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Introduction: Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS), a measure of cumulative antiretroviral therapy (ART) adherence, is associated with viral suppression and predicts future viremia in persons with HIV (PWH). However, its utility to identify those at risk for virologic failure (VF) and drug resistance is unknown. To address this, we aimed to establish the association between this adherence biomarker and VF with drug resistance in a cohort of PWH initiating first-line ART in KwaZulu-Natal, South Africa. Methods: PWH initiating TFV disoproxil fumarate (TDF)-based ART within a parent prospective cohort were evaluated. Using a nested design, DBS for TFV-DP were collected from cases who developed VF (HIV-1 RNA [greater than or equal to]1000 copies/ml) after [greater than or equal to]5 months on ART versus controls, matched 1:2 by site, age, gender, race and ART duration. Cases were categorized as having VF with or without resistance using genotyping. One-way analysis of variance (ANOVA) was used to compare TFV-DP for controls, cases with VF and resistance, and cases with VF without resistance. Data are presented as mean (standard deviation, SD) or geometric mean [95% confidence interval, 95% CI]. Results and discussion: One thousand participants were enrolled in the parent study between 2014 and 2016, of which 288 (29%) had DBS available. Of these, 94 (33%) were cases and 194 (67%) were controls; 59% were women. Mean age of our population was 33 (SD 8) years. Genotyping was available in 50 (53%) of the 94 cases. Geometric mean TFV-DP in DBS from controls was 708 [95% CI; 647-773] fmol/punch, which was higher compared to participants having VF with resistance (n = 36), 386 [95% CI; 241-617] fmol/punch and VF without resistance (n = 14), 61 [95% CI; 22-164] fmol/punch; p Conclusions: TFV-DP in DBS showed a stepwise association with VF and drug resistance in South African PWH. Participants having VF with resistance had mid-range concentrations of TFV-DP, which were higher than those for PWH without resistance. Future research on the clinical utility of TFV-DP concentrations in DBS to predict and prevent the development of VF and drug resistance is needed. Keywords: adherence; dried blood spots; HIV resistance; South Africa; tenofovir diphosphate; viral failure, 1 | INTRODUCTION Although current antiretroviral therapy (ART) is highly effective, durable adherence remains necessary to sustain viral suppression in persons with HIV (PWH). Unfortunately, up to 30-40% of PWH [...]

Background Food insecurity has been linked to suboptimal antiretroviral therapy (ART) adherence in persons with HIV (PWH). This association has not been evaluated using tenofovir diphosphate (TFV-DP) in dried blood spots (DBSs), a biomarker of cumulative ART adherence and exposure. Methods Within a prospective South African cohort of treatment-naive PWH initiating ART, a subset of participants with measured TFV-DP in DBS values was assessed for food insecurity status. Bivariate and multivariate median-based regression analysis compared the association between food insecurity and TFV-DP concentrations in DBSs adjusting for age, sex, ethnicity, medication possession ratio (MPR), and estimated glomerular filtration rate. Results Drug concentrations were available for 285 study participants. Overall, 62 (22%) PWH reported worrying about food insecurity and 44 (15%) reported not having enough food to eat in the last month. The crude median concentrations of TFV-DP in DBSs differed significantly between those who expressed food insecurity worry versus those who did not (599 [interquartile range {IQR}, 417–783] fmol/punch vs 716 [IQR, 453–957] fmol/punch; P =.032). In adjusted median-based regression, those with food insecurity worry had concentrations of TFV-DP that were 155 (95% confidence interval, −275 to −35; P =.012) fmol/punch lower than those who did not report food insecurity worry. Age and MPR remained significantly associated with TFV-DP. Conclusions In this study, food insecurity worry is associated with lower TFV-DP concentrations in South African PWH. This highlights the role of food insecurity as a social determinant of HIV outcomes including ART failure and resistance. [ABSTRACT FROM AUTHOR]

Objectives: HIV virological failure remains a major threat to programme success in sub‐Saharan Africa. While HIV drug resistance (HIVDR) and inadequate adherence are the main drivers of virological failure, the individual, clinical and health system characteristics that lead to poor outcomes are not well understood. The objective of this paper is to identify those characteristics among people failing first‐line antiretroviral therapy (ART). Methods: We enrolled a cohort of adults in HIV care experiencing virological failure on first‐line ART at five sites and used standard statistical methods to characterize them with a focus on three domains: individual/demographic, clinical, and health system, and compared each by country of enrolment. Results: Of 840 participants, 51% were women, the median duration on ART was 3.2 years [interquartile range (IQR) 1.1, 6.4 years] and the median CD4 cell count prior to failure was 281 cells/µL (IQR 121, 457 cells/µL). More than half of participants [53%; 95% confidence interval (CI) 49–56%] stated that they had > 90% adherence and 75% (95% CI 72–77%) took their ART on time all or most of the time. Conversely, the vast majority (90%; 95% CI 86–92%) with a completed genotypic drug resistance test had any HIV drug resistance. This population had high health system use, reporting a median of 3 (IQR 2.6) health care visits and a median of 1 (IQR 1.1) hospitalization in the preceding 6 months. Conclusions: Patients failing first‐line ART in sub‐Saharan Africa generally report high rates of adherence to ART, have extremely high rates of HIV drug resistance and utilize significant health care resources. Health systems interventions to promptly detect and manage treatment failure will be a prerequisite to establishing control of the HIV epidemic. [ABSTRACT FROM AUTHOR]

Purpose: Elevated levels of inflammation associated with human immunodeficiency virus (HIV) infection are one of the primary causes for the burden of age-related diseases among people with HIV (PWH). Circulating proteins can be used to investigate pathways to inflammation among PWH., Experimental Design: We profiled 73 inflammation-related protein markers and assessed their associations with chronological age, sex, and CD4 + cell count among 87 black South African PWH before antiretroviral therapy (ART)., Results: We identified 1, 1, and 14 inflammatory proteins significantly associated with sex, CD4 + cell count, and age respectively. Twelve out of 14 age-associated proteins have been reported to be associated with age in the general population, and 4 have previously shown significant associations with age for PWH. Furthermore, many of the age-associated proteins such as CST5, CCL23, SLAMF1, MMP-1, MCP-1, and CDCP1 have been linked to chronic diseases such as cardiovascular disease and neurocognitive decline in the general population. We also found a synergistic interaction between male and older age accounting for excessive expression of CST5., Conclusions and Clinical Relevance: We found that advanced age may lead to the elevation of multiple inflammatory proteins among PWH. We also demonstrated the potential utility of proteomics for evaluating and characterizing the inflammatory status of PWH., (© 2023 Wiley-VCH GmbH.)