Patients with more advanced HIV disease who are not taking highly active antiretroviral therapy (HAART) tend to have unfavourable changes in blood fat and sugar levels, according to the results of a study presented in the March edition of HIV Medicine.
The study also found that HIV-positive women and African Americans had more favourable lipid profiles than men or other races, respectively. In contrast, greater age and higher body mass index (BMI) were linked to less favourable changes in blood fat and sugar levels.
Previous studies have demonstrated that HAART can cause changes in the levels of fat in the blood. These may be linked to the development of lipodystrophy and heart disease. Commonly reported changes include increases in total blood cholesterol, low-density lipoprotein (LDL or ‘bad’) cholesterol and triglycerides, as well as decreases in high-density lipoprotein (HDL or ‘good’) cholesterol. In addition, elevations in blood sugar levels and resistance to the hormone insulin have been observed, and are linked to the development of diabetes.
Despite these findings, little is known about the effects of demographic factors such as race and age on these metabolic changes. This makes studies of the effect of HAART difficult to interpret, as many have primarily enrolled Caucasian men.
Furthermore, the effect of HIV itself on metabolic disturbances may be difficult to distinguish from the effects of HAART on blood fat and sugar levels. Previous studies have found that HIV infection tends to cause decreases in cholesterol levels and elevations in triglyceride levels. However, while early studies tended to concentrate on patients with advanced HIV disease prior to the advent of antiretroviral therapy, a more recent study of changes in blood fats after HIV infection included only male patients, the majority of whom had experience of variable antiretroviral treatment regimens at the start of the study.
To improve understanding of the effect of HIV and demographic factors on metabolic changes, researchers from the Community Program for Clinical Research on AIDS (CPCRA) in the United States measured blood fat (lipid) levels in 419 HIV-positive patients from 49 clinics. They also measured glucose and insulin levels in the patients' blood.
In contrast to previous studies, none of these patients had ever taken a protease inhibitor or non-nucleoside reverse transcriptase inhibitor, or had had more that four weeks’ treatment with any nucleoside analogue (NRTI) or more than one week’s treatment with 3TC (lamivudine, Epivir). The patient cohort also included 89 (21%) women, 252 (60%) African Americans and 58 (14%) patients with a history of injecting drug use.
“Demographic and HIV disease characteristics influence lipid, glucose and insulin parameters in antiretroviral-naïve patients,” conclude the investigators. “In patients with established HIV infection, deleterious lipid profiles were noted before HIV therapy was initiated. Patients with characteristics associated with more advanced HIV disease had unfavourable lipid profiles and evidence of insulin resistance.
“Interpretation of the effects of various HIV treatment regimen [sic] and drugs on metabolic parameters must take into account the stage of HIV disease and the demographic characteristics of the population studied,” they write.
The mean age of the patients was 38.2 years, with a mean CD4 cell count of 216 cells/mm3 and mean viral load of 95,500 copies/ml. One hundred and eight (26%) of the patients had had an AIDS-defining event, the majority of these being Pneumocystis pneumonia (PCP).
The researchers found that patients with lower CD4 cell counts and higher viral loads had lower levels of HDL (‘good’) cholesterol (p
Patients with a history of an AIDS-defining illness also had higher total cholesterol levels (p Pneumocystis carinii pneumonia and was related to recent diagnosis of this condition,” explain the researchers.
“Our data thus demonstrated that low CD4 lymphocyte count, high HIV RNA level and a history of AIDS-defining events, all markers of more advanced HIV disease, were all associated with higher concentrations of VLDL cholesterol and triglycerides," they state.
When they analysed the effect of HIV disease on blood glucose and insulin levels, the researchers found that patients with lower CD4 cell counts had lower insulin levels (p
After analysing demographic factors, they found that the women in the study had higher levels of HDL (‘good’) cholesterol (p
The authors state: “History of intravenous drug use and BMI both significantly and independently influenced lipid parameters.”
Analysis of glucose and insulin levels revealed a similar pattern. Women had higher insulin levels and insulin resistance than men (p
In contrast, however, African Americans had lower insulin levels and insulin resistance than other races (p
El-Sadr WM et al. Effects of HIV disease on lipid, glucose and insulin levels: results from a large antiretroviral-naïve cohort. HIV Med 6: 114-121, 2005.