Human Immunodeficiency Virus

Bone and Renal Effects of Antiretroviral Therapy Switching

Infectious Disease Advisor Contributing Writer
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Regular alcohol consumption presents its own set of risks related to bone health and the development of osteoporosis. According to the US National Institute of Health (NIH) Osteoporosis and Related Bone Diseases National Resource Center, excessive alcohol consumption can interfere with the balance of calcium and vitamin D, as well as hormone deficiencies, lower testosterone in men, irregular menstrual cycles in women, and elevated cortisol, which increases bone breakdown.12 In addition, alcohol effects balance and gait — people with alcoholism fall more frequently than people without alcoholism.12 Specifically, hip and vertebral fractures have been linked to heavy alcohol consumption.12 According to the NIH, abstaining from alcohol is the best strategy to prevent alcohol-induced bone loss.12 However, a well-balanced diet, vitamin D supplementation, and exercise can all mitigate the effects of alcohol.12 This population can also consider a bone mineral density test as a way to detect osteoporosis before a fracture occurs.12
Regular alcohol consumption presents its own set of risks related to bone health and the development of osteoporosis. According to the US National Institute of Health (NIH) Osteoporosis and Related Bone Diseases National Resource Center, excessive alcohol consumption can interfere with the balance of calcium and vitamin D, as well as hormone deficiencies, lower testosterone in men, irregular menstrual cycles in women, and elevated cortisol, which increases bone breakdown.12 In addition, alcohol effects balance and gait — people with alcoholism fall more frequently than people without alcoholism.12 Specifically, hip and vertebral fractures have been linked to heavy alcohol consumption.12 According to the NIH, abstaining from alcohol is the best strategy to prevent alcohol-induced bone loss.12 However, a well-balanced diet, vitamin D supplementation, and exercise can all mitigate the effects of alcohol.12 This population can also consider a bone mineral density test as a way to detect osteoporosis before a fracture occurs.12
Switching antiretroviral therapy in virologically suppressed patients provides a robust option for preserving bone health while continuing suppressive HIV treatment.

Hispanic/Latinx and Black adults initiating tenofovir alafenamide (TAF) or switching from tenofovir disoproxil Fumarate (TDF) to TAF showed significantly improved bone and renal parameters compared with patients taking TDF1, according to research presented at IDWeek 2019, held October 2 to October 6, in Washington, DC. Research from another session reported that patients switching from triple antiretroviral therapy (ART) containing TDF to a 2-drug regimen of dolutegravir (DTG) and rilpivirine (RPV) was associated with sustained improvement in bone mineral density.2

The first study analyzed pooled data on Hispanic/Latinx and Black participants from 7 randomized clinical trials (2 treatment-naïve, 5 suppressed switch) to assess the safety and efficacy of TAF-based regimens compared with TDF-based regimens for ART initiation or switching within these populations, which are typically underrepresented in clinical trials. Virologic suppression (HIV-1 RNA <50 copies/mL) and percentage change in bone mineral density were assessed, as were the renal tubular biomarker ratios of urine beta-2-microglobulin to creatinine and retinol binding protein tocreatinine.

Among the total pooled population of the 7 studies (N=5825), 1138 participants were Hispanic/Latinx and 1324 were Black. The median age among treatment naïve participants  was 34 years, median HIV-1 RNA was 4.6 log copies/mL, and CD4 count was 405 cells/mm. Among switch participants (n=4092), median age was 45 years, and CD4 was 653 cells/mm. There was no between-group difference in virologic suppression rate. In both naive and switch participants, TAF and TDF showed well-maintained virologic suppression rates and both were well-tolerated. At week 96, fewer effects on renal biomarkers was seen in all groups initiating TAF (P <.001); bone mineral density decreases were also smaller (P <.005) compared with TDF. All groups that switched from TDF to TAF showed tubular proteinuria decreases and bone mineral density improvements (P <.001 for both).

Investigators concluded, “These data in >2400 Hispanic/Latinx and Black [people living with HIV] demonstrate noninferior efficacy and safety advantages with TAF vs TDF.”1

Kahl and colleagues2 also highlighted ART regimens with favorable effects on bone density. Researchers reported on a substudy of the SWORD trials, which compared the effects of adjusting ART agents. The trials randomly assigned adults with HIV-1 RNA <50 copies/mL who received ART containing TDF for ≥ 6 months prior to study initiation to either receive DTG+RPV (early switch group) on day 1, or to continue current triple-therapy through week 48 at which time patients with viral suppression were switched to DTG+RPV (late switch). Bone mineral density for hip and lumbar spine were measured by centrally-read dual-energy X-ray absorptiometry (DEXA) scans for the primary end point, and secondary end points included bone mineral density change and bone turnover markers through week 148.

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Significant increases for total hip bone mineral density were observed among participants in both groups following the switch to DTG+RPV through 100 weeks, with a nonsignificant increase seen in participants in the early switch group at week 148. At 48 weeks post-switch, lumbar bone mineral density significantly increased from baseline and remained increased, though not significantly, from baseline through week 148. Bone mineral density was similar among participants in both groups through 100 weeks. Through week 148, a minimal increase in bone mineral density and a significant decrease in bone turnover markers were seen (P <.001 to 0.042 across all markers) from baseline among long switch participants.

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Study investigators concluded, “Switch to the DTG+RPV [2-drug regimen] was associated with sustained improvements in [bone mineral density] through [week] 148, along with reduction in bone markers. The favorable effects on skeletal health were observed despite the aging of study patients and other factors decreasing bone mineral density.”

As the population of people living with HIV ages, developing treatment regimens that account and compensate for possible age-related comorbidities such as osteoporosis and kidney disease is a necessity, and is an area that may greatly benefit from further study.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

1. DeJesus E, Villanueva JFA, Lopez JRA, et al. Tenofovir alafenamide (TAF) versus tenofovir disoproxil fumarate (TDF) in hispanic/latinx and black participants: Efficacy, bone and renal safety results from a pooled analysis of 7 clinical trials. Poster presented at: IDWeek 2019; October 2-6, 2019; Washington, DC. Poster 318.

2. Kahl L, McComsey GA, Poggio MC, et al. Switch from TDF containing regimen to DTG+RPV maintains bone mineral density and decreases bone turnover markers over 148 weeks. Poster presented at: IDWeek 2019; October 2-6, 2019; Washington, DC. Poster 319.

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