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The effects of intermittent, CD4-guided antiretroviral therapy on body composition and metabolic parameters.

ABSTRACT: To assess the effects of decreased antiretroviral therapy exposure on body fat and metabolic parameters.Substudy of the Strategies for Management of Anti-Retroviral Therapy study, in which participants were randomized to intermittent CD4-guided [Drug Conservation (DC) group] or to continuous [Viral Suppression (VS) group] antiretroviral therapy.Participants at 33 sites were coenrolled in the Strategies for Management of Anti-Retroviral Therapy Body Composition substudy. Regional fat was assessed annually by whole-body dual-energy X-ray absorptiometry and abdominal computed tomography. Fasting metabolic parameters were assessed at months 4, 8, and annually. Treatment groups were compared for changes in fat and metabolic markers using longitudinal mixed models.Two hundred and seventy-five patients were randomized to the DC (n = 142) or VS (n = 133) group and followed for a median of 2.0 years. By month 12, limb fat (DC-VS difference 9.8%, 95% confidence interval 3.5-16.1; P = 0.003) and subcutaneous abdominal fat (DC-VS difference 14.3 cm, 95% confidence interval -0.1 to 28.7; P = 0.05) increased in the DC group. There was no treatment difference in visceral abdominal fat (DC-VS difference -2.1%, 95% confidence interval -13.5 to 9.4; P = 0.72). Lipids significantly decreased in the DC group by month 4 and treatment differences persisted throughout follow-up (P < or = 0.001). By 12 months, hemoglobin A1C increased in the DC (+0.3%) and remained stable in the VS group (P = 0.003); the treatment difference remained significant throughout follow-up (P = 0.02).After 12 months, intermittent antiretroviral therapy increased subcutaneous fat, had no effect on visceral abdominal fat, decreased plasma lipids, and increased hemoglobin A1C compared with continuous antiretroviral therapy.

SUBMITTER: Martinez E

PROVIDER: S-EPMC2902280 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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The effects of intermittent, CD4-guided antiretroviral therapy on body composition and metabolic parameters.

Martinez Esteban E Visnegarwala Fehmida F Grund Birgit B Thomas Avis A Gibert Cynthia C Shlay Judith J Drummond Fraser F Pearce Daniel D Edwards Simon S Reiss Peter P El-Sadr Wafaa W Carr Andrew A

AIDS (London, England) 20100101 3

<h4>Objective</h4>To assess the effects of decreased antiretroviral therapy exposure on body fat and metabolic parameters.<h4>Design</h4>Substudy of the Strategies for Management of Anti-Retroviral Therapy study, in which participants were randomized to intermittent CD4-guided [Drug Conservation (DC) group] or to continuous [Viral Suppression (VS) group] antiretroviral therapy.<h4>Methods</h4>Participants at 33 sites were coenrolled in the Strategies for Management of Anti-Retroviral Therapy Bod ...[more]

PMID: 20057309

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Project description:International trials have shown that CD4+ T-cell-guided structured treatment interruptions (STI) of antiretroviral therapy (ART) lead to worse outcomes than continuous treatment. We simulated continuous ART and STI strategies with higher CD4+ T-cell interruption/reintroduction thresholds than those assessed in actual trials.Using a model of HIV, we simulated cohorts of African adults with different baseline CD4+ T-cell counts (< or = 200; 201-350; and 351-500 cells/microl). We varied ART initiation criteria (immediate; CD4+ T-cell count < 350 cells/microl or > or = 350 cells/microl with severe HIV-related disease; and CD4+ T-cell count <200 cells/microl or > or = 200 cells/microl with severe HIV-related disease), and ART interruption/reintroduction thresholds (350/250; 500/350; and 700/500 cells/microl). First-line therapy was non-nucleoside reverse transcriptase inhibitor (NNRTI)-based and second-line therapy was protease inhibitor (PI)-based.STI generally reduced life expectancy compared with continuous ART. Life expectancy increased with earlier ART initiation and higher interruption/reintroduction thresholds. STI reduced life expectancy by 48-69 and 11-30 months compared with continuous ART when interruption/reintroduction thresholds were 350/250 and 500/350 cells/microl, depending on ART initiation criteria. When patients interrupted/reintroduced ART at 700/500 cells/microl, life expectancies ranged from 2 months lower to 1 month higher than continuous ART. STI-related life expectancy increased with decreased risk of virological resistance after ART interruptions.STI with NNRTI-based regimens was almost always less effective than continuous treatment, regardless of interruption/reintroduction thresholds. The risks associated with STI decrease only if patients start ART earlier, interrupt/reintroduce treatment at very high CD4+ T-cell thresholds (700/500 cells/microl) and use first-line medications with higher resistance barriers, such as PIs.

