment clinic noted weight gain in several patients switched from efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC) to dolutegravir/abacavir/lamivudine (DTG/ABC/3TC). In this study, we evaluated weight change in patients with sustained virologic suppression switched from EFV/TDF/FTC to an INSTI-containing regimen. Methods We performed a retrospective observational cohort study among adults on EFV/TDF/FTC for at least two years who had virologic suppression. We assessed weight change over 18 months in patients who switched from EFV/TDF/FTC to an INSTI-containing regimen or a protease inhibitor (PI)-containing regimen versus those on EFV/TDF/FTC over the same period. In a sub-group analysis, we compared patients switched to DTG/ABC/3TC versus raltegravir- or elvitegravir-containing regimens. Results A total of 495 patients were included: 136 switched from EVF/TDF/FTC to an INSTI-containing regimen and 34 switched to a PI-containing regimen. Patients switched to an INSTI-containing regimen gained an average of 2.9 kg at 18 months compared to 0.9 kg among those continued on EFV/TDF/FTC (p=0.003), while those switched to a PI regimen gained 0.7 kg (p=0.81). Among INSTI regimens, those switched to DTG/ABC/3TC gained the most weight at 18 months (5.3 kg, p=0.001 compared to EFV/TDF/FTC). Conclusion Adults living with HIV with viral suppression gained significantly more weight after switching from daily, fixed dose EFV/TDF/FTC to an INSTI-based regimen compared to those remaining on EFV/TDF/FTC. This weight gain was greatest among patients switching to DTG/ABC/3TC.

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Section: Introductionmentioning

confidence: 99%

Brief Report: Weight Gain in Persons With HIV Switched From Efavirenz-Based to Integrase Strand Transfer Inhibitor–Based Regimens

Norwood

Turner

Bofill

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

230

149

View full text Add to dashboard Cite

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“…Integrase strand transfer inhibitors (INSTIs) inhibit HIV-integrase and prevent the viral DNA integrate into the DNA of the host CD4 cell; thus, they also prevent the HIV from replicating. However, this class of inhibitors is related to strong cytochrome P 450 3A4 drug interactions and renal dysfunction, which restricts its use (Park et al 2015). PIs target the HIV aspartyl protease, which prevent new and immature HIV from becoming a mature virus that can infect other CD4 cells.…”

Section: Discussionmentioning

confidence: 99%

Proteins, peptides, polysaccharides, and nucleotides with inhibitory activity on human immunodeficiency virus and its enzymes

Cheung

Wong

et al. 2015

Appl Microbiol Biotechnol

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Human immunodeficiency virus (HIV), the causative agent of acquired immune deficiency syndrome, has claimed innumerable lives in the past. Many biomolecules which suppress HIV replication and also other biomolecules that inhibit enzymes essential to HIV replication have been reported. Proteins including a variety of milk proteins, ribosome-inactivating proteins, ribonucleases, antifungal proteins, and trypsin inhibitors; peptides comprising cathelicidins, defensins, synthetic peptides, and others; polysaccharides and polysaccharopeptides; nucleosides, nucleotides, and ribozymes, demonstrated anti-HIV activity. In many cases, the mechanism of anti-HIV action has been elucidated. Strategies have been devised to augment the anti-HIV potency of these compounds.

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“…Inhibitors of the HIV integrase enzyme (raltegravir, dolutegravir and elvitegravir) inhibit the strand-transfer step of viral DNA integration into the host cell chromosomal DNA and comprise the latest class of antiretroviral medications (200, 207). Given the relatively recent introduction of the integrase inhibitors compared to other classes, the effect of integrase inhibitor treatment on body fat partitioning and metabolism is an area of ongoing research.…”

Section: Antixretroviral Therapy Adipogenesis and Adipocyte Functionmentioning

confidence: 99%

Adipose Tissue in HIV Infection

Koethe

2017

Comprehensive Physiology

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HIV infection and antiretroviral therapy (ART) treatment exert diverse effects on adipocytes and stromal-vascular fraction cells, leading to changes in adipose tissue quantity, distribution, and energy storage. A HIV-associated lipodystrophic condition was recognized early in the epidemic, characterized by clinically apparent changes in subcutaneous, visceral, and dorsocervical adipose depots. Underlying these changes is altered adipose tissue morphology and expression of genes central to adipocyte maturation, regulation, metabolism, and cytokine signaling. HIV viral proteins persist in circulation and locally within adipose tissue despite suppression of plasma viremia on ART, and exposure to these proteins impairs preadipocyte maturation and reduces adipocyte expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) and other genes involved in cell regulation. Several early nucleoside reverse transcriptase inhibitor and protease inhibitor antiretroviral drugs demonstrated substantial adipocyte toxicity, including reduced mitochondrial DNA content and respiratory chain enzymes, reduced PPAR-γ and other regulatory gene expression, and increased pro-inflammatory cytokine production. Newer-generation agents, such as integrase inhibitors, appear to have fewer adverse effects. HIV infection also alters the balance of CD4+ and CD8+ T cells in adipose tissue, with effects on macrophage activation and local inflammation, while the presence of latently-infected CD4+ T cells in adipose tissue may constitute a protected viral reservoir. This review provides a synthesis of the literature on how HIV virus, ART treatment, and host characteristics interact to affect adipose tissue distribution, immunology, and contribution to metabolic health, and adipocyte maturation, cellular regulation, and energy storage.

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Review of integrase strand transfer inhibitors for the treatment of human immunodeficiency virus infection

Cited by 36 publications

References 80 publications

Brief Report: Weight Gain in Persons With HIV Switched From Efavirenz-Based to Integrase Strand Transfer Inhibitor–Based Regimens

Brief Report: Weight Gain in Persons With HIV Switched From Efavirenz-Based to Integrase Strand Transfer Inhibitor–Based Regimens

Proteins, peptides, polysaccharides, and nucleotides with inhibitory activity on human immunodeficiency virus and its enzymes

Adipose Tissue in HIV Infection

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