Impact of Lipoatrophy on Patient-Reported Outcomes in Antiretroviral-Experienced Patients

The introduction of antiretroviral therapy has dramatically reduced mortality and morbidity in HIV-infected persons.^1,2 Nevertheless, antiretroviral therapy is still associated with numerous adverse effects. Among the most distressing effects are the changes in physical appearance associated with lipoatrophy. Depending on the length of treatment, changes consistent with lipoatrophy develop in approximately 20% of patients who receive antiretroviral therapy.³ Lipoatrophy is characterized by loss of subcutaneous fat in the limbs, buttocks, or face⁴ and is being increasingly recognized in HIV-infected persons (Figure).

Figure. Left: Facial lipoatrophy. (Reproduced from Burnouf M et al. Arch Dermatol. 2005.⁶⁴) Above: Limb lipoatrophy with vein prominence. (Reproduced with permission from Hawkins T. AIDS Patient Care STDS. 2006.⁶⁸)

The diagnosis of lipoatrophy is based on patient self-reports and a physician’s confirmation of the loss of subcutaneous fat. Objective methods to quantify subcutaneous fat loss include dual-energy x-ray absorptiometry, CT, MRI, ultrasonography, 3-dimensional laser scanning, and 3-dimensional photography.^5-7

The pathogenesis of lipoatrophy and its association with metabolic abnormalities is becoming better understood,⁸ but current treatment is limited and needs to be improved. Treatment options for antiretroviral-experienced patients include antiretroviral substitution, drug therapy (eg, insulin-sensitizing agents), and dermatological and surgical interventions. Switching the antiretroviral regimen (eg, replacing stavudine or zidovudine with abacavir) produces only a modest effect. There are conflicting and generally disappointing data on the benefit of using such medications as rosiglitazone to mitigate or correct the adverse effects that can be associated with lipoatrophy.

Given the lack of effective medical therapy, patients have turned to surgical and dermatological alternatives, which are mainly available for the treatment of facial lipoatrophy.⁸ Most HIV-infected patients with lipoatrophy seek treatment for their facial fat loss because of their high level of concern about involuntary disclosure of HIV status and the stigma related to HIV infection.⁹ Dermatological procedures with facial fillers have gained popularity, because they are currently the only therapy that can result in prompt improvement of lipoatrophy.¹⁰ However, these procedures are expensive (many health insurers are reluctant to cover the cost for what is considered primarily a cosmetic problem), require repeated treatments to maintain results, and can lead to scarring or a “lumpy” appearance.

Since the focus of this review is the impact of lipoatrophy on health-related quality of life (HRQL) and related constructs, a discussion of the treatment of lipoatrophy is beyond the scope of this article. Information on the treatment strategies for managing HIV-associated lipoatrophy can be found elsewhere.^6,11-14

Patients’ perceptions of the impact of chronic conditions are receiving greater attention from researchers, with a focus on the body shape changes that develop in some HIV-infected patients receiving antiretroviral therapy.¹⁵ To date, 3 reviews have been published addressing HRQL and related issues associated with adverse effects of antiretroviral therapy.^16-18 The main limitation of those reviews is that none included any clinical studies that recorded results from a patient-reported outcome questionnaire. It is now common to include patient-reported outcomes as end points in studies designed to assess the efficacy and safety of different therapeutic interventions. However, it is essential that a patient-reported outcome questionnaire meets certain development and psychometric scaling standards if it is to provide useful information.^19,20

The purpose of our study was to review the literature to determine the impact of lipoatrophy on those who live with the condition as reported by qualitative studies, clinical observations, and by use of patient-reported outcomes in clinical studies.

METHODS
This literature review was conducted to determine the impact of lipoatrophy on patients from their perspective and had 2 components: First, a search was designed to identify qualitative studies conducted in patients with lipoatrophy. Second, a search was conducted to identify articles reporting clinical studies of lipoatrophy where a patient-reported outcome end point was specified as part of the study design.

Searches were conducted using PubMed, PsycInfo, Web of Science, Cochrane Library, and Embase. The key words searched included lipoatrophy, HIV, HRQL, patient-reported outcome, health status, questionnaire, psychosocial impact, and qualitative. The search was refined as it progressed, and additional search terms (such as specific questionnaire names) were added as articles were retrieved.

The search yielded 957 studies concerning HIV-associated lipoatrophy. Of those, 890 studies did not have any patient-reported outcomes. The exclusion criteria were as follows: (1) lipodystrophy alone, (2) non-English, and (3) conference reports. Application of the exclusion criteria resulted in a list of 54 studies, which were further reviewed to identify trials that assessed patient-reported outcomes related to lipoatrophy. Thirty studies met all eligibility criteria: 14 were qualitative, and 16 used patient-reported outcome instruments.

RESULTSPsychosocial and Quality-of-Life Effects Reported in Qualitative Studies
Various studies have demonstrated the negative impact of antiretroviral therapy on patients living with HIV disease.

