hiv-associated facial lipoatrophy

© 2002 by the American Society for Dermatologic Surgery, Inc. • Published by Blackwell Publishing, Inc.ISSN: 1076-0512/02/$15.00/0 • Dermatol Surg 2002;28:979–986

HIV-Associated Facial Lipoatrophy

Julia James, MD,* Alastair Carruthers, MD,* and Jean Carruthers, MD

†

*

Division of Dermatology and

†

Department of Ophthalmology, University of British Columbia, Vancouver,

British Columbia, Canada

J. JAMES, MD, A. CARRUTHERS, MD, AND J. CARRUTHERS, MD HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS.

HIV-ASSOCIATED LIPODYSTROPHY syndrome hasonly recently been recognized, nevertheless there havebeen numerous reports describing the changes in bodyshape and associated metabolic disturbances. The con-dition is characterized by fat loss and/or redistribution,insulin resistance, and proatherogenic hyperlipidemia.This is distinct from HIV wasting syndrome, which ispredominantly due to loss of muscle mass.

Some investigators believe that there is a link be-tween HIV lipodystrophy and the introduction of HIVprotease inhibitors, both of which were reported inthe literature from 1997 onwards. The encouragingclinical, virologic, and immunologic effects of proteaseinhibitors mean that there has been some tolerance ofside effects, however, some studies show that lipodys-trophy has a prevalence of up to 83% and causes no-ticeable disfigurement.

1–6

This syndrome is a majorcause for concern, as the alteration in appearance hasa huge impact on these individuals’ lives, especiallynow that more successful HIV treatment has reducedthe anxiety associated with living with HIV.

Lipodystrophy Syndrome

The lipodystrophies are a rare group of inherited oracquired disorders that are characterized by regional

or generalized loss of subcutaneous fat. Lipodystrophyis uncommon in individuals who are not infected withHIV.

HIV-associated lipodystrophy syndrome can in-clude fat loss and/or fat accumulation in distinct re-gions of the body. Characteristically there is increasedfat around the abdomen, dorsocervical fat pad en-largement (buffalo hump), and sometimes breast hy-pertrophy.

3,5,7,8

Fat is lost from the limbs, buttocks,and face, especially the nasolabial regions, the tem-ples, and when severe, the eye sockets.

7,9

The fat wast-ing in the limbs leads to prominence of the subcutane-ous veins, and that of the face and buttocks leads tomarked hollowing and wrinkling of the skin.

Other manifestations of HIV-associated lipodystro-phy syndrome include insulin resistance, hyperglyce-mia, hypertriglyceridemia, hypercholesterolemia, andlow levels of high-density lipoprotein (HDL).

2,5,10

In-dividuals with these metabolic disturbances have thepotential to develop premature type 2 diabetes melli-tus and coronary artery disease.

11

Association of Lipodystrophy WithProtease Inhibitors

The introduction of protease inhibitors as antiretrovi-ral therapy represents a major development in HIVtreatment. When used in combination with other anti-retroviral drugs, protease inhibitors improve theCD4

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cell count and reduce plasma viral load further

Address correspondence and reprint requests to: Alastair Carruthers,MD, Carruthers Dermatology Center, Suite 820, 943 West Broadway,Vancouver, BC, Canada V524E1, or e-mail: [email protected].

background.

HIV-infected individuals are living long, healthylives. They are now concerned with less life-threatening prob-lems, especially lipodystrophy.

objective.

To review the current state of our knowledgeabout lipodystrophy in HIV-infected individuals.

methods.

The literature was reviewed and analyzed for rele-vant information. In addition, our clinical experience of manag-ing such individuals was utilized.

results.

Lipodystrophy and facial lipoatrophy and their rela-

tionship to HIV-infection are discussed. Their differences arenoted. The spectrum of appearance in individuals with facial li-poatrophy is described and a severity scale suggested whichshould be of value in assessing the results of treatment.

conclusion.

Lipodystrophy and lipoatrophy are intimatelyrelated to infection with HIV. In consequence, facial lipoatro-phy is a major stigma for HIV-infected individuals and canhave dramatic effects on their self-esteem and socialization. Ef-fective treatment is essential.

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james et al.: hiv-associated facial lipoatrophy

Dermatol Surg 28:11:November 2002

than reverse transcriptase inhibitors or antiviral nucle-oside analogs alone, dramatically changing the clinicalcourse of HIV disease. Therefore the use of highly ac-tive antiretroviral therapy (HAART) has become stan-dard practice in the treatment of all stages of HIV in-fection.

