Background: Tenofovir disoproxil fumarate (TDF) may be associated with proximal tubular dysfunction (PTD), but limited information is available in children. We investigated the association of TDF with the development of PTD in a pediatric cohort, the predictive value of ÃƒÅ¸2-microglobinuria as marker of early detection of PTD, and the phosphorus and creatinine difference between TDF exposed and unexposed individuals.
Methods: Prospective cohort study measuring prevalence of PTD in HIV-infected children and adolescents receiving TDF versus non-TDF-based treatments. Subjects were categorized based on their TDF exposure: No exposure, exposure <1 or >1 year. Generalized linear mixed models were used to detect the association between TDF and PTD in both groups, and the predictive ability of ÃƒÅ¸2-microglobinuria among TDF users. Tukey-Kramer procedure was used to make pairwise comparisons between the mean phosphorus and creatinine levels in each visit.
Results: 110 subjects on TDF and 68 on non-TDF regimens were followed for 12 months. 57% were males, 88% African-American, with a mean age of 15.7 years. 62% had undetectable viral load at enrollment with a mean CD4 count of 550 cells/mm3. 13 subjects had PTD (7%). Univariate analysis identified gender and duration of TDF exposure as significant variables in predicting PTD. Generalized linear mixed models showed that women had a slight increase in the odds of developing PTD when exposed to TDF for more than 1 year (OR: 1.09 (C.I. 1.03-1.14), OR: 1.03 (0.97-1.10). Lower levels of phosphorus (p-value=<0.0001) and creatinine clearance (p-value=0.03) were seen in subjects with longer TDF exposure. ÃƒÅ¸2-microglobinuria did not predict PTD among TDF users (p-value 0.21).
Conclusions: PTD was uncommon among children with HIV, but women had a slightly increased risk with TDF-exposures of more than one year. ÃƒÅ¸2-microglobulin was not a useful marker for early detection of PTD. Lower levels of serum phosphorus and creatinine clearance were noted in subjects receiving TDF, but its clinical implications still need to be elucidated.
Table of Contents
Table 1 Characteristics of the Outcome Variable and other risk
Factors over the 1 year study period...24
Table 2 Descriptive Statistics of other Covariates of Interest...25
Table 3 Univariate Analysis of Time Varying Risk Factors on the Development of PTD...26
Table 4 Univariate Analysis of Constant Risk Factors on the Development of PTD...27
Table 5 Association of TDF Exposure with PTD adjusted for Gender: 3 Levels of TDF...28
Table 6 Association of TDF Exposure with PTD adjusted for Gender: 2 levels of TDF...29
Table 7 Difference in Phosphorus mean level at Enrollment/follow-up visits and TDF Exposure...30
Table 8 Difference in Creatinine Clearance mean level at Enrollment/follow-up visits and TDF Exposure...31
Figure 1: Transport Mechanism of TDF in the Proximal Tubular Cell...32
Figure 2: Enrollment Schema...33
Figure 3: Number of PTD Occurrences per Visit...34
Figure 4 Difference in Phosphorus mean level at Enrollment/follow-up visits and TDF Exposure...35
Figure 5 Difference in Creatinine Clearance mean level at Enrollment/follow-up visits and TDF Exposure...36
About this Master's Thesis
|Committee Chair / Thesis Advisor|
|Tenofovir Associated Proximal Renal Tubular Dysfunction in HIV infected Children and Adolescents ()||2018-08-28||