Search

Objective adherence measures are of increasing interest in antiretroviral treatment (ART) monitoring. Hair ART levels predict virologic suppression, and hair is easy to collect and store. No previous study has examined hair levels in an India-based cohort or laboratory.Small hair samples were collected from HIV-positive participants on either efavirenz (EFV)-based or nevirapine (NVP)-based ART in a South India-based study. Hair samples were split and analyzed for EFV or NVP in the University of California, San Francisco -based Hair Analytical Laboratory and the analytic laboratory of the Division of Nutrition at St. John's Research Institute, Bangalore, India, using liquid chromatography/tandem mass spectrometry. Agreement (using Bland-Altman methods) and rank correlation between the 2 laboratories' hair levels were calculated. Rank correlation between self-reported adherence (SRA) over the previous month using a visual analog scale and hair ART levels was calculated.Among 75 participants (38 on NVP; 37 on EFV), the correlation between NVP levels generated by the 2 laboratories was 0.66 (P0.0001) and between EFV levels was 0.87 (P0.0001). Measurements from St. John's Research Institute were usually within 20% of those from the University of California, San Francisco Hair Analytical Laboratory. SRA was essentially uncorrelated with hair antiretroviral levels for either drug (all correlations0.04). Hair levels showed variability in adherence although SRA was85% in all participants.Hair ART levels measured by both an India-based laboratory and the standard U.S.-based laboratory showed generally high agreement and correlation, demonstrating local capacity. As in many other cohorts, hair ART levels and SRA were not well-correlated, likely indicating limitations in self-report and the need for objective adherence monitoring in resource-limited settings.

Cases of seroconversion on pre-exposure prophylaxis (PrEP) should be carefully investigated, given their public health implications and rarity. We report a case of transmitted drug resistance causing seroconversion on PrEP in spite of high adherence, confirmed with dried blood spot and segmental hair drug-level testing and single-genome sequencing.

BackgroundChildren/adolescents display suboptimal antiretroviral therapy (ART) adherence and outcomes versus adults. Hair ART concentrations are objective adherence measures that predict viremia in adults but longitudinal data on hair levels in pediatric populations is limited. We assessed the predictive utility of hair lopinavir (LPV) levels on viremia among youth on second-line ART.MethodsWe examined predictors of viremia (HIV-1 RNA >400 and >1000 copies/mL) at least 24 weeks after switch to LPV-based second-line ART in a cohort of HIV-infected Asian children followed between 2011 and 2014. Small hair samples, HIV-1 RNA, and self-reported adherence were collected biannually. Hair concentrations of LPV were measured through liquid chromatography/tandem mass spectrometry using validated methods. Time-to-first viremia was examined using discrete-time Cox models.ResultsOverall, 244 children met the inclusion criteria for the present analysis. Approximately half (55%) were boys and the median age 10 years [interquartile range (IQR) 7-13]; 40% were older than 11 years. At switch to second-line ART, median CD4 count was 300 (IQR 146-547) cells/mm and median HIV-RNA level was 5.0 (IQR 4.3-5.6) log10/mL. Median time of study follow-up was 48 weeks and a median of 3 (range 1-5) hair samples were collected from each participant. Adjusting for age, sex, country, self-reported adherence, CD4, and HIV-RNA, higher LPV hair concentrations were the strongest predictor of lower odds of viremia (HIV-RNA >400 copies/mL adjusted odds ratio = 0.41 per doubling in hair concentration, 95% confidence interval: 0.29 to 0.58, P < 0.001; HIV-RNA >1000 copies/mL, adjusted odds ratio = 0.54, 95% confidence interval: 0.45 to 0.65, P < 0.001).ConclusionsHair concentrations predict viremia among children with HIV on second-line ART and could guide clinical decisions for this population.

BACKGROUND Antiretroviral treatment (ART) adherence is often suboptimal in the perinatal period. We measured hair tenofovir (TFV) concentrations as a metric of adherence in postpartum women to understand patterns and predictors of adherence throughout this critical period. In addition, we examined the association between hair TFV concentrations and virologic outcomes. METHODS Between 12/2012 and 09/2016, hair samples were collected longitudinally from delivery through breastfeeding from women on ART in the Promoting Maternal and Infant Survival Everywhere study (NCT01061151) in sub-Saharan Africa. Hair TFV levels were measured using validated methods. Using generalized estimating equations, we estimated the association between hair TFV levels and virologic suppression (

Concentrations of antiretrovirals in hair are associated with virologic outcomes in cohorts of human immunodeficiency virus (HIV)-positive individuals but have never been examined in a clinical trial. We show for the first time the predictive utility of hair antiretroviral concentrations in a large HIV treatment-naive trial (AIDS Clinical Trials Group protocol A5257).

