Dataset Information

The rate of bone loss slows after 1-2 years of initial antiretroviral therapy: final results of the Strategic Timing of Antiretroviral Therapy (START) bone mineral density substudy.

ABSTRACT:

Objectives

Initial antiretroviral therapy (ART) causes loss of bone mineral density (BMD) over the first 1-2 years. Whether this loss continues with longer therapy is unclear. We determined changes in bone and spine BMD over 5 years in adults receiving immediate or deferred initial ART.

Methods

In the Strategic Timing of Antiretroviral Therapy (START) BMD substudy, ART-naïve adults with CD4 counts > 500 cells/μL were randomized to immediate or deferred ART. Deferred group participants not yet on ART were offered ART after May 2015. Mean per cent changes in total hip and lumbar spine BMD (measured annually by dual-energy X-ray absorptiometry) were compared between groups using longitudinal mixed models. Fracture rates were also compared between groups for all START participants.

Results

Substudy participants (immediate group, n = 201; deferred group, n = 210; median age 32 years; 80% non-white; 24% female) were followed for a mean 4.5 years until December 2016. In the immediate group, > 96% used ART throughout. In the deferred group, 16%, 58% and 94% used ART at years 1, 3 and 5, respectively. BMD decreased more in the immediate group initially; groups had converged by year 3 at the spine and year 4 at the hip by intent-to-treat (ITT). BMD changes after year 1 were similar in the immediate group and in those off ART in the deferred group [mean difference: spine, 0.03% per year; 95% confidence interval (CI) -0.4, 0.4; P = 0.88; hip, -0.2% per year; 95% CI -0.7, 0.3; P = 0.37]. Fracture incidence did not differ significantly between groups (immediate group, 0.86/100 person-years versus deferred group, 0.85/100 person-years; hazard ratio 1.01; 95% CI 0.76, 1.35; P = 0.98).

Conclusions

Significant ART-induced bone loss slowed after the first year of ART and became similar to that in untreated HIV infection.

SUBMITTER: Carr A

PROVIDER: S-EPMC8224176 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundObservational data have been conflicted regarding the potential role of HIV antiretroviral therapy (ART) as a causative factor for, or protective factor against, COPD. We therefore aimed to investigate the effect of immediate versus deferred ART on decline in lung function in HIV-positive individuals.MethodsWe did a nested substudy within the randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial at 80 sites in multiple settings in 20 high-income and low-to-middle-income countries. Participants were HIV-1 infected individuals aged at least 25 years, naive to ART, with CD4 T-cell counts of more than 500 per μL, not receiving treatment for asthma, and without recent respiratory infections (baseline COPD was not an exclusion criterion). Participants were randomly assigned to receive ART (an approved drug combination derived from US Department of Health and Human Services guidelines) either immediately, or deferred until CD4 T-cell counts decreased to 350 per μL or AIDS developed. The randomisation was determined by participation in the parent START study, and was not specific to the substudy. Because of the nature of our study, site investigators and participants were not masked to the treatment group assignment; however, the assessors who reviewed the outcomes were masked to the treatment group. The primary outcome was the annual rate of decline in lung function, expressed as the FEV1 slope in mL/year; spirometry was done annually during follow-up for up to 5 years. We analysed data on an intention-to-treat basis, and planned separate analyses in smokers and non-smokers because of the known effects of smoking on FEV1 decline. The substudy was registered at ClinicalTrials.gov number NCT01797367.FindingsBetween March 11, 2010, and Aug 23, 2013, we enrolled 1026 participants to our substudy, who were then randomly assigned to either immediate (n=518) or deferred (n=508) ART. Median baseline characteristics included age 36 years (IQR 30-44), CD4 T-cell count 648 per μL (583-767), and HIV plasma viral load 4·2 log10 copies per mL (3·5-4·7). 29% were female and 28% were current smokers. Median follow-up time was 2·0 years (IQR 1·9-3·0). We noted no differences in FEV1 slopes between the immediate and deferred ART groups either in smokers (difference of -3·3 mL/year, 95% CI -38·8 to 32·2; p=0·86) or in non-smokers (difference of -5·6 mL/year, -29·4 to 18·3; p=0·65) or in pooled analyses adjusted for smoking status at each study visit (difference of -5·2 mL/year, -25·1 to 14·6; p=0·61).InterpretationThe timing of ART initiation has no major short-term effect on rate of lung function decline in HIV-positive individuals who are naive to ART, with CD4 T-cell counts of more than 500 per μL. In light of updated WHO recommendations that all HIV-positive individuals should be treated with ART, regardless of their CD4 T-cell count, our results suggest an absence of significant pulmonary harm with such an approach.FundingUS National Heart Lung and Blood Institute, US National Institute of Allergy and Infectious Diseases, Division of AIDS, Agence Nationale de Recherches sur le SIDA et les Hipatites Virales (France), Australian National Health and Medical Research Council, Danish National Research Foundation, European AIDS Treatment Network, German Ministry of Education and Research, UK Medical Research Council and National Institute for Health Research, and US Veterans Health Administration Office of Research and Development.

Project description:Both HIV infection and antiretroviral therapy (ART) are associated with lower bone mineral density (BMD) and increased fracture risk. Because the relative contributions of ART and untreated HIV to BMD loss are unclear, it is important to quantify the effect of ART on bone. We compared the effect of early ART initiation (CD4 >500 cells/μL) with deferred ART on change in BMD in the START Bone Mineral Density substudy, a randomized trial evaluating the effect of immediate ART initiation versus deferring ART (to CD4 <350 cells/μL). BMD was measured annually at the lumbar spine and hip by dual-energy X-ray absorptiometry (DXA). Percent change in BMD by treatment assignment (intent-to-treat analysis) was estimated using longitudinal mixed models and linear regression. Baseline and follow-up DXA scans were available for 399 (195 immediate, 204 deferred) participants (median age 32 years, 80% non-white, 26% women, median CD4 count 642 cells/μL). ART (most commonly including tenofovir and efavirenz) was used for 95% and 18% of follow-up in the immediate and deferred ART groups, respectively. Through 2.2 years mean follow-up, immediate ART resulted in greater BMD declines than deferred ART at the hip (-2.5% versus -1.0%; difference -1.5%, 95% confidence interval [CI] -2.2 to -0.8, p < 0.001) and spine (-1.9% versus -0.4%; difference -1.6%, 95% CI -2.2 to -1.0, p < 0.001). BMD declines were greatest in the first year of ART. In the immediate ART group, spine BMD stabilized after year 1, whereas hip BMD declined progressively over 2 years. After year 1, BMD changes were similar in the immediate and deferred groups. No clinical, HIV-related, or ART characteristic predicted greater BMD loss in either group. All HIV treatment guidelines now recommend ART initiation at HIV diagnosis because of the reduced risk of serious clinical outcomes. Better understanding of the longer-term consequences of the observed reductions in BMD is needed.Clinical trials registrationNCT00867048. © 2017 American Society for Bone and Mineral Research.