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Find video protocols related to scientific articles indexed in Pubmed.
The development of simple anthropometric measures to diagnose antiretroviral therapy-associated lipodystrophy in resource limited settings.
AIDS Res Ther
PUBLISHED: 08-04-2014
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Lipohypertrophy does not appear to be an adverse ART reaction while lipoatrophy is clearly associated with the use of stavudine (d4T) and zidovudine (AZT). In low and middle income countries d4T has only recently been phased out and AZT is still widely being used. Several case definitions have been developed to diagnose lipodystrophy, but none of them are generalizable to sub-Saharan Africa where black women have less visceral adipose tissue and more subcutaneous adipose tissue than white women. We aimed to develop a simple, objective measure to define lipoatrophy and lipohypertrophy by comparing patient report to anthropometric and dual-energy X-ray absorptiometry (DXA) -derived variables.
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HIV infection: epidemiology, pathogenesis, treatment, and prevention.
Lancet
PUBLISHED: 06-05-2014
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HIV prevalence is increasing worldwide because people on antiretroviral therapy are living longer, although new infections decreased from 3.3 million in 2002, to 2.3 million in 2012. Global AIDS-related deaths peaked at 2.3 million in 2005, and decreased to 1.6 million by 2012. An estimated 9.7 million people in low-income and middle-income countries had started antiretroviral therapy by 2012. New insights into the mechanisms of latent infection and the importance of reservoirs of infection might eventually lead to a cure. The role of immune activation in the pathogenesis of non-AIDS clinical events (major causes of morbidity and mortality in people on antiretroviral therapy) is receiving increased recognition. Breakthroughs in the prevention of HIV important to public health include male medical circumcision, antiretrovirals to prevent mother-to-child transmission, antiretroviral therapy in people with HIV to prevent transmission, and antiretrovirals for pre-exposure prophylaxis. Research into other prevention interventions, notably vaccines and vaginal microbicides, is in progress.
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Isoniazid plus antiretroviral therapy to prevent tuberculosis: a randomised double-blind, placebo-controlled trial.
Lancet
PUBLISHED: 05-13-2014
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Antiretroviral therapy reduces the risk of tuberculosis, but tuberculosis is more common in people with HIV than in people without HIV. We aimed to assess the effect of isoniazid preventive therapy on the risk of tuberculosis in people infected with HIV-1 concurrently receiving antiretroviral therapy.
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Tuberculosis preventive therapy: an underutilised strategy to reduce individual risk of TB and contribute to TB control.
S. Afr. Med. J.
PUBLISHED: 04-06-2014
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Tuberculosis (TB) remains a global health problem, and South Africa (SA) has one of the world's worst TB epidemics. The World Health Organization (WHO) estimated in 1999 that one-third of the world's population was latently infected with TB. In SA up to 88% of HIV-uninfected young adults (31 - 35 years) are latently infected with TB. In the most recent meta-analysis, 6 - 12 months of isoniazid preventive therapy (IPT) was associated with a lower incidence of active TB than placebo (relative risk (RR) 0.68; 95% confidence interval (CI) 0.54 - 0.85), with the greatest benefit among individuals with a positive tuberculin skin test (TST) (RR 0.38; 95% CI 0.25 - 0.57). A clinical trial of IPT given with antiretroviral therapy (ART) for 12 months reduced TB incidence by 37% compared with ART alone (hazard ratio (HR) 0.63; 95% CI 0.41 - 0.94). The effect of IPT is limited in high-burden countries. IPT for 36 months v. 6 months reduced TB incidence among HIV-positive, TST-positive participants by 74% (HR 0.26; 95% CI 0.09 - 0.80). A study of more than 24 000 goldminers confirmed that IPT is safe, with only 0.5% experiencing adverse events. A meta-analysis of studies of IPT since 1951 did not show an increased risk of developing resistance. Alternative TB preventive therapy regimens, including high-dose isoniazid and rifapentine given weekly for 3 months, have been shown to have similar efficacy to IPT. Mathematical modelling suggests that scaling up continuous IPT targeted to HIV-positive persons, when used in combination with other treatment and prevention strategies, may substantially improve TB control.
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Plasma lopinavir concentrations predict virological failure in a cohort of South African children initiating a protease-inhibitor-based regimen.
Antivir. Ther. (Lond.)
