Pulmonary effects of immediate versus deferred antiretroviral therapy in HIV-positive individuals: a nested substudy within the multicentre, international, randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial

Abstract

Summary Background Observational 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. Methods We 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. Findings Between 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). Interpretation The 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. Funding US National Heart Lung and Blood Institute, US N...

Prevalence of chronic obstructive pulmonary disease in the global population with HIV: a systematic review and meta-analysis

“…77 One multiregional study included all WHO regions. 38 The fixed-ratio definition was used in 16 studies, 47,56,61,62,64,66,70,[72][73]75,[78][79][80][81]83 LLN was used in six, 38,47,56,66,75,83 ICD was used in five, 38,47,56,58,66,75,83 and patient-reported criteria were used in nine studies. 59,65,[67][68][69]74,76,77,82 One study was in Spanish.…”

“…The prevalence did not differ by sex, regardless of diagnostic criteria used (appendix, pp 21-23). When using fixed-ratio criteria, prevalence increased from never smokers to former smokers to Crothers (2013) 61 Cui (2010) 62 Drummond (2013) 64 George (2009) 66 Hollington (2013) 70 Kristoffersen (2012) 72 Kunisaki (2016) 38 Madeddu (2013) 74 Makinson (2015) 76 Nakamura (2014) 79 Pefura-Yone (2015) 47 Risso (2017) 81 Sampériz (2014) 82 Santoro (2017) 83 Vos (2017) 85…”

HIV Infection, Pulmonary Tuberculosis, and COPD in Rural Uganda: A Cross-Sectional Study

“…Importantly, the above studies do not include data on ART duration. Of further interest, the START study of immediate versus delayed ART initiation in newly diagnosed PLWH followed for a median of two years showed that very early ART initiation (CD4 >500) had no effect on lung function trajectory[34]. Unfortunately, because late presentation to HIV care remains common in SSA[35], these findings might not be generalizable to the regional population.…”

Incidence of chronic obstructive pulmonary disease in people with HIV in Ontario, 1996–2015: a retrospective population-based cohort study

“…Veterans Affairs study, 21 other studies have found no differences in the rate of lung function decline according to HIV treatment status. 42 Because most people with HIV who are in care in Ontario are receiving antiretroviral therapy, it is unlikely that low treatment uptake accounts for the increased risk of COPD in our cohort, particularly in later periods. 43 We identified COPD using health administrative data rather than spirometry.…”