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Risk factors of treatment-limiting anemia after substitution of zidovudine for stavudine in HIV-infected adult patients on antiretroviral treatment.

ABSTRACT: BACKGROUND: Anemia is the main concern among patients using a zidovudine (AZT)-based antiretroviral treatment (ART). Some studies suggested weight-adjusted AZT dosing as a way to reduce toxicity. We analyzed the risk factors associated with AZT-induced anemia in a cohort using AZT as substitution for stavudine (D4T). METHODS: We retrospectively studied HIV-infected patients in a referral hospital in Phnom Penh, Cambodia between 2003 and 2011. Factors associated with AZT-related anemia requiring AZT-discontinuation within the first year after AZT initiation were analyzed using Cox regression. RESULTS: Overall, 1180 patients, 60.5% female, were included. At AZT initiation, the median hemoglobin was 12.7 g/dL (IQR 11.7-13.9), the median weight: 51 kg (IQR 45-58) and the median time on ART prior to AZT substitution: 1.4 years (IQR 1.0-2.0). Within one year follow-up, 139 patients (11.8%) developed anemia requiring AZT discontinuation. Overall, there was no independent association of body weight with AZT discontinuation. AZT discontinuation was associated with lower hemoglobin level when starting AZT; older age and taking D4T-based ART less than one year prior to AZT. In exploratory analysis, a linear increase in risk of grade 2-4 anemia with lower body weight was seen if starting AZT substitution within less than one year of D4T-based ART. CONCLUSION: Our findings argue against the need of weight-based dosing of AZT to reduce anemia among patients using AZT as substitution for D4T. Whether this also applies to ART-naïve individuals remains to be assessed. Future studies with AZT dose reduction should assess efficacy and overall tolerance of AZT.

SUBMITTER: Phe T

PROVIDER: S-EPMC3608603 | biostudies-other | 2013

REPOSITORIES: biostudies-other

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Risk factors of treatment-limiting anemia after substitution of zidovudine for stavudine in HIV-infected adult patients on antiretroviral treatment.

Phe Thong T Thai Sopheak S Veng Chhunheng C Sok Sopheak S Lynen Lutgarde L van Griensven Johan J

PloS one 20130326 3

<h4>Background</h4>Anemia is the main concern among patients using a zidovudine (AZT)-based antiretroviral treatment (ART). Some studies suggested weight-adjusted AZT dosing as a way to reduce toxicity. We analyzed the risk factors associated with AZT-induced anemia in a cohort using AZT as substitution for stavudine (D4T).<h4>Methods</h4>We retrospectively studied HIV-infected patients in a referral hospital in Phnom Penh, Cambodia between 2003 and 2011. Factors associated with AZT-related anem ...[more]

PMID: 23555926

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Project description:BackgroundExisting studies have suggested decreased adherence and rebound in mortality in perinatally HIV-infected adolescents receiving antiretroviral therapy (ART) as compared to adults and young children.MethodsWe used both quantitative and qualitative approaches to identify factors influencing adherence among perinatally infected adolescents in Thailand. We analyzed data from 568 pairs of perinatally infected adolescents (aged 12-19) and their primary caregivers in the Teens Living With Antiretrovirals (TEEWA) study, a cross-sectional survey conducted in 2010-2012. We also conducted 12 in-depth interviews in 2014 with infected adolescents or their primary caregivers to elicit experiences of living with long-term ART.ResultsFrom the quantitative analysis, a total of 275 (48.4%) adolescents had evidence of suboptimal adherence based on this composite outcome: adolescents self-reported missing doses in the past 7 days, caregiver rating of overall adherence as suboptimal, or latest HIV-RNA viral load ≥1000 copies/ml. In multivariate logistic regression analysis, younger age, having grandparents or extended family members as the primary caregiver, caregiver-assessed poor intellectual ability, having a boy/girlfriend, frequent online chatting, self-reported unhappiness and easiness in asking doctors questions were significantly associated with suboptimal adherence. From the in-depth interviews, tensed relationships with caregivers, forgetfulness due to busy schedules, and fear of disclosing HIV status to others, especially boy/girlfriends, were important contributors to suboptimal adherence. Social and emotional support and counseling from peer group was consistently reported as a strong adherence-promoting factor.ConclusionOur findings highlight unique barriers of ART adherence among the perinatally infected adolescents. Future interventions should be targeted at helping adolescents to improve interpersonal relationships and build adaptive skills in recognizing and addressing challenging situations related to ART taking.

