injections can lead to dysfunctions in cortisol levels in people taking HIV
protease inhibitors, according to research published in the online edition of
the Journal of Acquired Immune Deficiency
Syndromes. Investigators in the United States found that 11% of their
HIV-positive patients developed hypothalamic-pituitary-adrenal (HPA) axis
dysfunction after treatment with local corticosteroid injections. All were taking
antiretroviral therapy based on a protease inhibitor (PI).The authors believe
that a drug interaction was the reason.
“The fact that all
cases of HPA-axis dysfunction in this cohort occurred in patients who were
treated with a PI underscores the significant concern regarding
drug-interactions in this population,” write the authors. “Considerable
morbidity can result from either over- or under-dosing of essential medicines.
Corticosteroid levels are known to increase when administered with ritonavir [Norvir] and other PIs, which are CYP34A
inhibitors and thus result in reduced clearance of steroid…levels.”
antiretroviral therapy mean that many HIV-positive people now have an
excellent prognosis and are living well into old age. This means that the
management of co-morbidities and the diseases of ageing are an increasingly
important part of HIV care. Osteoarthritis and musculoskeletal complaints are
common in older people and treatment with corticosteroid injections can offer
are metabolised by the liver using the CYP34A pathway. This is also utilised by
protease inhibitors, meaning there is a significant risk of drug interactions,
which could potentially lead to the development of HPA-axis dysfunction and
Cushing’s syndrome (prolonged exposure to elevated levels of cortisol).
Symptoms can include excessive tiredness, mood changes, increased appetite and
weight gain, hypertension, weakness, bruising and fungal skin infections.
Boston therefore examined the records of 170 HIV-positive people who had
received therapy with corticosteroid injections between 2002 and 2011. They
examined the prevalence of and for risk factors for HPA-axis dysfunction.
A total of 81
people (47%) were taking therapy based on a protease inhibitor, 56 (33%) were
taking another form of HIV therapy and 29 (17%) were treatment naive.
The participants had a
mean age of 52 years and 69% were male. Their mean CD4 cell count was 569
cells/mm3. The majority of participants (89%) had an undetectable viral
There were nine laboratory-confirmed cases (5%) of HPA-axis dysfunction. All the cases involved people whose HIV therapy was based on a protease inhibitor. This meant there was an
11% prevalence of HPA-axis dysfunction among people taking this class of
Among those who
developed HPA-axis dysfunction, three individuals received one corticosteroid
injection, two received two injections and four people had received three
injections in the previous six months. Eight of the participants received
injections containing triamcinolone and one person was treated with
methylprednisone. The median time between the first injection and the
development of HPA-axis dysfunction was 31 days.
(44%) required hospitalisation. There were no deaths and no cases of adrenal
crisis. All nine patients were treated with 3 to 5 mg prednisone. The durations of
steroid replacement therapy lasted between one week and more than three years.
The only risk
factor for the development of HPA-axis dysfunction was receipt of two or more
steroid injections in the previous six months (HR = 6.42; 95% CI, 1.20-34.33, p
“Our data show
that corticosteroid injections pose a substantial risk of disrupting the
endogenous HPA-axis dysfunction in HIV-infected patients on PIs leading to
clinical presentation with signs and symptoms of steroid excess or adrenal
insufficiency,” comment the authors. “The total number of steroid injections
over a relatively short period of time is a significant predictor of subsequent
development of HPA-axis dysfunction. It might be possible to reduce the risk of
this adverse event by decreasing the amount of corticosteroid used in these
injections for this at risk population. Pharmacokinetics studies could also be
helpful in future investigations.”