Distinct Lipidomic Signatures in People Living With HIV: Combined Analysis of ACTG 5260s and MACS/WIHS

Author(s):  
Jennifer Jao ◽  
Lauren C Balmert ◽  
Shan Sun ◽  
Grace A McComsey ◽  
Todd T Brown ◽  
...  

Abstract Context Disentangling contributions of HIV from antiretroviral therapy (ART) and understanding the effects of different ART on metabolic complications in persons living with HIV (PLHIV) has been challenging. Objective We assessed the effect of untreated HIV infection as well as different antiretroviral therapy (ART) on the metabolome/lipidome. Methods Widely targeted plasma metabolomic and lipidomic profiling was performed on HIV-seronegative individuals and people living with HIV (PLHIV) before and after initiating ART (tenofovir/emtricitabine plus atazanavir/ritonavir [ATV/r] or darunavir/ritonavir [DRV/r] or raltegravir [RAL]). Orthogonal partial least squares discriminant analysis was used to assess metabolites/lipid subspecies that discriminated between groups. Graphical lasso estimated group-specific metabolite/lipid subspecies networks associated with the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Correlations between inflammatory markers and metabolites/lipid subspecies were visualized using heat maps. Results Of 435 participants, 218 were PLHIV. Compared to HIV-seronegative individuals, ART-naive PLHIV exhibited higher levels of saturated triacylglycerols/triglycerides (TAGs) and 3-hydroxy-kynurenine, lower levels of unsaturated TAGs and N-acetyl-tryptophan, and a sparser and less heterogeneous network of metabolites/lipid subspecies associated with HOMA-IR. PLHIV on RAL vs ATV/r or DRV/r had lower saturated and unsaturated TAGs. Positive correlations were found between medium-long chain acylcarnitines (C14-C6 ACs), palmitate, and HOMA-IR for RAL but not ATV/r or DRV/r. Stronger correlations were seen for TAGs with interleukin 6 and high-sensitivity C-reactive protein after RAL vs ATV/r or DRV/r initiation; these correlations were absent in ART-naive PLHIV. Conclusion Alterations in the metabolome/lipidome suggest increased lipogenesis for ART-naive PLHIV vs HIV-seronegative individuals, increased TAG turnover for RAL vs ATV/r or DRV/r, and increased inflammation associated with this altered metabolome/lipidome after initiating ART. Future studies are needed to understand cardiometabolic consequences of lipogenesis and inflammation in PLHIV.

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S541-S541
Author(s):  
Amber Ladak ◽  
Henry N Young ◽  
Emily Tang ◽  
Jessica Curtis ◽  
Daniel B Chastain

Abstract Background Persons living with HIV (PLWH) are frequently hospitalized for reasons often unrelated to HIV. Transitioning of antiretroviral therapy (ART) while inpatient may not always be an immediate priority due to lack of knowledge, formulary restrictions, and patient status. This could lead to medication errors and gaps in therapy, which can persist at discharge, and could lead to viral rebound and disease progression. The purpose of this study was to identify effects of hospitalization on ART for PLWH. Methods This was an IRB approved, multi-center, retrospective cohort study of patients with HIV and/or AIDS based on ICD codes. Patients were included if they were at least 18 years old, receiving outpatient ART prior to admission, and hospitalized between March 2016 and March 2018. Patients were excluded if they were pregnant and only received intravenous zidovudine during their hospitalization. The primary objective was to determine the rate of ART restarted during hospitalization. Secondary objectives included rate at which inpatient ART was modified compared to outpatient regimen, and risk factors associated with regimen modification. Results Of 400 patients screened, 295 (74%) patients were on an outpatient ART regimen and were included in the study. Approximately half, 51%, were on a single tablet regimen (STR) outpatient. This population was majority male (59%) and of black race (87%). Median age was 49 years. Median CD4 count was 160 cells/mm3, while median HIV RNA for those with detectable viral load was 57,095 copies/mL. 236 of 295 patients (80%) received ART during their inpatient stay. However, 70 (30%) of these patients received a regimen that differed from their outpatient ART regimen. 69% of regimens were modified for reasons other than to optimize therapy. Patient sex, place of admission, and receipt of a STR or multi-tablet regimen (MTR) as an outpatient did not significantly impact rate of regimen modification. Conclusion Ensuring appropriate transition of ART during hospitalization remains an area in need of improvement. No one specific factor was associated with whether outpatient ART was appropriately and accurately restarted during hospitalization. Thus, there are many opportunities to improve transitions of care and antiretroviral stewardship. Disclosures All Authors: No reported disclosures


Author(s):  
Jason J Schafer ◽  
Neha S Pandit ◽  
Agnes Cha ◽  
Emily Huesgen ◽  
Melissa Badowski ◽  
...  

