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.
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.
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.
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.