Brief Report: Higher ART Adherence Is Associated With Lower Systemic Inflammation in Treatment-Naive Ugandans Who Achieve Virologic Suppression

Castillo‐Mancilla, José; Morrow, Mary; Boum, Yap; Byakwaga, Helen; Haberer, Jessica; Martin, Jeffrey N.; Bangsberg, David R.; MaWhinney, Samantha; Musinguzi, Nicholas; Huang, Yong; Tracy, Russell P.; Burdo, Tricia H.; Williams, Kenneth C.; Muzzora, Conrad; Hunt, Peter W.; Siedner, Mark J.

doi:10.1097/qai.0000000000001629

Cited by 30 publications

(22 citation statements)

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“…ARV adherence was determined through self-report, using the following question: ‘In the past month, how many days did you miss a dose of your ARVs?’ One month recall of ARV adherence is associated with objective measures of adherence (see the ‘Limitations’ section) (Buscher et al ., 2011 ). While we are aware that with modern ARV treatment, viral suppression can be achieved with only 80–84% adherence (Viswanathan et al ., 2015 ), in light of emerging data showing that even in the setting of viral suppression, suboptimal (<100%) adherence correlates with significant clinical outcomes, including higher inflammation and residual viral replication (Li et al ., 2014 ; Castillo-Mancilla et al ., 2018 a , b ), we opted for a stringent definition of adherence, using a bivariate model assessing adherence over the past month in which 1 = no missed doses and 0 = doses missed.…”

Section: Methodsmentioning

confidence: 99%

East African HIV care: depression and HIV outcomes

Meffert

Neylan²,

McCulloch

et al. 2019

Glob. Ment. Health

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Importance.Depression is a common co-morbidity for people living with HIV (PLWH) and is associated with elevated plasma HIV RNA levels. While depression correlates with deficits in antiretroviral (ARV) adherence, little data exist to inform the relationship between depression and HIV vial load more broadly.Objective.To examine the relationship between depression and viral load in the African Cohort Study (AFRICOS) independently of ARV adherence.Design.PLWH in Kenya, Uganda and Tanzania underwent screening for depression using the Center for Epidemiologic Studies Depression Scale (CESD) upon enrollment at AFRICOS HIV care sites.Setting.AFRICOS is an ongoing prospective longitudinal cohort study enrolling HIV-infected adults at HIV care centers including sites in Kenya, Tanzania and Uganda. These sites are administered by President's Emergency Plan For AIDS Relief programs.Participants.HIV+ individuals were eligible if they were at least 18 years old, receiving HIV care at the enrolling clinic and consented to data and specimen collection.Main outcome measure.CESD.Results.Among 2307 participants, 18–25% met the CESD threshold for depression. Depression was associated with decreased ARV adherence (OR 0.59, p = 0.01). Higher scores on three CESD items were significantly associated with 209–282% higher viral load, independently of ARV adherence among participants on ARVs ⩾6 months.Conclusions.PLWH had high prevalence of depression on the CESD. Diverse depression symptoms were independently associated with increases in viral load, underscoring the need for comprehensive treatment of depression.

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Section: Methodsmentioning

confidence: 99%

East African HIV care: depression and HIV outcomes

Meffert

Neylan²,

McCulloch

et al. 2019

Glob. Ment. Health

View full text Add to dashboard Cite

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“…Non-virologic parameters associated with excess risk of mortality, such as increased bacterial translocation or inflammation (9,10), are often assumed to be a consequence of the immune damage elicited by acute HIV infection, but no longer affected by HIV replication in individuals on ART. However, even during HIV RNA suppression in PWH, a lower ART adherence to 3-drug regimens (3DR) is associated with increased levels of inflammatory biomarkers, suggesting that a decrease in drug concentrations results in virologic phenomena in tissues, not detected in plasma, that elicit immune activation (11)(12)(13). Mounting evidence generated in SIV-infected macaques, HIVinfected humanized mice, and humans indicates that antiretrovirals are distributed very heterogeneously within lymphoid tissues (14,15).…”

Section: Introductionmentioning

confidence: 99%

Long-Term Changes of Inflammatory Biomarkers in Individuals on Suppressive Three-Drug or Two-Drug Antiretroviral Regimens