Abstract Background Switching antiretroviral therapy (ART) in people living with HIV (PLWH) can influence their risk for drug-drug interactions (DDIs). The purpose of this study was to assess changes in the incidence and severity of DDIs among PLWH who switched their ART to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). Methods This was a multicenter retrospective cohort study of PLWH on ART and at least one concomitant medication (CM) who switched to BIC/FTC/TAF between 3/2018 and 6/2019. Using the University of Liverpool’s HIV Drug Interaction Database, two DDI analyses were performed for each patient. The first assessed patients’ pre-switch ART regimens with their CM list. The second assessed the same CM list with BIC/FTC/TAF. Each ART-CM combination was given a score of zero (no or potential weak interaction), one (potential interaction), or two (contraindicated interaction). A paired t-test analyzed changes in total DDI scores following ART switches and linear regression examined factors contributing to DDI score reductions. Results Among 411 patients, 236 (57%) had at least one DDI present at baseline. On average, baseline DDI scores were 1.4 (SD 1.8) and decreased by 1-point (95% CI -1.1,-0.8) after patients switched to BIC/FTC/TAF (p < 0.0001). After adjusting for demographics, baseline ART and CM categories, switching to BIC/FTC/TAF led to significant DDI score reductions in patients receiving CMs for cardiovascular disease, neurologic/psychiatric disorders, chronic pain, inflammation, gastrointestinal/urologic conditions and conditions requiring hormonal therapy. Conclusion Treatment-experienced PLWH eligible to switch their ART, may experience significant declines in their number and severity of DDIs if switched to BIC/FTC/TAF.


2016 ◽  
Vol 3 (2) ◽  
pp. 96
Author(s):  
Siti Qamariyah Khairunisa ◽  
Irine Normalina ◽  
Nasronudin Nasronudin

Antiretroviral drug discovery has encouraged a revolution in the care of people living with HIV, although it has not been able to cure diseases and to increase the challenge in terms of drug side effects. Side effects of antiretroviral drugs are fairly common occurrences in HIV patients and generally occur within the first three months after initiation of antiretroviral therapy, although long-term side effects are also often found afterwards. This study aims to evaluate the number of CD4 T-cells in patients with AIDS before and after getting on ARV therapy and side effects arising during the taking of ARVs. Samples were collected from 10 patients infected by HIV/AIDS in a clinic in Surabaya. This study is an analytical survey. Data collection was conducted using secondary data obtained from the medical record card status on HIV paients in a clinic in Surabaya. Data results showed that the side effects that often occur in people with AIDS are appetite loss (90%), headache (80%), insomnia (80%) and nausea (70%). While many combinations of antiretroviral drugs have side effects such as a combination of AZT +3 TC + EFV, d4T +3 TC + followed by EFV and AZT +3 TC + NVP. The present study shows that combination antiretroviral therapy gives good results to the increased number of CD4 T-cellsin patients living with HIV, as shown by the tendency of an increase in the number of CD4 T-cells in 8 out of 10 AIDS patients who received a antiretroviral therapy.


2016 ◽  
Vol 3 (2) ◽  
pp. 92
Author(s):  
Edith Frederika ◽  
Irine Normalina ◽  
Nasronudin Nasronudin ◽  
Rury Mega