PUBLISHED: 02-12-2014
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Poor adherence to antiretroviral therapy contributes to pharmacokinetic variability and is the major determinant of virological failure. However, measuring treatment adherence is difficult, especially in children. We investigated the relationship between plasma lopinavir concentrations, pretreatment characteristics and viral load >400 copies/ml.
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Effects of rifampin-based antituberculosis therapy on plasma efavirenz concentrations in children vary by CYP2B6 genotype.
AIDS
PUBLISHED: 11-02-2013
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An efavirenz-based antiretroviral therapy (ART) regimen is preferred for children more than 3 years of age with tuberculosis. However, rifampin, a key component of antituberculosis therapy, induces CYP2B6. An increased dose of efavirenz is recommended in adults weighing more than 50 kg who require rifampin, but there is scant information in children being treated for tuberculosis.
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Neuronal toxicity of efavirenz: a systematic review.
Expert Opin Drug Saf
PUBLISHED: 07-29-2013
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Efavirenz commonly causes early neuropsychiatric side effects, but tolerance develops in most patients. There is emerging evidence that efavirenz use may damage neurons, which could result in impaired neurocognitive performance.
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Matrix metalloproteinases and tissue damage in HIV-tuberculosis immune reconstitution inflammatory syndrome.
Eur. J. Immunol.
PUBLISHED: 04-04-2013
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The HIV-TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) can complicate combined treatments for HIV-1 and TB. Little is known about tissue damage in TB-IRIS. Matrix metalloproteinases (MMPs) degrade components of the extracellular matrix and consequently may play a role in such immunopathology. Here we investigated the involvement of MMPs in TB-IRIS. We determined MMP transcript abundance and secreted protein in Mycobacterium tuberculosis stimulated PBMCs from 22 TB-IRIS patients and 22 non-IRIS controls. We also measured MMP protein levels in corresponding serum and the effect of prednisone - which reduces the duration of symptoms in IRIS patients - or placebo treatment on MMP transcript and circulating MMP protein levels. PBMCs from TB-IRIS had increased MMP-1, -3, -7, and -10 transcript levels when compared with those of controls at either 6 or 24 h. Similarly, MMP-1, -3, -7, and -10 protein secretion in stimulated cultures was higher in TB-IRIS than in controls. Serum MMP-7 concentration was elevated in TB-IRIS and 2 weeks of corticosteroid therapy decreased this level, although not significantly. TB-IRIS is associated with a distinct pattern of MMP gene and protein activation. Modulation of dysregulated MMP activity may represent a novel therapeutic approach to alleviate TB-IRIS in HIV-TB patients undergoing treatment.
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Mitochondrial genomics and antiretroviral therapy-associated metabolic complications in HIV-infected Black South Africans: a pilot study.
AIDS Res. Hum. Retroviruses
PUBLISHED: 03-15-2013
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Studies suggest that mitochondrial DNA (mtDNA) haplogroups are associated with antiretroviral therapy (ART)-related metabolic complications and distal sensory polyneuropathy (DSP), but there have been few studies in persons of African descent. We explored such associations in South African adults. Clinical and laboratory data and DNA specimens from a cross-sectional study were used. Sequencing and Phylotree determined African mtDNA subhaplogroups. Wilcoxon and regression analyses determined associations between mtDNA subhaplogroups and ART-related complications. The 171 participants represented six major haplogroups: L0 (n=78), L1 (n=3), L2 (n=30), L3 (n=53), L4 (n=1), and L5 (n=6). Analyses were restricted to 161 participants representing L0, L2, and L3: 78% were female; the median age was 36 years. All had been exposed to thymidine analogues, 42% were on lopinavir/ritonavir (lopinavir/r), and 58% were on either efavirenz or nevirapine. Median (IQR) ART duration was 22 (14-36) months. Median fasting triglycerides were 1.60 (1.13-1.75) and 1.04 (0.83-1.45) mmol/liter among L3e1 (n=22) and other subhaplogroups, respectively (p=0.003). Subhaplogroup L3e1 [adjusted OR (aOR) 3.16 (95% CI: 1.11-8.96); p=0.03] and exposure to lopinavir/r [aOR 2.98 (95% CI: 1.02-8.96); p=0.05] were independently associated with hypertriglyceridemia, after adjusting for age, sex, and ART duration. There were no significant associations between mtDNA haplogroups and cholesterol, dysglycemia, hyperlactatemia, or lipoatrophy, or DSP. Subhaplogroup L3e1 and lopinavir/r exposure were independently associated with hypertriglyceridemia in black South Africans on ART. This is the first report to link an African mtDNA variant with hypertriglyceridemia. If replicated, these findings may provide new insights into host factors affecting metabolic complications.
