Background/Objectives: Lipoprotein(a), Lp(a), is an independent causal risk factor for cardiovascular disease (CVD), where levels are regulated by the apolipoprotein(a), apo(a), gene. HIV-infected individuals are at significantly elevated CVD risk compared to HIV-uninfected individuals. The role of Lp(a) in HIV-related CVD remains unclear. We investigated the association between Lp(a) level, apo(a) size polymorphism and subclinical atherosclerosis in HIV-infected and HIV-uninfected women in the Women’s Interagency HIV Study. Methods: Lp(a) level, apo(a) size polymorphism and common carotid artery intima-media thickness (cIMT) were determined in 150 HIV-infected and 100 HIV-uninfected women. Lp(a) levels were square-root transformed to achieve normality. Linear regression models were used to evaluate the association of Lp(a) with cIMT adjusting for confounders. Results: The mean ages for the HIV+ and HIV- groups were 31 ± 4 and 30 ± 4 years, respectively. The majority of women were African-Americans (69% and 76% in the HIV+ and HIV- group, respectively). HDL-cholesterol, triglyceride and Lp(a) levels were significantly lower in the HIV+ vs. HIV- group. Prevalence of atherogenic small size apo(a) (<22 Kringles) was ~20% in both groups. Notably, Lp(a) level was predictive of cIMT in the HIV+ group [β = 0.00541, 95% CI = (0.000608, 0.010212), p =0.029], but not in the HIV- group [β = 0.00175, 95% CI = (-0.0045024, 0.0080024), p =0.584]. After accounting for confounders (age, race, smoking, BMI, blood pressure, HCV co-infection, menopause, blood lipids, treatment status, CD4+ T-cell count, and HIV/RNA viral load), the association remained significant [β = 0.00532, 95% CI = (0.0000672, 0.0105728), p =0.049] in the HIV+ group. Conclusions: Lp(a) level is associated with subclinical atherosclerosis in young HIV-infected women. Further research is needed to identify mechanisms underlying Lp(a)-associated increased CVD risk in HIV-infected individuals.
We previously demonstrated an association between lipoprotein (a) [Lp(a)] levels and atherosclerosis in human immunodeficiency virus (HIV)-seropositive women. The effects of antiretroviral therapy (ART) on Lp(a) levels in relation to apo(a) size polymorphism remain unclear. ART effects on allele-specific apo(a) level (ASL), an Lp(a) level associated with individual apo(a) alleles within each allele-pair, were determined in 126 HIV-seropositive women. ART effects were tested by a mixed-effects model across pre-ART and post-ART first and third visits. Data from 120 HIV-seronegative women were used. The mean age was 38 years; most were African-American (∼70%). Pre-ART ASLs associated with the larger (4.6 mg/dl vs. 8.0 mg/dl, P = 0.024) or smaller (13 mg/dl vs. 19 mg/dl, P = 0.041) apo(a) sizes were lower in the HIV-seropositive versus HIV-seronegative group, as was the prevalence of a high Lp(a) level (P = 0.013). Post-ART ASL and prevalence of high Lp(a) or apo(a) sizes and frequency of small size apo(a) (22 kringles) did not differ between the two groups. ART increased Lp(a) level (from 18 to 24 mg/dl, P < 0.0001) and both ASLs (P < 0.001). In conclusion, regardless of genetic control, Lp(a) can be modulated by HIV and its treatment. ART initiation abrogates HIV-induced suppression of Lp(a) levels and ASLs, contributing to promote CVD risk in HIV-seropositive individuals.
