JAC Advance Access first published online on January 3, 2008
This version published online on January 22, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm499
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Leading article |
Prolongation and quality of life for HIV-infected adults treated with highly active antiretroviral therapy (HAART): a balancing act
1 Immunodeficiency Clinic, University Health Network, University of Toronto, 200 Elizabeth Street, Toronto, Canada M5G 2C4 2 Department of Psychiatry, University of Toronto, 200 Elizabeth Street, Toronto, Canada M5G 2C4 3 Division of Infectious Diseases, University of Toronto, 200 Elizabeth Street, Toronto, Canada M5G 2C4
* Corresponding author. Tel: +1-416-340-4800 ext. 8609; Fax: +1-416-340-4890; E-mail: bob.burgoyne{at}uhn.on.ca
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Abstract |
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 Top Abstract IntroductionClassification of side effects...The conundrum: comparing QOL...Life in the HAART...Transparency declarationsReferences |
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Advances in highly active antiretroviral therapy (HAART) options for people living with HIV/AIDS have resulted in decreased morbidity and mortality. To some extent, the role of disease progression in eroding quality of life (QOL) erosion in the pre-HAART age is now supplanted by drug toxicities, one of the Achilles’ heels of HAART. This article reviews research findings on treatment and QOL outcomes a decade into the HAART era.
Key Words: AIDS , drug toxicities , QOL
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Introduction |
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TopAbstractIntroductionClassification of side effects...The conundrum: comparing QOL...Life in the HAART...Transparency declarationsReferences |
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A quarter of a century after the initial reports of HIV infection in the industrialized world, the global HIV/AIDS pandemic continues to spread relentlessly, with nearly 40 million people infected worldwide as of 2006.1 Since the advent of highly active antiretroviral therapy (HAART) in 1996, HIV-related mortality and morbidity rates have plummeted in areas with access to antiretrovirals (ARVs).2,3 Newer medications are continually being developed for clinical use, expanding the current armamentarium of ARVs to include over 20 agents in five distinct pharmacological classes: nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), entry inhibitors and, most recently, integrase inhibitors. Yet the challenges associated with successful HAART are significant, as clinicians and patients strive to balance adherence, efficacy, tolerability and toxicity. Herein, we outline the major drug toxicities of antiretroviral therapy and discuss their impact on quality of life (QOL).
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Classification of side effects of antiretroviral agents |
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TopAbstractIntroductionClassification of side effects...The conundrum: comparing QOL...Life in the HAART...Transparency declarationsReferences |
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For the purposes of this discussion, it is useful to group the important toxicities of HAART according to symptom presentation and symptom duration (Table 1). Primary among the symptomatic chronic toxicities is diarrhoea, particularly with PI-based regimens. This side effect is often accompanied by other gastrointestinal complaints such as nausea, vomiting and bloating. In published clinical trials of modern HAART regimens, rates of grade 2–4 diarrhoea were 11% to 16%, 2% to 3% and 6% to 13% with ritonavir-boosted lopinavir-, atazanavir- and fosamprenavir-based regimens, respectively.4–7 Much of this toxicity is thought to be related to the ritonavir component, but the important pharmacological boosting effect of this drug on the companion PI means that ritonavir boosting remains a preferred therapeutic strategy in published guidelines.8,9 Rates of grade 2–4 diarrhoea from trials of newer PIs in treatment-experienced patients are similar, at 10.9% for tipranavir/ritonavir (versus 9.4% for comparator PIs) and 3% for darunavir/ritonavir (versus 3% with comparator PIs).10,11
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Anaemia is a well-recognized toxicity of zidovudine that can be treatment-limiting. The cardinal symptoms of fatigue and shortness of breath on exertion usually compromise physical capacity and role functioning (i.e. time spent or performance in work or other usual activities). In the recently reported Study 934, the incidence of anaemia as a side effect for zidovudine/lamivudine in combination with efavirenz (5%) was significantly higher than for tenofovir/emtricitabine in combination with efavirenz (<1%).12 Anaemia was the major factor driving the higher rate of drug discontinuations in the zidovudine/lamivudine arm (9% versus 4%) and the higher proportion of patients in the tenofovir/emtricitabine arm reaching and maintaining the primary endpoint of <400 copies/mL HIV RNA at 48 weeks. Large cohort studies have consistently demonstrated that anaemia in HIV-infected individuals is an important predictor of mortality.13,14