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Complications of antiretroviral therapy initiation in hospitalised patients with HIV-associated tuberculosis.
PLoS ONE
PUBLISHED: 02-08-2013
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HIV-associated tuberculosis is a common coinfection in Sub-Saharan Africa, which causes high morbidity and mortality. A sub-set of HIV-associated tuberculosis patients require prolonged hospital admission, during which antiretroviral therapy initiation may be required. The aim of this study was to document the causes of clinical deterioration of hospitalised patients with HIV-associated tuberculosis starting antiretroviral therapy in order to inform healthcare practice in low- to middle-income countries.
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A novel Markov model projecting costs and outcomes of providing antiretroviral therapy to public patients in private practices versus public clinics in South Africa.
PLoS ONE
PUBLISHED: 02-06-2013
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Providing private antiretroviral therapy (ART) care for public sector patients could increase access to ART in low- and middle-income countries. We compared the costs and outcomes of a private-care and a public-care ART program in South Africa.
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Patient-nominated, community-based HIV treatment supporters: patient perspectives, feasibility, challenges, and factors for success in HIV-infected South African adults.
AIDS Patient Care STDS
PUBLISHED: 02-05-2013
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This study aimed to characterize the experience of having a treatment supporter among HIV-infected South African patients enrolled in a randomized controlled trial that compared the efficacy of patient-nominated treatment supporters administering partial directly observed antiretroviral therapy (DOT-ART) versus self-administered ART (Self-ART). Results of the parent study showed no virologic or sustained immunologic differences between groups, but revealed a significant survival benefit among the DOT-ART group. One hypothesis is that this survival benefit may be explained by differences in the training and involvement of the treatment supporters between groups. In the current study, results from a semi-structured exit interview of 172 participants indicate that most participants in both arms maintained a positive, satisfying relationship with a single supporter, typically family member or friend. Most patients (82.6%) perceived supporters as helpful with medication adherence, with no significant difference between groups (p=0.752). Additionally, supporters provided emotional, instrumental, and material support. DOT-ART patients were more likely than Self-ART patients to report that their supporter helped to decrease drug or alcohol use (p=0.03). Patients identified supporter trustworthiness, availability, good communication and reciprocity of support as factors beneficial to a successful relationship. These results suggest: (1) Patient-nominated peers are feasible candidates for ART supporters in this resource-constrained setting; (2) In addition to assistance with medications, treatment supporters have the capacity to promote healthy behaviors and provide other types of support, which may contribute to improved outcomes, particularly with enhanced training; (3) Trustworthiness, availability, good communication, and reciprocity are key factors in a successful patient-supporter relationship.
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Effect of different antiretroviral drug regimens on body fat distribution of HIV-infected South African women.
AIDS Res. Hum. Retroviruses
PUBLISHED: 01-18-2013
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No African studies have examined the effect of first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based and second-line protease inhibitor (PI)-based antiretroviral therapy (ART) on body composition. We compared body composition in HIV-infected black South African women receiving NNRTI-based ART (ART1, n=344), PI-based ART (ART2, n=91), and those not on ART (ART-naive, n=309). Accordingly, body composition was measured using dual energy x-ray absorptiometry (DXA) and anthropometry in a cross-sectional study. Despite similar body mass index (BMI), ART1 and ART2 had greater central fat mass (FM) [median (IQR): 44.2 (39.4-50.1) and 46.9 (39.3-52.8) vs. 41.1 (36.3-45.2) %FM, p<0.01] and less leg FM [41.2 (34.8-45.8) and 40.2 (32.9-45.7) vs. 43.9 (39.3-48.1) %FM, p<0.01] than ART-naive women. Within ART1, waist:hip was greater [0.87 (0.81-0.92) vs. 0.84 (0.78-0.89), p=0.006], while calf skinfold was lower [15.2 (9.4-21.5) vs. 17.4 (12.0-23.6) mm, p=0.033] in women receiving efavirenz compared to nevirapine. ART2 had a greater waist:hip, and abdominal, subscapular, and suprailiac skinfolds than ART1 (p<0.05). After adjusting for time on d4T (stavudine), ART2 had greater body fat than ART1 (p<0.05). With increasing time on d4T, the decrease in leg fat (%FM) was higher in ART1 than ART2 (p=0.012, for time×treatment effect). A similar interaction was reported for total time on ART treatment (p=0.002 for time×treatment effect). In conclusion, ART was associated with increased central fat and reduced peripheral fat. Changing to a PI-based regimen in ART2, which also substitutes stavudine with zidovudine, partially reversed the peripheral fat loss observed on ART1.
