Antiretroviral Therapies Associated with Lipoatrophy in HIV-Infected Women

Tien, Phyllis C.; Barrón, Yolanda; Justman, Jessica; Hyman, Charles; Cohen, Mardge H.; Young, Mary; Kovács, Andrea; Cole, Stephen R.

doi:10.1089/apc.2006.128

Cited by 20 publications

(16 citation statements)

References 38 publications

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“…9,17 While less clear, the use of ddI has also been reported to be associated with lipoatrophy and with depletion of mtDNA in fat. 28,29 In our study, the exclusion of the two patients on ddI (one nonlipoatrophic and one lipoatrophic) did not change the results of any analyses.…”

Section: Discussionmentioning

confidence: 86%

Mitochondrial Oxidative Phosphorylation Protein Levels in Peripheral Blood Mononuclear Cells Correlate with Levels in Subcutaneous Adipose Tissue within Samples Differing by HIV and Lipoatrophy Status

Shikuma

Gerschenson

Chow

et al. 2008

AIDS Research and Human Retroviruses

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Depletion of mitochondrial DNA (mtDNA) and mtDNA-encoded respiratory chain proteins in subcutaneous (SC) fat from patients with HIV lipoatrophy have clearly demonstrated the role of mitochondrial dysfunction in this syndrome. Research in HIV lipoatrophy, however, has been severely hampered by the lack of a suitable surrogate marker in blood or other easily obtained clinical specimens as fat biopsies are invasive and mtDNA levels in peripheral blood mononuclear cells (PBMC) do not consistently correlate with the disease process. We used a simple, rapid, quantitative 2-site dipstick immunoassay to measure OXPHOS enzymes Complex I (CI) and Complex IV (CIV), and rtPCR to measure mtDNA in 26 matched SC fat and PBMC specimens previously banked from individuals on potent antiretroviral (ARV) therapy with HIV lipoatrophy, on similar ARV therapy without lipoatrophy, and in HIV seronegative controls. Significant correlations were found between the respective PBMC and fat levels for both CI (r ϭ 0.442, p ϭ 0.024) and for CIV (r ϭ 0.507, p ϭ 0.008). Both CI and CIV protein levels were also significantly reduced in both PBMCs and fat in lipoatrophic subjects compared to HIV seronegative controls (p Յ 0.05), while a comparative reduction in mtDNA levels in lipoatrophic subjects was observed only in fat. We conclude that CI and CIV levels in PBMCs correlate to their respective levels in fat and may have utility as surrogate markers of mitochondrial dysfunction in lipoatrophy. 1255

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Section: Discussionmentioning

confidence: 86%

Mitochondrial Oxidative Phosphorylation Protein Levels in Peripheral Blood Mononuclear Cells Correlate with Levels in Subcutaneous Adipose Tissue within Samples Differing by HIV and Lipoatrophy Status

Shikuma

Gerschenson

Chow

et al. 2008

AIDS Research and Human Retroviruses

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“…However, another possible explanation for the association of HAART with lower BMI is that after initial gains in fat due to a restoration to health, longer duration of specific antiretroviral drugs (particularly stavudine and zidovudine, which were commonly used during the timeframe of our study) has been associated with lipoatrophy. 2,[44][45][46][47][48] Since HAART was primarily available during the second enrollment period, an examination of data from only this period showed that women on HAART had significantly ( p ¼ 0.04) lower median BMI (26.8) compared to those with no ART use (28.3). Among all study women, the median BMI among those on any ART (25.7) was also significantly lower ( p < 0.0001) than those on no ART (26.9).…”

Section: Discussionmentioning

confidence: 99%

Prevalence and Correlates of Elevated Body Mass Index among HIV-Positive and HIV-Negative Women in the Women's Interagency HIV Study