Project description:ContextMale hypogonadism adversely affects body composition, bone mineral density (BMD), and metabolic health. A previous report showed that pre-treatment testosterone (T) levels of <200 ng/dl is associated with greater improvement in spine BMD with T therapy. However, to date, there is no study that investigates whether baseline T levels also influence body composition and metabolic response to T therapy.ObjectiveThe aim of this study is to determine if there are differences in the changes in body composition, metabolic profile, and bone turnover markers, in addition to BMD, in response to T therapy in men with a baseline T level of <264 ng/dl compared to those with levels ≥264 ng/dl.MethodsThis is a secondary analysis of a single-arm, open-label clinical trial (NCT01378299) on pharmacogenetics of response to T therapy conducted between 2011 and 2016 involving 105 men (40-74 years old), with average morning T < 300 ng/dl, given intramuscular T cypionate 200 mg every 2 weeks for 18 months. Subjects were divided into those with baseline T levels of <264 ng/dl (N = 43) and those with ≥264 ng/dl (N = 57). T and estradiol (E2) were measured by liquid chromatography/mass spectrometry; serum bone turnover markers (C-telopeptide [CTX], osteocalcin, and sclerostin), adiponectin, and leptin were measured by enzyme-linked immunosorbent assay; glycated hemoglobin (HbA1c) was measured by high-performance liquid chromatography; and areal BMD and body composition was measured by dual-energy x-ray absorptiometry (DXA).ResultsMen with T < 264 ng/dl showed greater increases in total fat-free mass (FFM) at 18 months compared to those with T ≥ 264 ng/dl (4.2 ± 4.1 vs. 2.7 ± 3.8%; p = 0.047) and unadjusted appendicular FFM at 6 and 18 months (8.7 ± 11.5 vs. 4.4 ± 4.3%, 7.3 ± 11.6 vs. 2.4 ± 6.8%; p = 0.033 and p = 0.043, respectively). Men with T ≥ 264 ng/dl showed significant decreases in HbA1c at 12 months (-3.1 ± 9.2 vs. 3.2 ± 13.9%; p = 0.005), fasting glucose at 18 months (-4.2 ± 31.9 vs. 13.0 ± 57.3%; p = 0.040), LDL at 6 months (-6.4 ± 27.5 vs. 12.8 ± 44.1%; p = 0.034), and leptin at 18 months (-40.2 ± 35.1 vs. -27.6 ± 31.0%; p = 0.034) compared to those with T < 264 ng/dl. No significant differences in BMD and bone turnover markers were observed.ConclusionT therapy results in improvement in body composition irrespective of baseline T levels but T < 264 ng/dl is associated with greater improvement in FFM, whereas a T level of ≥264 ng/dl favors improvement in metabolic profile.

Project description:People living with HIV who are on antiretroviral treatment are at increased risk of developing premature cardiovascular disease. Children with perinatal HIV infection (PHIV) have survived through their adolescence and are entering adulthood. We determined the prevalence of metabolic syndrome, abnormal biochemical markers, and characterized body composition parameters in youth living with perinatal HIV infection. This cross-sectional study was conducted at the Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand from December 2017 to February 2018. PHIV-youths between 15 <25 years of age who were receiving ART were enrolled. Data collection included ART-related history, blood pressure, and anthropometric measurements. Body composition including android, gynoid fat mass, and total body fat were measured by dual-energy X-ray absorptiometry. Fasting blood was drawn to test for lipid profile, glucose, and high sensitivity c-reactive protein (hsCRP). One hundred and twenty PHIV-youths (48% female) were enrolled. Their mean age and the median duration on ART were 20.3 (SD2.6) and 14.1 (IQR 10.4-14.9) years, respectively; 76 (63%) were on first-line non-nucleoside reverse transcriptase inhibitors-based regimens. Thirty-three (28%), 74 (62%), and 13 (11%) of PHIV-youths were underweight (BMI < 18.5 kg/m2), normal (BMI 18.5-24.9 kg/m2), and overweight (BMI ≥ 25.0 kg/m2), respectively. The prevalence of metabolic syndrome was 10.6% (95%CI 5.0-16.0). Seventy-six of 113 (67.3%) of PHIV-youths had lipid alteration; the most prevalent types being low HDL (46.9%) and increased triglycerides (27.4%). Overall 43 (35.9%) had increased hsCRP (16.7% with immediate and 19.2% with high risk for CVD). Females had significantly higher percentage of android and gynoid fat, but lower Android to gynoid ratio (AGR) compared to males. There were 77%, 31%, and 21% of PHIV-youths in the overweight, normal weight, and underweight group with AGR in tertile 3, respectively. In conclusion, we documented presence of metabolic syndrome in 10.6% of PHIV-youths on ART. Increase AGR representing abdominal obesity was detected even in youths with normal BMI or underweight.

Dataset Information

The effects of intermittent, CD4-guided antiretroviral therapy on body composition and metabolic parameters.

Publications

The effects of intermittent, CD4-guided antiretroviral therapy on body composition and metabolic parameters.

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