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Role of the interleukin 10 family of cytokines in patients with immune reconstitution inflammatory syndrome associated with HIV infection and tuberculosis.
J. Infect. Dis.
PUBLISHED: 01-09-2013
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The interleukin 10 (IL-10) family comprises cytokines structurally related to IL-10 that share signaling receptors that have conserved signaling cascades. The immunopathogenesis of immune reconstitution inflammatory syndrome (IRIS) in patients with human immunodeficiency virus (HIV) infection and tuberculosis remains incompletely understood. We hypothesized that a deficiency of IL-10 and its homologs may contribute to the immunopathology of IRIS in these patients.
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Systematic review of antiretroviral-associated lipodystrophy: lipoatrophy, but not central fat gain, is an antiretroviral adverse drug reaction.
PLoS ONE
PUBLISHED: 01-01-2013
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Lipoatrophy and/or central fat gain are observed frequently in patients on antiretroviral therapy (ART). Both are assumed to be antiretroviral adverse drug reactions.
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The SLCO1B1 rs4149032 polymorphism is highly prevalent in South Africans and is associated with reduced rifampin concentrations: dosing implications.
Antimicrob. Agents Chemother.
PUBLISHED: 06-27-2011
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Among patients with tuberculosis, rifampin plasma concentrations and sputum conversion rates have been reported to be lower in Africans. Rifampin is a substrate of P-glycoprotein (coded for by the ABCB1 gene) and organic anion-transporting polypeptide 1B1 (coded for by SLCO1B1). The objectives were to identify genetic polymorphisms of drug transporters and the transcriptional regulators pregnane X receptor (PXR) and constitutive androstane receptor (CAR) with an impact on rifampin pharmacokinetics in South Africans. Fifty-seven patients with tuberculosis from Cape Town underwent pharmacokinetic sampling during treatment with rifampin, pyrazinamide, isoniazid, and ethambutol. DNA was genotyped for ABCB1, SLCO1B1, PXR, and CAR polymorphisms by using real-time PCR. NONMEM was used for data analysis. The allele frequency of the SLCO1B1 rs4149032 polymorphism was 0.70. Patients heterozygous and homozygous for this polymorphism had reductions in the bioavailability (and, thus, the area under the curve [AUC]) of rifampin of 18% and 28%, respectively. Simulations showed that increasing the daily rifampin dose by 150 mg in patients with the polymorphism would result in plasma concentrations similar to those of wild-type individuals and reduce the percentage of patients with peak plasma concentrations (C(max)) below 8 mg/liter from 63% to 31%. ABCB1, PXR, and CAR polymorphisms were not associated with differences in rifampin pharmacokinetics. SLCO1B1 rs4149032 was present in most patients and was associated with substantially reduced rifampin exposure. These data suggest that the standard recommended dose of rifampin should be reconsidered for South Africans.
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Effect of nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy on dysglycemia and insulin sensitivity in South African HIV-infected patients.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 05-24-2011
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Data on the prevalence of the complications of antiretroviral therapy (ART) (diabetes, central fat accumulation, peripheral fat wasting, and dyslipidemia) in sub-Saharan Africa are sparse. We examined the prevalence and associated risk factors of dysglycemia and insulin sensitivity in HIV-infected South Africans.
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Lopinavir exposure is insufficient in children given double doses of lopinavir/ritonavir during rifampicin-based treatment for tuberculosis.
Antivir. Ther. (Lond.)
PUBLISHED: 05-11-2011
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Coadministration of rifampicin dramatically reduces the concentrations of protease inhibitors. A pharmacokinetic study in healthy adults showed that doubling the dose of coformulated lopinavir/ritonavir was able to overcome the inducing effect of rifampicin. We evaluated this strategy in children treated with rifampicin-based antituberculosis therapy attending antiretroviral clinics in South Africa.
