Background
Reduced vitamin C concentrations (vitC) in HIV are associated with abnormal urinary loss: a renal leak. Renal leak indicates an underlying disease-related nutritional dysregulation independent of dietary intake. While ART use is associated with renal tubular dysfunction, there is insufficient understanding of the relationships between ART class, renal leak and reduced vitC concentrations.
Methods
Women in the DC Women’s Interagency HIV Study and NIH (N=96, 40 HIV+, 56 HIV-), were enrolled in a cross-sectional outpatient study to investigate antiretroviral therapy effects on VitC concentrations. To assess vitC renal leak, participants fasted overnight, and matched urine and fasting plasma samples were collected the following morning. Clinical history was obtained using structured questionnaires. VitC was measured by HPLC with coulometric electrochemical detection. VitC renal leak was defined as presence of urinary vitC at fasting plasma concentrations below 43.2µM, the vitC Minimum Elimination Threshold (MET) in women. Multivariable regression analysis was used to assess outcomes.
Results
Among women with HIV (WWH), 32 (86%) were on ART, 32 (86%) were on nucleoside reverse transcriptase inhibitors (NRTIs), 11 (30%) on non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 13 (35%) on protease inhibitors (PIs). The most common ART medication was Tenofovir (N=19, 48%), including Tenofovir alafenamide (TAF, N=4) and Tenofovir disoproxil (TDF, N=15). Overall, ART use was significantly associated with increased odds of renal leak (OR=12, p<0.001) and reduced plasma vitC concentrations (p<0.001). Renal leak was associated with NRTIs (OR=12, p<0.001) and NNRTIs (OR=22, p<0.022) but not PIs (OR=4.4, p=0.08). The strongest association with reduced plasma vitC was observed with NRTIs (p<0.001), followed by PIs (p=0.011) and NNRTIs (p=0.027). Tenofovir-use incurred 3-fold higher odds of renal leak when adjusted for HIV status and other ART use but did not reach statistical significance (p=0.21). Users of the newer pro-drug TAF had reduced odds of renal leak vs TDF, although this did not reach statistical significance (OR=0.5, p=0.5).
Conclusions
All classes of ART assessed are associated with renal leak and/or reduced vitC concentrations in HIV, with the strongest association observed with NRTIs such as Tenofovir. Longitudinal studies with larger cohorts are needed to study mechanisms and implications of ART-induced vitC dysregulation.
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