US Latinos have more unfavourable metabolic and body fat changes on HIV drugs

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A US study comparing metabolic and body composition changes in Latinos, whites and African-Americans after they initiated antiretroviral therapy found that Latinos had greater increases than the other two groups in glucose and insulin resistance, and were more likely to have lipoatrophy. The study, presented in the January 1st edition of the Journal of Acquired Immune Deficiency Syndromes, controlled for numerous factors, leading the authors to conclude that their findings were indicative of inherent racial/ethnic differences.

Antiretroviral therapy has long been associated with problematic changes in glucose and lipid metabolism and in body composition. However, it is difficult to ascertain the effects of particular drugs and drug combinations, in part because of the large number of factors that may contribute to the metabolic and body fat changes occurring in HIV-positive people. HIV itself appears to affect metabolic functioning independently of treatment. Also, aging is associated with metabolic and body fat changes, which means that some of the observed problems in HIV-positive people who are living much longer as a result of effective treatment may be related to the aging process.

The study analysed data from a subset of participants in the Flexible Initial Retrovirus Suppressive Therapies (FIRST) study, which randomised antiretroviral-naive people to three treatment arms. FIRST study participants who enrolled in a related metabolic study were asked to name the racial/ethnic group that best fitted them. Among the 422 metabolic study participants, 412 identified as either African-American, Latino or white; 398 of these people met the selection criteria for the substudy investigating racial/ethnic differences.

Glossary

metabolism

The physical and chemical reactions that produce energy for the body. Metabolism also refers to the breakdown of drugs or other substances within the body, which may occur during digestion or elimination.

glucose

A simple form of sugar found in the bloodstream. All sugars and starches are converted into glucose before they are absorbed. Cells use glucose as a source of energy. People with a constant high glucose level might have a disease called diabetes.

diabetes

A group of diseases characterized by high levels of blood sugar (glucose). Type 1 diabetes occurs when the body fails to produce insulin, which is a hormone that regulates blood sugar. Type 2 diabetes occurs when the body either does not produce enough insulin or does not use insulin normally (insulin resistance). Common symptoms of diabetes include frequent urination, unusual thirst and extreme hunger. Some antiretroviral drugs may increase the risk of type 2 diabetes.

cholesterol

A waxy substance, mostly made by the body and used to produce steroid hormones. High levels can be associated with atherosclerosis. There are two main types of cholesterol: low-density lipoprotein (LDL) or ‘bad’ cholesterol (which may put people at risk for heart disease and other serious conditions), and high-density lipoprotein (HDL) or ‘good’ cholesterol (which helps get rid of LDL).

insulin

A hormone produced by the pancreas that helps regulate the amount of sugar (glucose) in the blood.

The cohort of 398 included 243 African-Americans, 43 Latinos, and 112 whites. The group was 22% female, and 87% of females were African-American. There was an overall mean age of 38.

When the researchers compared the metabolic and body composition changes of African-Americans, Latinos and whites, they controlled for age, gender, hepatitis C status, CD4 cell count, viral load level, prior AIDS status and body mass index. They also controlled for cumulative time on ten antiretroviral drugs: indinavir (Crixivan), nelfinavir (Viracept), ritonavir (Norvir), efavirenz (Sustiva), nevirapine (Viramune), abacavir (Ziagen), ddI (didanosine, Videx), 3TC (lamivudine, Epivir), d4T (stavudine, Zerit) and AZT (zidovudine, Retrovir).

The most striking finding was that Latinos had more unfavorable glucose metabolism changes than either Africa-Americans or whites. Latinos had a significantly greater rate of increase in glucose levels than members of the other two groups, as well as a significantly greater rate of increase in insulin resistance levels (glucose: Latino vs African-American, p

Latinos also differed from African-Americans and whites on some measures of body composition. Latinos had a greater mean loss in waist subcutaneous tissue area, as well as a higher rate of fat loss. They had a greater mean loss in mid-arm subcutaneous tissue area.

The authors point out that in the United States, Hispanics have the highest rates of metabolic syndrome and diabetes. People with metabolic syndrome, a cluster of conditions including elevated glucose levels and excess abdominal fat, are at increased risk of diabetes, stroke and heart disease.

The analysis also showed that African-Americans had smaller increases in triglyceride levels than Latinos or whites, as well as lower rates of increase. The authors again relate this to findings in the general population, observing that African-Americans may have an inherently lower risk than whites of developing hypertriglyceridemia.

Nonetheless, all three groups experienced increases in triglyceride levels. They all had increases in HDL cholesterol and decreases in LDL cholesterol as well.

The authors conclude, “Changes over time in body composition and the more unfavorable metabolic parameters observed among the Latinos compared with the African-Americans and whites in our study may reflect not only the impact of HIV infection and [antiretroviral therapy] but also different genetic predisposition.” They call for efforts to increase understanding of the clinical implications of these findings.

References

Gilbert C et al. Racial differences in changes of metabolic parameters and body composition in antiretroviral therapy-naive persons initiating antiretroviral therapy. J Acquir Immune Defic Syndr 50: 44 – 53, 2009.