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Pharmacokinetics of lopinavir in HIV-infected adults receiving rifampin with adjusted doses of lopinavir-ritonavir tablets.
Antimicrob. Agents Chemother.
PUBLISHED: 05-02-2011
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Rifampin coadministration dramatically reduces plasma lopinavir (LPV) concentrations. In healthy volunteers, doubling the dose of a lopinavir-ritonavir (LPV/r) capsule formulation overcame this interaction, but a subsequent study of double doses of the tablet formulation was stopped early owing to hepatotoxicity. However, healthy-volunteer study findings may not apply to HIV-infected adults. We evaluated the steady-state pharmacokinetics of LPV in HIV-infected adults virologically suppressed on an LPV/r regimen who were given rifampin, and the dose of the LPV/r tablet formulation was gradually increased. The steady-state pharmacokinetics of LPV/r were evaluated at baseline, a week after commencing rifampin, a week after the LPV/r dose was increased 1.5 times, and a week after the LPV/r dose was doubled. Twenty-one participants were enrolled. The median [interquartile range (IQR)] predose LPV concentrations (C(0)) were 8.1 (6.2 to 9.8) mg/liter at baseline, 1.7 (0.3 to 3.0) mg/liter after 7 days of rifampin, 5.9 (2.1 to 9.9) mg/liter with 1.5 times the dose of LPV/r, and 10.8 (7.0 to 13.1) mg/liter with double-dose LPV/r. There were no significant differences in the LPV area under the plasma concentration-time curve from 0 to 12 h (AUC(0-12)), C(0), C(12), maximum concentration of drug in serum (C(max)), or half-life (t(1/2)) between the baseline and double-dose LPV/r time points. Treatment was generally well tolerated, with two participants developing asymptomatic grade 3/4 transaminitis. Doubling the dose of the tablet formulation of LPV/r overcomes induction by rifampin. Less hepatotoxicity occurred in our cohort of HIV-infected participants than was reported in healthy-volunteer studies.
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Factors influencing retention in care after starting antiretroviral therapy in a rural South African programme.
PLoS ONE
PUBLISHED: 03-28-2011
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The prognosis of patients with HIV in Africa has improved with the widespread use of antiretroviral therapy (ART) but these successes are threatened by low rates of long-term retention in care. There are limited data on predictors of retention in care, particularly from rural sites.
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Development of a standardized screening rule for tuberculosis in people living with HIV in resource-constrained settings: individual participant data meta-analysis of observational studies.
PLoS Med.
PUBLISHED: 01-18-2011
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The World Health Organization recommends the screening of all people living with HIV for tuberculosis (TB) disease, followed by TB treatment, or isoniazid preventive therapy (IPT) when TB is excluded. However, the difficulty of reliably excluding TB disease has severely limited TB screening and IPT uptake in resource-limited settings. We conducted an individual participant data meta-analysis of primary studies, aiming to identify a sensitive TB screening rule.
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Low lopinavir plasma or hair concentrations explain second-line protease inhibitor failures in a resource-limited setting.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 01-18-2011
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In resource-limited settings, many patients, with no prior protease inhibitor (PI) treatment on a second-line, high genetic barrier, ritonavir-boosted PI-containing regimen have virologic failure.
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Performance of serum C-reactive protein as a screening test for smear-negative tuberculosis in an ambulatory high HIV prevalence population.
PLoS ONE
PUBLISHED: 01-10-2011
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Delayed diagnosis has contributed to the high mortality of sputum smear-negative tuberculosis (SNTB) in high HIV prevalence countries. New diagnostic strategies for SNTB are urgently needed. C-reactive protein (CRP) is a non-specific inflammatory protein that is usually elevated in patients with tuberculosis, but its role in the diagnosis of tuberculosis is uncertain.
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The effect of vitamin A and zinc supplementation on treatment outcomes in pulmonary tuberculosis: a randomized controlled trial.
Am. J. Clin. Nutr.
PUBLISHED: 11-10-2010
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Low serum concentrations of vitamin A and zinc are common in tuberculosis and may have an adverse effect on host cell-mediated responses. The role of adjunctive micronutrient supplementation on treatment outcomes is uncertain.
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Randomized placebo-controlled trial of prednisone for paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome.