Power and colleagues²¹ conducted in-depth interviews with HIV-infected patients with self-reported lipoatrophy who were being treated at a sexually transmitted disease/HIV outpatient clinic in London. The 3 major topics relating to lipoatrophy that emerged were the effects on the HIV-infected person, impact on the social aspect of the HIV-infected person, and responses by the HIV-infected person. Effects included increased awareness of the condition, physical manifestations (uneven weight loss or weight gain, reduced libido, perception of rapid aging), psychological sequelae (preoccupation, depression, self-consciousness, and loss of self-confidence and self-esteem), and anxiety about public disclosure of their HIV status. From the social perspective, patients isolated themselves.

Patient responses varied depending on several factors. Those who were very ill before antiretroviral therapy was started and those who received several treatments accepted lipoatrophy as an unfortunate consequence of HIV disease. These patients were less likely to change or stop their current treatments. Others who were more concerned with lipoatrophy had taken positive steps to ameliorate the condition-by adopting healthy lifestyle habits (eg, eating more, joining a gym, taking anabolic steroids, and seeking corrective surgery).²¹

In an Internet survey by Collins and colleagues,²² the common psychological and social effects of lipoatrophy were poor body image, reduced self-esteem, social withdrawal, self-consciousness, reduced libido, depression, and poor HRQL. Some patients reported that their physician tended to minimize or disregard the impact of lipoatrophy. In another survey, significant correlations with perceived severity of body changes were found for all 4 domains of quality of life (social contacts, sexuality, self-esteem, and daily performance).²³

Two studies found that lipoatrophy was associated with the feeling of being recognizable as HIV-positive.^4,24 In the first study, 30.1% of HIV-infected participants with lipoatrophy felt that their disease could be recognized by their physical appearance compared with 18.3% of patients without lipoatrophy. This difference became more pronounced after adjustment for sex, age, stage of disease, CD4⁺ T-cell count, and duration of antiretroviral therapy.⁴

In the second study, patient-perceived body image score was the only study variable responsive to lipoatrophy severity ratings.²⁴ In the survey by Collins and associates,²² patients felt that they had no control over the divulgence of their diagnosis. One man believed that the changes in his facial appearance led to the “outing” of his diagnosis to his family-a fact he had kept hidden for 15 years.²² Body shape changes made patients look undernourished and unhealthy; they felt that they looked “grotesque” or “deformed” as a result. This had a profound effect on self-esteem: some patients described themselves as “unloved” and “unlovable.”²²

Patients interviewed by Power and coworkers²¹ reported that the changes made them look and feel older than their age. The impact was felt from changes not only on the face: one patient reported that fat loss from his legs made his varicose veins more prominent. Fat loss from the buttocks affected the way clothes fit and also caused pain or discomfort when he sat for some time. One patient reported visiting a beach and feeling the need to stay seated so that his flattened buttocks could not be seen.²¹

Depression, anger, denial, demoralization, and fear are common reactions to lipoatrophy. Some HIV-infected persons have attributed suicidal ideation to their lipoatrophy.²² Many feared that partners would no longer find them attractive. Others reported that their poor self-image and decreased self-esteem had a direct effect on their interest in sex and on their libido; thus, the quality of their personal relationships had suffered. Many of those without partners stated that worries about possible rejection would prevent them from starting new relationships. Social withdrawal was also commonly reported.²²

In a focus group study, psychological and social distress were major concerns of patients with body shape changes.²⁵ Participants reported that body changes threatened their self-confidence and caused anxiety, fear, and frustration. Body fat redistribution limited social functioning in many ways. Hurtful reactions of significant others caused emotional distress. Both men and women felt abnormal, less attractive, and less sexually appealing. Affected persons reduced their social contacts or simply stopped them altogether-which led to loneliness and isolation.²⁵

In a survey of adults and adolescents with HIV/AIDS, self-perception of peripheral fat loss was inversely associated with the quality of affective/social relationships with family and friends. This implies that patients who were less likely to perceive peripheral fat loss reported affective relationships of better quality. This finding also indicates the importance of affective support for persons living with HIV/AIDS when facing issues related to disease and treatment.²⁶ Another survey reported that most patients found facial changes of particular concern: 71% stated that these changes produced new problems in social interactions, and 20% of patients stated that the changes produced a severe negative impact.²⁷

Studies of the impact of lipoatrophy on medication adherence have shown inconsistent findings. Although a number of patients have indicated that they might discontinue antiretroviral treatment to reverse the impact of lipoatrophy,²⁵ nonadherence was not commonly reported.²² Ammassari and colleagues²⁸ evaluated the longitudinal relationship between adipose tissue alterations and adherence to antiretroviral therapy. At baseline, nonadherence was reported by 63% of participants, and adipose tissue alterations were self-perceived by 15% and clinically diagnosed in 25%. Using Cox regression analysis, the results ironically showed that better adherence to antiretroviral therapy was associated with a higher risk of adipose tissue alterations, and patient-perceived morphological changes were independently related to subsequent treatment nonadherence; however, clinically diagnosed adipose tissue alterations were not.

