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Longer Antiretroviral Therapy Favors Return to Normal HDL-C
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50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 12-15, 2010, Boston
Mark Mascolini
Longer duration of antiretroviral therapy correlated with a return from low to normal "good" high-density lipoprotein cholesterol (HDL-C) in a 2900-person French study [1]. Longer use of protease inhibitors (PIs), nonnucleosides (NNRTIs), nucleosides, and integrase inhibitors all boosted chances of regaining a normal HDL-C level, as did several markers of good antiretroviral response.
People with HIV infection run a higher risk of subnormal HDL-C levels, but the factors influencing a return to normal HDL have not been well studied. French clinicians addressed that question in a study of 2905 people whose HDL-C was measured periodically after a 12-hour fast. The researchers defined low HDL-C as a level below 0.9 mmol/L (35 mg/dL).
Through an average follow-up of 3.72 years, the investigators measured HDL-C 29,263 times. Cohort members had a median of 8 HDL-C measures. Age at inclusion in the cohort averaged 41.5 years, and 2002 cohort member (69%) were men. Most cohort members, 2507 (86%) had a CD4 count above 200 when they entered the group. HIV infection duration at the end of follow-up averaged 11.7 years. Among antiretroviral-treated people, 61% had taken a PI and 40% an NNRTI.
There were 1454 people with no low HDL-C levels during follow-up, 1324 with at least one low HDL-C, and 127 who always had a low HDL-C. Half of these people, then, had subnormal HDL-C at some point in 3.7 years of follow-up.
Statistical analysis considering antiretroviral classes and adjusted for number of HDL-C measurements and treatment with lipid-lowering drugs identified several independent predictors of transition from low to normal HDL-C at the following hazard ratios (HR) and 95% confidence intervals (CI):
Non-HIV-related factors
--Female gender: HR 2.05, 95% CI 1.80 to 2.33
--Triglycerides (per g/L): HR 0.87, 95% CI 0.85 to 0.89
--Low-density lipoprotein cholesterol (per mmol/L): HR 0.86, 95% CI 0.82 to 0.90
--Glucose (per mmol/L): HR 0.97, 95% CI 0.95 to 0.99
--No chronic hepatitis: HR 1.40, 95% CI 1.27 to 1.55
HIV-related factors
--CD4 count above 200: HR 1.33, 95% CI: 1.14 to 1.56
--CD4/CD8 ratio above 0.53: HR 1.30, 95% CI 1.19 to 1.43
--No history of AIDS diagnosis: HR 1.27, 95% CI 1.14 to 1.41
--Duration of HIV infection (per year): HR 1.01, 95% CI 1.002 to 1.02
--Viral load (per 10-fold higher): HR 0.82, 95% CI 0.78 to 0.85
Antiretroviral duration
--Overall duration (per year): HR 1.02, 95% CI 1.005 to 1.03
--NNRTI duration (per year): HR 1.10, 95% CI 1.08 to 1.12
--PI duration (per year) HR 1.09, 95% CI 1.05 to 1.11
--Integrase inhibitor duration (per year): HR 2.22, 95% CI 1.56 to 3.13
A statistical model that considered individual antiretrovirals found a greater chance of returning to normal HDL-C with each additional year of efavirenz (HR 1.05), nevirapine (HR 1.11), abacavir plus lamivudine (HR 1.33), zidovudine plus lamivudine (HR 1.03), abacavir plus lamivudine plus zidovudine (HR 1.09), tenofovir plus emtricitabine (HR 1.37), lopinavir (HR 1.11), darunavir (HR 1.33), atazanavir (1.12), and raltegravir (HR 1.96).
The researchers concluded that female gender and low triglycerides, glucose, and low-density lipoprotein all favor a return to normal HDL-C levels. But they proposed that variables related to control of HIV infection (particularly treatment with PIs, NNRTIs, and raltegravir) are the main drivers HDL-C normalization. They suggested that the association between a higher CD4/CD8 ratio and return to a normal HDL-C reflects quelling of the inflammatory state induced by poorly controlled HIV infection.
Reference
1. Meynard J, Lacombe K, Aber A, et al. Impact of antiretrovirals and immuno-virological status on transition between hypo and normo HDL-cholesterol status in 2862 HIV-infected patients. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). September 12-15, 2010. Boston. Abstract H-219.
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