AIDS
PUBLISHED: 09-03-2010
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Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a frequent complication of antiretroviral therapy in resource-limited countries. We aimed to assess whether a 4-week course of prednisone would reduce morbidity in patients with paradoxical TB-IRIS without excess adverse events.
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Improving the evidence base of Markov models used to estimate the costs of scaling up antiretroviral programmes in resource-limited settings.
BMC Health Serv Res
PUBLISHED: 07-02-2010
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Despite concerns about affordability and sustainability, many models of the lifetime costs of antiretroviral therapy (ART) used in resource limited settings are based on data from small research cohorts, together with pragmatic assumptions about life-expectancy. This paper revisits these modelling assumptions in order to provide input to future attempts to model the lifetime costs and the costs of scaling up ART.
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Population pharmacokinetics of lopinavir in combination with rifampicin-based antitubercular treatment in HIV-infected South African children.
Eur. J. Clin. Pharmacol.
PUBLISHED: 05-19-2010
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The population pharmacokinetics (PK) of lopinavir in tuberculosis (TB)/human immunodeficiency virus (HIV) co-infected South African children taking super-boosted lopinavir (lopinavir/ritonavir ratio 1:1) as part of antiretroviral treatment in the presence of rifampicin were compared with the population PK of lopinavir in HIV-infected South African children taking standard doses of lopinavir/ritonavir (ratio 4:1).
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Randomized controlled trial of trained patient-nominated treatment supporters providing partial directly observed antiretroviral therapy.
AIDS
PUBLISHED: 05-11-2010
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Directly observed therapy (DOT) for antiretroviral therapy (ART) may improve adherence, but there are limited data on its clinical effectiveness.
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Clinical deterioration during antituberculosis treatment in Africa: incidence, causes and risk factors.
BMC Infect. Dis.
PUBLISHED: 03-30-2010
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HIV-1 and Mycobacterium tuberculosis cause substantial morbidity and mortality. Despite the availability of antiretroviral and antituberculosis treatment in Africa, clinical deterioration during antituberculosis treatment remains a frequent reason for hospital admission. We therefore determined the incidence, causes and risk factors for clinical deterioration.
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Lack of association between stavudine exposure and lipoatrophy, dysglycaemia, hyperlactataemia and hypertriglyceridaemia: a prospective cross sectional study.
AIDS Res Ther
PUBLISHED: 03-22-2010
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Stavudine continues to be widely used in resource poor settings despite its toxicity. Our objective was to determine association between plasma stavudine concentrations and lipoatrophy, concentrations of glucose, lactate and triglycerides.
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Seven-year experience of a primary care antiretroviral treatment programme in Khayelitsha, South Africa.
AIDS
PUBLISHED: 01-09-2010
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We report on outcomes after 7 years of a community-based antiretroviral therapy (ART) programme in Khayelitsha, South Africa, with death registry linkages to correct for mortality under-ascertainment.
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Association of antiretroviral therapy adherence and health care costs.
Ann. Intern. Med.
PUBLISHED: 01-06-2010
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Antiretroviral therapy (ART) adherence predicts HIV disease progression and survival, but its effect on direct health care costs is unclear.
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Effectiveness and safety of antiretrovirals with rifampicin: crucial issues for high-burden countries.
Antivir. Ther. (Lond.)
PUBLISHED: 12-25-2009
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Coadministration of antitubercular and antiretroviral therapy is common in high-burden countries where tuberculosis is the commonest opportunistic infection. Concomitant use of rifampicin and many antiretroviral drugs is complicated by drug-drug interactions caused by the potent induction by rifampicin of genes involved in drug metabolism and transport, which could result in subtherapeutic antiretroviral drug concentrations. This review focuses on drug-drug interactions involving antiretrovirals used in resource-limited settings: the non-nucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz or nevirapine, and ritonavir-boosted protease inhibitors. The reduction of nevirapine concentrations with concomitant rifampicin is greater than with efavirenz, particularly during the lead-in dose period when subtherapeutic concentrations occur in the majority of patients. There is reassuring data on the effectiveness of standard doses of efavirenz with concomitant rifampicin, but the largest cohort study found a higher risk of virological failure with nevirapine. The drug-drug interaction between rifampicin and ritonavir-boosted protease inhibitors is more marked than with the NNRTIs, and therapeutic concentrations have only been achieved with adjusted doses of lopinavir/ritonavir or with saquinavir/ritonavir (400/400 mg every 12 h). The major barrier to using adjusted dose protease inhibitors with rifampicin is the high rates of hepatotoxicity seen in healthy volunteers. The alternative strategy followed in resource-rich settings is to replace rifampicin with rifabutin, but even if the price of rifabutin were to be dramatically reduced it would be difficult to implement in high-burden countries where standardized antitubercular regimens with fixed-dose combinations are used.