In a cohort of Asian patients, body shape changes affected the mood of 36% of patients and the work and/or social activity of 23% of patients; however, only 1% of affected patients reported a desire to discontinue antiretroviral therapy because of these changes.²⁹ Corless and associates³⁰ found that participants took medications moderately well despite a substantial number of self-reported HIV- and treatment-related body fat changes. The lack of a significant relationship between lipoatrophy and level of patient adherence to treatment was surprising in this study, because many participants described feelings of anger related to their body shape changes.³⁰

In contrast to the findings of the above studies, a survey by Kasper and colleagues³¹ found that 37% of patients with body fat alterations had changed (30%) or stopped (7%) antiretroviral therapy as a result. Of those patients who had not changed or stopped therapy, 57% had thought about doing so, while 46% planned to change if their symptoms worsened.

Some studies have compared the HRQL of HIV-infected persons according to whether lipoatrophy was present or not. Analysis of data from the Consumer Health Sciences survey showed a clinically meaningful increase in the negative impact on HRQL because of lipoatrophy in HIV-infected persons who were evaluated using the Medical Outcomes Study (MOS) instrument Short Form 8 (SF-8).³ Also, statistically significant differences in HRQL were observed between those with lipoatrophy and those without.³ A survey in Rwanda of antiretroviral-treated HIV-positive African men and women with (n = 50) and without (n = 50) body fat redistribution found that body fat alterations negatively affected psychological and social domains of HRQL.³² HIV-positive persons with body fat redistribution were less satisfied with their body image, self-esteem, and social life. They were more ashamed in public, reported less confidence about their health, and were more frequently embarrassed about body shape changes than patients who were HIV-positive but without body fat redistribution. However, in a cross-sectional study of HIV-positive patients treated with antiretroviral therapy, attitudes about the “quality of their health” and “impact of HIV on their well-being” did not differ significantly between those with body fat changes and those who did not have fat redistribution.⁴

Two studies have shown an association between certain demographic characteristics and impact of lipoatrophy on patients’ HRQL. In the African study mentioned above, there were sex differences seen in some domains of HRQL.³² Women with body fat redistribution reported a decrease in psychological well-being and less satisfying social relationships; feeling ashamed in pub-lic; and having problems related to dressing style and clothing size, fear of HIV disclosure, and further embarrassment associated with body shape changes.

Santos and colleagues²⁶ found that the self-perception of peripheral fat loss was associated with greater schooling and was more frequent among older patients, patients who used stavudine for longer periods, and patients who reported a lack of adherence to antiretroviral agents.

In summary, most of the studies identified in the literature were surveys of patients from clinical practice. Despite the paucity of hard data, it was possible to establish a picture of the negative impact of lipoatrophy from these reports. The impact of lipoatrophy ranged from psychological symptoms of distress to impairment of functioning ability and, ultimately, to a reduction in the person’s HRQL. The 3 main problems identified in patients with lipoatrophy in the above studies were mental (depression), emotional (anger, denial, demoralization, and fear), and social (deterioration of personal relationships). All the qualitative studies are summarized in Table 1 (A and B).

Studies Using Patient-Reported Outcome Instruments
Sixteen studies used a patient-reported outcome instrument. Of these, 3 studies used a visual analogue scale only.^33-35 Because none of these visual analogue scales were formally assessed, no further information is presented here. The remaining 13 studies assessed the psychological and/or HRQL impact of lipoatrophy using 1 or more patient-reported outcome questionnaire(s). Table 2 summarizes the study design, interventions, and patient-reported outcomes from these studies. Table 3 provides details of the specific patient-reported outcome instrument used in each study.

Fumaz and colleagues³⁶ conducted a pilot study in HIV-infected persons with facial lipoatrophy to assess the impact of lipoatrophy on mood (using the Beck Depression Inventory [BDI]³⁷), emotional status (using the Profile of Mood States–Adolescents [POMS-A]^38,39), and HIV-specific HRQL (using the MOS-HIV⁴⁰). The BDI scores indicated that participants were mildly depressed at baseline. POMS-A scores also suggested that participants’ emotional status was adversely affected at baseline. Following treatment for lipoatrophy, statistically significant improvements were observed in emotional status and mood for all groups; posttreatment BDI scores rose into the scale’s range representing “minimal” depression for all patients. Baseline data for MOS-HIV rating were highly variable, but some improvements in health perception and on the mental health and transitory health dimensions scales were found after treatment. However, no statistically significant differences were observed among the treatment groups for changes from baseline score.

Negredo and colleagues⁴¹ conducted a comparative, prospective study in a cohort of patients who had facial lipoatrophy for more than 6 months. For the MOS-HIV health domains, the areas with the lowest scores (greatest impact) at baseline were general health perception, mental health, and energy levels. By week 24, a statistically significant improvement was achieved in these 3 domains. This improvement was maintained at week 48. No significant differences were found among the 3 treatment groups.

Carr and colleagues⁴² used the EuroQol (EQ-5D)⁴³ self-report questionnaire to assess health status in patients with lipoatrophy. In this study, EQ-5D responses of patients and their physicians were similar at baseline and did not differ over 24 weeks. Of note, the EQ-5D is a generic instrument designed to value health states but is known for being highly skewed, with a large ceiling effect.^44,45 There is no evidence that its use is valid in an HIV-infected population, and its emphasis on physical health renders it unsuitable for assessing outcome in lipoatrophy.

