Switch from efavirenz or AZT associated with improvement in vitamin D levels

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Switching antiretroviral treatment from efavirenz or AZT was associated with an improvment in vitamin D levels, investigators report in the online edition of AIDS Research and Human Retroviruses. Calendar month and black race were also associated with vitamin deficiency.

Vitamin D levels increased significantly after patients stopped therapy with efavirenz or AZT and switched to treatment based on the protease inhibitor darunavir (Prezista) boosted by ritonavir. 

“The association between use of efavirenz and vitamin D deficiency is consistent with previous cross-sectional and prospective studies”, comment the investigators. They add, “to our knowledge, this is the first report to show rises in vitamin D levels after switching efavirenz-based antiretroviral treatment to PI [protease inhibitor]-based treatment.”

Glossary

monotherapy

Taking a drug on its own, rather than in combination with other drugs.

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

protease inhibitor (PI)

Family of antiretrovirals which target the protease enzyme. Includes amprenavir, indinavir, lopinavir, ritonavir, saquinavir, nelfinavir, and atazanavir.

immune system

The body's mechanisms for fighting infections and eradicating dysfunctional cells.

Vitamin D has several functions. It improves the functioning of the immune system and muscle strength; reduces inflammation; and assists in the formation of bone. Severe vitamin D deficiency (below 25 nmol/l) in HIV-negative patients has been associated with a higher risk of osteoporosis, muscle weakness, diabetes, and some cancers.

Several studies have shown a high prevalence of vitamin D deficiency in HIV-positive patients who are taking antiretroviral therapy. Some of this research has found an association between treatment with efavirenz (Sustiva, also in the combination pill Atripla) and low levels of the vitamin. This association has remained significant even after taking into account vitamin D levels in winter months and black race, both of which are known risk factors for low vitamin D levels.

Investigators wished to further examine the association between HIV infection, antiretroviral therapy and vitamin D deficiency.

They therefore monitored levels of the vitamin at baseline and then 96 weeks later in 219 patients participating in the MONET trial, a randomised comparison of protease inhibitor-based triple therapy with protease inhibitor monotherapy in patients with already suppressed viral load. Recruitment to the study took place in autumn 2007.

To be eligible for this trial patients were required to be taking HIV therapy and have a viral load below 50 copies/ml. They were then randomised to receive darunavir/ritonavir as monotherapy or darunavir/ritonavir in combination with two nucleoside reverse transcriptase inhibitors (NRTIs).

Most (80%) of the patients were male, 91% were Caucasian, and their mean age was 43. None were taking vitamin D supplements.

At baseline, 83 patients were taking a combination of drugs based on a non-nucleoside reverse transcriptase inhibitor (NNRTI); 61 were taking efavirenz and 22 nevirapine (Viramune). The most commonly used protease inhibitor was Kaletra (lopinavir/ritonavir).

On entry to the study, the majority of patients had deficient levels of vitamin D. This included 70% of those taking a protease inhibitor, approximately 70% of those treated with efavirenz or nevirapine, and all the patients who were taking a triple NRTI regimen.

Lower levels of vitamin D were significantly associated with calendar month (p = 0.01), black ethnicity (p = 0.04), treatment with efavirenz (p = 0.02), and use of AZT (p = 0.01).

Mean levels of vitamin D were lowest between January and April (35.8 nmol/l) and highest in September (mean 45.4 nmol/l).

The twelve black patients in the study had a mean baseline vitamin D level of 27.7 nmol/l. In comparison, the mean level of the vitamin among white patients at this time was 39.4 nmol/l.

For patients taking efavirenz, the mean baseline vitamin measurement was 35 nmol/l compared to a mean of 41.7 among those taking a protease inhibitor. The mean vitamin D level for AZT-treated patients was 34.6 nmol/l compared to 40.8 nmol/l for those receiving therapy with an alternative NRTI.

Severe vitamin D deficiency was present in 25% of efavirenz-treated patients at baseline, and only 2% had optimal levels of the vitamin. However, only 15% of those taking a protease inhibitor at the time of randomisation had severe vitamin D deficiency and 5% had optimal levels of the vitamin.

Factors significantly associated with severe vitamin D deficiency were treatment with AZT (p = 0.01) and black race (p = 0.012).

After 96 weeks of therapy with a darunavir/ritonavir-based regimen the proportion of patients with vitamin D deficiency had fallen. There was no difference in the prevalence of severe vitamin D deficiency when the patients were analysed according to their original antiretroviral regimen. Only black race (p = 0.02) and calendar month (p = 0.004) were associated with severe deficiency at this time.

Vitamin D levels were comparable between patients who received darunavir/ritonavir monotherapy and darunavir/ritonavir with two NRTIs (51.1 nmol/l vs. 55.3 nmol/l).

Mean vitamin D levels increased by 8 nmol/l in patients stopping efavirenz (p = 0.007), and by 8 nmol/l among those discontinuing AZT (p = 0.007).

“People with HIV infection should be monitored for vitamin D levels”, recommend the investigators.

They conclude, “for patients with severe vitamin D deficiency, the use of vitamin D supplements or switches of antiretroviral treatment could be considered.”

References

Fox J et al. Improvement in Vitamin D Deficiency Following Antiretroviral Regime Change: Results from the MONET Trial. AIDS Research and Human Retroviruses: online edition, doi:10.1089/aid.2010.0081, 2010 (click here for abstract).