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Association of Suboptimal Antiretroviral Therapy Adherence With Inflammation in Virologically Suppressed Individuals Enrolled in the SMART Study.

ABSTRACT: Suboptimal (ie, <100%) antiretroviral therapy (ART) adherence has been associated with heightened inflammation in cohort studies, even among people with virologic suppression. We aimed to evaluate this association among participants in the Strategies for Management of Antiretroviral Therapy (SMART) study who had virologic suppression (HIV-1 VL < 200 copies/mL) at enrollment. Based on self-reported adherence (7-day recall), plasma concentrations of interleukin 6 and D-dimer were 9% (95% confidence interval [CI], 1%-18%; P = .02) and 11% (95% CI, 1%-22%; P = .03) higher in participants who reported suboptimal vs 100% adherence, respectively. These findings confirm previous observations and support the hypothesis that suboptimal ART adherence, even in the context of virologic suppression, may have significant biological consequences. ClinicalTrials.gov number NCT00027352.

SUBMITTER: Castillo-Mancilla JR

PROVIDER: S-EPMC5772402 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Association of Suboptimal Antiretroviral Therapy Adherence With Inflammation in Virologically Suppressed Individuals Enrolled in the SMART Study.

Castillo-Mancilla Jose R JR Phillips Andrew N AN Neaton James D JD Neuhaus Jacqueline J Collins Simon S Mannheimer Sharon S Pett Sarah S Touzeau-Römer Veronique V Polizzotto Mark N MN Lundgren Jens D JD Gardner Edward M EM

Open forum infectious diseases 20171222 1

Suboptimal (ie, <100%) antiretroviral therapy (ART) adherence has been associated with heightened inflammation in cohort studies, even among people with virologic suppression. We aimed to evaluate this association among participants in the Strategies for Management of Antiretroviral Therapy (SMART) study who had virologic suppression (HIV-1 VL < 200 copies/mL) at enrollment. Based on self-reported adherence (7-day recall), plasma concentrations of interleukin 6 and D-dimer were 9% (95% confidenc ...[more]

PMID: 29362724

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Project description:High levels of adherence to antiretroviral therapy (ART) are necessary for achieving and maintaining optimal virological suppression, as suboptimal adherence leads to therapy failure and disease progression. It is well known that adherence to ART predicts therapy response, but it is unclear whether clinical outcomes of ART predict adherence. To examine the predictive power of current CD4+ T cell count for adherence of HIV-infected individuals to ART, we performed a cross-sectional analysis of 133 Dutch HIV patients with electronically measured adherence. In a multivariate analysis adjusting for a number of sociodemographic and clinical variables, high current CD4+ T cell count (>660 cells/mm3) was most strongly associated with lower adherence to ART (assessed as a continuous variable) during a two-month period immediately following the measurements of variables (P = 0.008). The twice-per-day (versus once-per-day) dosing regimen was also significantly associated with lower adherence (P = 0.014). In a second multivariate analysis aimed at determining the predictors of suboptimal (<100% of the doses taken) adherence, high current CD4+ T cell count was again the strongest independent predictor of suboptimal adherence to ART (P = 0.015), and the twice-per-day dosing regimen remained associated with suboptimal adherence (P = 0.025). The association between suboptimal adherence and virological suppression was significant in patients with high CD4+ T cell counts, but not in patients with low or intermediate CD4+ T cell counts (P = 0.036 and P = 0.52, respectively; P = 0.047 for comparison of the effects of adherence on virological suppression between patients with high vs. low or intermediate CD4+ T cell counts), suggesting that apart from promoting suboptimal adherence, high CD4+ T cell count also strengthens the effect of adherence on virological suppression. Therefore, sustained efforts to emphasize continued adherence are necessary, especially for patients with high CD4+ T cell counts.

Project description:BACKGROUND:The association between HIV and cardiovascular disease (CVD) has been reported in several studies. However, there is paucity of information on the prevalence of subclinical disease as well as its associated risk factors in sub-Saharan African population. The aim of this study was to determine the prevalence and associated risk factors of peripheral artery disease (PAD) among virologically suppressed HIV-infected participants in Kwara State, Nigeria. METHODS:This study was conducted between July 2018 and December 2018. A total of 150 HIV-infected participants aged between 20 and 55 years and 50 HIV non-infected age-matched controls were randomly recruited in the study. Sociodemographic, anthropometric and clinical data were collected using a well-structured questionnaire. Ankle brachial index (ABI) was measured, PAD was defined as ABI of < 0.9. Cryopreserved serum was used to evaluate lipid profile parameters. Student's t-test and Chi-square were used to compare continuous and categorical variables. Associations of CVD risk factors and clinical data, and lipid profile with low ABI were assessed using logistic regression analysis. RESULTS:The study participants had a mean age of 43.73 ± 8.74, majority were females (72.7%) with a mean duration on ART of 7.73 ± 3.52 years. Hypertension was present in 15.9%, diabetes 4%, family history of CVD 8.6% and metabolic syndrome 17.3% in the study group. The study participants recorded significantly lower mean values for ABI, HDL-C and significantly higher mean values of TG (P < 0.05) compared to the control group. The prevalence of low ABI (14.6%) was higher in the study group compared to the control group (2%). A significantly negative correlation between ABI and duration on ART (r = - 0.163, P = 0.041) and a positive correlation between viral load and TG were observed in the study group. TC (OR 1.784, P = 0.011), LDL-C (OR 1.824, P = 0.010) and CD4 cell count < 200 cells/mm3 (OR 2.635, P = 0.364) were associated with low ABI in the participants. CONCLUSION:Viral suppression with combined antiretroviral therapy and long term treatment is associated with dyslipidaemia, with increased risk of PAD. Prevalence of PAD in virologically-suppressed individuals does not differ from the controls in the population studied.

