CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

1 The Johns Hopkins Univ, Baltimore, MD, USA, 2 BJGMC Clinical Trials Unit, Pune, India, 3 Durban Univ of Tech, Durban, South Africa, 4 Les Cntrs GHESKIO, Port-Au-Prince, Haiti, 5 Inst Nacional de Infectologia (INI/Fiocruz), Rio de Janeiro, Brazil, 6 Univ of Colorado Denver, Aurora, CO, USA Background: Single biomarkers have been assessed in antiretroviral (ART)-naïve HIV-infected adults in multiple studies. Results show that specific biomarkers of inflammation or micronutrient concentrations are associated with adverse treatment outcomes. However, many of these biomarkers are correlated with each other. The objective of this study was to conduct exploratory factor analysis (EFA), by representing correlated variables with a smaller set of potential underlying factors, and to assess the relationship of these extracted factors with HIV clinical treatment failure (CTF). Methods: Within a multi-country randomized trial of ART efficacy (ACTG5175 PEARLS) among HIV-infected adults, we nested a case-control study (n=470; 236 cases, 234 controls) to identify underlying factors, based on 23 baseline (pre-ART) biomarkers of inflammation and micronutrient status, and determine their association with CTF. Cases were CTF, defined as incident WHO stage 3, 4 or death by 96 weeks of ART. Factors were extracted and Varimax rotation was for EFA. The factor scores were used in multivariable Cox proportional hazards models to determine the association of each factor with CTF. Results: Based on EFA, the baseline biomarkers could be explained as linear combinations of three factors. Factor 1 (“carotenoids”) had high loadings of α-carotene, β-carotene, β-cryptoxanthin, lutein and zeaxanthin. Factor 2 (“Other nutrients”) had high loadings of selenium, vitamin B6, vitamin E and lycopene. Factor 3 (“inflammation”) had high loadings of C-reactive protein (CRP), soluble CD14 (sCD14), Interleukin 18 (IL18) and ferritin). In multivariable models adjusting for gender, age, country, body mass index (BMI), CD4 count, viral load and TB status, there was an increased hazard of CTF (adjusted hazard ratio: 1.50, 95% CI: 1.22-1.84) per unit increase of “inflammation” factor score (factor 3 but not factor 1 or 2). Further adjusting for hemoglobin or albumin gave similar results. Conclusion: In our analysis of various inflammatory and nutritional markers, two factors (“carotenoids” and “other nutrients”) were extracted based on the grouping of nutritional markers while a third factor (“inflammation”) was extracted based on the grouping of inflammatory markers. Only the “inflammation” factor was associated with CTF. Our results corroborate the significant role of inflammation in HIV outcomes while directing the focus on key markers of inflammation. 649 ART EFFECTS ON RENAL AND BONE HEALTH IN LIFELONG HIV SURVIVORS Aviva Mattingly 1 , Sara Jones 2 , Aylin Unsal 1 , Julia Purdy 3 , James Reynolds 3 , Jeffrey Kopp 4 , Rohan Hazra 5 , Colleen Hadigan 1 1 NIAID, Bethesda, MD, USA, 2 Liedos Biomed Rsr Inc, Frederick, MD, USA, 3 NIH, Bethesda, MD, USA, 4 NIDDK, Bethesda, MD, USA, 5 NICHD, Bethesda, MD, USA Background: Antiretroviral therapy (ART) is associated with renal and bone toxicity, but little is known about the effects in adults exposed to ART from birth. Our goal was to evaluate renal function and bone health in adults with near lifelong HIV infection. Methods: We conducted prospective, longitudinal cohort studies at the NIH of 65 adults infected with HIV early in life and 21 matched healthy controls. Detailed assessments included Dual-energy X-ray absorptiometry (DEXA) for bone mineral density (BMD). Cross sectional comparisons of controls vs. HIV adults at last follow-up were made using Wilcoxon rank-sum tests and chi-squared tests. Paired t-test was used for longitudinal comparison of baseline vs. last follow-up in a subset of 33 HIV subjects. Linear regression was used for associations between variables. Results: Compared to controls, the HIV group had significantly higher albumin/creatinine (A/C) ratio, protein/creatinine (P/C) ratio, and anion gap. Also, NTX-telopeptides and osteocalcin were significantly elevated in HIV patients. The HIV group had lower whole body BMD and lower BMD Z-scores. Within the HIV group, lower GFR correlated with increased CD8 T-cells (r=-0.26, p=0.04). Years on tenofovir (TDF) correlated with higher anion gap (r=0.33, p=0.01) but did not correlate with any bone health parameters. However, longer duration of didanosine (DDI) and stavudine (D4T) use correlated with lower whole body BMD (DDI: r=-0.3, p=0.02 and D4T: r=-0.27, p=0.03) and lower BMD Z-scores (DDI: r=-0.29, p=0.03 and D4T: r=-0.29, p=0.02). Longitudinal analyses of patients revealed that a decline in GFR correlated with increasing years of TDF (r=-0.42, p=0.02) and increasing CD4 (r=-0.44, p=0.01) and CD8 T-cells (r=-0.41, p=0.02). BMD and bone markers tended to improve over time. At last follow up, AP Spine BMD (p=0.0001), whole body BMD (p<0.0001), and whole body BMD Z-scores (p=0.0014) increased vs. baseline. Osteocalcin (p=0.03) and NTX-telopeptides (p=0.03) significantly decreased in the HIV group over time. Conclusion: Subclinical markers of renal dysfunction were increased in HIV adults, while microalbuminuria, proteinuria and low GFR were uncommon in both groups. Further, patients with lifelong HIV had abnormal bone density as they approached the age of peak bone mass, associated with DDI and D4T exposure. Despite evidence of dysfunctional bone formation relative to healthy controls, there was a tendency for improvement in markers of bone turnover and BMD with time.

Poster and Themed Discussion Abstracts

CROI 2017 278