Switching antiretroviral therapy to minimize metabolic complications

Abstract Context Disentangling contributions of HIV from antiretroviral therapy (ART) and understanding the effects of different ART on metabolic complications in persons living with HIV (PLHIV) has been challenging. Objective We assessed the effect of untreated HIV infection as well as different antiretroviral therapy (ART) on the metabolome/lipidome. Methods Widely targeted plasma metabolomic and lipidomic profiling was performed on HIV-seronegative individuals and people living with HIV (PLHIV) before and after initiating ART (tenofovir/emtricitabine plus atazanavir/ritonavir [ATV/r] or darunavir/ritonavir [DRV/r] or raltegravir [RAL]). Orthogonal partial least squares discriminant analysis was used to assess metabolites/lipid subspecies that discriminated between groups. Graphical lasso estimated group-specific metabolite/lipid subspecies networks associated with the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Correlations between inflammatory markers and metabolites/lipid subspecies were visualized using heat maps. Results Of 435 participants, 218 were PLHIV. Compared to HIV-seronegative individuals, ART-naive PLHIV exhibited higher levels of saturated triacylglycerols/triglycerides (TAGs) and 3-hydroxy-kynurenine, lower levels of unsaturated TAGs and N-acetyl-tryptophan, and a sparser and less heterogeneous network of metabolites/lipid subspecies associated with HOMA-IR. PLHIV on RAL vs ATV/r or DRV/r had lower saturated and unsaturated TAGs. Positive correlations were found between medium-long chain acylcarnitines (C14-C6 ACs), palmitate, and HOMA-IR for RAL but not ATV/r or DRV/r. Stronger correlations were seen for TAGs with interleukin 6 and high-sensitivity C-reactive protein after RAL vs ATV/r or DRV/r initiation; these correlations were absent in ART-naive PLHIV. Conclusion Alterations in the metabolome/lipidome suggest increased lipogenesis for ART-naive PLHIV vs HIV-seronegative individuals, increased TAG turnover for RAL vs ATV/r or DRV/r, and increased inflammation associated with this altered metabolome/lipidome after initiating ART. Future studies are needed to understand cardiometabolic consequences of lipogenesis and inflammation in PLHIV.

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Changes in the Fungal Marker β-D-Glucan After Antiretroviral Therapy and Association With Adiposity

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz434 ◽

2019 ◽

Vol 6 (11) ◽

Cited By ~ 2

Author(s):

Sahera Dirajlal-Fargo ◽

Carlee Moser ◽

Katherine Rodriguez ◽

Vanessa El-Kamari ◽

Nicholas T Funderburg ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Intestinal Damage ◽

Linear Regression Models ◽

Open Label ◽

Metabolic Complications ◽

Cd4 Cell Count ◽

Treatment Naïve ◽

Total Fat ◽

Distribution Shifts ◽

Few Data

Abstract Background Bacterial translocation in HIV is associated with inflammation and metabolic complications; few data exist on the role of fungal translocation. Methods A5260s was a substudy of A5257, a prospective open label randomized trial in which treatment-naïve people with HIV (PWH) were randomized to tenofovir-emtricitabine (TDF/FTC) plus atazanavir-ritonavir (ATV/r), darunavir-ritonavir (DRV/r), or raltegravir (RAL) over 96 weeks. Baseline was assessed, and changes in β-D-glucan (BDG) were assessed at weeks 4, 24, and 96. Wilcoxon rank-sum tests were used to compare distribution shifts in the changes from baseline between treatment arms and linear regression models to assess associations between BDG and measures of inflammation, body composition, and insulin resistance. Results Two hundred thirty-one participants were randomized; 90% were male, the median age was 36 years, HIV-1 RNA was 4.56 log10c/mL, and CD4 cell count was 338 cells/mm3. There was an overall increase in BDG over 96 weeks (1.57 mean fold-change; 95% confidence interval, 1.39 to 1.77) with no differences between arms. Twofold higher BDG levels at week 96 were associated with increases in trunk fat (8%) and total fat (7%) over 96 weeks (P ≤ .035). At week 4, BDG correlated with I-FABP, a marker of enterocyte damage, and zonulin, a marker of intestinal permeability (r = .19–.20; P < .01). Conclusions In treatment-naïve participants initiating antiretroviral therapy (ART) with TDF/FTC and either RAL or ATV/r, DRV/r, BDG, a marker of fungal translocation, increased similarly in all arms over 96 weeks. This may represent continued intestinal damage during ART and resulting fungal translocation. Higher BDG was associated with larger fat gains on ART.