Lipodystrophy is another important chronic toxicity, but its heterogeneity has plagued attempts to characterize its frequency and underlying aetiology. An international case–control study thus included a combination of multiple demographic, clinical, laboratory and radiographic variables in an initial case definition for HIV-associated lipodystrophy.15 However, more recent analyses generally distinguish between lipoatrophy and lipohypertrophy, recognizing that body morphology changes can occur either alone or in combination, and along a continuum of severity. Lipoatrophy generally manifests as fat loss in the cheeks, extremities and buttocks, and may result in prominence of peripheral veins. Lipoatrophy is widely attributed to the mitochondrial toxicities of NRTIs, particularly thymidine analogues such as stavudine and zidovudine, and therapeutic strategies are based on stopping the offending drug. However, HIV infection itself may play a role in its genesis. Manifestations of lipohypertrophy, in contrast, include increased central adiposity, a dorsocervical fat pad, fat accumulation in the breasts for women, and increases in visceral fat in the omentum, mesentery and retroperitoneum. These features overlap considerably with the metabolic syndrome seen in non-HIV-infected adults. Therefore, as HAART-treated individuals are living longer, the rising prevalence of age-related cardiovascular risk factors may confound efforts to attribute lipodystrophy to individual drugs.
Peripheral neuropathy is another long-recognized toxicity of NRTIs, particularly with older agents such as zalcitabine, didanosine and stavudine. Although these agents are less frequently used in industrialized countries due to these and other toxicity concerns (zalcitabine is no longer available), the latter two are often used in resource-limited settings because of cost considerations. The symptoms of burning pain and paraesthesias are reversible if the offending agent is stopped early.
Injection site reactions (ISRs) are a unique toxicity of enfuvirtide, the only existing parenteral ARV. ISRs can be erythematous, tender, ecchymotic and/or pruritic, and occurred in 98% of users at least once in the TORO trials.16 A needle-free, gas-powered administration system (Biojector B2000; Bioject Inc., Portland, OR, USA) has subsequently been demonstrated to significantly reduce the severity of ISRs, though some patients still prefer the needle-based system.17
A variety of other ARV toxicities are also of clinical significance, but may have a less lasting impact on QOL because they tend to develop acutely or may be asymptomatic. Acute, symptomatic toxicities include the risk of hypersensitivity and rash with any drug, and in particular, the life-threatening reaction seen in 3% to 7% of patients taking abacavir. Its myriad manifestations can include anaphylaxis, fever, rash, respiratory and/or gastrointestinal symptoms, usually within 2–6 weeks of drug initiation. It is hoped that increased availability of pharmacogenomic testing for HLA*B5701 will reduce this incidence to nearly zero.18 Although the usually short-term neuropsychiatric manifestations of efavirenz toxicity, including difficulty concentrating, dizziness, vivid dreams and somnolence are well known and generally self-limited, a small proportion of efavirenz users develop severe depression, suicidal ideation, mania, paranoia or aggression.19
Pancreatitis can develop with NRTIs such as didanosine and zalcitabine, but may also be an indirect result of chronic hypertriglyceridaemia induced by other agents. Metabolic and laboratory abnormalities are usually asymptomatic, including dyslipidaemia and insulin resistance seen with multiple HAART regimens, and nephrotoxicity from tenofovir. The hyperlactataemia associated with NRTI use is also generally asymptomatic, but in severe cases can present as symptomatic, fulminant lactic acidosis. Similarly, hepatotoxicity may be noted initially as an asymptomatic laboratory abnormality, but may be symptomatic occasionally and/or present as fulminant liver failure. Significant hepatotoxicity has been reported in 5% to 10% of individuals on ARVs, and this figure increases in patients co-infected with hepatitis B or C.20,21 Many culprit drugs have been implicated, including the entire class of PIs, NNRTIs (particularly nevirapine when initiated at CD4 counts of >400 cells/mm3 in men or >250 cells/mm3 in women)22,23 and certain NRTIs, which can cause hepatic steatosis accompanying the lactic acidosis syndrome mentioned above. Osteopenia and osteonecrosis affect a disproportionate number of HIV-infected individuals, but the role of ARVs in these processes remains unclear.
