People with HIV in the normal weight range who gain a substantial amount of weight shortly
after starting antiretroviral therapy (ART) may have an increased risk of
cardiovascular disease and diabetes, according to findings from the D:A:D study
presented this week at the 20th International AIDS Conference in Melbourne.
Several observational studies - including the large
international Data Collection on Adverse events of Anti-HIV Drugs (D:A:D)
study - have found that people with HIV have higher rates of
cardiovascular disease and metabolic conditions such as diabetes. However, the
relative contributions of HIV infection itself, resulting inflammatory and
metabolic changes, antiretroviral toxicities, and other factors are not yet
fully understood. Many people with HIV gain weight after starting ART, and this
may have a detrimental effect on health.
Amit Achhra from the Kirby Institute in Sydney and colleagues looked at
the relationship between short-term changes in body mass index
(BMI) after treatment initiation and subsequent risk of cardiovascular disease
and diabetes in the D:A:D cohort.
Out of nearly 50,000 participants
in the full cohort, this analysis included 9321 people who were starting ART
for the first time, had no prior history of cardiovascular disease before
treatment initiation and had BMI data available from before and one year after
initiation. People who developed cardiovascular disease or diabetes within the
first year were excluded.
About three-quarters of
participants were men, the average age was approximately 40 years and about 5%
had a family history of heart disease. Before starting ART 6% were underweight (BMI <18.5), 64% were normal weight
(18.5-24.9), 23% were overweight (>25) and 6% were obese (>30).
The median CD4 T-cell count was
approximately 270 cells/mm3 in the latter three groups, but only 170
cells/mm3 in the underweight group, reflecting more advanced
Overall, about one-third of participants were current smokers - although heavier
people were less likely to smoke - and about 10% had hepatitis C virus
coinfection. As expected, overweight and obese participants had higher blood
pressure and were more likely to have pre-existing diabetes, rising from 1.6%
among underweight people to 6.8% in the obese group.
The researchers looked at a
composite cardiovascular disease endpoint that included myocardial infarctions or heart attacks, strokes,
sudden cardiac death and related surgical procedure such as coronary artery
bypass or angioplasty. Diabetes assessment was based on medical records or use
of anti-diabetic drugs.
Overall, participants gained weight after
starting ART, with a mean BMI change of 0.67 at one year. Weight gain was
greatest among people who were underweight (BMI <18.5) when they started
treatment, moderate among people who started out with normal weight (18.5-24.9)
or overweight (>25) and relatively stable among people who were obese
(>30) at ART initiation.
A total of 97 cardiovascular disease events
occurred during nearly 44,000 person-years of follow-up, for a rate of 2.21 per
1000 person-years. Of these, 46 were heart attacks, 33 were strokes and 18 were
The cardiovascular event rate (again, per
1000 person-years) rose with increasing body weight: 1.73 in the underweight group,
2.13 in the normal weight group, 2.41 in the overweight group and 2.78 in the
obese group. After adjusting for demographics and other factors, a 1-unit gain
in BMI was
associated with an 18% increased risk of cardiovascular events in the normal weight
group. However, people in the underweight, overweight and obese groups did not
see a significant change in risk.
diabetes, a total of 125 new events occurred among the 9193 participants who
did not have diabetes at study entry, a rate of 2.89 cases per 1000
person-years. As with cardiovascular disease, the likelihood of developing
diabetes rose with body weight, though the risk increased more sharply: 2.04,
2.01, 4.05 and 9.97 events per 1000 person-years in the respective weight
categories. After adjusting for other factors, a 1-unit gain in BMI was associated with about a 10% increased
risk of diabetes across all categories.
Findings were similar in sensitivity analyses that excluding people
with a history of injecting drug use and those with undetectable HIV viral load
(<400 copies/ml) at one year after starting ART. Achhra noted that people
who inject drugs IDU are at higher risk for heart problems not related to
gain in BMI post ART initiation could be associated with the increased risk of
cardiovascular disease, largely in those with normal/mid-levels of pre-ART
BMI," the researchers concluded. "Gain in BMI also associated with
risk of diabetes in all groups."
they added that there was "no appreciable change in risk of cardiovascular
disease with gain in BMI in those with high pre-ART BMI."
limitation, they noted that BMI may not reflect abdominal or central obesity -
which is most strongly related to metabolic abnormalities and heart disease -
and the study did not have access to information about diet or exercise, which
can affect risk independent of weight.