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Treated HIV Infection and Progression of Carotid Atherosclerosis in Rural Uganda: A Prospective Observational Cohort Study.
Siedner, MJ, Bibangambah, P, Kim, JH, Lankowski, A, Chang, JL, Yang, IT, Kwon, DS, North, CM, Triant, VA, Longenecker, C, et al
Journal of the American Heart Association. 2021;(12):e019994
Abstract
Background Although ≈70% of the world's population of people living with HIV reside in sub-Saharan Africa, there are minimal prospective data on the contributions of HIV infection to atherosclerosis in the region. Methods and Results We conducted a prospective observational cohort study of people living with HIV on antiretroviral therapy >40 years of age in rural Uganda, along with population-based comparators not infected with HIV. We collected data on cardiovascular disease risk factors and carotid ultrasound measurements annually. We fitted linear mixed effects models, adjusted for cardiovascular disease risk factors, to estimate the association between HIV serostatus and progression of carotid intima media thickness (cIMT). We enrolled 155 people living with HIV and 154 individuals not infected with HIV and collected cIMT images at 1045 visits during a median of 4 annual visits per participant (interquartile range 3-4, range 1-5). Age (median 50.9 years) and sex (49% female) were similar by HIV serostatus. At enrollment, there was no difference in mean cIMT by HIV serostatus (0.665 versus 0.680 mm, P=0.15). In multivariable models, increasing age, blood pressure, and non-high-density lipoprotein cholesterol were associated with greater cIMT (P<0.05), however change in cIMT per year was also no different by HIV serostatus (0.004 mm/year for HIV negative [95% CI, 0.001-0.007 mm], 0.006 mm/year for people living with HIV [95% CI, 0.003-0.008 mm], HIV×time interaction P=0.25). Conclusions In rural Uganda, treated HIV infection was not associated with faster cIMT progression. These results do not support classification of treated HIV infection as a risk factor for subclinical atherosclerosis progression in rural sub-Saharan Africa. Registration URL: https://www.ClinicalTrials.gov; Unique identifier: NCT02445079.
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24-Month HIV-free survival among HIV-exposed Infants in Lesotho: the PEAWIL cohort study.
Tukei, VJ, Machekano, R, Gill, MM, Tiam, A, Mokone, M, Isavwa, A, Nyabela, M, Mots'oane, T, Nchephe, S, Letsie, M, et al
Journal of the International AIDS Society. 2020;(12):e25648
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Abstract
INTRODUCTION Following the implementation of the provision of lifelong antiretroviral therapy to all HIV-positive pregnant or breastfeeding women for prevention of mother-to-child transmission (PMTCT) of HIV by the Kingdom of Lesotho in 2013, we assessed the effectiveness of this approach by evaluating 24-month HIV-free survival among HIV-exposed infants (HEIs). METHODS We conducted a prospective observational cohort study that enrolled HIV-positive and HIV-negative pregnant women, with follow-up of women and their infants for 24 months after delivery. Participant recruitment started in June 2014 and follow-up ended in September 2018. Trained nurses collected study information through patient interviews and chart abstraction at enrolment and every three to six months thereafter. Maternal HIV testing, infant mortality, HIV transmission and HIV-free survival rates were computed using Kaplan-Meier estimation. Cox regression hazard models were used to identify factors associated with infant HIV infection and death. RESULTS Between June 2014 and February 2016, we enrolled 653 HIV-positive and 941 HIV-negative pregnant women. Twenty-seven HIV-negative women acquired HIV during follow-up. Ultimately, 634 liveborn HEI (382 (52%) male, 303 (48%) female, 3 missing) and 839 who remained HIV-unexposed (HUIs) (409 (49.0%) male, 426 (51.0%) female, 4 missing) were followed; 550 HEIs and 701 HUIs completed the 24-month follow-up period. Of 607 (95.7%) HEIs who were tested for HIV at least once during follow-up, 17 were found to be HIV-positive. Two (9.5%) of 21 infants born to mothers who acquired HIV infection during follow-up were HIV-positive compared to 15 (2.4%) of 613 HEI born to women with known HIV infection. The risk of HIV transmission from HIV-positive mothers to their infants by 24 months of age was 2.9% (95% CI: 1.8 to 4.7). The estimated 24-month mortality rate among HEIs was 6.0% (95% CI: 4.4 to 8.2) compared to 3.8% (95% CI: 2.6 to 5.3) among HUIs (Log-rank p = 0.065). HIV-free survival at 24 months was 91.8% (95% CI: 89.2 to 93.7). Lower maternal age and birth weight were independently associated with increased HIV infection or death of infants. CONCLUSIONS The implementation of lifelong ART for PMTCT in the Lesotho public health system resulted in low HIV transmission, but survival of HEI remains lower than their HIV uninfected counterparts.
