Description of 20 included studies.

<p>Description of 20 included studies.</p

Effect of DIR on rate of clinical outcomes, according to DIR definitions, for 20 studies reporting clinical outcomes.

<p>Effect of DIR on rate of clinical outcomes, according to DIR definitions, for 20 studies reporting clinical outcomes.</p

Effect of DIR on rate of clinical outcomes, according to DIR definitions, for 10 studies reporting incidence data.

<p>Effect of DIR on rate of clinical outcomes, according to DIR definitions, for 10 studies reporting incidence data.</p

Flow of paper selection from those identified following literature search through to inclusion.

<p>Flow of paper selection from those identified following literature search through to inclusion.</p

Risk of bias assessment for 20 included studies.

<p>Risk of bias assessment for 20 included studies.</p

Discordant Immune Response with Antiretroviral Therapy in HIV-1: A Systematic Review of Clinical Outcomes

<div><p>Background</p><p>A discordant immune response (DIR) is a failure to satisfactorily increase CD4 counts on ART despite successful virological control. Literature on the clinical effects of DIR has not been systematically evaluated. We aimed to summarise the risk of mortality, AIDS and serious non-AIDS events associated with DIR with a systematic review.</p><p>Methods</p><p>The protocol is registered with the Centre for Review Dissemination, University of York (registration number CRD42014010821). Included studies investigated the effect of DIR on mortality, AIDS, or serious non-AIDS events in cohort studies or cohorts contained in arms of randomised controlled trials for adults aged 16 years or older. DIR was classified as a suboptimal CD4 count (as defined by the study) despite virological suppression following at least 6 months of ART. We systematically searched PubMed, Embase, and the Cochrane Library to December 2015. Risk of bias was assessed using the Cochrane tool for assessing risk of bias in cohort studies. Two authors applied inclusion criteria and one author extracted data. Risk ratios were calculated for each clinical outcome reported.</p><p>Results</p><p>Of 20 studies that met the inclusion criteria, 14 different definitions of DIR were used. Risk ratios for mortality in patients with and without DIR ranged between 1.00 (95% CI 0.26 to 3.92) and 4.29 (95% CI 1.96 to 9.38) with the majority of studies reporting a 2 to 3 fold increase in risk.</p><p>Conclusions</p><p>DIR is associated with a marked increase in mortality in most studies but definitions vary widely. We propose a standardised definition to aid the development of management options for DIR.</p></div

Search strategy.

<p>Search strategy.</p

Random-effects weighted male-to-female prevalence ratios for bacteriologically positive TB by age group (<i>n =</i> 19).

<p>Analysis includes surveys that report the number of individuals screened and the number of bacteriologically positive TB cases by sex and age. Horizontal axis shows age groups in years. Vertical axis shows random-effects weighted M:F ratios in prevalence of bacteriologically positive TB per 100,000 individuals with 95% confidence intervals.</p

PRISMA flow diagram.

<p>Mtb, Mycobacterium tuberculosis.</p

Male-to-female ratios of participation among eligible or invited individuals (<i>n =</i> 29).

<p>Analysis includes surveys that report the number of individuals who were eligible for screening and the number of individuals screened by sex. See <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1002119#pmed.1002119.s008" target="_blank">S2 Table</a> for survey details and references. Lao PDR, Lao People’s Democratic Republic.</p