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Antiretroviral Therapy Adherence Interruptions Are Associated With Systemic Inflammation Among Ugandans Who Achieved Viral Suppression.

ABSTRACT: BACKGROUND:Residual systemic inflammation, which is associated with non-AIDS clinical outcomes, may persist despite viral suppression. We assessed the effect of antiretroviral therapy (ART) adherence interruptions on systemic inflammation among Ugandans living with HIV who were virally suppressed. SETTING:We evaluated adults initiating first-line ART at a regional referral hospital clinic in Mbarara, Uganda. METHODS:Plasma concentrations of interleukin-6 (IL-6), D-dimer, soluble sCD14, sCD163, the kynurenine/tryptophan (K/T) ratio, and CD8 T-cell activation (HLA-DR/CD38 coexpression) were measured at baseline and 6 months after ART initiation among participants who achieved viral suppression (<400 copies/mL) at 6 months. ART adherence was monitored electronically. Time spent in an adherence interruption was computed as the percentage of days when the running average adherence was ?10%. We fit adjusted linear regressions to evaluate the effect of time spent in an interruption on the log-transformed plasma concentrations of the inflammation biomarkers. RESULTS:Of 282 participants, 70% were women, and the median age was 34 years. At baseline, median CD4 and median log viral load were 135 cells per microliter and 5.1 copies per milliliter, respectively. In the adjusted analysis, a running average adherence of <10% was associated with higher sCD14 (+3%; P < 0.008), sCD163 (+5%; P = 0.002), D-dimer (+10%; P = 0.007), HLA-DR/CD8 (+3%; P < 0.025), IL-6 (+14%; P = 0.008), and K:T ratio (+5%; P = 0.002). These findings were largely robust to adjustment for average adherence, as well as higher thresholds of running average adherence, albeit with decreased statistical significance. CONCLUSIONS:Increased time spent in adherence interruptions is associated with increased levels of inflammation, despite viral suppression above and beyond average adherence.

SUBMITTER: Musinguzi N

PROVIDER: S-EPMC6820698 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Antiretroviral Therapy Adherence Interruptions Are Associated With Systemic Inflammation Among Ugandans Who Achieved Viral Suppression.

Musinguzi Nicholas N Castillo-Mancilla Jose J Morrow Mary M Byakwaga Helen H Mawhinney Samantha S Burdo Tricia H TH Boum Yap Y Muzoora Conrad C Bwana Bosco M BM Siedner Mark J MJ Martin Jeffrey N JN Hunt Peter W PW Bangsberg David R DR Haberer Jessica E JE

Journal of acquired immune deficiency syndromes (1999) 20191201 4

<h4>Background</h4>Residual systemic inflammation, which is associated with non-AIDS clinical outcomes, may persist despite viral suppression. We assessed the effect of antiretroviral therapy (ART) adherence interruptions on systemic inflammation among Ugandans living with HIV who were virally suppressed.<h4>Setting</h4>We evaluated adults initiating first-line ART at a regional referral hospital clinic in Mbarara, Uganda.<h4>Methods</h4>Plasma concentrations of interleukin-6 (IL-6), D-dimer, so ...[more]

PMID: 31658181

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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.

Project description:IntroductionSuccessful management of pediatric and adult human immunodeficiency virus (HIV) disease includes lifelong administration of antiretroviral therapy (ART). The need for the continuous use of antiretroviral drugs throughout the life course poses a challenge to children, adolescents, and adults living with HIV and their caregivers. Historically, treatment interruptions have been viewed as a negative therapeutic strategy. Recently, however, treatment interruptions or treatment reduction strategies have become a focus of investigations as innovative approaches to the long-term management of HIV disease. Current challenges with treatment interruptions include identifying an appropriate timeframe for length of interruptions and identifying HIV patient populations in whom the treatment interruption can be successful.ObjectiveIn this review, we aimed at summarizing recent studies of planned and unplanned treatment interruptions in children and adults living with HIV.Materials and methodsWe searched two databases (PubMed and Cochrane Controlled Trials Register) using keywords (HIV OR AIDS OR acquired immunodeficiency syndrome OR HIV-1 OR antiretroviral) AND (treatment interruption OR planned interruption OR therapeutic interruption OR unplanned interruption), for published randomized and nonrandomized clinical trials and observational cohort studies in children and adults (from birth to 99 years of age) in global settings covering a period from 2012 to 2018. In this review, only the studies that contained pediatric and adolescent populations with baseline immunological, virological, and clinical characteristics and outcomes after treatment interruption were included.ResultsA total of 174 eligible citations from the two databases were identified. We identified 10 prospective treatment interruption studies on children (five studies) and adults (five studies) during 2012-2018 with a total of 863 pediatric and 273 adult subjects. Collectively, recent studies on children and adults with HIV infection suggest that treatment interruptions with proper monitoring can be successful by instituting well-defined immunological and virological parameters or thresholds such as CD4 count, CD4%, and HIV RNA viral load that identify low-risk populations with treatment failure. In addition to standard virological and immunological outcome measurements, selected biomarkers that help detect early immune activation may also be useful in the monitoring of treatment interruption.ConclusionTreatment interruptions in adult and especially pediatric patients with well-controlled HIV disease may provide an alternative opportunity to optimize long-term HIV management by minimizing drug-associated toxicity and improving long-term adherence and quality of life.

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Antiretroviral Therapy Adherence Interruptions Are Associated With Systemic Inflammation Among Ugandans Who Achieved Viral Suppression.

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Antiretroviral Therapy Adherence Interruptions Are Associated With Systemic Inflammation Among Ugandans Who Achieved Viral Suppression.

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