The Renal-Bone Axis and ART in Adolescents and Elderly With HIV

Particular antiretroviral therapy (ART) regimens may decrease bone mass density (BMD) in both adolescents living with HIV and older people living with HIV (PWHIV), according to multiple study results presented at the virtual Conference on Retroviruses and Opportunistic Infections (CROI), held from March 8 to 11, 2020.

Compared with individuals who are not infected with HIV, PWHIV who are receiving ART have a > more than 3-fold higher risk for low bone BMD. However, the effect of certain ART regimens on bone and renal outcomes in PWHIV who demonstrate virologic suppression and adolescents with HIV is not well established. Therefore, 3 different studies that were presented at CROI explored the association between ART and bone and renal outcomes in adolescents with HIV and older PWHIV.

The first-line regimens for adolescents with HIV includes tenofovir disoproxil fumarate (TDF), which is associated with bone and renal toxicity and decreased bone mass. However, it is not well established whether switching to TDF causes decreased bone accrual or bone loss in adolescents with HIV who are virologically suppressed; therefore, one study¹ aimed to explore this further. In total, 50 South African adolescents with HIV who were virologically suppressed (viral load <100 copies/mL) and switched from an abacavir-based to a TDF-based efavirenz regimen were included. Various bone and renal parameters were measured at the switch to TDF and at week 24 after the switch.

Results showed that adolescents with HIV who switched from abacavir to TDF showed no change in BMD, but had decreases in estimated glomerular filtration rates that were not clinically significant. However, either no change or decreases in lumbar spine BMD were observed in 32% of adolescents who were at an age when bone acquisition is critical. Of note, 93% of these cases occurred in females. Overall, the study authors concluded that, “Female adolescents living with HIV may require closer BMD monitoring when switching to TDF-containing regimens.”

In a second study of South African adolescents with HIV with virologic suppression,² researchers randomly assigned patients either to continue receiving a lopinavir/ritonavir-based ART or to switch to efavirenz, and data from the 2-year follow-up were presented. In total, 220 children with HIV and 220 children without the infection were included. Measurements were collected at baseline, 12 months (n=414; 94.1%), and 24 months (n=407; 92.5%).

Results demonstrated that adolescents with HIV who were receiving efavirenz had consistent bone accrual benefit and had lower pro-inflammatory cytokine profiles compared with patients receiving lopinavir/ritonavir. Overall, the study authors concluded that, “The results support our previous recommendation to switch children with sustained viral suppression on first line regimen with [lopinavir/ritonavir to efavirenz].”

Because much of the current data on the relationships among BMD, alterations in the renal-bone axis, and the use of ART are predominantly from a younger population, a third study was aimed at gaining a better understanding of this relationship among older adults with HIV.³ Researchers performed a subanalysis using data from a phase 4 study (ClinicalTrials.gov identifier: NCT01850212) to explore the relative contribution of ART and alterations in the renal and bone biomarkers to lower BMD in older PWHIV.

The study included a total of 440 men (aged >50 years) and women (postmenopausal) who were HIV-1 positive and receiving stable ART; 247 were included in the subanalysis. Patients were stratified into the following 4 groups on the basis of whether they had been always or never treated with TDF and/or protease inhibitors: non-TDF+nonprotease inhibitor, non-TDF+protease inhibitor, TDF+nonprotease inhibitor, or TDF+protease inhibitor. Assessments included BMD by dual X-ray absorptiometry, renal tubular markers, bone turnover markers, and bone regulation markers.

Results demonstrated that exposure to ART (not biomarkers) was the best predictor of low BMD in older PWHIV. Further, exposure to TDF+protease inhibitor was associated with a 4 times greater risk for low BMD at femoral neck, and exposure to TDF and/or protease inhibitor was associated with a 3-fold greater risk for low BMD at lumbar spine. Overall, the study authors concluded that, “These data do not support routine measurement of biomarkers to predict low BMD in older PWH.”

References

1. Braithwaite K, McPherson T, Arpadi S, et al. Bone and renal outcomes in virologically controlled adolescents switching to TDF. Poster presented at: CROI 2020; March 8-11, 2020; Boston, MA. http://www.croiconference.org/sites/default/files/uploads/croi2020-program-and-information-guide.pdf. Accessed March 25, 2020

2. Shen Y, Strehlau R, Shiau S, et al. Bone mass remains higher among children on efavirenz vs. lopinavir/ritonavir. Poster presented at: CROI 2020; March 8-11, 2020; Boston, MA. http://www.croiconference.org/sites/default/files/uploads/croi2020-program-and-information-guide.pdf. Accessed March 25, 2020.

3. Alvarez E, Campbell L, Garvia-Leon A, et al. Low bone mineral density in older people living with HIV: the renal-bone axis and ART. Poster presented at: CROI 2020; March 8-11, 2020; Boston, MA. http://www.croiconference.org/sites/default/files/uploads/croi2020-program-and-information-guide.pdf. March 25, 2020.

This article originally appeared on Infectious Disease Advisor