et al. 2022

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BackgroundBecause inflammation is associated with mortality and has been linked to HIV transcription in lymphoid tissues during ART, it is necessary to address the long-term effects of switching 3-drug (3DR) to 2-drug regimens (2DR) on inflammation.MethodsNested study in the Spanish AIDS Research Network. We selected PWH ART-naive initiating 3DR who achieved viral suppression in the first 48 weeks and either remained on 3DR or switched to 2DR (3TC+bPI; 3TC+DTG; DTG+RPV). We assessed the trajectories on inflammatory markers during ART using multivariate piecewise mixed models.ResultsWe analyzed 619 plasma samples from 148 patients (3DR, N=90; 2DR, N=58), the median follow-up was 4.6 (IQR 3.2-6.2) years. There were no significant differences in baseline characteristics between groups. After adjusting for potential confounders, patients with 3DR experienced a slow decline of IL6, hs-CRP, sCD14, sCD163, and D-dimer over time. In contrast, compared to 3DR, switching to 2DR was associated with increases in IL-6 (p=0.001), hs-CRP (p=0.003), and D-dimer (p=0.001) after year 3 from virologic suppression. 2DR was associated with a higher risk of hs-CRP quartile increase (aOR 3.3, 95%CI 1.1-10) and D-dimer quartile increase (aOR 3.7, 95%CI 1.1-13). The adjusted biomarker trajectories did not reveal a distinct pattern according to the type of 2DR used (bPI vs DTG).ConclusionsIn this study in virally suppressed individuals, maintaining 3DR was associated with a more favorable long-term inflammatory profile than switching to 2DR. The potential clinical implications of these findings on the development of non-AIDS events deserve further investigation.

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“…While long-term ART, particularly with use of specific antiretroviral drugs, has been associated with some metabolic complications, including hyperlipidemia and myocardial infarction [ 12 , 13 ], ART also has beneficial effects in decreasing inflammatory and coagulation biomarkers. Studies have shown declines in D-dimer levels following treatment initiation, and have further demonstrated that delayed ART, poor treatment adherence and interruption of ART may contribute to elevated coagulation markers and increased risk of death [ 4 , 14 – 16 ]. Nonetheless, compared to HIV-negative persons, higher D-dimer levels have been shown to persist even in PLHIV who maintain viral suppression on long-term ART [ 14 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Changes in D-dimer after initiation of antiretroviral therapy in adults living with HIV in Kenya

et al. 2020

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Background: Increased coagulation biomarkers are associated with poor outcomes among people living with HIV (PLHIV). There are few data available from African cohorts demonstrating the effect of antiretroviral therapy (ART) on coagulation biomarkers. Methods: From March 2014 to October 2014, ART-naïve PLHIV initiating non-nucleoside reverse transcriptase inhibitorbased ART were recruited from seven clinics in western Kenya and followed for up to 12 months. Demographics, clinical history and blood specimens were collected. Logistic regression models adjusted for intrasite clustering examined associations between HIV viral load and D-Dimer at baseline. Mixed linear effects models were used to estimate mean change from baseline to 6 months overall, and by baseline viral load, sex and TB status at enrollment. Mean change in D-dimer at 6 months is reported on the log10 scale and as percentage change from baseline. Results: Among 611 PLHIV enrolled, 66% were female, median age was 34 years (interquartile range (IQR) 29-43 years), 31 (5%) participants had tuberculosis and median viral load was 113,500 copies/mL (IQR: 23,600-399,000). At baseline, 311 (50.9%) PLHIV had elevated D-dimer (> 500 ng/mL) and median D-dimer was 516.4 ng/mL (IQR: 302.7-926.6) (log baseline D-dimer: 2.7, IQR: 2.5-3.0). Higher baseline D-dimer was significantly associated with higher viral load (p < 0.0001), female sex (p = 0.02) and tuberculosis (p = 0.02). After 6 months on ART, 518 (84.8%) PLHIV had achieved viral load < 1000 copies/mL and median D-dimer was 390.0 (IQR: 236.6-656.9) (log D-dimer: 2.6, IQR: 2.4-2.8). Mean change in log D-dimer from baseline to 6 months was − 0.12 (95%CI −0.15, − 0.09) (p < 0.0001) indicating at 31.3% decline (95%CI −40.0, − 23.0) in D-dimer levels over the first 6 months on ART. D-dimer decline after ART initiation was significantly greater among PLHIV with tuberculosis at treatment initiation (− 172.1, 95%CI −259.0, − 106.3; p < 0.0001) and those with log viral load > 6.0 copies/mL (− 91.1, 95%CI −136.7, − 54.2; p < 0.01). Conclusions: In this large Kenyan cohort of PLHIV, women, those with tuberculosis and higher viral load had elevated baseline D-dimer. ART initiation and viral load suppression among ART-naïve PLHIV in Kenya were associated with significant decrease in D-dimer at 6 months in this large African cohort.

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Brief Report: Higher ART Adherence Is Associated With Lower Systemic Inflammation in Treatment-Naive Ugandans Who Achieve Virologic Suppression

Cited by 30 publications

References 50 publications

East African HIV care: depression and HIV outcomes

East African HIV care: depression and HIV outcomes

Long-Term Changes of Inflammatory Biomarkers in Individuals on Suppressive Three-Drug or Two-Drug Antiretroviral Regimens

Changes in D-dimer after initiation of antiretroviral therapy in adults living with HIV in Kenya

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