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Effect of rifampicin-based antitubercular therapy and the cytochrome P450 2B6 516G>T polymorphism on efavirenz concentrations in adults in South Africa.
Antivir. Ther. (Lond.)
PUBLISHED: 08-26-2009
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Rifampicin induces expression of the cytochrome P450 isoenzyme 2B6 (CYP2B6), which metabolizes efavirenz. The CYP2B6 516G>T polymorphism impairs efavirenz metabolism and occurs more commonly in Africans than in Caucasians. We explored the effect of rifampicin-based antitubercular therapy and the 516G>T polymorphism on efavirenz concentrations in HIV-infected patients in South Africa.
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Dissection of regenerating T-Cell responses against tuberculosis in HIV-infected adults sensitized by Mycobacterium tuberculosis.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 07-23-2009
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Combination antiretroviral treatment (cART) reduces the risk of tuberculosis in HIV-infected people. Therefore a novel approach to gain insight into protection against tuberculosis is to analyze the T cells that expand in people sensitized by Mycobacterium tuberculosis (MTB) during cART.
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Clinical and financial burdens of secondary level care in a public sector antiretroviral roll-out setting (G. F. Jooste Hospital).
S. Afr. Med. J.
PUBLISHED: 07-11-2009
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Antiretroviral therapy (ART) is being extended across South Africa. While efforts have been made to assess the costs of providing ART via accredited service points, little information is available on its downstream costs, particularly in public secondary level hospitals.
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Neurologic manifestations of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome: a case series.
Clin. Infect. Dis.
PUBLISHED: 05-02-2009
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Paradoxical neurologic tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a potentially life-threatening condition that occurs within 3 months after starting combination antiretroviral therapy (ART). The reports in the published literature are anecdotal, and the prevalence and outcomes of neurologic TB-IRIS are unknown.
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Antiretroviral therapy adherence, virologic and immunologic outcomes in adolescents compared with adults in southern Africa.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 03-14-2009
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To determine adherence to and effectiveness of antiretroviral therapy (ART) in adolescents vs. adults in southern Africa.
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Safety and effectiveness of colistin compared with tobramycin for multi-drug resistant Acinetobacter baumannii infections.
BMC Infect. Dis.
PUBLISHED: 03-09-2009
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Nosocomial infections due to multi-drug resistant Acinetobacter baumannii are often treated with colistin, but there are few data comparing its safety and efficacy with other antimicrobials.
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Effect of rifampicin on efavirenz pharmacokinetics in HIV-infected children with tuberculosis.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 02-19-2009
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Rifampicin may reduce plasma efavirenz concentrations by inducing the expression of the cytochrome P450 2B6, which metabolizes efavirenz. However, there is no data in pediatric patient populations.
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Early severe morbidity and resource utilization in South African adults on antiretroviral therapy.
BMC Infect. Dis.
PUBLISHED: 02-10-2009
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High rates of mortality and morbidity have been described in sub-Saharan African patients within the first few months of starting highly active antiretroviral therapy (HAART). There is limited data on the causes of early morbidity on HAART and the associated resource utilization.
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Novel relationship between tuberculosis immune reconstitution inflammatory syndrome and antitubercular drug resistance.
Clin. Infect. Dis.
PUBLISHED: 02-05-2009
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Tuberculosis (TB) immune reconstitution inflammatory syndrome (IRIS) is emerging as an important early complication of combination antiretroviral therapy in patients with TB in developing countries. The differential diagnosis of TB IRIS includes deterioration caused by other human immunodeficiency virus-related morbidities and drug-resistant TB.
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Early and late direct costs in a Southern African antiretroviral treatment programme: a retrospective cohort analysis.
PLoS Med.
PUBLISHED: 01-09-2009
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There is a paucity of data on the health care costs of antiretroviral therapy (ART) programmes in Africa. Our objectives were to describe the direct heath care costs and establish the cost drivers over time in an HIV managed care programme in Southern Africa.
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Impact of immune reconstitution inflammatory syndrome on antiretroviral therapy adherence.
