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Effect of Antiretroviral Therapy on Bone and Renal Health in Young Adults Infected With HIV in Early Life.

ABSTRACT: HIV antiretroviral (ARV) therapy is associated with renal and bone toxicity, but little is known about the potential cumulative effects in adults exposed to ARVs from birth.To prospectively evaluate renal and bone health in young adults with lifelong HIV and extensive ARV exposure.Cross-sectional comparison of bone mineral density (BMD) by dual-energy X-ray absorptiometry, bone turnover, and renal function in young adults infected with HIV in early life (n = 65) to matched healthy controls (n = 23) and longitudinal evaluation (mean follow-up = 4.4 years) within a subset of the HIV cohort (n = 33).Government outpatient research clinic.Albumin/creatinine ratio, protein/creatinine ratio, anion gap, N-terminal telopeptides, and osteocalcin were significantly increased in persons with HIV compared with controls, whereas whole-body BMD and BMD z scores were lower. Within the HIV group, duration of tenofovir disoproxil fumarate (TDF) correlated with higher anion gap but did not correlate with bone parameters. Longer duration of didanosine and stavudine use correlated with lower BMD and BMD z scores. Longitudinal analyses revealed that BMD and bone metabolism significantly improved over time. No subject had an estimated glomerular filtration rate (eGFR) <60, but decline in eGFR correlated with increasing years of TDF exposure.Subclinical markers of renal dysfunction were increased in HIV-infected young adults and associated with TDF exposure, whereas lower bone density was associated with didanosine and stavudine exposure. The tendency for improvement in markers of bone health over time and the availability of less toxic ARV alternatives may herald improvements in renal and bone health for perinatally infected patients in adulthood.

SUBMITTER: Unsal AB

PROVIDER: S-EPMC5546869 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Effect of Antiretroviral Therapy on Bone and Renal Health in Young Adults Infected With HIV in Early Life.

Unsal Aylin B AB Mattingly Aviva S AS Jones Sara E SE Purdy Julia B JB Reynolds James C JC Kopp Jeffrey B JB Hazra Rohan R Hadigan Colleen M CM

The Journal of clinical endocrinology and metabolism 20170801 8

<h4>Context</h4>HIV antiretroviral (ARV) therapy is associated with renal and bone toxicity, but little is known about the potential cumulative effects in adults exposed to ARVs from birth.<h4>Objective</h4>To prospectively evaluate renal and bone health in young adults with lifelong HIV and extensive ARV exposure.<h4>Design</h4>Cross-sectional comparison of bone mineral density (BMD) by dual-energy X-ray absorptiometry, bone turnover, and renal function in young adults infected with HIV in earl ...[more]

PMID: 28531309

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Project description:For adults with human immunodeficiency virus (HIV) infection who have CD4+ T-cell counts that are greater than 200 and less than 350 per cubic millimeter and who live in areas with limited resources, the optimal time to initiate antiretroviral therapy remains uncertain.We conducted a randomized, open-label trial of early initiation of antiretroviral therapy, as compared with the standard timing for initiation of therapy, among HIV-infected adults in Haiti who had a confirmed CD4+ T-cell count that was greater than 200 and less than 350 per cubic millimeter at baseline and no history of an acquired immunodeficiency syndrome (AIDS) illness. The primary study end point was survival. The early-treatment group began taking zidovudine, lamivudine, and efavirenz therapy within 2 weeks after enrollment. The standard-treatment group started the same regimen of antiretroviral therapy when their CD4+ T-cell count fell to 200 per cubic millimeter or less or when clinical AIDS developed. Participants in both groups underwent monthly follow-up assessments and received isoniazid and trimethoprim-sulfamethoxazole prophylaxis with nutritional support.Between 2005 and 2008, a total of 816 participants--408 per group--were enrolled and were followed for a median of 21 months. The CD4+ T-cell count at enrollment was approximately 280 per cubic millimeter in both groups. There were 23 deaths in the standard-treatment group, as compared with 6 in the early-treatment group (hazard ratio with standard treatment, 4.0; 95% confidence interval [CI], 1.6 to 9.8; P=0.001). There were 36 incident cases of tuberculosis in the standard-treatment group, as compared with 18 in the early-treatment group (hazard ratio, 2.0; 95% CI, 1.2 to 3.6; P=0.01).Early initiation of antiretroviral therapy decreased the rates of death and incident tuberculosis. Access to antiretroviral therapy should be expanded to include all HIV-infected adults who have CD4+ T-cell counts of less than 350 per cubic millimeter, including those who live in areas with limited resources. (ClinicalTrials.gov number, NCT00120510.)