Project description:ObjectivesImmune non-responders (INR) have poor CD4 recovery and are associated with increased risk of serious events despite antiretroviral therapy (ART). A clinically relevant definition for INR is lacking.MethodsWe conducted a retrospective analysis of three large cohorts: Infectious Disease Clinic at the Atlanta Veterans Affairs Medical Center, the US Military HIV Natural History Study and Infectious Disease Program of the Grady Health System in Atlanta, Georgia. Two-stage modeling and joint model (JM) approaches were used to evaluate the association between CD4 (or CD4/CD8 ratio) slope within two years since ART initiation and a composite endpoint (AIDS, serious non-AIDS events and death) after two years of ART. We compared the predictive capacity of four CD4 count metrics (estimated CD4 slope, estimated CD4/CD8 ratio slope during two years following ART initiation and CD4 at 1 and 2 years following ART initiation) using Cox regression models.ResultsWe included 2,422 patients. Mean CD4 slope (±standard error) during two years of ART was 102 ± 2 cells/μl/year (95% confidence interval: 98-106 cells/μl/year), this increase was uniform among the three cohorts (p = 0.80). There were 267 composite events after two years on ART. Using the JM approach, a CD4 slope ≥100 cells/μL/year or CD4/CD8 ratio slope >0.1 higher rate per year were associated with lower composite endpoint rates (adjusted hazard ratio [HR] = 0.80, p = 0.04 and HR = 0.75 p<0.01, respectively). All four CD4 metrics showed modest predictive capacity.ConclusionsUsing a complex JM approach, CD4 slope and CD4/CD8 ratio slope the first two years after ART initiation were associated with lower rates of the composite outcome. Moreover, the uniformity observed in the mean CD4 slope regardless of the cohort suggests a common CD4 response pattern independent of age or CD4 nadir. Given the consistency observed with CD4 slope, availability and ease of interpretation, this study provides strong rationale for using CD4 gains <100 cells/μl/year to identify patients at risk for adverse events.

Project description:BackgroundMissing more than one tablet of contemporary antiretroviral therapy (ART) per month increases the risk of virological failure. Recent studies evaluating a comprehensive range of potential risk factors for suboptimal adherence are not available for high-income settings.MethodsAdults on ART with undetectable viral load (UDVL) were recruited into a national, multi-centre cohort, completing a comprehensive survey assessing demographics, socio-economic indicators, physical health, well-being, life stressors, social supports, HIV disclosure, HIV-related stigma and discrimination, healthcare access, ART regimen, adherence, side effects, costs and treatment beliefs. Baseline data were assessed, and suboptimal adherence was defined as self-reported missing ≥1 ART dose/month over the previous 3-months; associated factors were identified using bivariate and multivariate binary logistic regression.ResultsWe assessed 522 participants (494 [94.5%] men, mean age = 50.8 years, median duration UDVL = 3.3 years [IQR = 1.2-6.8]) at 17 sexual health, hospital, and general practice clinics across Australia. Seventy-eight participants (14.9%) reported missing ≥1 dose/month over the previous three months, which was independently associated with: being Australian-born (AOR [adjusted odds ratio] = 2.4 [95%CI = 1.2-4.9], p = 0.014), not being in a relationship (AOR = 3.3 [95%CI = 1.5-7.3], p = 0.004), reaching the "Medicare safety net" (capping annual medical/pharmaceutical costs) (AOR = 2.2 [95%CI = 1.1-4.5], p = 0.024), living in subsidised housing (AOR = 2.5 [95%CI = 1.0-6.2], p = 0.045), receiving home-care services (AOR = 4.4 [95%CI = 1.0-18.8], p = 0.046), HIV community/outreach services linkage (AOR = 2.4 [95%CI = 1.1-5.4], p = 0.033), and starting ART following self-request (AOR = 3.0 [95%CI = 1.3-7.0], p = 0.012).ConclusionsIn this population, 15% reported recent suboptimal ART adherence at levels associated in prospective studies with subsequent virological failure, despite all having an undetectable viral load. Associations were with social/economic/cultural/patient engagement factors, but not ART regimen/clinical factors. These associations may help identify those at higher risk of future virological failure and guide patient education and support.

Dataset Information

Association of Suboptimal Antiretroviral Therapy Adherence With Inflammation in Virologically Suppressed Individuals Enrolled in the SMART Study.

Publications

Association of Suboptimal Antiretroviral Therapy Adherence With Inflammation in Virologically Suppressed Individuals Enrolled in the SMART Study.

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