Boodram

Plankey

Cox

et al. 2009

AIDS Patient Care and STDs

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Since the introduction of highly active antiretroviral therapy (HAART) and the subsequent increased life expectancy in HIV-infected persons, non-HIV-related diseases have become an important cause of morbidity and mortality. This cross-sectional study reports the prevalence of overweight and obesity, and sociodemographic, psychological, and substance use-related risk factors for elevated body mass index (BMI) among 2157 HIVseropositive (HIVþ) in comparison to 730 HIV-seronegative (HIVÀ) participants in the Women's Interagency HIV Study (WIHS). Separate univariable and multivariate linear regression analyses were completed for HIVþ and HIVÀ women. Our study revealed a similar proportion of obesity (body mass index [BMI] !30) among HIVþ (33%) and HIVÀ women (29%) ( p ¼ 0.12), as well as comparable median BMI (HIVþ: 26.1 versus HIVÀ: 26.7, p ¼ 0.16). HIVþ compared to HIVÀ women, respectively, were significantly ( p < 0.01) older (median ¼ 35.6 versus. 32.5), but similar ( p ¼ 0.97) by race=ethnicity (57% African American, 28% Hispanic, and 15% white for both). In multivariate models for both HIVþ and HIVÀ women, African American race=ethnicity was significantly ( p < 0.05) associated with higher BMI, while higher quality of life score and illicit hard drug use were associated with lower BMI. Additionally, smoking, alcohol use, markers of advanced HIV infection (AIDS diagnosis, elevated HIV viral load, low CD4 count), and a history of antiretroviral therapy use (ART) were also associated with lower BMI among HIVþ women. In conclusion, risk factors for elevated BMI were similar for HIVþ and HIVÀ women in the WIHS. For HIVþ women, all markers of advanced HIV infection and ART use were additionally associated with lower BMI.

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“…Both types of adipose tissue redistribution have specific risk factors and have been associated with metabolic abnormalities, decreased quality of life, medication nonadherence, and depression. [1][2][3][4][5][6][7][8][9][10] Optimal treatment regimens for lipoatrophy and lipohypertrophy…”

mentioning

confidence: 99%

A Randomized Trial of Raltegravir Replacement for Protease Inhibitor or Non-Nucleoside Reverse Transcriptase Inhibitor in HIV-Infected Women with Lipohypertrophy

Lake

McComsey

Hulgan

et al. 2012

AIDS Patient Care and STDs

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Lipohypertrophy in HIV-infected patients is associated with metabolic abnormalities. Raltegravir (RAL) is not known to induce fat changes or severe metabolic perturbations. HIV-infected women with central adiposity and HIV-1 RNA less than 50 copies per milliliter on non-nucleoside reverse transcriptase inhibitor (NNRTI)-or protease inhibitor (PI)-based antiretroviral therapy (ART) continued their nucleoside reverse transcriptase inhibitor (NRTI) backbone and were randomized to switch to open label RAL immediately or after 24 weeks. The primary end point was 24-week between-group change in computed tomography (CT)-quantified visceral adipose tissue (AT) volume. Fasting lipids, glucose, C-reactive protein (CRP), anthropometric measurements, and patient-reported quality of life assessments were also measured. Thirty-six subjects provided 80% power to detect a 10% between-group difference in visceral AT over 24 weeks. Thirty-seven of 39 enrolled subjects completed week 24. At entry, subjects were 75% black or Hispanic, and on 62% PI-based and 38% NNRTI-based regimens. The median age was 43 years, CD4 count 558 cells per microliter, and body mass index (BMI) 32 kg/m 2 . After 24 weeks, no statistically significant changes in visceral or subcutaneous AT, anthropometrics, BMI, glucose, or CRP were observed. In subjects receiving RAL, significant improvements in total and LDL cholesterol ( p = 0.04), self-reported belly size ( p = 0.02) and composite body size ( p = 0.02) were observed. Body size changes correlated well with percent visceral AT change. No RAL-related adverse events occurred. Compared to continued PI or NNRTI, switch to RAL was associated with statistically significant 24-week improvements in total and LDL cholesterol but not AT volumes. Additional insights into AT and metabolic changes in women on RAL will be provided by 48-week follow-up of the immediate-switch arm.

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Antiretroviral Therapies Associated with Lipoatrophy in HIV-Infected Women

Cited by 20 publications

References 38 publications

Mitochondrial Oxidative Phosphorylation Protein Levels in Peripheral Blood Mononuclear Cells Correlate with Levels in Subcutaneous Adipose Tissue within Samples Differing by HIV and Lipoatrophy Status

Mitochondrial Oxidative Phosphorylation Protein Levels in Peripheral Blood Mononuclear Cells Correlate with Levels in Subcutaneous Adipose Tissue within Samples Differing by HIV and Lipoatrophy Status

Prevalence and Correlates of Elevated Body Mass Index among HIV-Positive and HIV-Negative Women in the Women's Interagency HIV Study

A Randomized Trial of Raltegravir Replacement for Protease Inhibitor or Non-Nucleoside Reverse Transcriptase Inhibitor in HIV-Infected Women with Lipohypertrophy

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