Antiretroviral drug discovery has encouraged a revolution in the care of people living with HIV, although it has not been able to cure diseases and to increase the challenge in terms of drug side effects. Side effects of antiretroviral drugs are fairly common occurrences in HIV patients and generally occurr within the first three months after initiation of antiretroviral therapy, although long-term side effects are also often found afterwards. This study aims to evaluate the number of CD4 T-cells in patients with AIDS before and after getting on ARV therapy, the side effects arising during the taking of ARVs are related to the increment of body weight among the HIVAIDS patients. Subjects were then narrowed down from 25 to 12 due to the incomplete data. The results showed that the top three most side effects which often occur in people with AIDS are appetite loss (20.0%), nausea (17.8%), and diarrhoea (15.6%). Meanwhile, about 58% of the subjects experienced increment of their body weight, and 42% were losing weight due to the side effects of the ARV therapy. Among those who lost their body weight, 50% were in the productive ages between 21–30 years old. The present study shows that combination antiretroviral therapy gives good results to the increased number of CD4 T-cells in patients living with HIV, as shown by the tendency of an increment in the number of CD4 T-cells in patients who received antiretroviral therapy. However, around 42% of those patients were losing weight because of the side effects of the therapy. Therefore, the importance of giving specific nutrient to overcome with the weight loss is needed to be given to the patients HIV instead of only giving the ARV treatment.


2015 ◽  
Vol 1 (1) ◽  
pp. 1-10
Author(s):  
Jit B. Darnal ◽  
Pawinee Doung-ngern ◽  
Lungten Z. Wangchuk ◽  
Mongal S. Gurung ◽  
Witaya Swaddiwudhipong

Introduction: A total of 217 HIV positive cases have been reported in Bhutan as of 2010. A descriptive study toassess the knowledge and behavioral practices among 116 of those persons living with HIV (PLHIV) was conducted in 2011. Methods: Data on demographic characteristics, sexual behavior, alcohol consumption: mobility and HIVknowledge both before and after testing positive for HIV were collected. Responses regarding behavior before and after HIV diagnosis were compared. Results: Of 116 participants, 52.6% were males; a majority of male PLHIV (72.1%) belonged to salaried group of people while housewife represented 47.3% among female respondents. Fortythree percent of male and 5.5% of female participants reported having exchange sex and 52.5% of male and 41.8% of female participants reported having non-exchange sex partners before HIV diagnosis. The consistent condom use had significantly increased after HIV diagnosis among males with exchange (12% vs. 60%, p=.04) and non-exchange (13% vs. 100%, p<.001) partners. Eighty-four percent of male and 61.8% of female participants reported consuming alcohol before HIV diagnosis. Only one male respondent reported injection drug use before HIV. There was a decrease in incidence of sexually transmitted infection (56.9% vs. 31.9%) after HIV diagnosis. Forty-three percent of males had traveled abroad before HIV diagnosis; among those, 30.8% reported having exchange sex while abroad. Conclusions: Our findings indicated that high-risk sexual behavior was common before HIV diagnosis and that sexual practices changed after diagnosis. Educational campaigns aimed at increasing HIV knowledge and safe sex, are critical to reduce HIV infections in Bhutan.


2021 ◽  
Vol 6 (2) ◽  
pp. 60-89
Author(s):  
Jimena Salido ◽  
Alejandro Czernikier ◽  
Cesar Trifone ◽  
María Laura Polo ◽  
María Ines Figueroa ◽  
...  

Background: Combined antiretroviral treatment (cART) for HIV infection is highly effective in controlling viral replication. However, it cannot achieve a sterilizing cure.  Several strategies have been proposed to achieve a functional cure, some of them based on immune-mediated clearing of persistently infected cells. Here, we aimed at identifying factors related to CD8TC and CD4TC quality before cART initiation that associate with the persistence of CD8TC antiviral response after cART, inflammation levels, and the size of the viral reservoir. Methods: Samples from 25 persons living with HIV were obtained before and after (15 months) cART initiation. Phenotype and functionality of bulk and HIV-specific T cells were assayed by flow cytometry ex vivo or after expansion in pre-cART or post-cART samples, respectively. Cell-Associated (CA) HIV DNA (total and integrated) and RNA (unspliced [US] and multiple spliced [MS]) were quantitated by real-time PCR on post-cART samples. Post-cART plasma levels of CXCL10 (IP-10), soluble CD14 (sCD14) and soluble CD163 (sCD163) were measured by ELISA.  Results: Pre-cART phenotype of CD8TCs and magnitude and phenotype of HIV-specific response correlated with the phenotype and functionality of CD8TCs post-cART. Moreover, the phenotype of the CD8TCs pre-cART correlated with markers of HIV persistence and inflammation post-cART. Finally, exhaustion and differentiation of CD4TCs pre-cART were associated with the composition of the HIV reservoir post-cART and the level of inflammation. Conclusions: Overall, this work provides data to help understand and identify parameters that could be used as markers in the development of immune-based functional HIV cure strategies.