Project description:BackgroundIn countries with a high seroprevalence of human immunodeficiency virus type 1 (HIV-1), HIV infection contributes significantly to infant mortality. We investigated antiretroviral-treatment strategies in the Children with HIV Early Antiretroviral Therapy (CHER) trial.MethodsHIV-infected infants 6 to 12 weeks of age with a CD4 lymphocyte percentage (the CD4 percentage) of 25% or more were randomly assigned to receive antiretroviral therapy (lopinavir-ritonavir, zidovudine, and lamivudine) when the CD4 percentage decreased to less than 20% (or 25% if the child was younger than 1 year) or clinical criteria were met (the deferred antiretroviral-therapy group) or to immediate initiation of limited antiretroviral therapy until 1 year of age or 2 years of age (the early antiretroviral-therapy groups). We report the early outcomes for infants who received deferred antiretroviral therapy as compared with early antiretroviral therapy.ResultsAt a median age of 7.4 weeks (interquartile range, 6.6 to 8.9) and a CD4 percentage of 35.2% (interquartile range, 29.1 to 41.2), 125 infants were randomly assigned to receive deferred therapy, and 252 infants were randomly assigned to receive early therapy. After a median follow-up of 40 weeks (interquartile range, 24 to 58), antiretroviral therapy was initiated in 66% of infants in the deferred-therapy group. Twenty infants in the deferred-therapy group (16%) died versus 10 infants in the early-therapy groups (4%) (hazard ratio for death, 0.24; 95% confidence interval [CI], 0.11 to 0.51; P<0.001). In 32 infants in the deferred-therapy group (26%) versus 16 infants in the early-therapy groups (6%), disease progressed to Centers for Disease Control and Prevention stage C or severe stage B (hazard ratio for disease progression, 0.25; 95% CI, 0.15 to 0.41; P<0.001). Stavudine was substituted for zidovudine in four infants in the early-therapy groups because of neutropenia in three infants and anemia in one infant; no drugs were permanently discontinued. After a review by the data and safety monitoring board, the deferred-therapy group was modified, and infants in this group were all reassessed for initiation of antiretroviral therapy.ConclusionsEarly HIV diagnosis and early antiretroviral therapy reduced early infant mortality by 76% and HIV progression by 75%. (ClinicalTrials.gov number, NCT00102960.)

Project description:BackgroundThe aim was to determine the association between bone health and inflammation, T-cell activation, and monocyte activation among HIV-infected persons on stable antiretroviral therapy.MethodsWe performed a cross-sectional analysis of all the subjects enrolling in the Stopping Atherosclerosis and Treating Unhealthy bone with RosuvastatiN in HIV trial with available skeletal assessments by dual-energy x-ray absorptiometry, inflammation, and immune activation markers. Analyses used were Wilcoxon rank-sum tests, Spearman correlation coefficients, and linear regression.ResultsOne hundred forty-two subjects were included: 78% men, 69% African American, median age 46.3 years, CD4 count 604 cells per microliter, and 77% with undetectable HIV-1 RNA. Twenty-three percent had osteopenia/osteoporosis at the hip, and 21% had this at the lumbar spine. Soluble vascular cell adhesion molecule-1 was correlated with hip (r = -0.22) and spine (r = -0.23) bone mineral density (BMD), and bone turnover markers (r = 0.20-0.33; all P < 0.05). No significant correlations were observed between the BMD and T-cell activation (%CD38HLA-DR on CD4 or CD8 T cells), monocyte activation (CD14CD16, sCD14, and sCD163), or inflammatory markers [interleukin (IL)-6, tumor necrosis factor-α, highly sensitive C-reactive protein, D-dimer, receptor activator of NF-kB ligand, osteoprotegerin, soluble tumor necrosis factor-RI and II]. In regression models including traditional bone risk factors, hip BMD was associated with age, race, and body mass index; spine BMD was associated with race, family history of hip fracture, trunk fat, tenofovir, and HIV RNA; bone resorption (c-terminal collagen crosslinks) was associated with intracellular adhesion molecule-1 and trunk fat; bone formation (P1NP) was associated with soluble vascular cell adhesion molecule-1, trunk and limb fat (P ≤ 0.05).ConclusionsFuture studies should evaluate the longitudinal association of the adhesion molecules to further elucidate potential contributory mechanisms of bone loss among HIV-infected persons on stable antiretroviral therapy.

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Effect of Antiretroviral Therapy on Bone and Renal Health in Young Adults Infected With HIV in Early Life.

Publications

Effect of Antiretroviral Therapy on Bone and Renal Health in Young Adults Infected With HIV in Early Life.

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