D Linked to HIV Disease Progression
EuroSIDA researchers found that more than 80% of HIV positive
people on antiretroviral therapy (ART) had vitamin D deficiency,
which was associated with higher risk of AIDS-related
illness and death.
growing body of evidence indicates that low vitamin D levels
are common and can lead to detrimental health effects in people
with HIV as well as the
population at large.
D may be obtained through food and is produced by the body
when the skin is exposed to sunlight. Darker skinned individuals
and people who live in colder climates where less skin is
exposed are more prone to low levels.
As described in the April
25, 2011, advance online edition of AIDS, Jean-Paul
Viard and fellow investigators with the EuroSIDA Study Group
examined the association between vitamin D levels and disease
progression in HIV positive people.
The study included 2000 participants in the large EuroSIDA
study from Europe and Argentina who were randomly selected
for vitamin D measurement using stored plasma samples. Participants
were taking combination antiretroviral
Levels of 25-hydroxyvitamin D, or 25(OH)D -- the precursor
to the physiologically active form -- were stratified into
tertiles, or thirds (< 12, 12-20, and > 20 ng/mL). The
researchers analyzed factors associated with low vitamin D
levels, as well as associations between vitamin D and AIDS-related
events, non-AIDS events, and all-cause mortality. Participants
were followed for a median of 5 years.
1985 participants with vitamin D levels available:
had 25(OH)D < 10 ng/mL, or deficient;
had levels between 10 and 30 ng/mL, or low;
had > 30 ng/mL, or normal.
The following factors were significantly associated with
greater likelihood of low vitamin D levels:
outside southern Europe or Argentina;
samples obtained during winter;
transmission route other than male-male sex (i.e.,
injection drug use or heterosexual transmission).
participants taking HIV protease inhibitors were less
likely to have low vitamin D.
to those in the lowest 25(OH)D tertile, those in the middle
and highest tertiles had significantly lower risk of clinical
disease progression during follow-up:
events occurred in 10% of people in the lowest,
6% in the middle, and 5% in the highest tertile;
adjusted incidence rate ratio 0.58 for middle tertile
and 0.61 for highest tertile, or about 40% lower
mortality rates were 11% in the lowest, 7% in the
middle, and 6% in the highest tertile; adjusted
incidence rate ratios 0.68 and 0.56, respectively.
events occurred in 9%, 7%, and 7%, respectively,
representing a slight but non-significant reduction
in the middle and highest tertiles.
were no significant differences between people in the
middle vs highest tertiles for any of these outcomes.
on these findings, the study authors wrote, "25(OH)D
deficiency was frequent in HIV-infected persons (83% on combination
ART), and was independently associated with a higher risk
of mortality and AIDS events."
Studies across Europe have found vitamin D levels below 10
ng/mL in 2% to 30% of adults in the general population, they
noted in their discussion. The U.S. SUN study found that about
30% of HIV positive people had levels below 20 ng/mL, compared
with about 40% of participants in the NHANES general population
survey. Thus "vitamin D deficiency might not be more
frequent in people living with HIV than in the general population."
The EuroSIDA investigators did not see a link between use
of ART overall or efavirenz (Sustiva) and lower vitamin D
levels as suggested in some prior studies. The observed link
between protease inhibitor use and higher 25(OH)D levels "is
of unclear biological relevance," they wrote.
the lowest vitamin D levels remained strongly associated with
AIDS-related events and all-cause mortality even after adjusting
for a large number of variables including season, race/ethnicity,
geographic origin, CD4 cell count, HIV viral load, anemia,
and kidney function (eGFR).
D deficiency therefore represents a new, independent, unfavorable
prognostic marker in HIV infection, but without further research
this cannot translate into clinical recommendations,"
the authors concluded.
results provide strong evidence that vitamin D deficiency
is an important cofactor in HIV disease progression, even
in the setting of widespread, efficient combination ART,"
they continued. "Whether the relationship between vitamin
D deficiency and events is causal must now be addressed, because
of potential public health consequences."
Investigator affiliations: Centre de Diagnostic et de Thérapeutique,
Hôtel-Dieu, APHP and Université Paris Descartes,
Paris, France; Service d'Explorations Fonctionelles, Hopital
Necker, APHP, Paris, France; Copenhagen HIV Program, Panum
Institute, Copenhagen, Denmark; Department of Infection and
Population Health, University College London Medical School,
London, UK; Medical University, Wroclaw, Poland; Hospital
JM Ramos Mejia, Buenos Aires, Argentina; Hospital Clinic i
Provincial, Barcelona, Spain; Odense University Hospital,
Odense, Denmark; Medizinische Poliklinik, Munich, Germany;
Centre for Viral Diseases Diseases, Rigshospitalet, Copenhagen,
Viard, JC Souberbielle, O Kirk, et al. Vitamin D and clinical
disease progression in HIV infection: results from the EuroSIDA
study. AIDS 25 (abstract).
April 25, 2011 (Epub ahead of print).