Loutfy and associates⁴⁶ assessed HRQL in HIV-infected patients with facial lipoatrophy using MOS-HIV and the slightly modified Dermatology Quality of Life Scales⁴⁷ and evaluated the effect of immediate versus delayed treatment. They also assessed anxiety and depression using the Hospital Anxiety and Depression Scale (HADS).⁴⁸ MOS-HIV scores were highly variable at baseline, but median values suggested that lipoatrophy had a mild to moderate impact on instrument subscales (physical health, mental health, and HRQL). Improvements from baseline to week 48 were observed in all domains of the MOS-HIV. However, statistical significance was attained only for the mental health summary score. Median baseline HADS scores demonstrated “definite” clinical anxiety for both the immediate and delayed treatment groups, “definite” clinical depression for the delayed group, and “borderline” clinical depression for the immediate treatment group. Statistically significant improvements were noted in both the depression and anxiety portions of the HADS from baseline to week 48 in both groups. However, this was an open-label study, and the results were subject to placebo effects.

In a 12-month study of 50 HIV-infected persons with moderate to severe facial lipoatrophy who received polylactic acid injections for the first 2 months, Cattelan and colleagues⁴⁹ measured self-perception of quality-of-life issues using the MOS-HIV questionnaire. A statistically significant improvement in overall HRQL was observed at the end of the study. The MOS-HIV questionnaire revealed significant differences between the baseline and month-12 scores for 6 of 11 dimensions, which included energy/fatigue, health distress, health transition, mental health, cognitive function, and quality-of-life dimensions.

In a randomized study reported by Moyle and colleagues,⁵⁰ the impact of treating facial lipoatrophy with polylactic acid on anxiety and depression was measured using the HADS. Anxiety and depression scores declined (indicating improvement) after 24 weeks of treatment for both immediate and delayed treatment groups, although this change was not statistically significant. Moyle and colleagues⁵¹ later reported on their assessment of the long-term efficacy of the interventions in their same study cohort at a recall visit 2 years after study entry. They found that the same trend for improvement in HADS scores at 24 weeks had persisted for up to 2 years. Patients from both the immediate and delayed treatment groups were still less depressed and anxious at the 2-year recall visit than at study entry. However, there were statistically significant improvements only in the depression scores in the delayed treatment group.

Lafaurie and coworkers⁵² used the SF-3653 to assess change in the HRQL in a prospective, open-label, single-arm study. The results demonstrated that after a median of 5 injections of polylactic acid, the mental and physical summary scales of the SF-36 questionnaire showed no statistically significant changes from baseline to the end of treatment or at the last follow-up. In contrast to these results, Carey and associates⁵⁴ reported improvements in social function and mental health scores of the SF-36 in HIV-positive adults with facial lipoatrophy who were randomized to 1 of 4 polylactic acid treatments administered every 2 weeks from week 0 (immediate group, n = 51) or after week 24 (deferred group, n = 50) in an open-label study. However, with regard to these 2 studies, the SF-36 has been shown to have inadequate psychometric properties when applied in a HIV-infected population.⁵⁵ Its emphasis on physical health is likely to make the instrument less relevant for lipoatrophy, because many items would be inappropriate to the study population and issues of importance are unlikely to be covered.

Patient satisfaction is another patient-reported outcome that has been measured in clinical studies. Four trials evaluated patient satisfaction with treatment of HIV-associated lipoatrophy.^56-60 In 3 of the studies, the degree of satisfaction with outcome of treatment was rated on a 5-point Likert scale where 1 = dissatisfied and 5 = very satisfied. In the APEX002 study, at the end of final treatment session and after 6 months and 12 months posttreatment, the average satisfaction rating was 4.71, 4.74, and 4.75, respectively.⁵⁶ Similarly in the Blue Pacific study, investigators reported high levels of satisfaction with the treatment.^57,58 Hanke and Redbord⁵⁹ reported that patients were “very satisfied” with their treatment. In the fourth study, which evaluated patient satisfaction with lipostructure or Colemans’s technique there was a high rate of patient satisfaction similar to that in the other studies.⁶⁰

A study by O’Donovan and associates⁶¹ explored psychosocial adjustment in persons with HIV-related facial lipoatrophy. Patients completed the following questionnaires at their initial assessment: Facial Appearance Questionnaire, Rosenberg Self-Esteem Scale⁶² (RSES), HADS, and SF-36. Self-esteem scores were low for all patients. Twenty-one (71%) were found to have “definite” or “borderline” clinical anxiety and 17 (48%) were found to have “definite” or “borderline” clinical depression, as assessed by the HADS. Patients also had significant limitations in their usual role activity (SF-36). In addition, 34 patients (97%) felt that lipoatrophy affected their confidence, 30 patients (85%) felt stigmatized and that their appearance was a marker of HIV infection, and 25 (71%) reported social anxiety related to their appearance.

The patient-reported outcome questionnaires used in the above studies included assessments of psychosocial or psychiatric morbidity, those developed specifically to assess outcomes in an HIV-infected population (HIV-specific), and questionnaires designed to assess HRQL in any patient group (generic measures). It is important to note that none of the scales used were developed specifically for HIV-infected persons with lipoatrophy.