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The conundrum: comparing QOL pre- and post-HAART |
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TopAbstractIntroductionClassification of side effects...The conundrum: comparing QOL...Life in the HAART...Transparency declarationsReferences |
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Health-related QOL is best assessed from the perspective of the individual patient, and much of the literature is thus based on studies in which patients score their QOL using previously validated scales. These scales present a numerical rating of QOL on a gradient ranging from low to high. QOL ratings may be altered in response to intrusive symptoms; side effects are also tantamount to symptoms. Deteriorations in QOL due to illness symptoms in the pre-HAART era may have been largely replaced by equally important deteriorations due to side effects in the HAART era. A key challenge for researchers and healthcare providers has been determining the clinical factors, such as specific identifiable symptoms or ARV toxicities, affecting QOL as well as the magnitude of these influences.
HIV-related symptoms attributable to both the underlying disease and treatment-associated adverse events affect a wide range of components of well-being.24–35 Although a formal meta-analysis of the existing literature has not been carried out to our knowledge, the overall impact of each discrete symptom or side effect, as judged by β values in regression analyses or estimated by effect size calculations, appears to be in the range of one-quarter to one-half effect size equivalent. In simpler terms, the presence of three symptoms or side effects, for example, is generally thought to yield deterioration in QOL equivalent to approximately one standard deviation. Much of the QOL research in the HIV field suggests that one standard deviation is generally equivalent to 
10% to 20% in scaled terms (e.g. 10–20 points on a 0–100 scale). By extension, the elimination of symptoms or side effects might be expected to result in QOL improvement of a similar magnitude (i.e. reducing three symptoms or side effects raises a QOL rating by an approximate equivalent of one standard deviation). If study findings suggest a relation between QOL and immunological factors, such as CD4 count, or virological factors, such as viral load, it is still likely that the lived experience of symptoms and/or side effects, variables clinically related to immunological and virological parameters, are actually most responsible for the variance in QOL ratings. Factors such as perceived social support and other psychological issues may predict QOL and play a mediating role in the subjective experience of distress related to symptomatology.36 However, the focus of our discussion is the interaction of clinical side effects and well-being.
Most pre-HAART research investigating QOL changes among people living with HIV/AIDS (PHA) was conducted over relatively short time periods, usually no longer than a 1 year duration.37–43 These studies generally revealed consistent patterns of QOL deterioration over time for PHA, especially for those who progressed to AIDS-defining illnesses. Since the introduction of HAART more than a decade ago, interest in the effects of more promising treatment regimens on both life prolongation and quality supplanted the earlier trend of characterizing the relation between disease progression and well-being. However, the breadth of published literature on QOL changes over time is surprisingly small. In contrast to pre-HAART trends, the general pattern of results of HAART-era studies is one of little change or modest improvement in average QOL ratings for PHA over periods of <2 years.27,44–49 There is a paucity of post-HAART research extending over longer (i.e. 2–4 year) time periods,25,31,32,50–52 with results similar to those of shorter duration in the HAART era. For the most part, mean QOL ratings appear to remain stable in spite of viral suppression and immunological repletion. This suggests that within-sample variability in QOL ratings appears to result from the alleviation of disease symptoms in tandem with emerging side effects for those with symptomatic disease upon HAART initiation and from the development of toxicities for those who are initially asymptomatic. An interesting question is whether or not the potential improvements in QOL during a structured, negotiated or patient-initiated treatment interruption may counterbalance or outweigh the health benefits of HAART. However, the reported quality research on this topic is lacking, with most findings based on biased samples and retrospective rather than prospective designs, and further discussion of this topic is not within the scope of our paper.