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Adverse Effects Associated With Antiretroviral Therapy and Potential Management Strategies

Journal of Pharmacy Practice ◽

10.1177/0897190005278510 ◽

2005 ◽

Vol 18 (4) ◽

pp. 258-277 ◽

Cited By ~ 5

Author(s):

Dorothea C. Rudorf ◽

Susan A. Krikorian

Keyword(s):

Antiretroviral Therapy ◽

Reverse Transcriptase ◽

Management Strategies ◽

Drug Effects ◽

Long Term Effects ◽

Reverse Transcriptase Inhibitors ◽

Metabolic Complications ◽

Organ Systems ◽

Gastrointestinal Problems ◽

Almost All

A variety of adverse drug reactions (ADRs) affecting many organ systems may be observed with antiretroviral therapy (ARV), and they can be differentiated into short- and long- term effects, class effects, or individual drug effects. Commonly seen ADRs include dermatological reactions, associated with nonnucleoside reverse transcriptase inhibitors (NNRTIs) and some protease inhibitors (PIs), and gastrointestinal problems, a major side effect of PIs and of some nucleoside reverse transcriptase inhibitors (NRTIs). Metabolic complications are frequently reported in HIV-infected patients on ARV and often coexist. Lipodystrophy, hyperinsulinemia/hyperglycemia, and bone disorders (osteoporosis, osteonecrosis) are mainly associated with PIs, while lactic acidemia/acidosis are primarily a problem of NRTIs. Hyperlipidemia may be caused by almost all PIs, few NRTIs, and NNRTIs. All antiretroviral drug classes may cause both asymptomatic and symptomatic hepatotoxicity, although nevirapine is the agent most implicated in hepatic events. More drug-specific ADRs include nephrotoxicity (indinavir and tenofovir), central nervous system problems (efavirenz), hematological disturbances (zidovudine), and hypersensitivity reactions (abacavir). Anticipation of ADRs may influence a patient’s decision to delay ARV or to choose specific and potentially less active agents. Occurrence of ADRs may significantly impact a patient’s quality of life and drug adherence. Pharmacists counseling HIV-infected patients should be aware of common ADRs with ARV and potential management strategies.

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Effects of Different Types of Exercise on Body Composition and Fat Distribution in HIV-Infected Patients: A Brief Review

Canadian Journal of Applied Physiology ◽

10.1139/h05-117 ◽

2005 ◽

Vol 30 (2) ◽

pp. 233-245 ◽

Cited By ~ 17

Author(s):

Florin M. Malita ◽

Antony D. Karelis ◽

Emil Toma ◽

Remi Rabasa-Lhoret

Keyword(s):

Body Composition ◽

Antiretroviral Therapy ◽

Resistance Training ◽

Exercise Training ◽

Body Fat ◽

Aerobic Training ◽

Fat Distribution ◽

Functional Independence ◽

Body Fat Distribution ◽

Metabolic Complications

HIV infection and its treatment is associated with unfavourable metabolic and morphological abnormalities. These metabolic abnormalities, particularly alterations in body composition and fat distribution, may increase the risk for cardiovascular and metabolic complications, as well as reduce functional independence and lower self-esteem. Thus there is an urgent need to develop interventions intended to manage secondary side effects of HIV or antiretroviral therapy-related complications. In poly-treated patients, nonpharmacological interventions are a logical first step. Exercise training in particular may help alleviate some of the metabolic adverse effects associated with antiretroviral therapy by favourably altering body composition and patterns of body fat distribution. Studies have shown that exercise training, particularly aerobic training, can help reduce total body and visceral fat, as well as normalizing lipid profiles in HIV-infected patients. The results for resistance training, however, are less conclusive. Knowledge of the use of resistance and aerobic training and its attendant effects on insulin resistance and adipocytokines may represent an effective nonpharmacologic means for treating metabolic complications of HIV-infected persons who are receiving appropriate antiretroviral therapy. In this brief review we examine the effects of aerobic and resistance training on body composition, body fat distribution, and selected metabolic outcomes. Key words: lipodystrophy, highly active anti-retroviral therapy, aerobic training, resistance training

