• Poster 44: Why Some Fat Deposits Waste but Others Expand in Patients Using Protease Inhibitors: Hypothesis and Supporting Data (Authored by W.J. Fessel. Kaiser Permanente Med. Ctr., San Francisco, CA)
  Click here to view the original abstract

• Poster 45: A Prospective Open Label Pilot Trial of a Maintenance Nevirapine (NVP)-Containing Regimen in Patients with Undetectable Viral Loads (VL) on Protease Inhibitor (PI) Regimens for at Least 6 Months (Authored by P. Tebas, K. Yarasheski, W.G. Powderly, E. Kane, D. Marin, J. Simpson, S. Claxton, M. Klebert, and K. Henry. Washington Univ., St. Louis, MO; and Regions Hosp., St. Paul, MN)
  Click here to view the original abstract

• Poster 52: Reversibility of Peripheral Fat Wasting (Lipoatrophy) on Stopping Stavudine Therapy (Authored by T. Saint-Marc, M. Partisani, I. Poizot-Martin, and J.L. Touraine. E. Herriot Hosp., Lyon, France)
  Click here to view the original abstract

Fat Redistribution, Fat Loss, and Fat Accumulation: Opening Day of the Conference Poses More Questions and Offers Few Answers

The metabolic changes experienced by people with HIV on antiviral therapy are receiving much attention on the first day the 7th Annual Conference on Retroviruses and Opportunistic Infections. Unfortunately, more questions than answers continue to come from the various studies. The entire class of protease inhibitors and one nucleoside reverse transcriptase inhibitor, d4T, continue to be the primary suspects in causing the body composition changes thousands of us are experiencing on these drugs. However, risk factors for developing the disorder, and reversibility of the body changes by stopping or changing the drugs continue to remain unanswered questions requiring rigorous long-term study.

The conference did present data on what is currently known around risk factors for developing lipodystrophy for people with HIV and on HAART therapy. Those risk factors are:

• Age -- older people are more at risk.

• Symptomatic HIV disease.

• Effective viral load suppression (the better the drugs work to suppress the virus, the more likely it is they will cause lipodystrophy).

• Increased duration on protease inhibitors.

Lipodystrophy also appears to be associated with elevated cholesterol and triglyceride levels, and also appears to be associated with an increase in the cortisol:DHEA ratio. What is not known is whether these changes are specifically related to drug toxicity of HAART, the natural course of HIV, or a combination of things.

An interesting hypothesis from poster 44 -- in a study conducted at Kaiser Permanente Medical Center in San Francisco, and whose abstracts were presented in the poster session at the conference -- suggests that fat wasting in the face, arms, legs, and buttocks is caused by nucleoside reverse transcriptase inhibitors affecting the white fat prevalent in these areas. Additionally, the study hypothesized that accumulation of fat in the stomach, back, and neck are caused by protease inhibitors affecting the brown fat found in these areas. Unfortunately, the study group was very small and follow-up studies are needed to prove or disprove this theory.

The effect of switching drug combinations to reduce or reverse the body composition changes is being explored in a number of studies. Much of the study data is conflicting, making the decision to change therapies because of lipodystrophy difficult for the PWA and provider. Of note was a small study involving 36 people conducted at Herriot Hospital in Lyon, France (see: poster 52). The study evaluated the reversibility of lipoatrophy (loss of fat from the face, arms, and legs) when stopping the drug d4T. After nine months, four patients reported their body shape returned to normal, seven patients reported "major improvement", and another twenty one patients reported "partial improvement." While this study is too small to draw the conclusion that stopping d4T will partially or fully reverse lipodystrophy, it does point to the need for larger long-term studies of stopping d4T and the affect on body composition.

Another study of switching drug combinations to reduce lipodystrophy involved substitution of a protease inhibitor with nevirapine (Viramune). This study conducted at Washington University in St. Louis and Regions Hospital in St. Paul involved a total of forty HIV-positive people who were switched from two NRTIs plus one PI to two NRTIs plus Viramune (see: poster 45).

At 24 weeks no improvements were noted in the fat redistribution syndrome, but some improvements were noted in triglyceride and cholesterol levels. Clearly, larger long-term studies are needed to evaluate the efficacy of this change, and inclusion of the specific NRTIs in the pre and post-switch regimens are needed to evaluate their effect on the metabolic abnormalities in combination with the PI.

Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.