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Co-medications and Drug-Drug Interactions in People Living with HIV in Turkey in the Era of Integrase Inhibitors.
Yeşilbağ, Z, Şengül, Eİ, Şenoğlu, S, Aydın, ÖA, Karaosmanoğlu, HK
Current HIV research. 2020;(6):415-425
Abstract
BACKGROUND Long life expectancy in people living with human immunodeficiency virus (PLWH) caused an increase in comorbidities and co-medications. We aimed to analyse comedications and drug-drug interactions (DDIs) in antiretroviral therapy (ART)-naive PLWH in the era of integrase inhibitors. METHODS A retrospective observational study was conducted between January 2016-August 2019. Patients' characteristics and chronic co-medications were recorded. The University of Liverpool HIV drug interaction database was used for DDIs. RESULTS Among 745 patients, the chronic co-medication rate was 30.9%. Older age (p<0.001, OR:6.66, 95% CI: 3.86-11.49) and female gender (p=002, OR:2.25, 95%:1.14-4.44) were independently associated with co-medication. Cardiovascular system (CVS) and central nervous system (CNS) drugs were the most common co-medications. Older age patients (p<0.001, OR:12.04, 95% CI:4.63-36.71), having heterosexual (HS) contact (p=0.003, OR:3.8, 95% CI:1.57-9.22) were independently associated with CVS drugs use, while being men who have sex with men (MSM) (p=0.03, OR:2.59, 95% CI:1.11-6.03) were associated with CNS drugs use. DDIs were seen in 37.4% of patients with co-medications. Antidiabetics (23.3%), CNS (22.1%) and CVS drugs (19.8%) most commonly had DDIs. Contraindication was most commonly seen between inhaled corticosteroids and elvitegravir/cobicistat. A number of non-ART drugs, elvitegravir/cobicistat, antidiabetics, vitamins were independently associated with the presence of DDIs. CONCLUSION Results suggested the need for attention about co-medication in PLWH regardless of whether they are young or older. CNS drugs should be questioned more detailed in MSM, as well as CVS drugs in older HS patients. Elvitegravir/cobicistat is significantly associated with DDIs and switching to an unboosted INSTI should be considered in patients with multiple comorbidities.
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The impact of integrase inhibitor-based regimens on markers of inflammation among HIV naïve patients.
Quiros-Roldan, E, Castelli, F, Bonito, A, Vezzoli, M, Calza, S, Biasiotto, G, Zanella, I, ,
Cytokine. 2020;:154884
Abstract
The use of combination anti-retroviral therapy (cART) correlates with longer and healthier life and with nearly normal life expectancy in people living with HIV. However, cART does not completely restore health. Chronic immune activation and inflammation persist in treated patients and have been described as predictors for clinical events and mortality in HIV-infected patients. Limited information is available on the impact of the various cART regimens on inflammation/immunoactivation. The aim of this work was to explore the impact of elvitegravir, dolutegravir, raltegravir (integrase strand transfer inhibitors, INSTIs) and atazanavir (protease inhibitor, PI) on several soluble markers of immune activation and inflammation during the first year of effective combination anti-retroviral therapy (cART). We conducted an observational retrospective cohort study in HIV-infected cART-naïve patients who initiated an INSTI or atazanavir regimen between March 2015 and February 2016 and a serum sample was available at baseline, 6 and 12 months after initiation. We compared the trend of D-Dimer, TNF- α, IL-2, IL-6, IL-7, IL-10, CCL4/MIP1-β, CCL5/RANTES, s-CD14, s-CD163, hs-CRP levels among the 4 arms of treatment. Percentage of variation from baseline was also measured for all markers. A total of 36 patients were included. We observed heterogeneous modifications in inflammation markers among arms. In particular, we noted that EVG have significant negative effect on s-CD14, hs-CRP, IL-6 and D-Dimer in respect to other INSTIs and this different effect occurs mainly during the first 6 months of cART. IL-7 values increased in the three arms with INSTIs (significantly only in EGV, 159.8%, p = 0.0003) and decreased significantly in patients on PI (-48.96%; p = 0.04) over the period. In conclusion, our results provide further data on changes of inflammatory marker levels, especially for the new INSTIs. Our data show that among INSTIs, EVG seems to have a worse impact on inflammation.
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Maintenance of virologic suppression and improvement in comorbidities after simplification to raltegravir plus boosted darunavir among treatment-experienced HIV-infected patients.
Casado, JL, Vizcarra, P, Blanco, JL, Montejano, R, Negredo, E, Espinosa, N, Montero, M, Mena, A, Palacios, R, Lopez, JC, et al
International journal of STD & AIDS. 2020;(5):467-473
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Effects of atazanavir, darunavir, and raltegravir on fat and muscle among persons living with HIV.
