Metabolic complications such as dyslipidemia, insulin resistance, and altered fat distribution (loss of subcutaneous fat and relatively increased central fat) are common in adults infected with the human immunodeficiency virus who are receiving highly active antiretroviral therapy and may increase their risk of cardiovascular disease. This review discusses progress in understanding the pathogenetic mechanisms and treatment strategies for addressing cardiovascular risk in this population.

Cardiovascular risk and body-fat abnormalities in HIV-infected adults.

Background. Patients with human immunodeficiency virus (HIV) infection need lifelong medical care, but many do not remain in care. The effect of poor retention in care on survival is not known, and we sought to quantify that relationship.Methods. We conducted a retrospective cohort study involving persons newly identified as having HIV infection during 1997–1998 at any United States Department of Veterans Affairs hospital or clinic who started antiretroviral therapy after 1 January 1997. To be included in the study, patients had to have seen a clinician at least once after receiving their first antiretroviral prescription and to have survived for at least 1 year. Patients were divided into 4 groups on the basis of the number of quarters in that year during which they had at least 1 HIV primary care visit. Survival was measured through 2002. Because data were available for only a small number of women, female patients were excluded from the study.Results. A total of 2619 men were followed up for a mean of >4 years each. The median baseline CD4 + cell count and median log 10 plasma HIV concentration were 228 × 10 6 cells/L and 4.58 copies/mL, respectively. Thirty-six percent of the patients had visits in <4 quarters, and 16% died during follow-up. In Cox multivariate regression analysis, compared with persons with visits in all 4 quarters during the first year, the adjusted hazard ratio of death was 1.42 (95% confidence interval, 1.11–1.83; P < .01), 1.67 (95% confidence interval, 1.24–2.25; P < .001), and 1.95 (95% confidence interval, 1.37–2.78; P < .001) for persons with visits in 3 quarters, 2 quarters, and 1 quarter, respectively.Conclusions. Even in a system with few financial barriers to care, a substantial portion of HIV-infected patients have poor retention in care. Poor retention in care predicts poorer survival with HIV infection. Retaining persons in care may improve survival, and optimal methods to retain patients need to be defined.

http://www.incarecampaign.org/files/79414/Giordano%20-%20Retention%20in%20Care%20-%20A%20Challenge%20to%20Survival.pdf

Retention in care: a challenge to survival with HIV infection.

Adiponectin is a plasma protein expressed exclusively in adipose tissue. Adiponectin levels are linked to insulin sensitivity, but a direct effect of chronically elevated adiponectin on improved insulin sensitivity has not yet been demonstrated. We identified a dominant mutation in the collagenous domain of adiponectin that elevated circulating adiponectin values in mice by 3-fold. Adiponectinemia raised lipid clearance and lipoprotein lipase activity, and suppressed insulin-mediated endogenous glucose production. The induction of adiponectin during puberty and the sexual dimorphism in adult adiponectin values were preserved in these transgenic animals. As a result of elevated adiponectin, serum PRL values and brown adipose mass both increased. The effects on carbohydrate and lipid metabolism were associated with elevated phosphorylation of 5′-AMP-activated protein kinase in liver and elevated expression of peroxisomal proliferator-activated receptor γ2, caveolin-1, and mitochondrial markers in white adip...

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A Transgenic Mouse with a Deletion in the Collagenous Domain of Adiponectin Displays Elevated Circulating Adiponectin and Improved Insulin Sensitivity

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(04)15489-5.pdf

No effect of rosiglitazone for treatment of HIV-1 lipoatrophy: randomised, double-blind, placebo-controlled trial

Lipodystrophy is a medical condition characterized by complete or partial loss of adipose tissue. Not infrequently, lipodystrophy occurs in combination with pathological accumulation of adipose tissue at distinct anatomical sites. Patients with lipodystrophy exhibit numerous metabolic complications, which indicate the importance of adipose tissue as an active endocrine organ. Not only the total amount but also the appropriate distribution of adipose tissue depots contribute to the metabolic state. Genetic and molecular research has improved our understanding of the mechanisms underlying lipodystrophy. Circulating levels of hormones secreted by the adipose tissue, such as leptin and adiponectin, are greatly reduced in distinct subpopulations of patients with lipodystrophy. This finding rationalizes the use of these adipokines or of agents that increase their circulating levels, such as peroxisome proliferator-activated receptor γ (PPARγ) agonists, for therapeutic purposes. Other novel therapeutic approaches, including the use of growth hormone and growth-hormone-releasing factors, are also being studied as potential additions to the therapeutic armamentarium. New insights gained from research and clinical trials could potentially revolutionize the management of this difficult-to-treat condition.

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Lipodystrophy: pathophysiology and advances in treatment

The insulin-sensitizing drugs thiazolidinediones (TZDs), such as rosiglitazone, improve insulin sensitivity and also promote adipocyte differentiation in vitro. The authors hypothesized that TZDs might be beneficial to patients with HIV disease to improve insulin sensitivity and the distribution of body fat by increasing peripheral fat. The ability of rosiglitazone (8 mg/d) to improve insulin sensitivity (from hyperinsulinemic-euglycemic clamp) and to improve body fat distribution (determined from computed tomography measurements of visceral adipose tissue [VAT] and subcutaneous adipose tissue [SAT]) was determined in 8 HIV-positive patients. Before treatment, the insulin sensitivity of the patients was reduced to approximately 34% of that in control subjects. The rate of glucose disposal during a hyperinsulinemic-euglycemic clamp (Rd) was 3.8 +/-.4 (SEM) mg glucose/kg lean body mass/min compared with 11.08 +/- 1.1 (p<.001) in healthy age- and body mass index (BMI)-matched control subjects. After rosiglitazone treatment of 6 to 12 weeks, Rd increased to 5.99 +/-.9 (p=.02), an improvement of 59 +/- 22%. SAT increased by 23 +/- 10% (p=.05), and, surprisingly, VAT was decreased by 21 +/- 8% (p=.04) with a trend for increased SAT/VAT that failed to reach statistical significance. There were no significant changes in blood counts, viral loads, or CD4 counts with rosiglitazone treatment. The study demonstrates that rosiglitazone therapy improves insulin resistance and body fat distribution in some patients with HIV disease.

Mark R Wax

Papers

Improved insulin sensitivity and body fat distribution in HIV-infected patients treated with rosiglitazone: a pilot study.