Author(s):  
Tobias Broger ◽  
Bianca Sossen ◽  
Elloise du Toit ◽  
Andrew D. Kerkhoff ◽  
Charlotte Schutz ◽  
...  

2020 ◽  
Vol 18 (6) ◽  
pp. 388-395
Author(s):  
Daniel Vargas-Pacherrez ◽  
Helma P. Cotrim ◽  
Leonardo Pires ◽  
Vitor Cunha ◽  
Vitor Coelho ◽  
...  

Introduction: The global prevalence of metabolic syndrome (MS) among people living with HIV/AIDS varies from 20% to 33%. Objective: to estimate the prevalence of metabolic syndrome and associated factors in a group of HIV-infected patients on antiretroviral therapy. Methods: This is a cross-sectional study with HIV-infected patients from a reference center in Bahia, Brazil. We evaluated clinical, socio-demographic and anthropometric data. MS was defined according to the guidelines of International Diabetes Federation. Results: We evaluated 152 patients with mean age of 47.3±11.6 years, 59.2% male. The main comorbidities detected were diabetes (3.3%) hypertriglyceridemia (9.3%) and metabolic syndrome (MS,38.2%). Patients with MS were predominantly women (55.2% vs 31.9%; p=0.005), older [52.1 (10.4) vs 44.3 (11.3); p<0.001], and had overweight (74.1% vs 23.4%; p<0.001). After multivariate analysis MS remained associated with age (OR = 1.076; 95% CI: 1.030 – 1.125), female sex (OR = 2.452; 95% CI: 1.114 – 5.374) and family history of hypertension (OR = 3.678; 95% CI: 1.431 – 9.395). Conclusion: Almost half of the HIV-infected patients in Bahia presents with MS which seems to be driven by classical risk factors.


2019 ◽  
Author(s):  
Jenevieve Opoku ◽  
Rupali K Doshi ◽  
Amanda D Castel ◽  
Ian Sorensen ◽  
Michael Horberg ◽  
...  

BACKGROUND HIV cohort studies have been used to assess health outcomes and inform the care and treatment of people living with HIV disease. However, there may be similarities and differences between cohort participants and the general population from which they are drawn. OBJECTIVE The objective of this analysis was to compare people living with HIV who have and have not been enrolled in the DC Cohort study and assess whether participants are a representative citywide sample of people living with HIV in the District of Columbia (DC). METHODS Data from the DC Health (DCDOH) HIV surveillance system and the DC Cohort study were matched to identify people living with HIV who were DC residents and had consented for the study by the end of 2016. Analysis was performed to identify differences between DC Cohort and noncohort participants by demographics and comorbid conditions. HIV disease stage, receipt of care, and viral suppression were evaluated. Adjusted logistic regression assessed correlates of health outcomes between the two groups. RESULTS There were 12,964 known people living with HIV in DC at the end of 2016, of which 40.1% were DC Cohort participants. Compared with nonparticipants, participants were less likely to be male (68.0% vs 74.9%, <i>P</i>&lt;.001) but more likely to be black (82.3% vs 69.5%, <i>P</i>&lt;.001) and have a heterosexual contact HIV transmission risk (30.3% vs 25.9%, <i>P</i>&lt;.001). DC Cohort participants were also more likely to have ever been diagnosed with stage 3 HIV disease (59.6% vs 47.0%, <i>P</i>&lt;.001), have a CD4 &lt;200 cells/µL in 2017 (6.2% vs 4.6%, <i>P</i>&lt;.001), be retained in any HIV care in 2017 (72.9% vs 59.4%, <i>P</i>&lt;.001), and be virally suppressed in 2017. After adjusting for demographics, DC Cohort participants were significantly more likely to have received care in 2017 (adjusted odds ratio 1.8, 95% CI 1.70-2.00) and to have ever been virally suppressed (adjusted odds ratio 1.3, 95% CI 1.20-1.40). CONCLUSIONS These data have important implications when assessing the representativeness of patients enrolled in clinic-based cohorts compared with the DC-area general HIV population. As participants continue to enroll in the DC Cohort study, ongoing assessment of representativeness will be required.


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