Adrian, S, Miao, H, Feng, H, Scherzinger, A, Nardini, G, Beghetto, B, Roncaglia, E, Ligabue, G, Milic, J, Guaraldi, G, et al
HIV research & clinical practice. 2020;(4):91-98
Abstract
BACKGROUND Antiretroviral therapy (ART) is associated with gain in quantity of fat and muscle, but the impact on quality is less understood. The objective of this study was to compare fat and muscle density among people with HIV (PWH) on stable raltegravir (RAL), atazanavir with ritonavir (ATV/r), or darunavir with ritonavir (DRV/r), and explore implications on muscle function. METHODS Participants from the Modena HIV Metabolic Clinic taking RAL, ATV/r, or DRV/r with at least 1 computed tomography (CT) scan were included. CT scans were reanalyzed for area and density of truncal fat and musculature. Multivariate models explored the effect of ART on fat and muscle density. RESULTS One hundred six participants were receiving ATV/r, 48 DRV/r, and 141 RAL. In multivariate models (reference ATV/r), only DRV/r was associated with greater subcutaneous (SAT) and visceral adipose tissue (VAT) area, lower lateralis muscle density (more fat), and greater lateralis intermuscular fat area. Compared to ATV/r, RAL was independently associated with less psoas intermuscular fat area. Among all, greater paraspinal muscle density correlated with better physical function. No associations between ART group and physical function were seen among men; DRV/r was associated with stronger grip strength among women. CONCLUSION DRV/r was associated with greater fat area and lower density of both fat and muscle, and RAL with less intermuscular psoas fat. Higher density psoas and paraspinal musculature were associated with better physical function, suggesting potential clinical relevance of these findings.
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Multi-platform metabonomics unravel amino acids as markers of HIV/combination antiretroviral therapy-induced oxidative stress.
Sitole, LJ, Tugizimana, F, Meyer, D
Journal of pharmaceutical and biomedical analysis. 2019;:112796
Abstract
Infection by the human immunodeficiency virus (HIV) elicits an immune response wherein neutrophils produce reactive oxygen species (ROS) to defend against pathogen invasion. Consequently, disproportionate levels of ROS in relation to antioxidants lead to oxidative stress (OS), which plays a key role in HIV disease progression and pathogenesis. There is a close relationship between oxidative stress status and HIV infection/progression, both separately and in the presence of combination antiretroviral therapy (cART). Biomarkers of oxidative stress present an additional means of monitoring HIV disease progression and/or management. Thus, the objective of this study was to apply untargeted nuclear magnetic resonance (NMR)-based metabonomics followed by targeted quantitative gas chromatography-mass spectrometry (GC/MS) analyses to identify predictors of oxidative stress in HIV infected individuals, with or without cART. Untargeted NMR-based metabonomics allowed a global profiling of metabolic perturbations in HIV-infected sera. The cohort consisted of 21 HIV-negative control subjects (HIV-) and 113 HIV-infected individuals, of which 100 were on cART. Significant differences in metabolic features corresponding to changes in glucose, lipids, phenylalanine, glutamic acid, aspartic acid and branched amino acids were observed, which point to oxidative stress and insulin resistance. To further confirm oxidative stress, targeted GC/MS-based metabonomics, performed in succession, allowed for a quantitative description of a total of 9 oxidative stress-related metabolites. Significant up-regulation of aspartic acid, phenylalanine and glutamic acid were observed in the HIV-infected cohorts as compared to controls. Tryptophan and tyrosine were down-regulated whereas cystine levels were increased in HIV-infected and untreated individuals as compared to both HIV treated and negative control subjects. Pathway analysis also revealed 11 metabolic pathways to be significantly altered by infection and/or treatment. These pathways included aminoacyl-tRNA biosynthesis, nitrogen metabolism and phenylalanine, tyrosine and tryptophan biosynthesis. This pilot study demonstrated the use of multiplatform metabonomic strategies to elucidate metabolic markers that would be essential in predicting HIV/cART-induced oxidative stress. This could aid and contribute in HIV treatment and management programmes.
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Maintenance of Viral Suppression after Optimization Therapy from Etravirine Plus Raltegravir to Rilpivirine Plus Dolutegravir in HIV-1-Infected Patients.
Riccardi, N, Del Puente, F, Taramasso, L, Di Biagio, A
Journal of the International Association of Providers of AIDS Care. 2019;:2325958218821657
Abstract
Non-nucleoside reverse-transcriptase inhibitor plus integrase strand transfer inhibitor-based dual therapies are an attractive simplification, nucleoside reverse transcriptase inhibitor-sparing strategy for experienced human immunodeficiency virus-infected patients. Thus, we performed a 24-week real-life observational study to assess efficacy and safety of switching from raltegravir plus etravirine to dolutegravir plus rilpivirine in 7 previously heavily treated patients. This simplification strategy reduced pill burden and preserved viral suppression in treatment-experienced patients with no major mutations to rilpivirine at historical genotyping.