Some of the specific features that have drawn the most attention in HIV-related QOL research are diarrhoea, anaemia and lipodystrophy syndrome. Diarrhoea can have a significant negative impact on QOL and be responsible for decreased functional ability, social functioning, mental health and general health perceptions.53,54 Research with patients on HAART found that those with diarrhoea had poorer QOL ratings compared with matched controls without diarrhoea.55 These findings are corroborated in qualitative research in which diarrhoea produced a debilitating impact on daily and social life, energy, emotional well-being and sexual function.56 Diarrhoea may be managed, and some degree of improvement in QOL can be achieved, through conservative measures such as diet modification and loperamide use.57
The effects of anaemia on overall functioning and well-being for PHA have been well described. The alleviation of anaemia through the treatment of co-existing disease conditions, discontinuation of culprit drugs and/or recombinant human erythropoietin is associated with improved QOL.58
Research employing open-ended survey techniques, single-item questions thematically associated with body changes or other grounded qualitative study methods corroborated initial apprehensions concerning the effects of lipodystrophy syndrome on QOL.59–62 However, one of the first published studies in which a standardized QOL measure was employed did not find significant differences in ratings of patients with clinically defined lipodystrophy compared with those without lipodystrophy.63 In another study, patients with lipodystrophy-related body changes were twice as likely to feel recognizable as being HIV-positive yet were not different in attitudes to health condition or self-reported general well-being compared with patients with no evidence of lipodystrophy.64 Similarly, a study systematically examining the relationship between severity of lipodystrophy and a broad range of standardized measures of QOL and mental health among PHA with physically visible manifestations of lipodystrophy found minimal associations, with the exception of a marked impact of lipodystrophy on self-perceived body image. Body image ratings were below the 10th percentile for the majority of the study sample, using body image normative values for the general population as the reference standard, and body image ratings were inversely associated with the severity of lipodystrophy reported.65 Given that the overall reported symptom and side effect profile were significantly associated with mental health and QOL ratings in that study, it may be that standardized instruments are poorly equipped for detecting the effects of lipodystrophy-related body changes on QOL in general, but are well equipped for capturing the effects on body self-concept. One additional study found that patients with lipodystrophy reported higher rates of body-related concerns and associated effects on psychological and social domains of QOL compared with a control group of PHA without lipodystrophy, though the former group was not more likely to report a desire to avoid sexual intimacy.66
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Life in the HAART age: the balancing act |
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TopAbstractIntroductionClassification of side effects...The conundrum: comparing QOL...Life in the HAART...Transparency declarationsReferences |
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As can be seen, length of life and QOL in the HAART age is a delicate system difficult to keep in balance. ARV therapy has the potential to confer significant benefits by controlling HIV disease and extending life, while posing unpleasant side effects that erode QOL. Maintaining or improving QOL, therefore, depends on paying careful attention to the management of disease progression, illness symptoms and treatment side effects. Questions concerning the salutary effects of immunological restoration juxtaposed with the potential for adverse treatment effects remain at the forefront of outcome research for the HIV-infected population.
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Transparency declarations |
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TopAbstractIntroductionClassification of side effects...The conundrum: comparing QOL...Life in the HAART...Transparency declarationsReferences |
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Neither author has a commercial or financial interest in the antiretroviral pharmaceutical industry.
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References |
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1 . UNAIDS. Report on the Global AIDS Epidemic 2006. (2006) Geneva: UNAIDS.
2
.
Hogg RS, Heath K, Yip B, et al. Improved survival among HIV-infected individuals following initiation of antiviral therapy. JAMA (1998) 279:450–4.
