Cholesterol Screening and Statin Prescription is Low Among HIV-Infected Patients on Protease-Inhibitor Regimens in Botswana.
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ABSTRACT:
SUBMITTER: Mosepele M
PROVIDER: S-EPMC5543697 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:BackgroundWhile dolutegravir has been added by WHO as a preferred second-line option for the treatment of HIV infection, boosted protease inhibitor (bPI)-based regimens are still needed as alternative second-line options. Identifying optimal bPI-based second-line combinations is essential, given associated high costs and funding constraints in low- and middle-income countries. We assessed the cost-effectiveness of three alternative bPI-based second-line regimens in Burkina Faso, Cameroon and Senegal.MethodsWe used data collected over 2010-2015 in the 2LADY trial/post-trial cohort. Patients with first-line antiretroviral therapy (ART) failure were randomly assigned to tenofovir/emtricitabine + lopinavir/ritonavir (TDF/FTC LPV/r; arm A), abacavir + didanosine + lopinavir/ritonavir (arm B), or tenofovir/emtricitabine + darunavir/ritonavir (arm C). Costs (US dollars, 2016), quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios were computed for each country over 24 months of follow-up and extrapolated to 5 years using a simulated patient-level Markov model. We assessed uncertainty using cost-effectiveness acceptability curves, scenarios and prices threshold analysis.ResultsIn each country, over 24 months, arm A was significantly less costly than arms B and C (incremental costs ranging from US$410-$US721 and US$468-US$546 for B and C vs A, respectively) and offered similar health benefits (incremental QALY: - 0.138 to 0.023 and - 0.179 to 0.028, respectively). Over 5 years, arm A remained the least costly, health benefits not being significantly different between arms. Compared with arms B and C, in each study country, Arm A had a ≥ 95% probability of being cost-effective for a large range of cost-effectiveness thresholds, irrespective of the scenario considered.ConclusionsUsing TDF/FTC LPV/r as a bPI-based second-line regimen provided the best economic value in the three study countries.Trial registrationClinicalTrials.gov Identifier: NCT00928187.
| S-EPMC7018873 | biostudies-literature
Project description:Antiretroviral therapies (ART) are strongly associated with weight gain and metabolic syndrome (MetS) development in HIV-infected patients. Few studies have evaluated the association between gut microbiota and integrase strand transfer inhibitor (INSTI)-based and protease inhibitor (PI)-based regimens in HIV-infected patients with MetS. To assess this, fecal samples were obtained from HIV-infected patients treated with different regimens (16 PI + MetS or 30 INSTI + MetS) and 18 healthy controls (HCs). The microbial composition was characterized using 16S rRNA amplicon sequencing. The INSTI-based and PI-based regimens were associated with a significant decrease in α-diversity compared to HCs. The INSTI + MetS group showed the lowest α-diversity between both regimens. A significant increase in the abundance of short-chain fatty acid (SCFA)-producing genera (Roseburia, Dorea, Ruminococcus torques, and Coprococcus) was observed in the PI + MetS group, while Prevotella, Fusobacterium, and Succinivibrio were significantly increased in the INSTI + MetS group. Moreover, the Proteobacteria/Firmicutes ratio was overrepresented, and functional pathways related to the biosynthesis of LPS components were increased in the INSTI + MetS group. The gut microbiota of patients receiving INSTIs showed a more pronounced dysbiosis orchestrated by decreased bacterial richness and diversity, with an almost complete absence of SCFA-producing bacteria and alterations in gut microbiota functional pathways. These findings have not been previously observed.
| S-EPMC10146710 | biostudies-literature
Project description:The effects of ezetimibe on cholesterol metabolism in HIV-infected patients receiving boosted protease inhibitors have not been thoroughly assessed. The aim of this study was to assess cholesterol homeostasis in patients with PI associated dyslipidemia and its relationship with the response to treatment with the cholesterol-absorption inhibitor ezetimibe.Fifteen patients with ritonavir-boosted PI-containig therapy and LDL-cholesterol?>?3.36 mmol/L (>130 mg/dL) were assessed at baseline and after an 8-week course of ezetimibe 10 mg/d. Serum non-cholesterol sterols were measured at each visit as markers of cholesterol synthesis and absorption. Total-, LDL-, and HDL-cholesterol triglycerides, apolipoproteins A1 and B, high sensitivity C-reactive protein, CD4 cells and HIV-1 RNA were also measured.Ezetimibe treatment was well tolerated in all patients and resulted in significant reductions in total cholesterol (-11.4%, p?=?.002), LDL-cholesterol (-20.4%, p?=?.003), non-HDL-cholesterol (-13.4%, p?=?.002) and apolipoprotein B (-9.1%, p?=?.021). Treatment with ezetimibe was associated with decreased cholesterol absorption markers (campesterol-to-cholesterol ratio -43.0%, p?=?.001; sitosterol-to-cholesterol ratio -41.9%, p?=?.001) and increased synthesis markers (lathosterol-to-cholesterol ratio 53.2%, p?=?.005). Baseline absorption or synthesis markers were unrelated to the response to treatment. CD4 cell count and plasma HIV-1 RNA remained unchanged.The level of cholesterol absorption or synthesis does not appear to be a major determinant of the responsiveness to ezetimibe in patients on ritonavir-boosted PI-containing therapy.EudraCT: 2006-006156-36.
| S-EPMC4169814 | biostudies-literature
Project description:Background:Human immunodeficiency virus (HIV)-infected pregnant women on protease inhibitor (PI)-based combination antiretroviral therapy (cART) have a greater risk for adverse birth outcomes, and an association with steroid hormone levels has been implicated. The objective of this study was to investigate the association between PI-cART and estradiol levels in pregnancy. Methods:Fifty-five HIV-infected and 49 HIV-uninfected Canadian pregnant women were followed prospectively throughout gestation. All HIV-infected women were on a PI-based cART regimen. Maternal plasma samples were collected at 12-18 weeks, 24-28 weeks, 34-38 weeks, at delivery, and from the cord. Birth outcomes were recorded. Levels of estradiol, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), cortisol, and adrenocorticotropic hormone (ACTH) were quantified by enzyme-linked immunosorbent assay. Results:(median [interquartile range] for cord estradiol: 23.9 ng/mL [16.4-36.4] for HIV-infected exposed to PI-cART and 15.7 ng/mL [12.2-21.2] for HIV-negative; P = .0025). HIV-infected women had higher DHEAS levels in cord plasma that correlated with cord and maternal delivery estradiol levels. Cortisol and ACTH levels did not differ between groups. In the HIV-infected women, cord estradiol levels correlated negatively with birth weight centile (r = -0.47, P = .0016). Conclusions:Our data suggest that PI-cART exposure in pregnancy is associated with elevated levels of estradiol, likely driven by higher fetal DHEAS production. Cord estradiol levels were inversely correlated with birth weight centile in infants born to PI-cART-exposed women, suggesting that fetal exposure to high estradiol levels may be contributing to cART-associated fetal growth restriction.
| S-EPMC5850422 | biostudies-literature
Project description:Eleven protease mutations have been associated with reduced susceptibility to darunavir. In this study of 87 HIV-1-infected patients experiencing virological failure to second-line regimens containing protease inhibitors boosted with ritonavir (viral load >1,000 HIV RNA copies/ml), we observed a low prevalence (3%) of ?3 darunavir resistance-associated mutations, indicating that this drug may be a good option for third-line antiretroviral therapy in southern India.
| S-EPMC3581023 | biostudies-literature
Project description:There are limited real-world mutational and virological outcomes data of treatment-experienced persons diagnosed with HIV-1 subtype C (HIV-1 C) who are failing Integrase Strand Transfer Inhibitor-based regimens. Requisition forms sent for HIV-1 genotypic resistance testing (GRT) between May 2015 and September 2019 were reviewed and participants experiencing virologic failure while on dolutegravir (DTG) or raltegravir (RAL) cART at sampling recruited. Sanger sequencing of the HIV-1 Pol gene was performed from residual plasma samples and drug resistance mutational (DRM) analysis performed using the Stanford University HIV drug resistance database. 40 HIV-1C integrase sequences were generated from 34 individuals, 24 of whom were on DTG cART, three on RAL cART and seven on an unknown (DTG or RAL)-anchored cART at time of GRT. 11/34 (32%) individuals had DRMs to DTG and other integrase inhibitors. 7/11 (64%) patients had exposure to a RAL-based cART at the time of sampling. Out of the 11 individuals with DRMs, one (9%) had 2-class, 6 (55%) had 3-class, and 4 (36%) had 4-class multidrug-resistant HIV-1C. 7/11 individuals (64%) are currently virologically suppressed. Of the four individuals not virologically suppressed, three had extensive DRMs involving 4-classes of ARV drugs and one individual has demised. Resistance to DTG occurs more often in patients exposed to RAL cART. Individuals with 4-class DRMs plus integrase T97 and E157Q mutations appear to have worse outcomes. There is a need for frequent VL monitoring and GRT amongst treatment-experienced HIV-1C diagnosed individuals.
| S-EPMC8066386 | biostudies-literature
Project description:HIV-1 (Human immunodeficiency virus type 1)׳s infection is considered as one of most harmful disease known by human, the survivability rate of the host reduced significantly when it developed into AIDS. HIV drug resistance is one of the main problems of its treatment and several drug designs have been done to find new leads compound as the cure. In this study, in silico virtual screening approach was used to find lead molecules from the library or database of natural compounds as HIV-1 protease inhibitor. Virtual screening against Indonesian Herbal Database with AutoDock was performed on HIV-1 protease. From the virtual screening, top ten compounds obtained were 8-Hydroxyapigenin 8-(2",4"-disulfatoglucuronide), Isoscutellarein 4'-methyl ether, Amaranthin, Torvanol A, Ursonic acid, 5-Carboxypyranocyanidin 3-O-(6"-O-malonyl-beta-glucopyranoside), Oleoside, Jacoumaric acid, Platanic acid and 5-Carboxypyranocyanidin 3-O-beta-glucopyranoside.
| S-EPMC3937575 | biostudies-literature
Project description:Previous studies have demonstrated a link between protease inhibitor (PI)-based therapy and lipid dysregulation. The main objective of this study was to examine whether cocaine use may modify PI-associated dyslipidemia in adults. Between June 2003 and June 2014, 957 human immunodeficiency virus (HIV)-infected participants in Baltimore, Maryland were enrolled in a study that investigated HIV/antiretroviral therapy-associated comorbidities. Multiple linear and logistic regression models were fitted to examine the associations between PI therapy and lipid profiles for the pooled sample and cocaine use subgroups, respectively. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C) ratio, and atherogenic index of plasma (AIP) levels were positively associated with duration of PI-based therapy in long-term cocaine users (all p < 0.05). However, longer-term PI therapy was significantly associated with increased HDL-C in non-chronic cocaine users (β = 0.109, SE = 0.042, p < 0.05). The participants who received PI therapy ≥12 months and used cocaine ≥15 years were more likely to have hypertriglyceridemia (OR = 2.82, 95% CI = 1.63, 4.88) and abnormal AIP (OR = 1.73, 95% CI = 1.08, 2.79) as compared to their counterparts. Our findings showed that long-term cocaine use may exacerbate adverse effects of PI therapy on lipid metabolism, suggesting that reduced cocaine use may be considered an alternative approach to managing PI-associated dyslipidemia in chronic cocaine users with HIV infection.
| S-EPMC7032655 | biostudies-literature
Project description:BackgroundHIV infection is associated with significant neurocognitive deficits making maximization of cognitive function among children receiving antiretroviral therapy (ART) a public health imperative. Non-protease inhibitors (non-PIs) achieve higher drug levels in the cerebral spinal fluid (CSF) compared to PIs, potentially leading to better neurocognitive function by reducing CSF viral load and inflammation. ART that maximises children's neurodevelopment and school achievement could result in improved quality of life and productivity as adults, but little research to date has examined whether non-PI ART is associated with better neurocognitive outcomes. We compared the neurocognitive function between children living with HIV receiving PI-based and non PI-based ART.MethodsWe recruited a consecutive sample of clinically stable Ugandan children living with HIV aged 5-12 years who received PI-based or non PI-based ART for ≥ 1 year (viral load < 1000 copies). Neurocognitive function was assessed using the Kaufman Assessment Battery for Children, the Test of Variables of Attention, and Bruininks-Oseretsky Test of Motor Proficiency. Age-adjusted neurocognitive z-scores for the two groups were compared using linear regression models in STATA version 13. The Hommel's method was used to adjust for multiple testing.ResultsWe enrolled 76 children living with HIV; 34 on PI ART and 42 on non-PI ART. Mean (±SD) age was greater in the non-PI vs. PI group (9.5 ± 1.9 vs. 8.5 ± 2.0) years (p = 0.03). Children in the non-PI group had lower socioeconomic scores (5.7 ± 3.3 vs. 7.4 ± 2.8, p = 0.02). There was no difference in neurocognitive function between the groups (adjusted p > 0.05) for KABC and TOVA. Children in the PI group had better total BOT scores than their counterparts (46.07 ± 1.40) vs. 40.51 (1.24), p = 0.03).ConclusionsWe detected no difference in neurocognitive function among children on PI and non PI-based ART therapy based on KABC and TOVA tests. Children on PI based ART had better motor function than their counterparts. We recommend a prospective study with a larger sample size.
| S-EPMC8073947 | biostudies-literature
Project description:Infants born to HIV-infected women receiving antiretroviral treatment (ART) can be breastfed through at least 6 months with very low risk of HIV acquisition. We aimed to identify demographic and cultural factors that may influence mothers' willingness to breastfeed for the recommended duration.We evaluated factors associated with early cessation of breastfeeding (i.e. before 5 months post-partum) in a randomized clinical trial evaluating different ART regimens used for prevention of mother-to-child transmission during breastfeeding in Botswana. Univariate and multivariable Cox regressions were used to describe predictors of early exclusive BF cessation.Among 677 women who started breastfeeding, the median time to breastfeeding cessation was 178 days (IQR 150-181) and 25.1% weaned early. In multivariable analysis, urban location (aHR = 1.86 95%CI 1.27-2.73; P = 0.002), salaried employment or being a student (aHR = 2.78 95% CI 1.63-4.75; P < 0.001) and infant hospitalisation before weaning (aHR = 2.04 95% CI 1.21-3.45; P = 0.008) were independently and significantly associated with early BF cessation.Improved support for breastfeeding among employed mothers, especially in urban settings, may allow HIV-infected women who are receiving ART prophylaxis to breastfeed longer.
| S-EPMC4969096 | biostudies-literature