Low vitamin D concentrations associated with poor clinical and virological outcomes among people starting HIV therapy

Michael Carter
Published: 19 May 2014

Low vitamin D concentrations are associated with an increased risk of HIV disease progression among people starting antiretroviral therapy, investigators report in the online edition of The Journal of Infectious Diseases. Virological failure also had an association with low vitamin D levels at the start of therapy, and there was evidence suggesting a relationship with between vitamin D levels and immunological outcomes. The study was conducted in eight low-and middle-income countries and the US. The authors believe that studies exploring the impact of vitamin D supplementation on HIV treatment outcomes are warranted.

Concentrations of vitamin D are related to exposure to sunlight, latitude, season and skin pigmentation. The vitamin is important to a healthy immune system. Several studies involving people living with HIV have shown a high prevalence of low vitamin D concentrations.

However, few studies have examined the relationship between low vitamin D concentrations at the initiation of antiretroviral therapy and clinical outcomes. The connection between baseline vitamin D levels and virological and immunological outcomes is unexplored.

Data collected during the PEARL (Prospective Evaluation of Antiretrovirals in Resource Limited Settings) study provided information for investigators to explore the relationship between low baseline vitamin D levels and treatment outcomes.

The study population consisted of people living with HIV who experienced progression to WHO (World Health Organization) stage 3/4 disease within 96 weeks of starting therapy; people who experienced virological failure (two consecutive viral load measurements above 1000 copies/ml 16 weeks after initiating treatment); and people with immunological failure (CD4 count below 100 cells/mm3 after 48 weeks of treatment). These patients were compared to randomly selected individuals to see if baseline vitamin D levels were associated with an increased risk of poorer outcomes.

Recruitment took place between 2005 and 2007. Participants were enrolled in Brazil, Haiti, India, Malawi, Peru, South Africa, Thailand, the United States and Zimbabwe.

Almost half (49%) of all participants in the study had low vitamin D concentrations at baseline. Prevalence of low vitamin D varied between countries, ranging from 27% in Brazil to 78% in Thailand and 72% in India. Prevalence was 92% among African-Americans in the US.

After controlling for country and HIV treatment regimen, the factors significantly associated with low vitamin D were race, season of sampling (winter/spring), high or low body mass index (BMI) and lower HIV viral load.

Analysis that took into account history of previous AIDS-defined illness and controlled for season, baseline CD4 count and viral load, BMI and race showed that low vitamin D concentrations at the start of therapy were associated with a twofold increase in the risk of clinical disease progression (HR = 2.13; 95% CI, 1.09-4.18).

The investigators cite other studies showing it is “biologically plausible” that low vitamin levels would increase the risk of poor clinical outcomes.

Low vitamin D at baseline more than doubled the risk of virological failure (HR = 2.13; 95% CI, 1.81-3.50). The authors note that theirs is the first study to identify vitamin D as a factor in the virological outcomes of therapy.

There was also evidence suggesting that low vitamin D increased the risk of a poor CD4 response to treatment. However, there were too few cases for this to be proved.

“The associations found in this paper raise questions of reverse causation: does advanced HIV disease cause low [vitamin D] concentrations; or, is low [vitamin D] concentration a general marker for poor health,” write the authors. “The fact that this was prospective and that severely ill persons were excluded from the study makes this unlikely. Also, [vitamin D] concentrations were comparable to those found in studies of non-HIV infected persons in similar populations.”

The investigators believe their findings support the concept of vitamin D supplementation as an adjunct to HIV therapy, concluding “a well-designed clinical trial is needed.”


Havers F et al. 25-hydroxyvitamin D insufficiency is associated with HIV disease progression and virological failure post-antiretroviral therapy initiation in diverse multinational settings. J Infect Dis, online edition, 2014.

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