With the advent and subsequent widespread uptake of antiretroviral treatment, HIV is no longer a fatal disease but a chronic condition, allowing children with perinatally acquired HIV to survive childhood into adolescence and beyond. We are, however, beginning to recognise that antiretroviral treatment alone does not stop other associated maladies from occurring such as growth failure.
Studies have shown that HIV infection results in stunting and pubertal delay. Puberty is a key period of growth, having such a delay may reduce the mass of bone one develops, impairing future bone mineral density. Less dense bones are weaker, which increases the likelihood of fracturing. Antiretroviral treatment alone may not be enough to maintain children's health.
HIV is associated with vitamin D deficiency, regardless of regional differences in sun exposure. Additionally, essential minerals like calcium may not be as easily accessible in poorer regions affected by HIV. Why are vitamin D and calcium important for bone development?
Bones are constantly being remodeled by two types of bone cell: Osteoblasts and Osteoclasts.
Osteoblasts use calcium to strengthen the osteoid matrix as they form new bone. The stored calcium give bone its strength and mass, so when there is less calcium, bones become thin and lose their strength.
Calcium has other functions outside of bones such as muscle movement, so the amount of calcium ions in the blood must be carefully regulated. If there is not enough calcium in the blood, osteoclasts disassemble the bone tissue, creating space for further bone remodeling as well as releasing the calcium ions into the blood stream. This process is called bone resorption.
These balances between osteoblastic and osteoclastic action to maintain both bone structure and calcium levels are modulated by a hormone released from the parathyroid gland. So how is Vitamin D important?
Where bone regulation is concerned, vitamin D is important for maintaining calcium levels by encouraging calcium absorption in the gut.
If there is a deficiency in vitamin D (from HIV, antiretroviral therapy, a lack of sunlight, or otherwise), the intestines will absorb less calcium, reducing the calcium levels in the blood, encouraging the production of PTH which reduces the bone's calcium content. If the bones become too weak, they are at risk of breaking.
For adolescents, puberty is the most important period of growth until, at the end of puberty, peak bone mass is achieved. If this is inhibited by HIV, as adolescents reach adulthood they are much more likely to have lower bone mineral density, which is why this trial seeks to provide children living with HIV with adequate vitamin D and calcium to strengthen their bones.