New data indicate that lipid problems can vary, depending on a woman's HIV status, whether or not she's on HIV treatment, or which antiretrovirals she is using. One suggestion from the Women's HIV Interagency Study (WIHS) is that non-protease inhibitor (PI) drug regimens are advantageous in terms of reducing the risk of cardiovascular disease among women living with the virus.
From puberty onward, Kathryn Anastos, MD, and her colleagues write in the May 1 issue of the Journal of Acquired Immune Deficiency Syndromes, cholesterol levels differ between women and men. Studies have shown that premenopausal women, on average, have lower total cholesterol and "bad" LDL cholesterol than men of similar ages. After menopause, the reverse becomes true – women end up with higher total and LDL cholesterol levels than age-matched men. "Good" HDL cholesterol levels are, on average, higher in women throughout adulthood.
Research conducted over the years also shows that lipid abnormalities are not new to HIV-positive people. Since 1989 – long before the availability of PIs and the widespread use of combination drug treatment – increased levels of triglycerides and decreased levels of total, LDL, and HDL cholesterol were documented in people with HIV infection, especially those with more advanced disease. More recently, the use of PIs, nucleoside reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse transcriptase inhibitors (NNRTIs) has been shown to have varying affects on lipid levels.
Much of what is known about lipid abnormalities in HIV, and during antiretroviral treatment, comes from studies in which the vast majority of participants are men. As women represent a growing proportion of those infected with, and being treat for, HIV infection – compounded by the natural lipid variations between men and women – there has been a need to better understand the lipid alterations in this patient population.
The WIHS evaluation conducted by Dr. Anastos' group involved 623 HIV-negative and 1,556 HIV-positive women. Among the HIV-positive women, 636 were not on treatment, 419 were on a non-PI regimen, and 501 were on a PI-inclusive drug combination.
The first analysis by Dr. Anastos' group involved differences in average LDL cholesterol measurements. Levels were not different among the HIV-negative women compared to those documented in the untreated HIV-positive women or the HIV-positive women using a non-PI treatment regimen. Only women using an HIV drug regimen containing a PI had higher LDL cholesterol levels.
Average HDL cholesterol levels were "markedly lower" among the untreated HIV-positive women compared to the average levels documented in all other groups. HIV-positive women on a non-PI regimen had similar HDL cholesterol levels to those of the HIV-negative women. HDL cholesterol was significantly higher among women on a non-PI regimen compared to those on a PI drug combination.
As for total cholesterol, the untreated HIV-positive women had lower levels (166 mg/dL) than the HIV-negative women (175 mg/dL), a statistically significant difference. Women using PIs had significantly higher levels of total cholesterol compared to the HIV-negative women and the HIV-positive women not receiving treatment, but not the HIV-positive women using a non-PI regimen.
The WIHS researchers also reported that the untreated HIV-positive women had higher triglyceride levels than the HIV-negative women, but lower levels than both the PI and no-PI drug regimen users.
The influence of individual HIV drugs was also explored by the WIHS team. Epivir® (lamivudine), Videx® and Videx® EC (didanosine), Viramune® (nevirapine), and Sustiva® (efavirenz) were independently associated with higher HDL levels. Norvir® (ritonavir), Crixivan® (indinavir) combined with Norvir, and Viracept® (nelfinavir) were associated with higher LDL cholesterol levels. Zerit® (stavudine), Ziagen® (abacavir), and all Norvir-containing drug regimens were associated with higher triglycerides. Viread® (tenofovir) was associated with lower triglycerides.
In conclusion, the authors confirmed the longstanding observation that, even among women, HIV infection itself is associated with lipid abnormalities. The abnormalities are even more severe among user of PI-inclusive regimens – compared to few notable abnormalities among non-PI regimen users – "suggesting that non-PI regimens may be superior in avoiding cardiovascular risk in women."
Source:
Anastos K, Lu D, Shi Q, et al. Association of serum lipid levels with serostatus, specific antiretroviral agents, and treatment regimens. J Acquir Immune Defic Syndr 45(1):34-42, 2007.