DISCUSSION
This is the first comprehensive review of the literature for clinical studies that have assessed the impact of lipoatrophy from the patient’s perspective. Our research revealed that many qualitative studies have been conducted in HIV-infected persons to address the psychosocial and wider quality-of-life impact of lipoatrophy. The evidence available suggests that HIV-associated lipoatrophy has a profound impact on many aspects of a patient’s life. The changes in appearance induced by lipoatrophy not only make persons look and feel older than their age²¹ but also convey a visual impression of HIV-associated illness.²² Self-esteem and self-consciousness are affected, and depression is a common reactive response, with irritability and social withdrawal often developing over time.^22,25 These emotional responses can, in turn, cause problems with personal and family relationships and, ultimately, lead to social isolation.^25-27

The results from our study also showed that patient-reported impact of lipoatrophy has only recently been addressed in clinical trials that used standardized patient-reported outcome instruments. The findings of the clinical studies identified in the literature largely supported the findings of the qualitative studies. The studies identified by our review used patient-reported outcomes to evaluate the impact of corrective treatments, such as abacavir substitution for a thymidine NRTI, use of dermal fillers, and infiltration with autologous fat, from a patient’s perspective. Although specifically designed to assess the change in patient-reported outcome scores following treatment, these studies also provide some insight into the impact of lipoatrophy on a person’s HRQL. The results from these studies appear to suggest that a proportion of participants were anxious and/or depressed and that these conditions improved following successful treatment of their lipoatrophy.^{36,41,46,50,51}

Impact on HRQL was assessed using MOS-HIV, SF-36, and EQ-5D.^{36,41,42,46,52,54} Baseline data for the reviewed studies were variable, but Loutfy and colleagues⁴⁶ were able to show that lipoatrophy had a mild to moderate impact on the MOS-HIV domains. Conflicting results were found in studies that used SF-36,^52,54 and the studies that used EQ-5D were unable to show the benefits of lipoatrophy treatments.^42,52 As mentioned earlier, this is likely to be the result of inadequate psychometric properties of these instruments and their unsuitability for this patient population.

Although the clinical studies captured in our literature review do provide useful insights into the impact of lipoatrophy, they all possess limitations when results are evaluated for impact of lipoatrophy, and these are discussed below. In general, our research on the impact of lipoatrophy in HIV-positive persons was hindered by the lack of reports of sufficient well-powered clinical trials in the literature that used a suitable patient-reported outcome instrument.

Focus on Short-Term Treatment
Almost all the clinical studies included here focused only on short-term treatments, such as dermal fillers, to correct or improve lipoatrophy; few data exist on long-term treatment approaches. Only one study, reported by Carr and colleagues,⁴² evaluated abacavir substitution as a treatment option for lipoatrophy. The reason most patients seek treatment for facial lipoatrophy is their concern that their fat loss publicizes their HIV-positive status. For persons who want to seek or retain employment, short-term improvement seems crucial. Review of the studies indicated that providers are sensitive to these patient concerns despite knowing that long-term therapy will likely be needed. Among all the treatment options, facial fillers are currently the only therapy that can result in prompt improvement of facial lipoatrophy. As a result, most clinical research is now concentrated on the evaluation of dermal fillers.

Lack of Well-Controlled Trials
All of the randomized studies identified were open-label and uncontrolled, which introduces concerns related to experimental bias and placebo effect and limits the robustness of the study’s results.

Lack of Suitable Patient-Reported Outcome Scales
The studies we reviewed were hampered by the lack of availability of a suitable patient-reported outcome scale. Because no psychometrically sound lipoatrophy-specific instrument currently exists, researchers were required to select from the best available alternatives. Unfortunately, the instruments available reduced the capability of studies to demonstrate change in patient-reported outcome constructs associated with real changes in the patient’s condition. The scaling and psychometric properties of the 2 most widely used standardized instruments (MOS-HIV and SF-36) are generally inadequate. In particular, their low levels of reliability mean that both instruments generate high levels of measurement error. Consequently, the sensitivity of these instruments to change in a patient’s condition following treatment is limited. Furthermore, both instruments demonstrate marked end effects, with the MOS-HIV having substantial ceiling effects (in excess of 50%).

The areas identified by the review of psychosocial impact clearly go beyond those measured by the patient-reported outcome instruments reviewed. Although some of the reviewed patient-reported outcomes do capture specific areas of impact (eg, depression), it is questionable whether they address such issues in a way that is relevant for this diagnostic group. While there may be occasions when depression is a critical factor for assessment, a study that focuses on symptomatic impact in a single area fails to take into account the full impact of the condition on the patient.

Because none of the patient-reported outcome instruments reviewed were developed specifically for use in lipoatrophy, they do include content that is not relevant for these patients. Irrelevant content in the instruments used may place unnecessary burden on the patient. None of the patient-reported outcome instruments used in the studies on lipoatrophy in this review assesses the full range of concerns of persons with lipoatrophy. Thus, they fail to take account of the full impact of the condition on the patient.

Impact of Lipoatrophy Nested Within the Effects of Lipodystrophy
Separating the effect of lipoatrophy from lipodystrophy was difficult because several studies have reported combined results for patients with lipoatrophy and those with lipohypertrophy. In a few studies, which have assessed the impact of lipodystrophy on HRQL, a majority of the patients had suffered from lipoatrophy, and it is difficult to tease out the lipoatrophy-specific effects from the overall impact of lipodystrophy on HRQL.

Insufficient Information Reported
There was insufficient information reported for some of the studies. Four studies mentioned improvements in quality-of-life assessment after treatment of lipoatrophy but did not give the details of the quality-of-life measure used.^63-66 Cavalcanti and colleagues⁶⁷ used the MOS-HIV to assess changes in health status in a randomized, placebo-controlled trial evaluating the use of rosiglitazone for lipoatrophy. However, the authors did not present results for the patient-reported outcome scale.

CONCLUSIONS
The results of this literature review provided considerable evidence to demonstrate that lipoatrophy negatively impacts the psychosocial well-being and HRQL of HIV-infected patients receiving antiretroviral therapy. However, our study also revealed that the concerns of patients with lipoatrophy have not been adequately addressed in clinical trials because of the lack of a lipoatrophy-specific, patient-reported outcome instrument to assess the impact of this condition and its treatment.

The patient-reported outcome instruments that have been used in clinical research are not optimal for evaluating treatment interventions, and the strength of the literature would increase considerably if the effects of body shape changes on patient HRQL were determined with an adequately validated instrument. There is an urgent need for a validated, reliable, patient-reported outcome instrument to understand the full impact of lipoatrophy on the HRQL in HIV-infected persons and to better evaluate the potential benefits of therapeutic interventions for HIV-related lipoatrophy.

Drs Bhor, Dietz, and Rajogopalan are employees of Abbott Laboratories, the sponsor of this research. Dr McKenna and Ms Doward and Ms Wilburn are employees of Galen Research Ltd, which was sponsored by Abbott Laboratories to perform this research. No potential conflict of interest relevant to this article was reported by the authors.

References:

References1. Palella FJ, Baker RK, Moorman AC, et al. Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr. 2006;43:27-34.
2. Highleyman L. Mortality trends: toward a new definition of AIDS? BETA. 2005;17(2):18-28.
3. Rajagopalan R, Laitinen D, Dietz B. Impact of lipoatrophy on quality of life in HIV patients receiving antiretroviral therapy (ART). Adverse Drug Reaction and Lipodystrophy Workshop in HIV; July 19-21, 2007; Sydney, Australia. Abstract P-21.
4. Oette M, Juretzko P, Kroidl A, et al. Lipodystrophy syndrome and self-assessment of well-being and physical appearance in HIV-positive patients. AIDS Patient Care STDS. 2002;16:413-417.
5. Yang Y, Paton NI. Laser scanning as a tool for assessment of HIV-related facial lipoatrophy: evaluation of accuracy and reproducibility. HIV Med. 2005;6:321-325.
6. Sutinen J. Interventions for managing antiretroviral therapy-associated lipoatrophy. Curr Opin Infect Dis. 2005;18:25-33.
7. Lafaurie M, Dolivo M, Boulu D, et al. Treatment of facial lipoatrophy with injections of polylactic acid in HIV-infected patients: results from a cohort of 94 patients. 11th Conference on Retroviruses and Opportunistic Infections; February 8-11, 2004; San Francisco. Abstract 726.
8. Confrancesco J, Brown T, Martins CR. Management options for facial lipoatrophy. AIDS Reader. 2004;14:639-649.
9. Barton SE, Engelhard P, Conant M. Poly-L-lactic acid for treating HIV-associated facial lipoatrophy: a review of the clinical studies. Int J STD AIDS. 2006;17:429-435.
10. Margolis DM. Treatment for lipoatrophy: facing the real costs. AIDS. 2007;21:1819-1820.
11. Engelhard P. Correction options for lipoatrophy in HIV-infected patients. AIDS Patient Care STDS. 2006;20:151-160.
12. del Mar Gutierrez M, Mateo G, Domingo P. Strategies in the treatment of HIV-1-associated adipose redistribution syndromes. Expert Opin Pharmacother. 2007;8:1871-1884.
13. Martin A, Mallon PW. Therapeutic approaches to combating lipoatrophy: do they work? J Antimicrob Chemother. 2005;55:612-615.
14. Jones D. HIV facial lipoatrophy: causes and treatment options. Dermatol Surg. 2005;31(11 pt 2):1519-1529.
15. McKenna SP, Doward LC. Editorial: the needs-based approach to quality of life assessment. Value Health. 2004;7(suppl 1):S1-S3.
16. Cholewínska G. Effect of antiretroviral therapy on the quality of patient’s life. HIV AIDS Rev. 2005;4:35-41.
17. Martínez E, Garcia-Viejo MA, Blanch J, Gatell JM. Lipodystrophy syndrome in patients with HIV infection. Drug Saf. 2001;24:157-166.
18. Echavez M, Horstman W. Relationship between lipoatrophy and quality of life. AIDS Reader. 2005;15:369-375.
19. Doward LC, McKenna SP. Defining patient-reported outcomes. Value Health. 2004;7(suppl 1):S4-S8.
20. Doward LC, Meads DM, Thorsen H. Requirements for quality of life instruments in clinical research. Value Health. 2004;7(suppl 1):S13-S16.
21. Power R, Tate HL, McGill SM, Taylor C. A qualitative study of the psychosocial implications of lipodystrophy syndrome on HIV positive individuals. Sex Transm Infect. 2003;79:137-141.
22. Collins E, Wagner C, Walmsley S. Psychosocial impact of the lipodystrophy syndrome in HIV infection. AIDS Reader. 2000;10:546-550.
23. Goetzenich A, Corzillius M, Mauss S, et al. Impact of lipodystrophy on quality of life. 13th International AIDS Conference; July 9-14, 2000; Durban, South Africa. Abstract WePpB1381.
24. Burgoyne R, Collins E, Wagner C, et al. The relationship between lipodystrophy-associated body changes and measures of quality of life and mental health for HIV-positive adults. Qual Life Res. 2005;14:981-990.
25. Reynolds NR, Neidig JL, Wu AW, et al. Balancing disfigurement and fear of disease progression: patient perceptions of HIV body fat redistribution. AIDS Care. 2006;18:663-673.
26. Santos CP, Felipe YX, Braga PE, et al. Self-perception of body changes in persons living with HIV/AIDS: prevalence and associated factors. AIDS. 2005;19(suppl 4):S14-S21.
27. Forrester J, Whittaker W, Workman C. Peripheral fat depletion (lipoatrophy) and other body shape changes-impact on psychosocial quality of life. 13th International AIDS Conference; July 9-14, 2000; Durban, South Africa. Abstract WePeD4566.
28. Ammassari A, Antinori A, Cozzi-Lepri A, et al. Relationship between HAART adherence and adipose tissue alterations. J Acquir Immune Defic Syndr. 2002;31(suppl 3):S140-S144.
29. Paton NI, Earnest A, Ng YM, et al. Lipodystrophy in a cohort of human immunodeficiency virus-infected Asian patients: prevalence, associated factors, and psychological impact. Clin Infect Dis. 2002;35:1244-1249.
30. Corless IB, Kirksey KM, Kemppainen J, et al. Lipodystrophy-associated symptoms and medication adherence in HIV/AIDS. AIDS Patient Care STDS. 2005;19:577-586.
31. Kasper TB, Arboleda CH, Halpern MT. The impact of patient perceptions of body shape changes and metabolic abnormalities on ART. 13th International AIDS Conference; July 9-14, 2000; Durban, South Africa. Abstract WePpB138.
32. Mutimura E, Stewart A, Crowther NJ. Assessment of quality of life in HAART-treated HIV-positive subjects with body fat redistribution in Rwanda. AIDS Res Ther. 2007;4:19.
33. Valantin M, Aubron-Olivier C, Ghosn J, et al. Polylactic acid implants (New-Fill) to correct facial lipoatrophy in HIV-infected patients: results of the open-label study VEGA. AIDS. 2003;17:2471-2477.
34. Carr A, Workman C, Carey D, et al. No effect of rosiglitazone for treatment of HIV-1 lipoatrophy: randomised, double-blind, placebo-controlled trial. Lancet. 2004;363:429-438.
35. Mauss S, Corzillius M, Wolf E, et al; DAGNA Lipantiretoviral therapy study group. Risk factors for the HIV-associated lipodystrophy syndrome in a closed cohort of patients after 3 years of antiretroviral treatment. HIV Med. 2002;3:49-55.
