HIV and Low Vitamin D: A Look at Mechanisms

HIV and tuberculosis (TB) have both been associated with low vitamin D levels, and so has treatment with efavirenz.

In order to examine the relationships among these 4 things—HIV, TB, efavirenz, and low vitamin D levels—certain facts need to be considered:

· Efavirenz interferes with cholesterol and vitamin D synthesis, but the dose-response relationship is unclear.

· Tuberculosis is the most common opportunistic infection and cause of death in HIV patients.

· Rifampicin and efavirenz have numerous similar and related drug interactions and toxicities.

· When used long-term, rifampicin and efavirenz induce CYP3A4 and CYP2B6, which are responsible for activating vitamin D.

Nevertheless, the predictive risk factors for vitamin D deficiency in patients receiving efavirenz with or without rifampicin are unclear.

The August 2016 of the journal Medicine included a study that shows low plasma cholesterol, high CYP3A activity, and high plasma efavirenz concentrations predict idiosyncratic severe vitamin D deficiency.

The observational study enrolled Ethiopian adults with or without comorbid tuberculosis who had CD4+ counts of 200 cells/mm³ or less.

Both HIV regimens employed (zidovudine/lamivudine/efavirenz and stavudine/lamivudine/efavirenz) included efavirenz600 mg. TB-infected patients also received rifampicin-based therapy.

The researchers collected plasma cholesterol, 4b-hydroxycholesterol, and 25(OH)D3 concentrations at weeks 0, 4, 16, and 48.

Patients do not tend to experience seasonal vitamin D production trends in arid equatorial Ethiopia. Every patient had insufficient or deficient vitamin D levels at enrollment, and none achieved target vitamin D levels (>72.5 ng/L) during follow-up. The researchers attributed this to HIV infection.

Most rifampicin users had severe vitamin D deficiency at baseline. However, efavirenz users who did not take concomitant rifampicin experienced more severe vitamin D deficiency. Severe vitamin D deficiency (<25 ng/L) tripled in the first 4 weeks of efavirenz therapy in this group.

Efavirenz lowers cholesterol levels, while rifampicin has the opposite effect. The opposing effects on cholesterol may explain the tempered effect of combined therapy on vitamin D. Meanwhile, greater CYP3A4 activity was associated with lower vitamin D levels at 0 and 4 weeks only.

Because improved HIV control increases vitamin D levels, deficiency resolved spontaneously in many patients. This population was more deficient than comparable populations in other equatorial countries, but the severity of the patients’ HIV/AIDS explains the high baseline deficiency rate.

Although vitamin D levels improve with HIV treatment, patients remain deficient without adequate supplementation.