Fw: CATIE News - Can lipodystrophy improve over the long term?

[Guest guest]

- CATIE News - Can lipodystrophy improve over the long term?

Sent: Apr 12, 2010 4:23 PM

CATIE News - Can lipodystrophy improve over the long term? Shortly after highly

active antiretroviral therapy (HAART) became available in high-income countries

in the mid-to-late 1990s, reports emerged of strange changes in body shape among

some HAART users. These changes can be divided into two basic types:

lipoatrophy – loss of the fatty layer just under the skin (subcutaneous fat).

This can cause the cheeks to have a sunken appearance and veins can appear to

bulge in the limbs lipohypertrophy – buildup of fat in the belly, breasts (in

women) and, in rare cases, the back of the neck. Some people may experience one

of these fat-related problems while others may have both processes taking place

at the same time. Additionally, inside the body, other changes, such as problems

managing blood sugar levels and increased cholesterol and other fatty substances

in the blood, are taking place. Together, all of these physical and biochemical

changes are called the HIV lipodystrophy syndrome.

When HIV-related lipoatrophy first appeared, it was blamed on the newest family

of anti-HIV drugs at the time—protease inhibitors. However, much research in the

past 10 years suggests that exposure to two drugs in particular, d4T (stavudine,

Zerit) and, to a lesser extent, AZT (zidovudine, Retrovir and in Combivir and

Trizivir), is linked to the problem of fat wasting.

Nowadays, the use of d4T is generally shunned in high-income countries and

instead other drugs are preferred, such as the following:

Truvada – (tenofovir + FTC) Kivexa – (abacavir + 3TC) Researchers in France have

been analysing long-term data collected from men with HIV-related lipodystrophy.

Their findings suggest that lipodystrophy can improve for some men. However, the

improvement is generally slow and modest.

Study details Researchers in Southern France at hospitals in Cahors and Toulouse

have been collecting health-related information from HIV-positive men who were

patients at local clinics. As part of regular care, these men received

occasional low-dose X-ray scans called DEXA. This type of scan is useful for

objectively assessing changes in body composition—fat, muscle, bone and so on.

Using the results from DEXA scans and other information in the medical charts of

the men, the research team assessed changes in body composition that occurred

over an average of four years.

The average profile of participants at the start of the study was as follows:

age – 46 years length of time HIV positive – 10 years current CD4+ count – 495

cells lowest-ever CD4+ count – 206 cells body mass index (BMI), a simple way of

assessing a person’s weight relative to their height – 23 Results—four years

later In analysing the DEXA scans and other tests over four years, here are some

of the changes researchers found:

total body fat increased by 1.3 kg (almost 3 pounds) fat in the trunk of the

body increased by a bit more than a half-kilo (600 grams or 1.3 pounds) fat in

the lower limbs increased by 300 grams (more than half a pound) BMI was stable

the density of bones decreased Before participants had their first DEXA scan,

85% had received AZT and 79% had received d4T. But over the course of the study,

55% of participants used AZT and 23% used d4T.

In comparing data from everyone, researchers found that some participants had

improvements in lipodystrophy (58%) but others did not. So they conducted

further analyses to find possible reasons for this.

Taking many factors into account, researchers found that the following factors

were statistically linked to improvements in lipodystrophy:

having a high CD4+ cell count having a high ratio of the proportion of trunk fat

to the proportion of lower limb fat a greater interval between DEXA scans The

longer AZT was used in this study, the greater the risk for lipodystrophy

worsening.

Putting it in perspective In this French study, a shift away from the use of

thymidine analogues (d4T and AZT) was linked to increased fat in the limbs in

some participants. According to the researchers, this fat was very likely

subcutaneous fat. It suggests that in some HIV-positive people lipoatrophy may

be partially reversed. However, the average person is not likely to notice an

increase of 300 grams (less than one pound) of fat distributed over two legs

over a period of four years. This change also suggests that any improvement in

fat is a slow process. The sooner doctors switched patients from thymidine

analogues to safer nukes, the greater the likelihood that an increase in

subcutaneous fat occurred. The researchers also found that lipoatrophy and

lipohypertrophy occurred together. This goes against previous findings that

suggested that these two events are separate. A large proportion of participants

(40%) had thin bones—osteopenia or its more severe form, osteoporosis. Decreases

in bone density occurred whether or not lipodystrophy improved. Bear in mind The

French study had several important limitations, as follows:

It was a retrospective study, meaning it looked back on already collected data.

Such studies are prone to cause biased interpretation of events. Retrospective

studies may be faster and cheaper to conduct than other study designs but their

findings need to be confirmed in a clinical trial of a more robust design. The

prescription of nukes in this study was not randomly assigned or in any way

controlled, as it would be in a prospective clinical trial. This lack of

randomization adds another layer of potential bias when interpreting results.

Only adult males were enrolled in this study, so its conclusions may not apply

to women and children. There was no information provided about co-infections

such as hepatitis C and the study’s findings may not apply to co-infected

people. Despite all of these potential weaknesses, the French study appears to

be the longest published review of DEXA scans used for assessing changes in

HIV-related lipoatrophy. Its findings will hopefully stimulate other researchers

to conduct a different study to confirm and extend the French findings over a

longer period.

Surprising results from trial ANRS 136 In France, an ongoing study called ANRS

136 (Monoi) randomly assigned participants to darunavir-ritonavir-based HAART or

darunavir-ritonavir monotherapy. Darunavir is sold under the brand name

Prezista.

After 48 weeks, 8 out of 74 people assigned to HAART developed fat wasting

(lipoatrophy) vs. 1 out of 67 people assigned to darunavir-ritonavir

monotherapy. Among participants who received HAART, the following nukes were

used:

tenofovir + FTC (Truvada) – 5 people 3TC + abacavir (Kivexa) – 1 person AZT +

3TC (Combivir) – 2 people 3TC (lamivudine) + ddI (didanosine, Videx EC) – 1

person Although the number of people with lipoatrophy in the Monoi study is

small, the finding with Truvada and Kivexa is surprising because these nuke

combinations are generally perceived as safe and not associated with

lipoatrophy. Longer results from ANRS 136 are awaited to see if there continues

to be a difference between participants who use nukes and those who do not.

— R. Hosein

 

 

CATIE-News Subscription Information CATIE-News is a moderated mailing list

operated by the Canadian AIDS Treatment Information Exchange to distribute

information about HIV/AIDS and related infections in Canada.

To see a directory of archived messages, visit CATIE's Web site at

http://www.catie.ca/catienews.nsf

To subscribe to the list, visit

http://orders.catie.ca/subscription/subscribe.shtml

To cancel your subscription to the list, visit

http://orders.catie.ca/subscription/unsubscribe_news.shtml

For assistance with your subscription from a real human being, please send a

message to web@...

CATIE-News is written by Hosein, with the collaboration of other members of

the Canadian AIDS Treatment Information Exchange, in Toronto. Your comments are

welcome.

Permission to Reproduce: This document is copyrighted by the Canadian AIDS

Treatment Information Exchange (CATIE). All CATIE materials may be reprinted

and/or distributed without prior p

Sent via BlackBerry by AT & T