36. Fumaz CR, Muñoz-Moreno JA, Ferrer MJ, et al. Psychological assessment of HIV-infected patients with facial lipoatrophy before and after reparatory treatment. 15th International AIDS Conference; July 11-16, 2004; Bangkok, Thailand. Abstract WePeB5930.
37. Beck AT, Ward CH, Mendleson M, Mock J. An inventory for measuring depression. Arch Gen Psychiatry. 1961;4:561-571.
38. McNair DM, Lorr M, Droppleman LF. Manual for the Profile of Mood States (POMS). San Diego: Educational and Industrial Testing Service; 1971.
39. McNair DM, Lorr M, Droppleman LF. EdITS Manual for the Profile of Mood States (POMS). San Diego: Educational and Industrial Testing Service; 1992.
40. Wu AW, Revicki DA, Jacobson D, Malitz FE. Evidence for reliability, validity, and usefulness of Medical Outcomes Study HIV Health Survey (MOS-HIV). Qual Life Res. 1997;6:481-493.
41. Negredo E, Higueras C, Adell X, et al. Reconstructive treatment for antiretroviral-associated facial lipoatrophy: a prospective study comparing autologous fat and synthetic substances. AIDS Patient Care STDS. 2006;20:829-837.
42. Carr A, Workman C, Smith DE, et al; Mitochondrial Toxicity (MITOX) study group. Abacavir substitution for nucleoside analogs in patients with HIV lipoatrophy: a randomized trial. JAMA. 2002;288:207-215.
43. The EuroQol Group. EuroQol-a new facility for the measurement of health-related quality of life. Health Policy. 1990;16:199-208.
44. Brazier JE, Harper R, Jones NM, et al. Validating the SF-36 health survey questionnaire: new outcome measure for primary care. BMJ. 1992;305:160-164.
45. Brazier J, Jones N, Kind P. Testing the validity of the EuroQoL and comparing it with the SF-36 health survey questionnaire. Qual Life Res. 1993;2:169-180.
46. Loutfy MR, Raboud JM, Antoniou T, et al. Immediate versus delayed polyalkylimide gel injections to correct facial lipoatrophy in HIV-positive patients. AIDS. 2007;21:1147-1155.
47. Morgan M, McCreedy R, Simpson J, Hay RJ. Dermatology quality of life scales-a measure of the impact of skin diseases. Br J Dermatol. 1997;136:202-206.
48. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67:361-370.
49. Cattelan AM, Bauer U, Trevenzoli M, et al. Use of polylactic acid implants to correct facial lipoatrophy in human immunodeficiency virus 1-positive individuals receiving combination antiretroviral therapy. Arch Dermatol. 2006;142:329-334.
50. Moyle GJ, Lysakova L, Brown S, et al. A randomized open-label study of immediate versus delayed polylactic acid injections for the cosmetic management of facial lipoatrophy in persons with HIV infection. HIV Med. 2004;5:82-87.
51. Moyle GJ, Sabin CA, Cartledge J, et al; Rave (Randomized Abacavir versus Viread Evaluation) Group UK. A randomized comparative trial of tenofovir DF or abacavir as replacement for a thymidine analogue in persons with lipoatrophy. AIDS. 2006;20:2043-2050.
52. Lafaurie M, Dolivo M, Porcher R, et al. Treatment of facial lipoatrophy with intradermal injections of polylactic acid in HIV-infected patients. J Acquir Immune Defic Syndr. 2005;38:393-398.
53. Ware JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30:473-483.
54. Carey DL, Baker D, Rogers GD, et al; Facial LipoAtrophy Study in HIV Investigators. A randomized, multicenter, open-label study of poly-L-lactic acid for HIV-1 facial lipoatrophy. J Acquir Immune Defic Syndr. 2007;46:581-589.
55. O’Keefe EA, Wood R. The impact of human immunodeficiency virus (HIV) infection on quality of life in a multiracial South African population. Qual Life Res. 1996;5:275-280.
56. Engelhard P, Knies M. Safety and efficacy of New-Fill (Polylactic acid) in the treatment of HIV-Associated Lipoatrophy of the face (HALF). 14th International AIDS Conference; July 7-12, 2002; Barcelona, Spain. Abstract WePeB6011.
57. Mest DR, Humble G. Safety and efficacy of intradermal poly-L-lactic acid (Sculptra) injections in patients with HIV-associated facial lipoatrophy. Antivir Ther. 2004;9:L36. Abstract 56.
58. Mest DR, Humble G. Safety and efficacy of poly-L-lactic acid injections in persons with HIV-associated lipoatrophy: the US experience. Dermatol Surg. 2006;32:1336-1345.
59. Hanke CW, Redbord KP. Safety and efficacy of poly-L-lactic acid in HIV lipoatrophy and lipoatrophy of aging. J Drugs Dermatol. 2007;6:123-128.
60. Levan P, Nguyen TH, Lallemand F, et al. Correction of facial lipoatrophy in HIV-infected patients on highly active antiretroviral therapy by injection of autologous fatty tissue. AIDS. 2002;16:1985-1987.
61. O’Donovan CA, Hourihan M, Petrak J, Murphy M. Psychosocial adjustment to facial lipoatrophy in people with HIV. Antivir Ther. 2005;10:L24. Abstract 34.
62. Rosenberg M. Society and the Adolescent Self-Image. Princeton, NJ: Princeton University Press; 1965.
63. Burgess CM, Quiroga RM. Assessment of the safety and efficacy of poly-L-lactic acid for the treatment of HIV-associated facial lipoatrophy. J Am Acad Dermatol. 2005;52:233-239.
64. Burnouf M, Buffet M, Schwarzinger M, et al. Evaluation of Coleman lipostructure for treatment of facial lipoatrophy in patients with human immunodeficiency virus and parameters associated with the efficiency of this technique. Arch Dermatol. 2005;141:1220-1224.
65. Day JN, Raabe A, Shiner AM, Wilkins EL. Intradermal polylactic acid (Newfill) for treatment of severe HIV-associated facial lipoatrophy. 8th Annual conference of the British HIV Association; April 19-21, 2002; York, United Kingdom. Abstract O13.
66. Honda M, Yogi A, Ishizuka N, et al. Effectiveness of subcutaneous growth hormone in HIV-1 patients with moderate to severe facial lipoatrophy. Intern Med. 2007;46:359-362.
67. Cavalcanti R, Raboud J, Shen S, et al. A randomized, placebo-controlled trial of rosiglitazone for HIV-related lipoatrophy. J Infect Dis. 2007;195:1754-1761.
68. Hawkins T. Appearance-related side effects of HIV-1 treatment. AIDS Patient Care STDS. 2006;20:6-18.