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Dolutegravir Plus Rilpivirine as a Switch Option in cART-Experienced Patients: 96-Week Data.
Capetti, AF, Cossu, MV, Sterrantino, G, Barbarini, G, Di Giambenedetto, S, De Socio, GV, Orofino, G, Di Biagio, A, Celesia, BM, Rusconi, S, et al
The Annals of pharmacotherapy. 2018;(8):740-746
Abstract
BACKGROUND Data from clinical studies confirm the efficacy of switching to dolutegravir (DTG) plus rilpivirine (RPV) in selected patients. OBJECTIVE The primary objective is to report the 96-week virological suppression in our cohort, assessing the durability of this strategy in complicated situations. The secondary objective is to describe the safety and metabolic profile. METHODS All patients who had switched to DTG plus RPV between October 1, 2014, and September 30, 2015, were analyzed using a retrospective-prospective design, approved by ethics committees. Routine metabolic, immunological, and virological data were regularly sent to the coordinating center. Viral control was classified as HIV-1 RNA ≥50 copies/mL, 1 to 49 copies/mL, or undetectable (no virus detected [NVD]). RESULTS We followed 145 patients for a median of 101 weeks. The median age was 52 years; 31.7% were women, and 9.6% non-Caucasian; 50.3% had failed at least 1 antiretroviral regimen; and 15% had ≥50 copies/mL at baseline. The reasons for switching were as follows: simplification (51.7%), toxicity (36.5%), drug-drug interactions (6.9%), persistent low-level viremia (3.0%), nonadherence (2.1%), and viral failure (1.4%). By week 96, seven patients dropped out. At week 96, none had ≥50 HIV-1 RNA copies/mL, 138 (95.2%) had <50 copies/mL, and 123 (84.8%) had NVD. The low- to high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio decreased significantly ( P = 0.04). Of the 287 baseline altered laboratory parameters, 32.7% normalized by week 96. Serum glucose and total- and LDL-cholesterol normalization were statistically significant. CONCLUSIONS Switching to DTG plus RPV improved viral suppression and LDL-C/HDL-C ratio.
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Improvement of lipid profile after switching from efavirenz or ritonavir-boosted protease inhibitors to rilpivirine or once-daily integrase inhibitors: results from a large observational cohort study (SCOLTA).
Taramasso, L, Tatarelli, P, Ricci, E, Madeddu, G, Menzaghi, B, Squillace, N, De Socio, GV, Martinelli, C, Gulminetti, R, Maggi, P, et al
BMC infectious diseases. 2018;(1):357
Abstract
BACKGROUND Dyslipidemia represents a significant non-infectious comorbidity among people living with HIV. The aim of this study is to evaluate the impact on lipid profile of switches from an efavirenz (EFV) or protease inhibitor/ritonavir (PI/r)-based regimen to a rilpivirine (RPV) or a once-daily integrase inhibitor-based regimen. METHODS We analyzed data from SCOLTA prospective database. All patients with HIV-RNA < 50 copies/ml in therapy with two NRTI + EFV or PI/r were included if they switched from EFV to dolutegravir (group EFV-DTG), elvitegravir (EFV-EVG), or RPV (EFV-RPV) and from PI/r to DTG (PI/r-DTG), PI/r to EVG (PI/r-EVG), or PI/r to RPV (PI/r-RPV). Total cholesterol (TC), TC/HDL ratio, LDL-cholesterol (LDL) and triglycerides (TG) were compared at baseline, six months and one year. Comparisons among groups were performed by a general linear model. RESULTS Four hundred and ninety patients were enrolled, 24.9% female, mean age 47.3 years (±10.1). According to ART switch, 11.4% were classified in group EFV-DTG, 3.9% in EFV-EVG, 23.9% in EFV-RPV, 17.6% in PI/r-DTG, 17.8% in PI/r-EVG, and 25.5% in PI/r-RPV. After adjusted analysis, TC significantly decreased in all groups but EFV-EVG, TC/HDL in all but EFV-DTG and EFV-EVG, while the reduction of TG was significant only in switches to RPV (EFV-RPV and PI/r-RPV). The one year decrease of TC, TC/HDL, LDL and TG was higher in patients with higher baseline levels of the same variable (p < .0001 for all). CONCLUSIONS In SCOLTA, all switches from PI/r regimens gave advantages on lipid profile, while stopping EFV had consistently favorable lipid effects only if replaced by RPV.