Data on the relationship of antiretroviral exposure to measures of human immunodeficiency virus (HIV) persistence are limited. To address this gap, multiple viral, immunologic, and pharmacologic measures were analyzed from individuals with sustained virologic suppression on therapy (median 7 years) in the AIDS Clinical Trials Group A5321 cohort. Among 110 participants on tenofovir-(TFV)-disoproxil-fumarate (TDF)/emtricitabine (FTC)-containing regimens, we found no significant correlation between hair concentrations of individual antiretrovirals (ARVs) in the regimen and measures of HIV persistence (plasma HIV-1 RNA by single copy assay, cell-associated-DNA, cell-associated RNA) or soluble markers of inflammation. These findings suggest that higher systemic ARV exposure may not impact HIV persistence or inflammation.

Aims: mesenchymal stromal/stem cells (MSCs) is one of the most promising cell therapies to treat immune related diseases such as GvHD, Crohn's disease, osteoarthritis as well as to support function of heart, liver, and central nervous system. Many advanced clinical trials has been taking place to investigate the safety and efficacy of MSC therapy, however, it remains challenging to compare the results of these trials due to variations in culture conditions and tissue origins. These variations pose the urgent need of a standardized large-scale production and quality control of these cells become more urgent, as the use of MSCs are spreading around the globe and disease backgrounds. Numerous culture protocols for MSCs are available using FBS-containing, human platelet lysate/plasma supplementing, or serum-free xeno-free condition, either commercial or self-prepared media. In this study, we have established a standardized expansion protocol that can be used for MSCs derived from bone marrow (BM), adipose tissue (AD), and umbilical cord (UC). Methods: we tested commercial xeno-free, serum-free media (MesenCult™-ACF Plus Medium/Stem Cell Technologies, MSC NutriStem® XF Medium/BI, Stempro® MSC SFM Medium/ThermoFisher, PowerStem MSC1 Medium/PAN, and StemMACS™ MSC Expansion Media/Miltenyi) in order to identify a common culture condition for all of these MSC sources. The cells were analysed for their population doubling time from P2 to P6, expression of surface markers including the positive markers CD73, CD90, and CD105, and the negative markers CD34, CD45, CD11b, CD19, and HLA-DR. Karyotype was conducted at early and later passage (P3 and P6, respectively). MSCs were tested for their differentiation capacity into osteoblast/osteocyte, adipocyte, and chondrocyte lineages. Bacterial and fungal sterility and mycoplasma test were performed and endotoxin concentration was determined before the cells were transfused into patients. Results: using UC for the primary screening, we identified two medium candidates that supported the isolation and culture of UC-MSCs. MSCs derived from BM and AD are capable of expansion in these media as well. However, one candidate induced an increased HLA-DR expression so that it failed to fulfill the minimal criteria of MSCs (Dominici et al., 2006). The last one showed the best results for MSCs from all tested tissues. Under our established protocol, MSCs grew exponentially until P6, which was the highest analyzed passage. The cells expressed CD73, CD90, CD105 in more than 95% cells and showed less than 2% of negative markers (CD34, CD45, CD11b, CD19, and HLA-DR). Karyotype analysis confirmed no chromosomal aberrations of the cultured cells. The cells were able to differentiate into osteoblast/osteocyte, adipocyte, and chondrocyte lineages. We are now conducting phase 1 clinical trial to address the safety and feasibility of UC-MSCs in the treatment of bronchopulmonary dysplasia and chronic obstructive pulmonary disease. Conclusion: we have established a standardized protocol for the xeno-free, serum-free culture of MSCs from different sources. BM-, AD-, and UC-derived MSCs expand in large-scale and maintain their cellular characteristics, karyotype integrity, and can be applied for cell therapy. Disclosures No relevant conflicts of interest to declare.