Patient Prefer Adherence
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We determined the impact of immune reconstitution inflammatory syndrome (IRIS) on antiretroviral therapy (ART) adherence in a cohort of 274 human immunodeficiency virus (HIV)-infected South African adults initiating ART.
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A time-to-event pharmacodynamic model describing treatment response in patients with pulmonary tuberculosis using days to positivity in automated liquid mycobacterial culture.
Antimicrob. Agents Chemother.
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Days to positivity in automated liquid mycobacterial culture have been shown to correlate with mycobacterial load and have been proposed as a useful biomarker for treatment responses in tuberculosis. However, there is currently no quantitative method or model to analyze the change in days to positivity with time on treatment. The objectives of this study were to describe the decline in numbers of mycobacteria in sputum collected once weekly for 8 weeks from patients on treatment for tuberculosis using days to positivity in liquid culture. One hundred forty-four patients with smear-positive pulmonary tuberculosis were recruited from a tuberculosis clinic in Cape Town, South Africa. A nonlinear mixed-effects repeated-time-to-event modeling approach was used to analyze the time-to-positivity data. A biexponential model described the decline in the estimated number of bacteria in patients sputum samples, while a logistic model with a lag time described the growth of the bacteria in liquid culture. At baseline, the estimated number of rapidly killed bacteria is typically 41 times higher than that of those that are killed slowly. The time to kill half of the rapidly killed bacteria was about 1.8 days, while it was 39 days for slowly killed bacteria. Patients with lung cavitation had higher bacterial loads than patients without lung cavitation. The model successfully described the increase in days to positivity as treatment progressed, differentiating between bacteria that are killed rapidly and those that are killed slowly. Our model can be used to analyze similar data from studies testing new drug regimens.
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Effect of antiretroviral therapy on the diagnostic accuracy of symptom screening for intensified tuberculosis case finding in a South African HIV clinic.
Clin. Infect. Dis.
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Current symptom screening algorithms for intensified tuberculosis case finding or prior to isoniazid preventive therapy (IPT) in patients infected with human immunodeficiency virus (HIV) were derived from antiretroviral-naive cohorts. There is a need to validate screening algorithms in patients on antiretroviral therapy (ART).
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Corticosteroid-modulated immune activation in the tuberculosis immune reconstitution inflammatory syndrome.
Am. J. Respir. Crit. Care Med.
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HIV-tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an immunopathological reaction to mycobacterial antigens induced by antiretroviral therapy. Prednisone reduces morbidity in TB-IRIS, but the mechanisms are unclear.
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The role of the infectious diseases unit at Groote Schuur Hospital in addressing South Africas greatest burden of disease.
S. Afr. Med. J.
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The greatest burden of disease in South Africa (SA) comes from infectious diseases (ID), with human immunodeficiency virus (HIV) and tuberculosis (TB) dominating the health landscape. However, other infections including community-acquired and imported infections and the rise in hospital-acquired infections pose a considerable threat to public health.
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Burden of antituberculosis and antiretroviral drug-induced liver injury at a secondary hospital in South Africa.
S. Afr. Med. J.
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G F Jooste Hospital (GFJH) is a secondary-level referral hospital in a high HIV and tuberculosis (TB) co-infection setting.
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The safety, effectiveness and concentrations of adjusted lopinavir/ritonavir in HIV-infected adults on rifampicin-based antitubercular therapy.
PLoS ONE
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Rifampicin co-administration dramatically reduces plasma lopinavir concentrations. Studies in healthy volunteers and HIV-infected patients showed that doubling the dose of lopinavir/ritonavir (LPV/r) or adding additional ritonavir offsets this interaction. However, high rates of hepatotoxicity were observed in healthy volunteers. We evaluated the safety, effectiveness and pre-dose concentrations of adjusted doses of LPV/r in HIV infected adults treated with rifampicin-based tuberculosis treatment.
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Baseline predictors of sputum culture conversion in pulmonary tuberculosis: importance of cavities, smoking, time to detection and W-Beijing genotype.
PLoS ONE
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Time to detection (TTD) on automated liquid mycobacterial cultures is an emerging biomarker of tuberculosis outcomes. The M. tuberculosis W-Beijing genotype is spreading globally, indicating a selective advantage. There is a paucity of data on the association between baseline TTD and W-Beijing genotype and tuberculosis outcomes.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.