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Lipodystrophy and metabolic complications of highly active antiretroviral therapy

The Indian Journal of Pediatrics ◽

10.1007/s12098-009-0216-9 ◽

2009 ◽

Vol 76 (10) ◽

pp. 1017-1021 ◽

Cited By ~ 11

Author(s):

Ankit Parakh ◽

Anand Prakash Dubey ◽

Ajay Kumar ◽

Anshu Maheshwari

Keyword(s):

Antiretroviral Therapy ◽

Highly Active Antiretroviral Therapy ◽

Metabolic Complications ◽

Highly Active

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Antiretroviral-therapy-associated lipoatrophy: current status and future directions

Sexual Health ◽

10.1071/sh04058 ◽

2005 ◽

Vol 2 (3) ◽

pp. 153 ◽

Cited By ~ 22

Author(s):

David Nolan ◽

Simon Mallal

Keyword(s):

Antiretroviral Therapy ◽

Subcutaneous Fat ◽

Transcriptase Inhibitor ◽

Clinical Syndrome ◽

Hiv Treatment ◽

Hiv Protease ◽

Current Status ◽

Metabolic Complications ◽

Racial Origin ◽

Body Composition Change

Lipoatrophy is perhaps the most visibly recognisable component of antiretroviral-therapy-associated lipodystrophy due to the rarity of this form of body composition change in the general population. In this respect, it is apparent that lipoatrophy represents a form of drug toxicity specifically involving the subcutaneous fat tissue, resulting in pathological fat loss that preferentially affects the limbs and face. It is now clear that the choice and duration of nucleoside analogue reverse transcriptase inhibitor (NRTI) therapy (stavudine > zidovudine) is the dominant risk factor for clinical lipoatrophy, as well as for the pathological changes to adipose tissue that underlie the clinical syndrome. Host factors have also emerged as important modulators of lipoatrophy severity in patients receiving these NRTI drugs, including age, racial origin, and severity of immune deficiency. On the other hand, the use of selected HIV protease inhibitor drugs is more closely associated with metabolic complications such as dyslipidemia and insulin resistance and has not been convincingly linked to lipoatrophy. This review examines the clinical and pathological manifestations of lipoatrophy, and also presents information regarding the safety profile of alternative NRTI drugs, such as tenofovir and abacavir, that have not been associated with lipoatrophy risk. With increasing knowledge of lipoatrophy pathogenesis, it is likely that moderate and severe forms of this complication can now be considered a preventable complication of HIV treatment. However, it is also important to recognise that there is an ongoing burden of disease in patients who have been affected by lipoatrophy over the past six years, and that therapeutic management of established lipoatrophy will remain a challenge into the future.

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Optimal antiretroviral therapy for aging

Sexual Health ◽

10.1071/sh11026 ◽

2011 ◽

Vol 8 (4) ◽

pp. 534 ◽

Cited By ~ 4

Author(s):

Damien V. Cordery ◽

David A. Cooper

Keyword(s):

Antiretroviral Therapy ◽

Highly Active Antiretroviral Therapy ◽

Treatment Guidelines ◽

Age Groups ◽

Developed Countries ◽

Neurological Complications ◽

Antiretroviral Drugs ◽

People Living With Hiv ◽

Metabolic Complications ◽

Long Term Treatment

The introduction of highly active antiretroviral therapy (HAART) has irrevocably changed the nature of the HIV epidemic in developed countries. Although the use of HAART does not completely restore health in HIV-infected individuals, it has dramatically reduced morbidity and mortality. Increases in life expectancy resulting from effective long-term treatment mean that the proportion of older people living with HIV has increased substantially in the past 15 years. Increasing age is associated with many complications including cardiovascular disease, neurological complications, kidney and liver dysfunction, and metabolic complications such as dyslipidaemia and diabetes. HIV infection and antiretroviral drugs have also been associated with similar complications to those seen with increasing age. The increase in HIV prevalence in older age groups has not been accompanied by the development of treatment guidelines or recommendations for appropriate antiretroviral therapy or clinical management in these patients.

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