CONFERENCE ON RETROVIRUSES
AND OPPORTUNISTIC INFECTIONS

March 8–11, 2020

 

Conference Dates and Location: 
February 23-26, 2015 | Seattle, Washington
Abstract Number: 
731

PCSK9 Is Elevated in HIV+ Patients and May Mediate HIV-Associated Dyslipidemia

Author(s): 

Payal Kohli1, Peter Ganz1, Yifei Ma1, Rebecca Scherzer1, Kristinalisa Maka1, Scott Wasserman2, Rob Scott2, Priscilla Hsue1
1 Division of Cardiology, University of California San Francisco, San Francisco, CA, United States. 2 Amgen, Thousand Oaks, CA, United States.

Abstract Body: 

Background: Proprotein convertase subtilisin kexin 9 (PCSK9) is induced by inflammation and leads to elevated levels of LDL cholesterol, increasing cardiovascular risk. Increased PCSK9 might explain the dyslipidemia observed in HIV-infected individuals, which has been previously attributed to HIV medication, HIV disease, and/or chronic inflammation. We aimed to compare PCSK9 levels in HIV-infected individuals and uninfected controls and to identify predictors of elevated PCSK9 in HIV disease.

Methods: We measured PCSK9 levels in 567 participants (495 HIV, 72 controls) from an outpatient cohort in San Francisco using a high affinity ELISA assay. Generalized linear models with log link function were used to determine factors associated with PCSK9.

Results: The median age of participants was 50 years (IQR 43-55) and 89% were male, 34% smokers, 25% hypertensive; the median LDL was 103 mg/dL (IQR 80-127), and 21% were on statins. HIV-infected individuals and controls were similar in age, gender, and had similar rates of traditional risk factors except for prior CAD, which was more common among those with HIV (7% vs. 0%). Most (56%) percent of HIV subjects were treated and suppressed on antiretroviral medication with a median HIV duration of 14.5 years, median CD4+ count of 527 (IQR 346-732) cells/mm3 and nadir CD4+ count of 240 (IQR 96-394) cells/mm3. Unadjusted PCSK9 levels were 11% higher in HIV subjects vs. controls [mean 430 ng/ml (SD 166) vs. 386 ng/ml (SD134), p=0.015]; in addition, of the patients with extremely elevated PCSK9 levels (>800 ng/ml, n=20), 95% were HIV-infected. After adjustment for demographic factors (age, gender, race) and statin use, HIV remained independently associated with 10% higher PCSK9 levels (p=0.03); results were similar in the treated and suppressed cohort. In addition, older age, other race (comprised of mixed ethnicities, Middle Eastern and Pacific Islanders), statin use, Hepatitis C (HCV), higher triglycerides, current smoking and Lp(a)>90 nmol/L were all independently associated with higher PCSK9 levels in adjusted analysis. In contrast, neither inflammatory markers (IL-6, hs-CRP) nor CD4+ count or HIV viral load were associated with higher PCSK9.

Conclusions: PCSK9 is increased in HIV-infected individuals. Traditional risk factors, HCV, and Lp(a)>90 nmol/L were also independently associated with PCSK9. Future studies should explore whether PCSK9 inhibition may be used to treat dyslipidemia and statin resistance in HIV+ patients.

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PCSK9 is 10% higher (9% CI 2-22%) (after adjustment for demographics, statin use and cardiovascular risk factors) in HIV-Infected compared with uninfected persons. Note that there are many HIV+ patients having very high PCSK9 levels (>800 ng/mL), suggesting that PCSK9 inhibition may prove to be an attractive target for treating HIV-associated dyslipidemia.

Session Number: 
P-P2
Session Title: 
Dyslipidemia: Mediators and Treatment
Presenting Author: 
Kohli, Payal
Presenter Institution: 
University of California San Francisco
Poster: