Use Of Efavirenz Research Articles

Unlocking The Secrets of Efavirenz: A Comprehensive Drug Information Resource

Efavirenz is an antiretroviral medicine generally used to treat HIV infection. As a non-nucleoside reverse transcriptase inhibitor (NNRTI), it inhibits the replication of the contagion. Efavirenz is well absorbed when taken orally, reaching peak tube attention within 3-5 hours. Its long elimination half-life of 52-76 hours allows for formerly diurnal dosing and improves patient compliance. Efavirenz is primarily metabolized in the liver by cytochrome P450 enzymes, particularly CYP2B6 and CYP3A4, and undergoes expansive hepatic metabolism to form inactive metabolites. The medicine is substantially excreted in the feces, with a small quantum excreted in the urine. Efavirenz may interact with other medicines and substances due to its influence on the exertion of CYP3A4 and its metabolism through CYP2B6. Medicine-medicine relations should be precisely considered to avoid compromising the efficacity and safety of co-administered medicines. There are certain contraindications to the use of Efavirenz. People with known acuity to the medicine or its factors shouldn’t take Efavirenz. Efavirenz isn’t recommended for pregnant women due to the increased threat of fetal neural tube blights. Effective contraception is essential for women of travail eventually taking Efavirenz. In conclusion, Efavirenz is a precious formerly-diurnal dosing antiretroviral medicine that supports patient compliance.

Low CD4 counts predict excessive weight gains during first-line treatment for HIV.

Weight gain is common after antiretroviral initiation, especially among females, those of black race and lower baseline CD4, although this may potentially be due to lower baseline weight. Use of tenofovir disoproxil fumarate or efavirenz can suppress weight gain. Data were pooled from the ADVANCE (n = 1053), NAMSAL (n = 613) and WHRI001 (n = 536) trials investigating first-line regimen. Week 96 weight and body mass index (BMI) was stratified by baseline CD4. Multivariable models of weight change and incident obesity (BMI ≥30 kg/m2) were adjusted for baseline CD4, age, sex, tenofovir disoproxil fumarate, efavirenz, baseline BMI and trial. Participants across all treatment arms experienced weight gain from baseline to week 96, with baseline CD4 count, baseline HIV RNA, tenofovir alafenamide and dolutegravir use, and female sex significant predictors. Mean unadjusted weight change was highest with CD4 < 100 (+8.6 kg; SD = 8.2) and lowest with CD4 ≥ 350 (+3.0 kg; SD = 6.5). This weight gain in CD4 < 100 was highest for participants on tenofovir alafenamide-inclusive treatment, such that absolute weight at week 96 was highest in the CD4 < 100 group. Although not statistically significant, obesity rate (BMI ≥ 30 kg/m2) in those taking TAF/FTC + DTG with CD4 < 100 overtook that seen in CD4 ≥ 350, despite lower baseline obesity prevalence. The unadjusted findings were corroborated in multivariable longitudinal models. Participants with low CD4 may demonstrate significant 'overshoot' weight gain, in addition to 'return to health', with a trend towards increased risk of obesity when initiated on TAF/FTC + DTG. Use of tenofovir disoproxil fumarate and efavirenz were associated with smaller weight gains. Effective weight management strategies are needed, especially for individuals with low baseline CD4.

Nicotine Metabolite Ratio Decreases After Switching Off Efavirenz-Based Therapy in People With HIV Who Smoke.

Rates of cigarette smoking in people with HIV (PWH) are two to three times higher than in people without HIV. Nicotine is metabolized by CYP2A6 and the nicotine metabolite ratio (NMR; 3-hydroxycotinine/cotinine) is a measure of nicotine clearance. Higher NMR has been observed in PWH and is associated with lower quit rates. Efavirenz, a mainstay antiretroviral therapy (ART) globally, partially upregulates its own metabolism through CYP2A6. We hypothesized that efavirenz also upregulates nicotine metabolism by CYP2A6, resulting in a higher NMR, and switching to non-efavirenz ART would decrease the NMR, potentially leading to improved quit rates. We compared the NMR during and after efavirenz use among PWH in a longitudinal, multisite cohort. Eligibility criteria included: (i) active cigarette smoking, (ii) ART switched from efavirenz-based to non-efavirenz-based regimen, (iii) plasma available at pre- and post-ART switch, and (iv) viral suppression during study period. Plasma cotinine and 3-hydroxycotinine were measured by liquid chromatography-tandem mass spectrometry. T-tests compared the NMR on and off efavirenz. Samples were collected between 2010 and 2019 in 72 PWH. The mean NMR difference after switching to a non-efavirenz-based regimen was -0.24 (SD: 0.37, P < 0.001); 44 PWH had at least a 0.1 decrease in NMR. Effect modification by race was present; Black PWH had a larger mean decrease. Our findings suggest that previously observed higher NMR among PWH may be due to direct pharmacologic effects of ART. Assessing the effect of ART on the NMR suggests that avoiding nicotine metabolism inducers could potentially increase quit rates.

Efavirenz-Based Antiretroviral Therapy but Not Pregnancy Increased Unbound Piperaquine Exposure in Women during Malaria Chemoprevention.

Dihydroartemisinin-piperaquine (DP) is highly effective for malaria chemoprevention during pregnancy, but the standard dosing of DP that is used for nonpregnant adults may not be optimal for pregnant women. We previously reported that the pharmacokinetic exposure of total piperaquine (PQ; both bound and unbound to plasma proteins) is reduced significantly in the context of pregnancy or efavirenz (EFV)-based antiretroviral therapy (ART). However, as PQ is >99% protein-bound, reduced protein binding during pregnancy may lead to an increase in the pharmacologically active unbound drug fraction (fu), relative to the total PQ. We investigated the impact of pregnancy and EFV use on the fu of PQ to inform the interpretation of pharmacokinetics. Plasma samples from 0 to 24 h after the third (final) DP dose were collected from pregnant women at 28 weeks gestation who were receiving or not receiving EFV-based ART as well as from women 34 to 54 weeks postpartum who were not receiving EFV-based ART, who served as controls. Unbound PQ was quantified via ultrafiltration and liquid chromatography-tandem mass spectrometry, with fu being calculated as PQunbound/PQtotal. The geometric mean fu did not differ between pregnant and postpartum women (P = 0.66), but it was 23% (P < 0.01) greater in pregnant women receiving EFV-based ART, compared to that in postpartum women who were not receiving EFV-based ART. The altered drug-protein binding, potentially due to the displacement of PQ from plasma proteins by EFV, resulted in only a 14% lower unbound PQ exposure (P = 0.13) in the presence of a 31% lower total PQ exposure (P < 0.01), as estimated by the area under the concentration time curve from 0 to 24 h post-last dose in pregnant women who were receiving EFV-based ART. The results suggest that the impact of pregnancy and EFV-based ART on the exposure and, in turn, the efficacy of PQ for malaria prevention may not be as significant as was suggested by the changes in the total PQ exposure. Further study during the terminal elimination phase (e.g., on day 28 post-dose) would help better characterize the unbound PQ exposure during the full dosing interval and, thus, the overall efficacy of PQ for malaria chemoprevention in this special population.

167 Unusual case of tuberculous chancre at the exact site of application of the Mantoux test

We report an unusual case of cutaneous tuberculosis that developed at the exact site where a Mantoux test (also known as PPD test) was performed. A 25 year old male patient, recently diagnosed with HIV infection and acquired immunodeficiency syndrome (AIDS), in use of lamivudine, efavirenz and dolutegravir for two months, reported cough, night sweats and weight loss. Mantoux test was performed, ordered by his general practitioner, however, the patient presented an intense inflammatory response at the test site with subsequent ulcer formation within four weeks.

Metabolic syndrome in people with HIV from Guatemala: analysis of components and risk factors.

People with HIV (PWH) in Latin America are at a greater risk of developing comorbidities due to the increasing burden of obesity and metabolic syndrome in the region. We explored the associations between social, cardiovascular and HIV-related risk factors with metabolic syndrome in PWH from Guatemala. Cross-sectional study analyzing demographic, clinical and laboratory data from PWH. Metabolic syndrome diagnosis and components are defined by the harmonized Joint Scientific Statement criteria. Data were collected from July 2019 to March 2020 and analyzed using correlations and logistic regression. Median age was 39years [IQR 31-48], 56.8% of participants were male and 31.5% (n = 266, 95% CI 0.28-0.34) had metabolic syndrome. Age (adjusted odds ratio (aOR): 1.03, 95% CI 1.02-1.05, p <0.001), urban dweller (aOR: 1.48, 95% CI 1.00-2.18, p = 0.049), low physical activity (aOR: 1.45, 95% CI 1.01-2.08, p = 0.046), hyperuricemia (aOR: 3.31, 95% CI 1.93-5.67, p <0.001), current CD4+ T cell count < 200 cells/mm3 (aOR: 1.96, 95% CI 1.19-3.23, p = 0.009), 6months of efavirenz (aOR: 1.89, 95% CI 1.29-2.77, p = 0.001), and obesity (aOR: 37.0, 95% CI 7.70-178.2, p < 0.001) were independently associated with metabolic syndrome. Prevalence of metabolic syndrome in this study was high and driven mainly by social and cardiovascular risk factors such as age, urban dwelling, obesity, hyperuricemia and low physical activity. Efavirenz use and CD4 count were the only HIV-related factors associated with metabolic syndrome.

Brief Report: Nicotine Metabolism Ratio Increases in HIV-Positive Smokers on Effective Antiretroviral Therapy: A Cohort Study.

People with HIV (PWH) smoke tobacco at much higher rates than the general population. Previous research has shown that PWH have faster nicotine metabolism than HIV-uninfected individuals, which may underlie this disparity, but the cause is unknown. We investigated whether higher nicotine metabolite ratio (NMR; 3-hydroxycotinine:cotinine), a validated biomarker of nicotine metabolism through CYP2A6, was associated with antiretroviral use among HIV-infected smokers. We conducted a retrospective cohort study of HIV-positive smokers in the University of Pennsylvania Center for AIDS Research cohort. We compared the NMR before viral suppression (>10,000 copies/mL) and after viral suppression on antiretroviral therapy (<200 copies/mL). We used mixed-effects linear regression to analyze the change in NMR after viral suppression and assessed for effect modification by efavirenz use. Eighty-nine individuals were included in the study. We observed effect modification by efavirenz use (interaction term for efavirenz use, P < 0.001). Among those on nonefavirenz regimens, the mean NMR increased by 0.14 (95% confidence interval: 0.05 to 0.23, P = 0.002). Among those on efavirenz-containing regimens, the mean NMR increased by 0.53 (95% confidence interval: 0.39-0.66, P < 0.001). We observed a clinically and statistically significant increase in NMR after viral suppression among smokers with HIV, which more than doubled among those on efavirenz-based regimens. Higher NMR among HIV-positive smokers on antiretroviral therapy may help explain the higher rates of tobacco use and lower quit rates among PWH in care. These findings suggest that regimen choice and other modifiable factors may be targets for future attempts to increase success rates for tobacco cessation among PWH.

Incidence and predictors of nevirapine and efavirenz-associated rash among Indonesian HIV patients

Many drugs used for the treatment of HIV disease can cause drug hypersensitivity reactions. Since 2002, World Health Organization (WHO) has recommended the use of nevirapine and efavirenz as part of first line antiretroviral therapies for several years. Both of the drugs had equivalent clinical efficacy but differences in toxicity profile. We aimed to determine the incidence and predictors of nevirapine and efavirenz-associated rash among Indonesian HIV-infected patients. A retrospective cohort study was conducted among Indonesian patients who were using nevirapine or efavirenz between January 2004 to December 2013. All eligible predictors were analyzed using bivariate and multivariate analysis. 2,071 patients received nevirapine and 1,212 received efavirenz as first line therapies. The cumulative incidence of nevirapine-associated rash was 14% (95%CI: 12.5-15.5%) and evafirenz-associated rash was 4.5% (95%CI: 3.4-5.8%). Severe reactions occurred 1% patients receiving NVP and 0.1% patients receiving EFV, but no patients died due to these conditions. Predictors independently related with nevirapine-associated rash were female gender (adjusted RR = 1.622; 95%CI: 1.196-2.199; p = 0.002), baseline absolute CD4 count above 200 cells/mm3 (adjusted RR = 1.387; 95%CI: 1.041-1.847; p = 0.025), and hepatitis C co-infection (adjusted RR = 1.507; 95%CI: 1.138-1.995; p = 0.004). Baseline ALT level > 1.25 times upper normal limit (adjusted RR = 1.508; 95%CI: 0.998-2.278; p = 0.051) had a tendency to be a good predictor. None of the risk factors investigated was associated with developing efavirenz-associated rash. Female, baseline absolute CD4 count above 200 cells/mm3, hepatitis C co-infection and baseline ALT levels more than 1.25 times upper normal limit were predictors for nevirapine-associated rash in HIV patients.

Efavirenz Is Not Associated with an Increased Risk of Depressive Disorders in Patients Living with HIV: An 11-Year Population-Based Study in Taiwan.

(1) Background: This study aimed to determine the association between the use of efavirenz and depressive disorders among human immunodeficiency virus (HIV)-infected patients. (2) Methods: A retrospective cohort study was conducted using Taiwan’s National Health Insurance Database. We identified patients receiving anti-retroviral therapy (ART) between 2000 and 2009; these patients were followed until 2010 for diagnoses of depressive disorders using the Cox proportional hazard model to estimate hazard ratios. (3) Results: After up to 11 years of follow-up, the incidence of depressive disorders for the efavirenz-treated group was estimated at 12.2/1000 person-years (PYs), and the control group was at 12.5/1000 PY (p = 0.822). The independent risk factors for depressive disorders included an insurance premium of less than NTD 17,820 (New Taiwan Dollars—NTD) (adjusted hazard ratio (aHR) 2.59, 95% confidence interval (CI), 1.79–3.76, p < 0.001), and between NTD 17,821 and NTD 26,400 (aHR 1.55, 95% CI, 1.04–2.31, p = 0.030), living in Southern Taiwan (aHR 1.49, 95% CI, 1.21–1.84, p = 0.002), and with a psychiatric history (excluding depressive disorders) (aHR 4.59, 95% CI, 3.51–6.01, p = 0.030). (4) Conclusions: This study concluded that ART-treated patients with a past history of psychiatric disorders, lower insurance premium, and living in Southern Taiwan have an increased risk of depressive disorders, which are not associated with the use of efavirenz.

A Meta-Analytic Review of the Effect of Antiretroviral Therapy on Neurocognitive Outcomes in Adults Living with HIV-1 in Low-and Middle-Income Countries.

HIV-associated neurocognitive impairment remains a challenge even in the era of antiretroviral therapy (ART). Over 90% of people living with HIV are in low- and middle-income countries. Hence, it is not surprising that such countries bear a considerable burden of comorbidities like HIV-associated neurocognitive impairment despite an overall increase in life expectancy. The literature suggests differences in patient characteristics, clinical profile, prevalent HIV subtypes, treatment choices, pharmacogenetics, and socioeconomic factors between low- and middle-income countries compared with high-income countries. Therefore, we aimed to evaluate the effect of ART on neurocognitive outcomes in low- and middle-income countries. A comprehensive search of five databases (PubMed, CINAHL, CENTRAL, PsychInfo, Google scholar) for studies published between 1996 to 2020 was performed to identify studies that reported neurocognitive outcomes in ART-treated and ART naïve HIV positive individuals. Two independent reviewers conducted study screening, data extraction, and evaluation of the risk of bias. Pooled effect size estimates (Hedges' g) and 95% CI were computed using random-effects models. Sensitivity analysis, subgroup analysis, meta-regression, and evaluation of publication bias were also conducted. Forty studies (24 cross-sectional, 13 longitudinal studies, and two randomized controlled trials) contributed to a series of meta-analyses. We found significant small to moderate effects of antiretroviral therapy for global cognition (Hedges' g observed = 0.30; 95% CI: 0.15, 0.44; k = 25; p = 0.0003; I2 = 92.1%; tau = 0.32; Q = 305.1), executive function (Hedges' g = 0.24, 95%CI: 0.02,0.46; p-0.04; k = 8; I2 = 37.5%; tau = 0.23; Q = 11.2), and speed of information processing (Hedges' g = 0.25, 95% CI: 0.05, 0.45; k = 9; p = 0.02; I2 = 86.4%; tau = 0.21; Q = 58.9). We found no significant ART effect on attention-working memory, learning and memory, motor function, and verbal fluency. No significant effect was seen with the duration of therapy, efavirenz use, and Central Penetrating Effectiveness (CPE) of antiretroviral therapy. Subgroup analyses identified study design (between-group and within-group; cross-sectional and longitudinal) and normative scores as significant sources of heterogeneity. Meta-regression analysis indicated that nadir CD4 modified the magnitude of ART's effect on cognitive outcomes. Age, gender, and country income-group were not significant moderators. Our findings provide systematic evidence that antiretroviral therapy improves neurocognitive outcomes in the domains of global cognition, executive function and speed of information processing, of people living with HIV in low- and middle-income countries, especially those with advanced immunosuppression. However, these findings are not definitive as they are limited by the probability of publication bias, high heterogeneity, and exclusion of significant confounders. Prospero registration number: CRD42020203791.

Anticholinergic medication use in elderly people living with HIV and self-reported neurocognitive impairment: a prospective cohort study.

Anticholinergic (ACH) medications have been associated with neurocognitive impairment, particularly in the elderly. This study determined prospectively the prevalence of prescribed ACH medications and their association with self-reported neurocognitive impairment (SRNI) in elderly people living with HIV (PLWH) of the Swiss HIV Cohort Study (SHCS). A literature review was performed to identify ACH medications, which were scored 0 to 3 (higher score indicating more ACH burden). Prescriptions were reviewed in July 2019 for all SHCS participants ≥65 years old to assess the prevalence of ACH medications. Association between ACH burden and neurocognitive impairment was evaluated using the SHCS SRNI questions addressing memory loss, attention difficulties and slowing in reasoning. One thousand and nineteen PLWH (82% male) with a median age of 70 (IQR = 67-74) years were included. Most participants were on ART (99%). The average number of non-HIV drugs was 5.1 ± 3.6, representing a polypharmacy prevalence of 50%. Two hundred participants (20%) were on ≥1 ACH medication, with an average ACH score of 1.7 ± 1.3. SRNI, adjusted for age, sex, CD4, nadir CD4, viral load, efavirenz use and polypharmacy, was associated with depression (OR = 4.60; 95% CI = 2.62-8.09) and a trend was observed with being on ≥1 ACH medication (OR = 1.69; 95% CI = 0.97-2.95). In a subgroup analysis of participants without depression (n = 911), SRNI was associated with the use of ≥1 ACH medication (OR = 2.51; 95% CI = 1.31-4.80). ACH medication use is common in elderly PLWH and contributes to SRNI. The effect of ACH medications on neurocognitive impairment warrants further evaluation using neurocognitive tests.

Increased risk of prediabetes among virally suppressed adults with HIV in Central Kenya detected using glycated haemoglobin and fasting blood glucose.

AimsAs survival among people living with HIV (PLHIV) improves with universal HIV treatment, new strategies are needed to support management of co‐morbidities like type 2 diabetes (T2D). We assessed prediabetes and T2D prevalence and risk factors using haemoglobin A1c (HbA1c) among PLHIV on antiretroviral therapy (ART) in Central Kenya.MethodsThis cross‐sectional study, conducted at a rural and urban site, enrolled PLHIV aged ≥35 years on ART for at least 5 years. HbA1c was assayed using Cobas b 101®, a point‐of‐care device. HbA1c levels ≥6.5% were considered diagnostic of T2D. For pre‐diabetic HbA1c levels (5.7%–6.4%), participants were requested to return the following day for a fasting blood glucose (FBG) to rule out T2D. Risk factors were assessed using multivariable log‐binomial regression.ResultsOf the 600 completing study procedures, the prevalence of diabetes was 5% (30/600). Ten participants were known to have diabetes; thus, prevalence of newly diagnosed T2D was 3.4% (20/590). Prevalence of prediabetes (HbA1c 5.7%–6.4%) was 14.2% (84/590). Significant predictors of elevated HbA1c were increase in age (Prevalence ratio [PR]: 1.10, CI: 1.02, 1.18, p = .012), hypertension (PR: 1.43, CI: 1.07–2.3, p = .015), central adiposity (PR: 2.11, CI: 1.57–2.84, p < .001) and use of Efavirenz (PR: 2.09, CI: 1.48, 2.96, p < .001).ConclusionThere is a high prevalence of prediabetes, a significant predictor of T2D, among PLHIV in Central Kenya. Point‐of‐care HbA1c may help identify PLHIV with prediabetes in a single screening visit and provide an opportunity for early intervention.

Associations between efavirenz concentrations, pharmacogenetics and neurocognitive performance in people living with HIV in Nigeria.

Objective:Efavirenz (EFV) use is associated with neuropsychiatric side effects, which may include poor neurocognitive performance. We evaluated single nucleotide polymorphisms in genes that contribute to EFV pharmacokinetics and examined them in association with EFV concentrations in plasma and hair, as well as neurocognitive performance.Design:Cross-sectional study in which adults with HIV receiving 600-mg EFV for at least 2 months were recruited and paired hair and dried blood spots (DBS) samples collected.Methods:Participants (N = 93, 70.3% female) were genotyped for seven single nucleotide polymorphisms in CYP2B6, NRII3 and ABCB1 using DBS. EFV was quantified in DBS and hair using validated liquid-chromatography–tandem-mass-spectrometry methods, with plasma EFV concentrations derived from DBS levels. Participants were also administered a neurocognitive battery of 10 tests (seven domains) that assessed total neurocognitive functioning.Results:Strong correlation (r = 0.66, P < 0.001) was observed between plasma and hair EFV concentrations. The median (interquartile range) hair EFV concentration was 6.85 ng/mg (4.56–10.93). CYP2B6 516G>T, (P < 0.001) and CYP2B6 983T>C (P = 0.001) were each associated with hair EFV concentrations. Similarly, 516G>T (P < 0.001) and 983T>C (P = 0.009) were significantly associated with plasma EFV concentration. No other genetic associations were observed. Contrary to other studies, total neurocognitive performance was significantly associated with plasma EFV concentrations (r = 0.23, P = 0.043) and 983T>C genotype (r = 0.38, P < 0.0005).Conclusion:This study demonstrated approximately three-fold and two-fold higher EFV plasma and hair concentrations, respectively, among CYP2B6 516TT compared with 516GG. Higher EFV concentrations were associated with better neurocognitive performance, requiring further study to elucidate the relationships between adherence, adverse effects and outcomes.

Transportability From Randomized Trials to Clinical Care: On Initial HIV Treatment With Efavirenz and Suicidal Thoughts or Behaviors.

In an analysis of randomized trials, use of efavirenz for treatment of human immunodeficiency virus (HIV) infection was associated with increased suicidal thoughts/behaviors. However, analyses of observational data have found no evidence of increased risk. To assess whether population differences might explain this divergence, we transported the effect of efavirenz use from these trials to a specific target population. Using inverse odds weights and multiple imputation, we transported the effect of efavirenz on suicidal thoughts/behaviors in these randomized trials (participants were enrolled in 2001-2007) to a trials-eligible cohort of US adults initiating antiretroviral therapy while receiving HIV clinical care at medical centers between 1999 and 2015. Overall, 8,291 cohort participants and 3,949 trial participants were eligible. Prescription of antidepressants (19% vs. 13%) and injection drug history (16% vs. 10%) were more frequent in the cohort than in the trial participants. Compared with the effect in trials, the estimated hazard ratio for efavirenz on suicidal thoughts/behaviors was attenuated in our target population (trials:hazard ratio (HR) =2.3 (95% confidence interval (CI): 1.2, 4.4); transported: HR=1.8 (95% CI: 0.9, 4.4)), whereas the incidence rate difference was similar (trials: HR=5.1 (95% CI: 1.6, 8.7); transported: HR=5.4 (95% CI: -0.4, 11.4)). In our target population, there was greater than 20% attenuation of the hazard ratio estimate as compared with the trials-only estimate. Transporting results from trials to a target population is informative for addressing external validity.

Efficacy of vitamin D supplementation among persons living with HIV/AIDS in São Paulo city, Brazil

Hypovitaminosis D is now considered a pandemic, especially among more vulnerable populations and in HIV-infected subjects, with 80% presenting levels below 30 ng/mL. As there is no consensus on the more adequate dosage needed to correct such deficiency, the objective of this study was to evaluate 25 (OH) vitamin D supplementation in HIV-1 patients deficient of vitamin D. A total of 73 HIV-1-infected patients were included, drawn from a cohort of 435 patients; 37 patients were randomized to the active group, supplemented once a week with 50,000 UI vitamin D by mouth (group 1) and 36 to the placebo group (group 2). The study period ranged from June 2016 to September 2017. Variables involved in vitamin D metabolism and risk factors associated with hypovitaminosis were evaluated. The mean age was 45 years and 31.5 % were women. Vitamin D supplementation was effective in normalizing serum levels after six months in group 1 (mean 35 ng/mL compared to 21 ng/mL for the placebo group; p = 0.04). No patient reached blood levels considered toxic (>100 UI). Efavirenz use can negatively influence vitamin D levels and supplementation is necessary as a likely adjunct to improving CD4+ T cells, resulting in greater effectiveness of the treatment. A weekly oral dose of 50,000 IU of vitamin D was sufficient to normalize the vitamin deficiency, safely and with good adherence among persons living with HIV/AIDS in Brazil.

Randomized Trial of Ruxolitinib in Antiretroviral-Treated Adults With Human Immunodeficiency Virus.

Inflammation is associated with end-organ disease and mortality for people with human immunodeficiency virus (PWH). Ruxolitinib, a Jak 1/2 inhibitor, reduces systemic inflammation for individuals without human immunodeficiency virus (HIV) and HIV reservoir markers ex vivo. The goal of this trial was to determine safety and efficacy of ruxolitinib for PWH on antiretroviral therapy (ART). AIDS Clinical Trials Group (ACTG) A5336 was an open-label, multisite, randomized controlled trial (RCT). Participants were randomly assigned (2:1) using centralized software to ruxolitinib (10 mg twice daily) plus stable ART for 5 weeks vs ART alone, stratified by efavirenz use. Eligible participants were suppressed on ART for ≥2 years, without comorbidities, and had >350 CD4+ T cells/µL. Primary endpoints were premature discontinuation, safety events, and change in plasma interleukin 6 (IL-6). Secondary endpoints included other measures of inflammation/immune activation and HIV reservoir. Sixty participants were enrolled from 16 May 2016 to 10 January 2018. Primary safety events occurred in 2.5% (1 participant) for ruxolitinib and 0% for controls (P = .67). Three participants (7.5%) prematurely discontinued ruxolitinib. By week 5, differences in IL-6 (mean fold change [FC], 0.93 vs 1.10; P = .18) and soluble CD14 (mean FC, 0.96 vs 1.08; relative FC, 0.96 [90% confidence interval {CI}, .90-1.02]) levels for ruxolitinib vs controls was observed. Ruxolitinib reduced CD4+ T cells expressing HLA-DR/CD38 (mean difference, -0.34% [90% CI, -.66% to -.12%]) and Bcl-2 (mean difference, -3.30% [90% CI, -4.72% to -1.87%]). In this RCT of healthy, virologically suppressed PWH on ART, ruxolitinib was well-tolerated. Baseline IL-6 levels were normal and showed no significant reduction. Ruxolitinib significantly decreased markers of immune activation and cell survival. Future studies of Jak inhibitors should target PWH with residual inflammation despite suppressive ART. NCT02475655.

The association between the use of efavirenz and the occurrence of depressive disorders among HIV-treated patients: An application of Bayesian cox regression

OBJECTIVES: Efavirenz therapy plays an important role in controlling the progression of HIV/AIDS. However, efavirenz often causes short-term side effects for the central nervous system, and it remained controversial as to whether efavirenz leads to depression or even suicidal attempt when applied for a longer period of time. The purpose of this study is to determine the association between the use of efavirenz and depressive disorders. METHODS: This study explored the use of efavirenz on HIV-infected patients using National Health Insurance Research Database (NHIRD) in Taiwan by Bayesian survival analysis and investigated whether the use of efavirenz has the risk of depressive disorders. To reduce the dependence of statistical modeling assumptions, this study applied propensity score matching to research data. RESULTS: Based on the result of this study, it can be found that the use of efavirenz (HR = 1.009, 95% CI=–0.505 0.554), gender (HR = 0.324, 95% CI = –2.544 0.381) were not significantly associated with the occurrence of depressive disorders, whereas age of HIV diagnosis (HR = 1.021, 95% CI = 0.011 0.055) was significantly associated with the occurrence of depressive disorders. This study concludes that the use of efavirenz does not in-crease the risk of depressive disorders among HIV-treated patients. CONCLUSIONS: For the care of HIV-infected patients (especially the older ones), the psychological harm from society, such as lack of social support, social stigma or unemployment is higher than the harm of medicine.

Death-related factors in HIV/AIDS patients undergoing hemodialysis in an intensive care unit.

ABSTRACTHIV-infected patients are at high risk for developing critical diseases, including opportunistic infections (OI), with consequent admission in intensive care units (ICU). Renal disfunctions are risk factors for death in HIV/AIDS patients, and survival rates in patients undergoing hemodialysis are smaller than the ones observed in the general population. In this context, this study aimed to investigate death-related factors in HIV/AIDS patients in an intensive care setting. This is a retrospective cross-sectional study performed through the analysis of medical records from 271 HIV/AIDS-diagnosed patients hospitalized in an intensive care unit of an infectious disease hospital, in Fortaleza, Ceara State, Brazil. Patients were divided into two groups: those who underwent dialysis during hospitalization and those who did not. Clinical and demographic parameters that could be associated with death were evaluated. Results indicated a prevalence of death of 19.1% (CI 95%: 14.8-24.3). The median age of patients was 47 years, with a male predominance (71.3%). The main causes of admission were pulmonary tuberculosis (16.9%), followed by neurotoxoplasmosis (14.9%). In the bivariate analysis, for those that did not undergo dialysis, age, fever, dyspnea, oliguria, disorientation, kidney injury, use of lamivudine and efavirenz, length of hospitalization, CD4 count, WBC count, platelet count, urea, sodium and LDH levels were the associated variables. In those who needed dialysis, the use of stavudine, abacavir and ritonavir, and the length of hospitalization were associated factors. Renal toxicity by the antiretroviral agents and length of hospitalization increased the risk of death among HIV patients under dialysis.

Longitudinal trends and determinants of patient-reported side effects on ART-a Swedish national registry study.

The use of patient-reported outcomes (PROs) to systematically quantify adverse events (AE) will assist in the improvement of medical care and the QoL of patients living with HIV (PLWH). The aim of this study was to investigate the associations between self-reported side effects and other PROs, demographics and laboratory data, and further evaluate the Health Questionnaire (HQ) as a tool for following trends in patient-reported side effects over time in relation to trends in prescribed third agent in ART. The Swedish National Registry InfCareHiv includes an annual self-reported nine-item HQwhich is used in patient-centered HIV care in all Swedish HIV units. In this study, the experience of side effects was addressed. We analyzed 9,476 HQs completed by 4,186 PLWH together with details about their prescribed ART and relevant biomarkers collected during 2011-2017. Data were analyzed using descriptive statistics, Pearson's correlation coefficient and mixed logistic regression. The cross-sectional analysis of the HQs showed that the frequency of reported side effects decreased from 32% (2011) to 15% (2017). During the same period, there was a shift in ART prescription from efavirenz (EFV) to dolutegravir (DTG) (positive correlation coefficient r = 0.94, p = 0.0016). Further, PLWH who reported being satisfied with their physical health (OR: 0.47, p = <0.001) or psychological health (OR: 0.70, p = 0.001) were less likely to report side effects than those less satisfied. Self-reported side effects were found to have a close relationship with the patient's ratings of their overall health situation and demonstrated a strong correlation with the sharp decline in use of EFV and rise in use of DTG, with reported side effects being halved. This study supports the feasibility of using the HQ as a tool for longitudinal follow up of trends in PROs.

Drug-drug interaction between itraconazole capsule and efavirenz in adults with HIV for talaromycosis treatment.

To assess the pharmacokinetic of itraconazole capsule formulation and its active metabolite, hydroxyitraconazole, in adults with HIV diagnosed with talaromycosis in an endemic area, and to evaluate the drug-drug interaction between itraconazole/hydroxyitraconazole (ITC/OH-ITC) and efavirenz. Open-label, single arm, sequential pharmacokinetic study. Eligible subjects were adults with HIV, ≥18 years old, with confirmed talaromycosis, initiating itraconazole capsule as part of standard talaromycosis treatment, in whom efavirenz-based ART was anticipated. Steady-state pharmacokinetic assessments (pre-dose and at 1, 3, 4, 5, 6, 8 and 12 h post dose) were performed for itraconazole/hydroxyitraconazole without and with efavirenz use. Mid-dose efavirenz concentrations were also assessed. Pharmacokinetics parameters were calculated using non-compartmental analysis. Ten subjects (70% male) were enrolled. At entry, median (range) age was 29.5 years (22-64), and CD4 cell count was 18.0 (1-39) cells/mm3. Geometric mean (95% CI) of itraconazole and hydroxyitraconazole AUC0-12 without efavirenz were 9097 (6761-12 239) and 11 705 (8586-15 959) ng·h/mL, respectively, with a median metabolic ratio of OH-ITC : ITC of 1.3 (95% CI 0.9-1.9). Intra-subject comparison revealed that both itraconazole and hydroxyitraconazole exposures were significantly reduced with concomitant efavirenz use, with the mean AUC0-12 of itraconazole and hydroxyitraconazole being 86% (71%-94%) and 84% (64%-97%) lower, respectively. With efavirenz, itraconazole trough concentrations were also below the recommended therapeutic level (0.5 μg/mL). All subjects had mid-dose efavirenz concentrations >1000 ng/mL. Concomitant administration of itraconazole capsule with efavirenz significantly reduced itraconazole and hydroxyitraconazole exposures. The clinical impact of this drug-drug interaction on talaromycosis treatment or prophylaxis in the era of potent ART needs further evaluation.