Use of d4T is associated with buffalo hump

The first ever case-controlled study of ‘buffalo hump,’ an aspect of the lipodystrophy syndrome of antiretroviral-associated side-effects in HIV-positive patients, has found that the condition has a significant association with the use of d4T (stavudine, Zerit), and fat loss - a side-effect that has long been associated with d4T. The study, which is published in the January edition of HIV Medicine, also found that buffalo hump was rare, occurring in only 2% of individuals taking potent anti-HIV therapy.

It is well established that treatment with antiretroviral therapy can cause metabolic and body fat changes known as lipodystrophy, a syndrome that can involve fat loss from the limbs, buttocks or face, and/or fat accumulation around the abdomen or at the back of the neck and between the shoulders. The medical term for fat accumulation at the back of the neck is cervical lipomatosis, but it has become popularly known as buffalo hump. This condition is not thought to be medically dangerous in itself, but it can be uncomfortable, stigmatising and affects body self-image. Previous studies have suggested that it occurs in 2 – 13% of individuals taking HIV therapy.

Fat loss in individuals taking anti-HIV drugs has been associated with the use of particular antiretroviral drugs (d4T and, to a lesser extent, AZT (zidovudine, Retrovir), but relatively little is known about the exact causes of buffalo hump.

Spanish investigators therefore wished to determine the prevalence and risk factors for buffalo hump, and to analyse the clinical and metabolic characteristics of individuals with this condition.

The lipomatosis cervical (LIPOCER) study was a multicentre, observational, case controlled study involving over 4,000 antiretroviral-treated patients at ten Spanish hospitals.

Patients who had fat accumulation over the dorsocervical spine, supraclavicular or dorsal regions were diagnosed as having cervical lipomatosis – buffalo hump. These patients were matched with control individuals who were of similar age and body weight.

Information was obtained on the patients’ demography, HIV disease status, use of antiretrovirals, CD4 cell counts, viral loads, cholesterol, triglycerides, glucose and uric acid levels. A subset of patients also had hormone and insulin levels monitored and a second set of patients were tested for insulin resistance.

Of the 4,214 patients eligible for inclusion in the study, a total of 80 (2%) were diagnosed as having a buffalo hump. Four of these patients could not, however, be matched with control patients meaning that the investigators’ analysis consisted of 76 matched pairs.

Univariate analysis revealed that buffalo hump was associated with longer duration of HIV infection (p = 0.0001), treatment with saquinavir (p = 0.001), indinavir (p = 0.048)), efavirenz (p = 0.032), d4T (p = 0.0001) and tenofovir (p = 0.006). The condition was also associated with other aspects of the lipodystrophy syndrome including waist-to-hip ratio (p = 0.0001), fat loss (p = 0.0001), fat gain on the breasts, also known as gynaecomasty (p = 0.005), elevated total cholesterol (p = 0.055), lower HDL or ‘good’ cholesterol (p = 0.001), and high triglycerides (p = 0.0001). It was also associated with neuropathy (p = 0.028), which is also a recognised side-effect of d4T.

In the subsequent multivariate analysis, only use of d4T (p = 0.0073) and fat loss (p = 0.0001), one of d4T’s major side-effects, were associated with buffalo hump.

“Cervical lipomatosis was mainly associated with the presence of other disorders of fat distribution and lipid metabolism, suggesting that it forms part of the lipodystrophy syndrome”, write the investigators.

They add, “time of exposure to d4T was independently associated with the presence of cervical lipomatosis”. This finding, they note, is new. Although d4T and AZT have been associated with fat loss, fat accumulation has previously been associated with the use of protease inhibitors, a conclusion not supported by their analysis. The investigators also speculate that insulin resistance plays a key role in the development of both the metabolic and body fat changes seen in the lipodystrophy syndrome.