Baseline levels of hsCRP, IL-6 and D-dimer for Deaths and Matched Controls.

a<p>p-value obtained from a conditional logistic model with a single covariate corresponding to log₁₀ transformed biomarker level.</p

Median Baseline Characteristics of Deaths and Matched Controls.

a<p>p-value obtained from univariate conditional logistic model. NA = not applicable as characteristic was a matching factor.</p

Risk of Early Death Associated with Baseline Biomarker Levels.

<p>See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0024243#pone-0024243-t003" target="_blank">Table 3</a>, footnote.</p

Risk of Death Associated with Baseline Biomarker Levels.

<p>Odds ratios are derived from separate conditional logistic regression models for each biomarker (two unadjusted univariate and two adjusted models for each biomarker, one with quartiles and one with continuous level of biomarker after log₁₀ transformation); adjusted models include HIV disease state, hemoglobin, platelet, aspartate aminotransferase, and white blood cell count (dichotomized at the median). Percentile cut-off points (IQR on log10 scale) are hsCRP: <1.80, 1.80–5.15, 5.15–20.05, ≥20.05 (0.36–1.31); D-dimer: <0.71, 0.71–1.11, 1.11–1.92, ≥1.92 (0.15–0.28); IL-6: <2.14, 2.14–4.92, 4.92–11.22, ≥11.22 (0.33–1.05).</p

Phidisa II Study Design and Flow Diagram for Case-Control Substudy.

<p>Phidisa II Study Design and Flow Diagram for Case-Control Substudy.</p

Risk of Late Death Associated with Baseline Biomarker Levels.

<p>See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0024243#pone-0024243-t003" target="_blank">Table 3</a>, footnote 1.</p

Morbidity and Mortality According to Latest CD4+ Cell Count among HIV Positive Individuals in South Africa Who Enrolled in Project Phidisa

<div><p>Background</p><p>Short-term morbidity and mortality rates for HIV positive soldiers in the South African National Defence Force (SANDF) would inform decisions about deployment and HIV disease management. Risks were determined according to the latest CD4+ cell count and use of antiretroviral therapy (ART) for HIV positive individuals in the SANDF and their dependents.</p><p>Methods and Findings</p><p>A total of 7,114 participants were enrolled and followed for mortality over a median of 4.7 years (IQR: 1.9, 7.1 years). For a planned subset (5,976), progression of disease (POD) and grade 4, potentially life-threatening events were also ascertained. CD4+ count and viral load were measured every 3 to 6 months. Poisson regression was used to compare event rates by latest CD4+ count (<50, 50–99, 100–199, 200–349, 350–499, 500+) with a focus on upper three strata, and to estimate relative risks (RRs) (ART/no ART). Median entry CD4+ was 207 cells/mm³. During follow-up over 70% were prescribed ART. Over follow-up 1,226 participants died; rates ranged from 57.6 (< 50 cells) to 0.8 (500+ cells) per 100 person years (py). Compared to those with latest CD4+ 200–349 (2.2/100py), death rates were significantly lower (p<0.001), as expected, for those with 350–499 (0.9/100py) and with 500+ cells (0.8/100py). The composite outcome of death, POD or grade 4 events occurred in 2,302 participants (4,045 events); rates were similar in higher CD4+ count strata (9.4 for 350–499 and 7.9 for 500+ cells) and lower than those with counts 200–349 cells (13.5) (p<0.001). For those with latest CD4+ 350+ cells, 63% of the composite outcomes (680 of 1,074) were grade 4 events.</p><p>Conclusion</p><p>Rates of morbidity and mortality are lowest among those with CD4+ count of 350 or higher and rates do not differ for those with counts of 350–499 versus 500+ cells. Grade 4 events are the predominant morbidity for participants with CD4+ counts of 350+ cells.</p></div

Rates of Grade 4 Event Types by Latest CD4 Count (cells/mm³) and ART Status: Morbidity and Mortality Cohort.

<p><b>Notes:</b> Relative rate estimates obtained using Poisson Regression</p><p>¹Adjusted for age, gender, and history of POD. Unadjusted relative rates for total pooled within CD4 category</p><p>Rates of Grade 4 Event Types by Latest CD4 Count (cells/mm³) and ART Status: Morbidity and Mortality Cohort.</p

Relative Rates of Morbidity and Mortality by Latest CD4 Count (cells/mm³) and ART Status: Morbidity and Mortality Cohort.

<p><b>Notes:</b>¹ Adjusted for age, gender, history of AIDS or TB, and time-updated viral load (<400, 400–999, 1000+).</p><p>²Adjusted for age, gender, history of AIDS or TB, and time-updated viral load (log10).</p><p>Relative Rates of Morbidity and Mortality by Latest CD4 Count (cells/mm³) and ART Status: Morbidity and Mortality Cohort.</p

Phidisa Mortality and Morbidity and Mortality (MM) Cohorts.

<p>The mortality cohort is made up of 7,114 HIV+ participants: 1,771 enrolled into Phidisa 2 (the clinical trial), 3,418 into Phidisa 1 (cohort study) and 1,925 into Phidisa 1A (cohort study). Of these 7,114 participants, 5,976 participants were in the morbidity and mortality cohort. This includes the 1,771 participants from Phidisa 2, the 1,925 participants from Phidisa 1A and 2,280 participant form Phidisa 1 who reconsented into Phidisa 1A. The participants excluded from the MM cohort are the 1,138 participants enrolled in Phidisa 1 only in which morbidity data was not collected.</p