Recently, fat redistribution and metabolic effectssuch as insulin resistance and hyperlipidemia havebeen considered as possible side effects of protease in-hibitor use.

2,12,13

There are several better-known ad-verse effects of protease inhibitors, for instance, renalcalculi and gastrointestinal intolerance with indinavir;diarrhea, nausea and perioral paresthesia with ritonavir;and diarrhea with nelfinavir.

13

Prevalence of lipodystrophy in HIV-infected patientstaking protease inhibitors has been documented inmany studies. Carr and Cooper

14

performed two stud-ies and found that 64% of patients receiving proteaseinhibitor therapy developed lipodystrophy, whereasonly 3% of protease inhibitor-naïve patients developedit. One year later the same authors reported 83% and4%, respectively.

6

They estimated that the mean time tolipodystrophy was 10 months after commencing pro-tease inhibitor treatment. Ho et al.

1

found that 24% ofpatients who had taken indinavir for more than 3months developed facial lipoatrophy. Those taking nu-cleoside reverse transcriptase inhibitors (NRTIs) andthose who had been on indinavir for less than 3 monthsdid not develop facial lipoatrophy.

1

Lipodystrophy has not been found to be more likelyin those with a family history of diabetes mellitus.

2

There is also no significant association of lipodystro-phy with age, sex, body mass index (BMI), ethnicity,route of HIV transmission, CD4

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cell count, viral load,history of AIDS-defining illness, or concomitant anti-retroviral treatment.

1,2,15

Several studies have compared the prevalence of lipo-dystrophy in protease inhibitor-treated patients withthat in NRTI-treated patients. Bonnet et al.

15

foundthat 47% of patients on protease inhibitors developedlipodystrophy compared to none of the NRTI-treatedgroup, but the sample of patients taking only NRTIswas very small. Mallal et al.

16

studied a larger groupof patients and established that 54% of protease inhib-itor-treated patients developed lipodystrophy, whereasonly 13% of NRTI-treated protease inhibitor-naïvepatients did. NRTIs predisposed to slowly progressivefat loss that is accelerated when a protease inhibitor isadded. Therefore protease inhibitors are the primaryinfluence in lipodystrophy, but they may act synergis-tically with NRTIs.

16

Carr et al.

17

observed lipodystrophy in patients tak-ing protease inhibitors, NRTIs, and those taking both.There was no significant difference in physical or bodycomposition parameters between patients with NRTI-

lipodystrophy syndrome and those with protease in-hibitor-associated lipodystrophy syndrome. However,NRTI-lipodystrophy syndrome had more recent onsetsymptoms and weight loss, higher lactate and alanineaminotransferase, and lower albumin, cholesterol, triglyc-erides, glucose, and insulin compared to protease inhib-itor-associated lipodystrophy syndrome. They concludedthat both protease inhibitors and NRTIs contributeto lipodystrophy syndrome, particularly if associatedwith lactic acidemia, but have some distinguishableclinical and metabolic effects.

17

These studies show that lipodystrophy is more com-mon in HIV-infected patients taking NRTIs or proteaseinhibitors than in untreated individuals. It would appearthat protease inhibitors have more of an effect thanNRTIs, but they may act synergistically. The prevalenceof abnormal fat redistribution has been shown to be upto 83%, but there is no conclusive evidence to showwhether it is due to HAART or part of the HIV diseaseprocess. Further research is needed to understand HIV-associated lipodystrophy in the era of HAART, whichhas been accompanied by increased survival of HIV-infected individuals and reduced complications.

Pathogenesis of Lipodystrophy

The underlying mechanisms of HIV-related lipodys-trophy are not known. One hypothesis proposes thatprotease inhibitors bind to and inhibit proteins in-volved in lipid metabolism. There is homology be-tween the amino acid sequences of the catalytic site ofHIV protease, which protease inhibitors bind to, andtwo proteins involved in lipid metabolism regulation:low-density lipoprotein receptor-related protein (LRP)and cytoplasmic retinoic acid binding protein type 1(CRABP-1). Protease inhibitor binding of LRP exacer-bates hyperlipidemia by reducing postprandial chylo-micron clearance. When protease inhibitors bind toCRABP-1, retinoic acid cannot bind and less

cis

-9-ret-inoic acid is produced leading to reduced differentia-tion and increased apoptosis of peripheral adipocyteswith impaired fat storage and lipid release. Cyto-chrome P-450 3A is the enzyme required to convertretinoic acid to

cis

-9-retinoic acid, and protease inhib-itors potently inhibit it, therefore exacerbating thedysfunction of peripheral adipocytes.

18

It has been postulated that central and dorsocervi-cal adipocytes may be more metabolically active thanthe peripheral ones. The impaired peripheral fat stor-age and hyperlipidemia associated with protease in-hibitor treatment would then lead to preferential cen-tral accumulation of fat.

12

More recently, lipoatrophy has been attributed tomitochondrial toxicity induced by NRTIs. Some patientstreated only with NRTIs develop peripheral lipoatro-



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phy, and dorsocervical/abdominal fat accumulation,with lactic acidemia. NRTIs deplete mitochondrial DNA(mtDNA) and induce toxicity by inhibiting mtDNApolymerase

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. The resulting apoptosis or complement(C3) deficiency can lead to abnormal fat distribution.

19

A recent study by Côté et al.

20

measured mtDNA fromblood cells using polymerase chain reaction (PCR). Sig-nificantly decreased levels of mtDNA were found inHIV-positive patients treated with NRTIs, particularlyStavudine, who had lactic acidemia and lipodystrophy.

20

There are several other possible mechanisms for thedevelopment of lipodystrophy in HIV-infected patients.Accumulation of fat may occur as a refeeding effect as-sociated with increased appetite following suppressionof HIV replication with antiretroviral therapy, but thisdoes not explain the lipoatrophy. There may be a corre-lation between urinary free cortisol and accumulationof central fat through an inappropriate hormonal stressresponse and increased sensitivity of the central adipo-cytes. Lipodystrophy may develop if there is parallel in-creased release of catecholamines, which elevate restingmetabolic rate and enhance lipolysis.

21,22

The insulin resistance that is often associated withlipodystrophy is probably due to the increased circu-lating lipids, which interfere with glucose uptake andimpair islet-cell secretion, leading to impaired glucosetolerance. Insulin resistance has been shown to accom-pany the loss of peripheral fat in lipodystrophy, and islinked with elevated levels of the soluble type 2 tumornecrosis factor-

�

receptor (sTNFR-2). High levels ofsTNFR-2 can be used as an indicator of immune acti-vation and are associated with the course of HIV in-fection and with insulin resistance in obesity. Thissuggests that inflammation may contribute to the patho-genesis of lipodystrophy and insulin resistance.

10

Risk factors for developing lipodystrophy may in-clude low body weight before treatment, elevated trig-lyceride and C-peptide, and low HDL levels after 1year of therapy, total duration of HAART, and the useof certain antiretroviral agents or combinations of drugs.

6

Despite these insights into the pathogenesis of HIV-associated lipodystrophy, further research is needed toclarify the situation. It can be seen from the hypothe-ses discussed above that the causes of lipodystrophyand metabolic abnormalities seen in HIV infection areprobably multifactorial.

Facial Lipoatrophy Severity Scale

Facial lipoatrophy presents to varying degrees and it ishelpful to be able to classify the severity in order to de-cide on a treatment regime. Currently there is no pub-lished facial lipoatrophy severity scale, however, wepropose a system for the classification of facial lipoat-rophy based on the effects on the cheeks (see Figure 1).

Grade 1 is mild and localized facial lipoatrophy, andthe appearance is almost normal. Grade 2 has deeperand longer central cheek atrophy, with the facial mus-cles (especially zygomaticus major) beginning to showthrough. In grade 3 facial lipoatrophy, the atrophicarea is even deeper and wider with the muscles clearlyshowing. In grade 4, atrophy covers a wide area and ex-tends up toward the orbit. The facial skin lies directlyon the muscles over a wide area. Grades 3 and 4 areclearly abnormal and the quality of life for these pa-tients is typically lower than that of normal individuals.

Psychologic Effects of Facial Lipoatrophy

There is very little in the literature on this subject, de-spite the enormous psychosocial impact that facial li-poatrophy has on HIV-infected patients. However,Collins et al.

23

carried out a survey of HIV-infectedpatients with lipodystrophy syndrome to find outwhat they perceived were the psychologic and socialeffects of lipodystrophy. The questions concentratedon body changes related to fat redistribution and notthe metabolic effects. It was found that individualswith lipodystrophy had poor body image and low self-esteem, became socially withdrawn, found their sexualrelationships were adversely affected, were often forcedinto disclosing their HIV status due to facial lipoatro-phy, commonly were depressed, often thought the doc-tor found their lipodystrophy to be less important thanthey did, were noncompliant with HAART due to lipo-dystrophy, and the costs of supplements and surgeryhad an economic impact on them. Many patients foundthat coping with lipodystrophy was harder than justliving and surviving with HIV.

23

The psychologic and social impact of lipodystrophysyndrome on HIV-infected individuals is quite consid-erable and it adversely affects their quality of life. Thechanges to the body lower self-esteem and body im-age, leading to social and sexual problems, and quiteoften anxiety and depression follow. These patientshave previously coped with HIV infection, and in theera of HAART, new hope is placed on the success ofthese therapies, but the adverse effects are discourag-ing. Patients must weigh the benefits and risks of anti-retroviral therapy if they see no definitive treatmentfor facial lipoatrophy and other features of fat redistri-bution.

Lipodystrophy Treatment Options

There are no established methods of treatment for li-podystrophy syndrome, but several experimental treat-ments have been undertaken for various componentsof it. Exercise can decrease central fat accumulation,but this can worsen peripheral lipoatrophy. Another

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Figure 1. Facial lipoatrophy severity scale. Grade 1: mild and localized facial lipoatrophy. Grade 2: deeper and longer atrophy, with the fa-cial muscles beginning to show through. Grade 3: atrophic area is even deeper and wider, with the muscles clearly showing. Grade 4: li-poatrophy covers a wide area, extending up toward the eye sockets, and the facial skin lies directly on the muscles.



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approach to reduce abdominal and dorsocervical fataccumulation is liposuction. The dorsocervical fat ac-cumulations are more fibrous compared to patientshaving liposuction for reasons other than HIV-associ-ated lipodystrophy, but the results are generally good.The fat does not often reappear and patients are onthe whole highly satisfied.

24,25

It may be possible to improve lipodystrophy byswitching patients from protease inhibitors, if they arethe suspected cause, to nonnucleoside reverse tran-scriptase inhibitors (NNRTIs). Partial improvement hasbeen observed in body shape and metabolic abnormal-ities in such patients approximately 6 months afterstopping protease inhibitors, with no significant changein CD4 count or viral load.

26

Alterations in bodyshape may also improve with recombinant humangrowth hormone (rHGH). When administered subcu-taneously, lean tissue is augmented and destruction offat is promoted, however, circulating lipid levels arenot reduced. Lipoatrophy may be worsened and hy-perglycemia can be precipitated, especially if rHGH isgiven parenterally.

27

One treatment strategy that would seem wise to tryfor patients with lipodystrophy and high blood lipidlevels is lipid-lowering agents. Statins and/or fibratesare effective at lowering cholesterol and triglyceridesin some, but not all patients with HIV-associated lipo-dystrophy.

28

Fibrates occasionally induce gallstones,rash, erectile dysfunction, and gastrointestinal symp-toms. Adverse effects of statins include hepatotoxicity,gastrointestinal upset, and myopathy. The majority ofthe statins interact with cytochrome P-450 3A, whichis inhibited by protease inhibitors, occasionally lead-ing to hepatitis and myositis with combined use.

29

Dose reductions of statins are required when adminis-

tered with protease inhibitors, but there are insuffi-cient data to calculate how far the dose should be re-duced, and no data for other antiretroviral agents.

Insulin resistance due to HIV-associated lipodystro-phy can be improved with antidiabetic agents in orderto reduce the risk of cardiovascular events. Thesedrugs enhance the sensitivity of peripheral tissues toinsulin, resulting in increased muscle and liver re-sponses. Hadigan et al.

30

found that compared to pla-cebo, metformin therapy resulted in significant de-creases in insulin levels, BMI, and diastolic bloodpressure in HIV-infected patients with glucose intoler-ance and lipodystrophy. There were no serious ad-verse effects, such as raised lactate levels or liver dys-function, which can occur with troglitazone.

Some individuals with lipodystrophy use anabolicsteroids; although they only increase muscle mass, thefat redistribution is masked by the enlarged musclebulk. It would appear that serum lipids and insulinlevels are not worsened through use of anabolic ste-roids,

31

but facial lipoatrophy continues to deteriorate.

32

A novel proposal for treatment of lipodystrophy isleptin replacement therapy. This appears to returnlipid levels and insulin resistance to normal, and topromote weight loss. However, although fat is lost fromthe abdomen, leptin cannot normalize the lipoatrophyin other parts of the body, such as the face.

33

Facial lipoatrophy is a prominent element of HIV–associated lipodystrophy syndrome that is not greatlyimproved with any of the treatment strategies describedabove. One of the first treatments for lipoatrophy ofthe nasolabial regions was injection of liquid silicone.Since the 1960s, facial lipoatrophy has been treatedwith small, regular injections of silicone into the deepdermis and fat over several months.

34–36

Only 1–2 ml

Figure 1. Continued.

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are injected at a time to produce a gradual and even fi-broplastic reaction, as larger injections appear to resultin migration of the silicone and visible inclusion cysts.This use of silicone oil is not approved in the UnitedStates or Canada. At the time of writing, there are nopublications on the use of injectable silicone in thetreatment of HIV-associated facial lipoatrophy.

Collagen implant therapy became the favored alter-native to silicone injections when the FDA licensedZyderm (bovine collagen) for implant therapy in1981.

37

Skin testing for an allergic response is neces-sary before starting treatment, and then several ses-sions of injections are required at 2- to 4-week inter-vals.

38

Approximately 1 ml is injected into the dermisat a time, as greater amounts can result in multiplesmall papules or beading at the site.

39

The soft tissueaugmentation produced by collagen does not last aslong as that produced by silicone injections, as the col-lagen is rapidly degraded and longevity is measured inweeks compared to months for silicone. Along withthe expense of the product, another disadvantage of col-lagen implants is the reported adverse reactions. Local-ized hypersensitivity reactions occur in some patients,even following a negative skin test, and long-term gran-ulomatous reactions with or without arthralgia mayalso occur several months after implantation.

40–42

Another substance that has been used for soft tissueaugmentation is injectable lyophilized particulate hu-man fascia lata (Fascian). It is harvested from humancadavers, then processed and sterilized ready for re-constitution and injection.

43

Fascian is human-derivedand so pretesting for an allergic response is not neces-sary. One study quotes 0.02% rate of allergic reac-tions following Fascian injection, so it can be seen thatthe allergenicity is very low.

44

The grafts are reportedto last longer than the effects of collagen injectionsand there are few reported adverse effects. Cymetra ismicronized Alloderm, which is preserved human der-mis. It has been available in the United States since1995, but there are no published reports of its use fortreatment of facial lipoatrophy. Both Fascian and Cy-metra share some of the problems seen with bovinecollagen, in other words, the lack of permanence of re-sponse and the expense of the treatment.

Autologous fat has been used as a volume replace-ment agent for many years. It has been used success-fully in those whose lipoatrophy is not caused by HIV,and also in the HIV-related condition with fat beingremoved from the abnormal deposits and injected intothe face. However, in our experience, the excess fatdeposits on the abdomen and dorsal neck do not usu-ally accompany the facial lipoatrophy and, indeed, thefacial lipoatrophy-affected individuals usually do nothave sufficient fat for realistic donor harvesting. Inother words, the fat available for transplantation isminimal. Finally, since these individuals have a condi-tion that produces a degree of fat loss throughout thebody, it does not appear logical to use an augmentingagent that is likely to disappear in the future, with ourcurrent HIV management.

Treatment of HIV-associated facial lipoatrophy shoulduse permanent augmenting agents since it is not antici-pated that this process is reversible. The two perma-nent injectable agents that are available in NorthAmerica are silicone oil, which has been mentionedabove, and Artecoll. Artecoll is a mixture of poly-methylmethacrylate (PMMA) beads mixed in bovinecollagen which is used as a delivery vehicle. While thebovine collagen disappears, there is some fibroplasiaaround the beads and therefore the permanent volumeis approximately 50–60% of the injected volume. Thiscontrasts with injectable silicone, which increases insize and produces a final volume of perhaps 200% ofthe injected volume. Artecoll has been used extensivelyin Europe and in Canada but its reported use in HIV-associated lipoatrophy is currently limited.

Polytetrafluoroethylene (PTFE) has been used as apermanent filling substance for facial lines and wrin-kles, especially deeper skin creases and folds. It is anextremely inert biomaterial, being nonallergenic, non-carcinogenic, and having no foreign-body response.

45

The structure is highly porous to allow the penetrationof cells and vessels once implanted, with minimal in-flammatory reaction.

46

There are two commonly usedforms of PTFE for insertable augmentation, GoreTexand SoftForm. SoftForm is a hollow tube with a spe-cial implantation device, whereas GoreTex can beformed into tubes, strips, and patches. Typically the

Table 1.

Universal Precautions of the Centers for Disease Control

52

1. Use barrier precautions to prevent skin and mucous membrane exposure, including gloves, masks, and protective eyewear during procedures likely to generate blood droplets, and gowns or aprons during procedures likely to generate splashes.

2. Hands and skin surfaces should be washed immediately and thoroughly if contaminated by blood or body fluids.3. All health care workers should take precautions to prevent injuries caused by needles, scalpels, and other sharp instruments. Needles should not

be recapped, bent, or broken or removed from disposable syringes. After use, they should be placed in puncture-resistant containers.4. Mouthpieces, resuscitation bags, or ventilation devices should be available in areas where resuscitation is predictable.5. Health care workers with exudative lesions or weeping dermatitis should refrain from direct patient contact.6. Because of the risk of prenatal transmission, pregnant health care workers should be especially familiar with universal precautions.



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implants are inserted into the desired position throughsmall incisions under local anesthetic.

47,48

Adverse ef-fects include foreign body reactions, incorrect posi-tioning, implant visibility, and infection.

49,50

So farthere are no publications on the use of PTFE materialsin HIV-associated facial lipoatrophy.

Although HIV-associated lipodystrophy remains diffi-cult to treat while maintaining the efficacy of antiret-roviral therapy, there are several promising treatmentsfor various components of the syndrome. The success-ful resolution of facial lipoatrophy seems to be hardestto achieve, but there are several methods of treatmentavailable, and the use of a permanent agent would bemost desirable. The injection of silicone oil alone or incombination with PTFE implants would seem to havethe most potential for alleviating this distressing prob-lem. We are preparing a manuscript documenting ourexperience combining PTFE with injectable silicone oilin the management of HIV-related facial lipoatrophy.

Operating Precautions for HealthCare Professionals

HAART improves longevity in HIV-infected individu-als, resulting in more of these patients requiring sur-gery for HIV- and non-HIV-related conditions. Astudy performed several years ago found that 15% ofpatients who died of AIDS had undergone surgery atleast once during the time that they were infected withHIV.

51

There is some risk to health care workers dur-ing surgical procedures, but HIV is not the greatestrisk. The risk of viral infection from needlestick inju-ries is 0.3% for HIV, 3.0% for hepatitis C, and 30.0%for hepatitis B.

52

The risk of becoming infected withHIV may be even lower when the patient is know tobe HIV positive, as health care professionals use morecare when handling the patient and have immediateaccess to prophylaxis should exposure occur. In addi-tion, many of these individuals are on treatment andtherefore have low or undetectable viral levels.

Exposure to HIV can be avoided through strict in-fection control procedures, including universal pre-cautions. Operating theater policy should contain pre-cautions appropriate to the care of high-risk patients,but be applicable to the care of all patients. The levelof precautions necessary depends on local factors,such as HIV prevalence in a given area and the type ofsurgery performed. Universal precautions recommendthat blood and body fluid safety measures be used forall patients (see Table 1).

53

These infection controlmeasures apply in the dermatology operating theateras for any other, but further precautions include glov-ing for minor procedures and use of face shields orgoggles to protect against bloody procedures.

54

Exposure can occur despite the presence of univer-sal precautions, so it is important to have effectiveprophylaxis available for health care workers. Chemo-prophylaxis with zidovudine reduces the risk of infec-tion by 80%, as long as the recipient does not have astrain of HIV that is resistant to zidovudine. As this isbecoming increasingly more common, a combinationof zidovudine and lamivudine taken for 4 weeks is rec-ommended. In those exposed to a source with likelyresistant HIV, a protease inhibitor such as indinavircan be added.

55

Conclusion

Lipodystrophy syndrome, characterized by fat redis-tribution, hyperlipidemia, and insulin resistance is fre-quently seen in HIV-infected individuals. Often it seemsto relate to protease inhibitor therapy, but additionalresearch is needed to determine the pathogenesis. Pa-tients with lipodystrophy must weigh the impact thesyndrome has on their lives against the benefits ofHAART, which clearly decreases complications of HIVand improves survival.

Management of HIV-associated lipodystrophy mustbe specific for each patient. The central fat accumula-tion can be reduced through exercise, liposuction, andadministration of rHGH, and the metabolic abnor-malities moderated through switching from proteaseinhibitors to NNRTIs and use of lipid-lowering or an-tidiabetic agents. Facial lipoatrophy is difficult to treatsuccessfully, although we report elsewhere the success-ful management of these individuals with a combina-tion of GoreTex implants and silicone oil injections.Further studies are required to determine the best ap-proaches to treatment of HIV-associated facial lipoat-rophy and to find the best antiretroviral strategies formanaging these complications.

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