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CROI 2011: Low Vitamin D Levels Less Likely with Rilpivirine than Efavirenz

HIV positive people who use antiretroviral regimens containing the investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (TMC278) saw smaller changes in their vitamin D levels and were less likely to develop severe deficiency than people taking efavirenz, according to a presentation at the 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011) this month in Boston.

A type of bone loss known as osteolmalacia is related to low vitamin D levels. It is well known that people with HIV have lower vitamin D levels on average and are at a higher risk for bone loss.

Certain antiretroviral drugs such as efavirenz (Sustiva, also in the Atripla coformulation) and certain protease inhibitors may have a metabolic effect on vitamin D levels, specifically though their effect on the CYP34A enzyme system that processes drugs in the liver. It has already been shown in the MONET trial that vitamin D levels increased in people who switched to a boosted darunavir (Prezista)-based regimen from an efavirenz-based regimen.

A study presented at CROI further elucidated the effect of efavirenz on vitamin D levels. David Wohl from the University of North Carolina School of Medicine led a study comparing 2 different NNRTI regimens -- rilpivirine + tenofovir/emtricitabine (Truvada) or efavirenz + Truvada -- to assess their effects on vitamin D.

The researchers measured 25-hydroxyvitamin D levels in stored samples from a subset of the 690 treatment-naive participants in the Phase 3 ECHO trial, mostly from North America, Europe, Latin America, and Asia. About 20% were women and about 25% were black or African-American; people with darker skin do not get as much vitamin D from sunlight and tend to have lower levels.

The overall efficacy of the 2 drugs was similar in a combined analysis of the ECHO and THRIVE studies presented last summer at the International AIDS Conference in Vienna, even though people taking rilpivirine had a higher rate of virological failure.

Vitamin D levels were characterized as optimal/sufficient, insufficient, deficient, or severely deficient. Participants who had insufficient or deficient levels at the beginning of the trial were compared in one analysis. One of the most interesting findings from this ECHO sub-analysis was that 72% of all participants had suboptimal baseline levels of vitamin D, despite the fact that 14% in the rilpivirine arm and 12% in the efavirenz arm were taking vitamin D supplements.

At 24 weeks, vitamin D levels dropped in both arms, yet did so slightly more in the efavirenz arm. But at the end of 48 weeks, vitamin D levels in the rilpivirine group returned to baseline, while those in the efavirenz arm did not. At the end of the study, participants in the rilpivirine arm showed a 2% vitamin D loss while those in the efavirenz arm had an 8% loss.

Among people with deficient levels at the start of the trial, 4% taking rilpivirine and 20% taking efavirenz developed severe vitamin D deficiency by the end of the study. At the end of the study, average vitamin D levels were unchanged from baseline in the rilpivirine arm but were significantly different in the efavirenz arm.

Even though there was little difference in vitamin D levels at 24 weeks, a majority of the participants were assessed during winter months in North America at this point in the trial -- a time when people get less exposure to sunlight. Levels started to diverge at that point and the risk of severe vitamin D loss by the end of the study was significantly higher in the efavirenz arm.

The major take-away message from this study is that many people with HIV have low vitamin D levels, and if a decision is made to start a regimen containing rilpivirine, they are less likely to develop deficient vitamin D levels over time. More studies need to be completed to gain a better understanding of the implications of lower vitamin D levels in people with HIV.

Investigator affiliations: Univ of North Carolina at Chapel Hill, NC; Hosp de Santa Maria, Lisbon, Portugal; Barts and The London NHS Trust, London, UK; Hosp Geral de Nova Iguaçu, Brazil; Faculty of Med, Ramathibodi Hosp, Thailand; Hosp Bichat Claude Bernard, Paris, France; Tibotec BVBA, Beerse, Belgium; Tibotec Inc, Titusville, NJ.

3/18/11

References

D Wohl, M Doroana, C Orkin, et al. Change in Vitamin D Levels Smaller and Risk of Development of Severe Vitamin D Deficiency Lower among HIV-1-infected, Treatment-naive Adults Receiving TMC278 Compared with EFV: 48-Week Results from the Phase III ECHO Trial. 18th Conference on Retroviruses and Opportunistic Infections. Boston. February 27-March 2, 2011. Abstract 79LB.