Project description:This study examined whether the type of anemia in persons living with HIV/AIDS (PLWHA) changed from the beginning of highly antiretroviral therapy (HAART) and had implications for treatment outcomes and quality of life (QOL). If present, the anemia-type was defined as microcytic, macrocytic or anemia of chronic disease (ACD) at study months 0, 6, 12, and 18. Multinomial logistic regression quantified sociodemographic and HIV-treatment factors associated with incident microcytic anemia or ACD over 18 months. Repeated measures linear regression models estimated the anemia-type associated change in the CD4 cell-count, QOL, body mass index (BMI) and frailty over 18 months. Cox proportional hazard models estimated associations between anemia-type and time to (a) gain at least 100 CD4 cells/L and (b) hospitalization/death. Analyses were implemented in Statistical Analysis Software (v.9.4) from which odds ratios (ORs) mean differences (?) and corresponding 95% confidence intervals (CI) were estimated. At enrollment, ACD, macrocytic and microcytic anemia was present in 36.8% (n = 147), 11.3% (n = 45) and 9.5% (n = 38), respectively with 42% (n = 170) anemia-free. By the study end, only 23% (n = 115) were without anemia. Among the 251 with anemia at the study end, 53.3% (n = 195) had macrocytic anemia, 12.8% (n = 47) had ACD and 2.5% (n = 9) had microcytic anemia. Incident macrocytic anemia was positively associated with baseline hyperferritinemia (OR = 1.85, 95%CI: 1.03?3.32), inversely associated with wealth (OR = 0.87, 95%CI: 0.67?1.03) and inversely associated with efavirenz-containing HAART (OR = 0.42, 95%CI: 0.21?0.85). ACD incidence decreased by 53% (95%CI: 0.27?0.79) per 100 cells/L increase in baseline CD4-cell count and decreased by 90% (95%CI: 0.01,0.87) among adults treated with nevirapine-containing HAART. ACD was associated with a lower BMI at months 6 (? = -0.33, 95% CI: -0.64, -0.01) and 12 (? = -0.41, 95%CI: -0.73, -0.09), with lower QOL (? = -3.2, 95%CI: -5.94, -0.53) at month 12 and with elevated frailty (? = 1.2; 95%CI: 0.46, 1.86) at month 12. Macrocytic anemia did not predict a post-enrollment change in CD4, BMI or QOL during follow-up. However, the time to gain 100 CD4 cells/L was 43% slower (p < 0.05) and the frailty was higher at month 12 for PLWHA with the baseline or sustained macrocytic vs. no anemia. A substantial decline in ACD and microcytic anemia occurred in tandem with large increase in the macrocytic anemia over 18 months on HAART. Interventions to mitigate all anemia-particularly ACD, is expected to improve the immune recovery rate, lower frailty, and enhanced QOL.

Project description:BackgroundAntiretroviral treatment (ART) has been shown to have a beneficial effect on the weight evolution but its effect on height remains unclear. We described patterns of height evolution and identified predictors of catch-up growth in HIV-infected children on ART.MethodsTo describe the height evolution from birth to adulthood, we developed a nonlinear mixed effect model using data from perinatally HIV-infected children who initiated ART from 1999 to 2013 in a prospective cohort study in Thailand. The main covariates of interest were: sex, ART regimen (dual nucleoside reverse-transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor (NNRTI)-, or protease inhibitor (PI)-based), baseline CD4 percentage, HIV-RNA load and CDC HIV Classification stage and occurrence of AIDS-defining events.ResultsA total 477 children (43% boys) contributed 18,596 height measurements over a median duration of 6.3 years on ART (interquartile range, 3.0 to 8.3). At ART initiation, median age was 6.2 years (1.8 to 9.6), 16% of children were underweight (weight-for-age z-score < - 2), 49% presented stunting (height-for-age z-score < - 2), and 7% wasting (weight-for-height z-score < - 2). The most frequent regimen at ART initiation was NNRTI-based (79%). A model with 4 components, birth length and 3 exponential functions of age accounting for the 3 growth phases was developed and show that the height-growth velocity was inversely associated with the age at ART initiation, the adult height was significantly lower in those who had experienced at least one AIDS-defining event while, as expected, the model found that adult height in females was lower than in males. Age at ART initiation, type of ART regimen, CDC stage, CD4 percentages, and HIV-RNA load were not associated with the final height.ConclusionsThe younger the children at ART initiation, the greater the effect on height-growth velocity, supporting the World Health Organization's recommendation to start ART as early as possible. However, final adult height was not linked to the age at ART initiation.

Project description:BACKGROUND:Inflammation and hemostasis perturbation may be involved in vascular complications of HIV infection. We examined atherogenic biomarkers and subclinical atherosclerosis in HIV-infected adults before and after beginning highly active antiretroviral therapy (HAART). METHODS:In the Women's Interagency HIV Study, 127 HIV-infected women studied pre and post HAART were matched to HIV-uninfected controls. Six semiannual measurements of soluble CD14, tumor necrosis factor (TNF) alfa, soluble interleukin (IL) 2 receptor, IL-6, IL-10, monocyte chemoattractant protein 1, D-dimer, and fibrinogen were obtained. Carotid artery intima-media thickness was measured by B-mode ultrasound. RESULTS:Relative to HIV-uninfected controls, HAART-naive HIV-infected women had elevated levels of soluble CD14 (1945 vs 1662 ng/mL, Wilcoxon signed rank P < 0.0001), TNF-? (6.3 vs 3.4 pg/mL, P < 0.0001), soluble IL-2 receptor (1587 vs 949 pg/mL, P < 0.0001), IL-10 (3.3 vs 1.9 pg/mL, P < 0.0001), monocyte chemoattractant protein 1 (190 vs 163 pg/mL, P < 0.0001), and D-dimer (0.43 vs 0.31 ?g/mL, P < 0.01). Elevated biomarker levels declined after HAART. Although most biomarkers normalized to HIV-uninfected levels, in women on effective HAART, TNF-? levels remained elevated compared with HIV-uninfected women (+0.8 pg/mL, P = 0.0002). Higher post-HAART levels of soluble IL-2 receptor (P = 0.02), IL-6 (P = 0.05), and D-dimer (P = 0.03) were associated with increased carotid artery intima-media thickness. CONCLUSIONS:Untreated HIV infection is associated with abnormal hemostasis (eg, D-dimer), proatherogenic (eg, TNF-?), and antiatherogenic (eg, IL-10) inflammatory markers. HAART reduces most inflammatory mediators to HIV-uninfected levels. Increased inflammation and hemostasis are associated with subclinical atherosclerosis in recently treated women. These findings have potential implications for long-term risk of cardiovascular disease in HIV-infected patients, even with effective therapy.

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Risk factors of treatment-limiting anemia after substitution of zidovudine for stavudine in HIV-infected adult patients on antiretroviral treatment.

Publications

Risk factors of treatment-limiting anemia after substitution of zidovudine for stavudine in HIV-infected adult patients on antiretroviral treatment.

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