Surprising Changes in Body Fat With Darunavir Monotherapy

Exposure to the nukes d4T (stavudine, Zerit) and, to a lesser extent, AZT (zidovudine, Retrovir) can cause the loss of subcutaneous fat (the fatty layer just under the skin). The wasting away of this fatty layer is called lipoatrophy. This wasting of subcutaneous fat can alter a person's appearance, causing the veins in the arms and legs to appear as if they are bulging and causing parts of the face, particularly the cheeks and temples, to sink.

In high-income countries, safer nukes such as these are commonly used:

• tenofovir + FTC co-formulated into one pill called Truvada

• abacavir + 3TC co-formulated into one pill called Kivexa

Researchers at several hospital clinics in France are conducting a study called Monoi (ANRS 136). In this study, the effects of monotherapy with darunavir-ritonavir are compared to HAART regimens containing darunavir-ritonavir. Preliminary results from Monoi suggest that participants who received darunavir monotherapy had a statistically increase in the fat content of their limbs. This intriguing finding is discussed later in our report.

Study Details

Monoi is an ongoing study that enrolled HAART users whose viral load had been less than 50 copies/mL and randomly assigned them to one of the following regimens:

• darunavir-ritonavir 600-100 mg twice daily (monotherapy)

• darunavir-ritonavir 600-100 mg twice daily and two nukes (HAART)

A sub-study of Monoi (144 out of 225 participants) included DEXA scans of the limbs and other parts of the body. Assessments of limb fat are used in some HIV clinical trials to help researchers determine whether subcutaneous fat (the fatty layer just under the skin) is increasing or decreasing. The participants who had DEXA scans were distributed as follows:

• monotherapy: 67 people

• HAART: 74 people

The average profile of participants who received DEXA scans was as follows:

• 22% females, 78% males

• age: 45 years

• length of time HIV positive: 12 years

• weight: 70 kg (154 lbs)

• body mass index (BMI): 24

• total limb fat: 5 kg

Results -- Changes in Limb Fat

Over the course of the study, limb fat changed in each regimen group as follows:

• monotherapy: an increase of 340 g

• HAART: a decrease of 20 g

This difference was statistically significant.

Over the course of the study, changes in fat in the trunk of the body were as follows:

• monotherapy: an increase of 730 g

• HAART: an increase of 600 g

This difference was not statistically significant.

The proportion of participants who lost at least 20% of the fat in their limbs during the study was as follows:

• monotherapy: 2% (1 out of 67 people)

• HAART: 11% (8 out of 74 people)

This difference was also not statistically significant.

Results -- Fat and Sugar

Differences in triglycerides and cholesterol levels in the blood between the two study regimens were not statistically significant.

Blood sugar levels fell in the HAART group and rose modestly in the monotherapy group. This difference was statistically significant.

Further Analyses

Taking into account many factors, researchers found that people who lost their subcutaneous fat in this study tended to be younger (averaging 39 years) compared to people who did not lose this fatty layer (averaging 46 years). Because of the relatively small number of people with fat wasting, it is not clear if this finding is clinically meaningful or an accidental discovery.

The study team also found that participants who gained fat deep within their bellies were more likely to have a high level of belly fat at the start of the study compared to people who tended to not gain belly fat.

The regimens that volunteers took prior to joining Monoi did not apparently have any impact on subsequent changes in body composition during the study.

Putting It in Perspective

Monoi is ongoing and an analysis of its data is needed after the two-year mark to find out if the changes noted during the first year are sustained.

While an average increase in limb fat of about 340 grams (less than one pound) with DEXA scans in people taking monotherapy is intriguing, it is not clear if this increase will be noticed by people taking these medicines, at least over the first year of therapy. The finding that there was an increase in limb fat in people not taking nukes is unusual and, if sustained, may require confirmation in another, larger, study. The number of people affected by fat loss in Monoi is relatively small and while eight cases occurred in the group taking HAART, one case did occur in a person taking darunavir-ritonavir monotherapy. Altogether, the interim results from Monoi are provocative and interesting and may stimulate debate among researchers. The two-year results are eagerly awaited.

References

1. Valantin M-A, Flandre P, Kolta S, et al. Fat tissue distribution changes in HIV-infected patients with viral suppression treated with darunavir/ritonavir monotherapy versus 2 NRTI + darunavir/r in the Monoi-ANRS 136 randomized trial: results at 48 weeks. In: Program and abstracts of the 17th Conference on Retroviruses and Opportunistic Infections, 16-19 February 2010, San Francisco, U.S. Abstract 721.

2. Degris E, Delpierre C, Sommet A, et al. Longitudinal study of body composition of 101 men with lipodystrophy: DXA criteria for lipodystrophy evolution. Journal of Clinical Densitometry. 2010; in press.