Efavirenz and ritonavir-boosted lopinavir use exhibited elevated markers of atherosclerosis across age groups in people living with HIV in Ethiopia

Gleason, Rudolph L.; Caulk, Alexander W.; Seifu, Daniel; Rosebush, Julia C.; Shapiro, Alyssa M.; Schwartz, Matthew H.; Eckard, Allison Ross; Amogne, Wondwossen; Abebe, Workeabeba

doi:10.1016/j.jbiomech.2016.05.018

Cited by 23 publications

(29 citation statements)

References 58 publications

(67 reference statements)

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“…The 2007 European Society of Cardiology consensus guidelines proposed a 12-m/second threshold as high risk for CVD events [14]. A few small studies have assessed arterial stiffness in people living with HIV in low-income areas of SSA [19–23], but none have evaluated the impact of chronic immune activation over time. This study therefore aimed to characterize the contribution of immune activation to arterial stiffness in HIV-infected Malawian adults initiating ART with advanced immunosuppression, compared with that in HIV-uninfected adults, and to determine how this changed over time on ART.…”

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confidence: 99%

HIV-Related Arterial Stiffness in Malawian Adults Is Associated With the Proportion of PD-1–Expressing CD8+ T Cells and Reverses With Antiretroviral Therapy

Kelly

Mwandumba

Heyderman

et al. 2019

The Journal of Infectious Diseases

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Background The contribution of immune activation to arterial stiffness and its reversibility in human immunodeficiency virus (HIV)–infected adults in sub-Saharan Africa is unknown. Methods HIV-uninfected and HIV-infected Malawian adults initiating antiretroviral therapy (ART) with a CD4+ T-cell count of <100 cells/μL were enrolled and followed for 44 weeks; enrollment of infected adults occurred 2 weeks after ART initiation. We evaluated the relationship between carotid femoral pulse wave velocity (cfPWV) and T-cell activation (defined as HLA-DR+CD38+ T cells), exhaustion (define as PD-1+ T cells), and senescence (defined as CD57+ T cells) and monocyte subsets, using normal regression. Results In 279 HIV-infected and 110 HIV-uninfected adults, 142 (37%) had hypertension. HIV was independently associated with a 12% higher cfPWV (P = .02) at baseline and a 14% higher cfPWV at week 10 (P = .02), but the increases resolved by week 22. CD4+ and CD8+ T-cell exhaustion were independently associated with a higher cfPWV at baseline (P = .02). At 44 weeks, arterial stiffness improved more in those with greater decreases in the percentage of CD8+ T cells and the percentage of PD-1+CD8+ T cells (P = .01 and P = .03, respectively). When considering HIV-infected participants alone, the adjusted arterial stiffness at week 44 tended to be lower in those with higher baseline percentage of PD-1+CD8+ T cells (P = .054). Conclusions PD-1+CD8+ T-cells are associated with HIV-related arterial stiffness, which remains elevated during the first 3 months of ART. Resources to prevent cardiovascular disease in sub-Saharan Africa should focus on blood pressure reduction and individuals with a low CD4+ T-cell count during early ART.

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confidence: 99%

HIV-Related Arterial Stiffness in Malawian Adults Is Associated With the Proportion of PD-1–Expressing CD8+ T Cells and Reverses With Antiretroviral Therapy

Kelly

Mwandumba

Heyderman

et al. 2019

The Journal of Infectious Diseases

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“…The long-term effect of this cumulative exposure to high total cholesterol levels on cardiovascular health as these young children age into adolescence and young adulthood has not yet been quantified, but studies in HIV-uninfected children have shown that the atherosclerotic disease process begins at an early age with risk factors measured in childhood predicting vascular changes in young adulthood [28,29]. One recent study in Ethiopia observed higher pulse wave velocity among pediatric participants (6–17 years of age) on LPV/r-based regimens for an average of 3 years compared to participants on NVP-based regimens [30]. Measures of total cholesterol in their LPV/r-exposed participants however, were much higher than those measured in our P1060 LPV/r study population at 7 years of follow-up (Median (IQR): 199 (173–244) versus 156 (131–184) mg/dL) [30].…”

Section: Discussionmentioning

confidence: 99%

“…One recent study in Ethiopia observed higher pulse wave velocity among pediatric participants (6–17 years of age) on LPV/r-based regimens for an average of 3 years compared to participants on NVP-based regimens [30]. Measures of total cholesterol in their LPV/r-exposed participants however, were much higher than those measured in our P1060 LPV/r study population at 7 years of follow-up (Median (IQR): 199 (173–244) versus 156 (131–184) mg/dL) [30].…”

Section: Discussionmentioning

confidence: 99%

Metabolic effects of initiating lopinavir/ritonavir-based regimens among young children

Patel

Lindsey

Angelidou

et al. 2018

Aids

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“…Although ART restores immune function, inflammatory markers do not return to normal levels, indicating ongoing low-grade inflammation, which is associated with CVD risk [16–18]. Older ART regimens evidently carry a high risk of metabolic side-effects, including lipodystrophy, altered glucose metabolism and dyslipidaemia, and have been associated with increased carotid intima-media thickness (CIMT), a marker of subclinical atherosclerosis [19]. Newer ART regimens have a lower risk of metabolic side-effects, yet markers of endothelial damage still seem to be higher in the HIV-positive population on ART compared to the HIV-negative population [20, 21].…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular disease risk in an urban African population: a cross-sectional analysis on the role of HIV and antiretroviral treatment

et al. 2019

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BackgroundLife expectancy is increasing in the HIV-positive population and age-related non-communicable diseases, such as cardiovascular disease, (CVD) are seen more frequently. This study investigated to what extent HIV and antiretroviral therapy (ART) is associated with CVD risk in an urban African population.MethodsA cross-sectional study was performed in Johannesburg, South Africa, between July 2016 and November 2017. Both HIV-positive adults (ART-naïve, or on first- or second-line ART), as well as age and sex matched HIV-negative controls who were family or friends of the HIV-positive participants were included. Data were collected on demographics, cardiovascular risk factors, HIV-related characteristics, carotid intima-media thickness (CIMT) and carotid distensibility. The association between HIV, ART and CIMT and distensibility was analysed with linear regression models, adjusting for age, gender and CVD risk factors.ResultsThe study included 548 participants, 337 (62%) females, age 38.3 ± 9.5 years of whom 104 (19.0%) were HIV-positive, ART-naïve; 94 (17.2%) were on first-line ART; 197 (35.9%) were on second-line ART; and 153 (27.9%) were HIV-negative. Participants on second-line ART had higher CIMT and lower distensibility compared to the other groups (p < 0.001). After adjustment for age, these outcomes were similar between groups. Further adjustment for CVD and HIV-related factors did not alter the findings.ConclusionNeither HIV nor ART was associated with CIMT or carotid distensibility in this urban African population. Longitudinal studies are needed to fully understand the relationship between HIV and CVD across different populations.

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Efavirenz and ritonavir-boosted lopinavir use exhibited elevated markers of atherosclerosis across age groups in people living with HIV in Ethiopia

Cited by 23 publications

References 58 publications

HIV-Related Arterial Stiffness in Malawian Adults Is Associated With the Proportion of PD-1–Expressing CD8+ T Cells and Reverses With Antiretroviral Therapy

HIV-Related Arterial Stiffness in Malawian Adults Is Associated With the Proportion of PD-1–Expressing CD8+ T Cells and Reverses With Antiretroviral Therapy

Metabolic effects of initiating lopinavir/ritonavir-based regimens among young children

Cardiovascular disease risk in an urban African population: a cross-sectional analysis on the role of HIV and antiretroviral treatment

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