Objective: To examine predictors and consequences of prescription opioid use among a cohort of women living with HIV (WLWH) and women without HIV from 2000 to 2019. Materials and Methods: The Women's Interagency HIV Study is a multisite, prospective cohort study. Cumulative proportion of visits with prescription opioid use was categorized as follows: minimal (0%–9%), intermediate (10%–39%), and chronic (>40%). Logistic regression examined independent predictors, and proportional hazards regression estimated unadjusted and adjusted hazards of all-cause mortality, comparing intermediate and chronic prescription opioid use with minimal use. Results: Annual prevalence of prescription opioid use significantly increased from 12.6% to 19.3% from 2000 to 2019 (p < 0.0001). Prescription opioid use was minimal in 75%, intermediate in 16%, and chronic in 9% of women. WLWH had 56% higher odds of chronic prescription opioid use compared with women without HIV. Even after adjusting for quality-of-life scores including ratings of pain, women with intermediate and chronic prescription opioid use had greater odds of being sexual minorities (lesbian or bisexual), unemployed, and were more likely to report benzodiazepine and nonprescription substance use compared with those with minimal use. Intermediate and chronic prescription opioid use were each associated with an almost 1.5-fold increased risk of all-cause mortality. Conclusions: Despite federally mandated opioid prescribing guidelines, prescription opioid use and related mortality significantly increased in women experiencing physical and psychosocial vulnerabilities. The higher mortality rate found among prescription opioid users may reflect the many underlying chronic medical and psychosocial conditions for which these opioids were prescribed, as well as complications of opioids themselves. Findings underscore the need for non-opioid and nonpharmacological interventions for chronic pain, particularly in sexual minorities and WLWH. Avoiding concurrent use of opioids with benzodiazepines and nonprescription drugs might reduce mortality. Clinical Trial Registration Number: NCT00000797
HIV coinfection is associated with more rapid liver fibrosis progression in hepatitis C (HCV) infection. Recently, much work has been done to improve outcomes of liver disease and to identify targets for pharmacological intervention in coinfected patients. In this study, we analyzed clinical data of 1,858 participants from the Women’s Interagency HIV Study (WIHS) to characterize risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis. We assessed 887 non-synonymous single nucleotide variants (nsSNV) in a subset of 661 coinfected participants for genetic associations with changes in liver fibrosis risk. The variants utilized produced amino acid substitutions that either altered an N-linked glycosylation (NxS/T) sequon or mapped to a gene related to glycosylation processes. Seven variants were associated with an increased likelihood of liver fibrosis. The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. Although warranting replication, ALPK2 rs3809973 may show utility to detect individuals at increased risk for liver disease progression.
In the general population, lipoprotein(a) [Lp(a)] has been established as an independent causal risk factor for cardiovascular disease. Lp(a) levels are to a major extent regulated by a size polymorphism in the apolipoprotein(a) [apo(a)] gene. The roles of Lp(a)/apo(a) in human immunodeficiency virus (HIV)-related elevated cardiovascular disease risk remain unclear.The associations between total plasma Lp(a) level, allele-specific apo(a) level, an Lp(a) level carried by individual apo(a) alleles, and common carotid artery intima-media thickness were assessed in 150 HIV-infected and 100 HIV-uninfected women in the WIHS (Women's Interagency HIV Study). Linear regression analyses with and without adjustments were used. The cohort was young (mean age, ≈31 years), with the majority being Blacks (≈70%). The prevalence of a small size apo(a) (≤22 Kringle repeats) or a high Lp(a) level (≥30 mg/dL) was similar by HIV status. Total plasma Lp(a) level (P=0.029) and allele-specific apo(a) level carried by the smaller apo(a) sizes (P=0.022) were significantly associated with carotid artery intima-media thickness in the HIV-infected women only. After accounting for confounders (age, race, smoking, body mass index, blood pressure, hepatitis C virus coinfection, menopause, plasma lipids, treatment status, CD4+ T cell count, and HIV/RNA viral load), the association remained significant for both Lp(a) (P=0.035) and allele-specific apo(a) level carried by the smaller apo(a) sizes (P=0.010) in the HIV-infected women. Notably, none of the other lipids/lipoproteins was associated with carotid artery intima-media thickness.Lp(a) and allele-specific apo(a) levels predict carotid artery intima-media thickness in HIV-infected young women. Further research is needed to identify underlying mechanisms of an increased Lp(a) atherogenicity in HIV infection.
