Low levels of vitamin D associated with poorer long-term CD4 cell gains in women who start HIV treatment late

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Vitamin D insufficiency is associated with poorer CD4 cell recovery among women who start HIV treatment late, US investigators report in the online edition of AIDS. After taking into account factors such as viral load, the authors found a significant relationship between low levels of vitamin D and impaired immune reconstitution.

“Our study found that vitamin D insufficiency is associated with late CD4 recovery after HAART [highly active antiretroviral therapy] initiation,” comment the investigators.

Vitamin D has an important role in overall health. Deficient levels have been linked to immune dysfunction, cardiovascular disease, impaired control of infections and depression.


immune reconstitution

Improvement of the function of the immune system as a consequence of anti-HIV therapy.


In HIV, an individual who is ‘treatment naive’ has never taken anti-HIV treatment before.

body mass index (BMI)

Body mass index, or BMI, is a measure of body size. It combines a person's weight with their height. The BMI gives an idea of whether a person has the correct weight for their height. Below 18.5 is considered underweight; between 18.5 and 25 is normal; between 25 and 30 is overweight; and over 30 is obese. Many BMI calculators can be found on the internet.


A mental health problem causing long-lasting low mood that interferes with everyday life.

CD4 cells

The primary white blood cells of the immune system, which signal to other immune system cells how and when to fight infections. HIV preferentially infects and destroys CD4 cells, which are also known as CD4+ T cells or T helper cells.

Several studies have found a high prevalence of vitamin D deficiency in people with HIV. Moreover, research conducted in HIV-positive men starting antiretroviral treatment late found that low levels of the vitamin were associated with impaired immune reconstitution.

Investigators from the Women’s Interagency HIV Study (WIHS) wanted to see if this was also the case in HIV-positive women.

They therefore designed a study involving 204 women who initiated HIV therapy when their CD4 cell count was below 200 cells/mm3. The investigators examined the relationship between vitamin D levels and the magnitude of CD4 cell recovery at three time points:

  • Six months after the initiation of treatment – association with a CD4 cell recovery of at least 50 cells/mm3.
  • Twelve months after treatment initiation – association with an increase in CD4 cell count of 100 cells/mm3 or more.
  • 24 months after starting therapy – association with a CD4 cell gain of 200 cells/mm3.

Vitamin D insufficiency was defined as ≤30 ng/dl.

Most of the women (60%) were African American and 89% had vitamin D insufficiency prior to starting HIV therapy.

Those with vitamin D insufficiency were more likely to aged over 38 years (94 vs 85%) and overweight or obese (98 vs 82%) than women with adequate levels of the vitamin. There was no relationship between CD4 cell recovery and vitamin D six and twelve months after initiating treatment.

Six months after starting HIV therapy, the presence of an undetectable viral load was associated with increased chances of having a CD4 cell gain of at least 50 cells/mm3 (OR = 8.89; 95% CI, 3.72-21.23).

Follow-up at twelve months after the initiation of treatment showed that an undetectable viral load was similarly associated with a CD4 cell gain of 100 cells/mm3 or more at this time point (OR = 7.68; 95% CI, 3.46-17.03).

However, after 24 months of therapy, vitamin D insufficiency was found to reduce the changes of a CD4 cell gain of 200 cells/mm3 by 80% (OR = 0.20; 95% CI, 0.05-83). Once again, an undetectable viral load was associated with robust gains in CD4 cell count (OR = 11.38; 95% CI, 4.31-30.05).

The mean increase in CD4 cell count from baseline to month 24 was 188 cells/mm3 for women with vitamin D sufficiency compared to 134 cells/mm3 among those with insufficient levels of this vitamin.

Controlling for age, race, body mass index (BMI), HIV treatment history and undetectable viral load, the investigators found a significant relationship between vitamin D levels and immune reconstitution over time (p < 0.01).

“There may be biological mechanisms that explain the effect of vitamin D insufficiency on late CD4 cell recovery after HAART initiation,” comment the investigators. “Vitamin D insufficiency could be related to production of naïve T cells.”

They conclude, “vitamin D insufficiency is associated with impaired late CD4 recovery on HAART in the WIHS cohort. The mechanism of this association…may be impaired late vitamin D-associated production of naïve CD4 cells during immune reconstitution, however this merits further exploration.”


Aziz M et al. Vitamin D insufficiency may impair CD4 recovery among Women’s Interagency HIV Study (WIHS) participants with advanced disease on HAART. AIDS 26, online edition. DOI:10.1097/0b013e32835b9a1, 2012.