3
.
Palella FJ, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med (1998) 338:853–60.
4
.
Walmsley S, Bernstein B, King M, et al. Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection. N Engl J Med (2002) 346:2039–46.
5 . Johnson M, Grinsztejn B, Rodriguez C, et al. 96-week comparison of once-daily atazanavir/ritonavir and twice-daily lopinavir/ritonavir in patients with multiple virologic failures. AIDS (2006) 20:711–8.[Web of Science][Medline]
6 . Smith K, Weinberg W, DeJesus E, et al. Efficacy and safety of once-daily boosted fosamprenavir (FPV/r) or atazanavir (ATV/r) with tenofovir (TDF)/emtricitabine (FTC) in antiretroviral-naive HIV-infected patients: 24-week results from COL103952 (ALERT). 6th Interscience Conference on Antimicrobial Agents and Chemotherapy San Francisco California, 2006. Abstract H-1670a.
7 . Eron J Jr, Yeni P, Gathe J, et al. The KLEAN study of fosamprenavir-ritonavir versus lopinavir-ritonavir, each in combination with abacavir-lamivudine, for initial treatment of HIV infection over 48 weeks: a randomized non-inferiority trial. Lancet (2006) 368:476–82.[CrossRef][Web of Science][Medline]
8 . Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. (2006) October.
9
.
Hammer SM, Saag MS, Schechter M, et al. Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society—USA panel. JAMA (2006) 296:827–43.
10 . Boehringer-Ingelheim. Aptivus® (tipranavir) capsules, 250 mg. Prescribing information at aptivus.com. accessed 25 May 2007.
11 . Valdez Madruga J, Lafeuillade A, Beatty G, et al. TMC114/r is well tolerated by treatment-experienced patients in POWER 1, 2 and 3: integrated clinical safety analysis. In: XVI International AIDS Conference, Toronto, Canada (2006) Abstract TUPE0062.
12
.
Gallant JE, DeJesus E, Arribas JR, et al. Tenofovir DF, etricitabine and efavirenz vs zidovudine, lamivudine and efavirenz for HIV. N Engl J Med (2006) 354:251–60.
13 . Mocroft A, Kirk O, Barton SE, et al. Anaemia is an independent predictive marker for clinical prognosis in HIV-infected patients from across Europe. AIDS (1999) 13:943–50.[CrossRef][Web of Science][Medline]
14
.
Sullivan PS, Hanson DL, Chu SY, et al. Epidemiology of anemia in human immunodeficiency virus (HIV)-infeced persons: results from the multistate adult and adolescent spectrum of HIV disease surveillance report. Blood (1998) 91:301–8.
15 . Carr A. An objective case definition of lipodystrophy in HIV-infected adults: a case-control study. Lancet (2003) 361:726–35.[CrossRef][Web of Science][Medline]
16 . Nelson M, Arasteh K, Clotet B, et al. Durable efficacy of enfuvirtide over 48 weeks in heavily treatment-experienced HIV-1-infected patients in the T-20 versus optimized background regimen only 1 and 2 clinical trials. J Acquir Immune Defic Syndr (2005) 40:404–12.[CrossRef][Web of Science][Medline]
17 . Harris M, Joy R, Larsen G, et al. Enfuvirtide plasma levels and injection site reactions using a needle-free gas-powered injection system (Biojector). AIDS (2006) 20:719–23.[Web of Science][Medline]
18 . Rauch A, Nolan D, Martin A, et al. Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in the Western Australian HIV Cohort Study. Clin Infect Dis (2006) 43:99–102.[CrossRef][Web of Science][Medline]
19 . Lochet P, Peyriere H, Lotthe A, et al. Long-term assessment of neuropsychiatric adverse reactions associated with efavirenz. HIV Med (2003) 4:62–6.[CrossRef][Medline]
20
.
Sulkowski MS, Thomas DL, Chaisson RE, et al. Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection. JAMA (2000) 283:74–80.
21 . Reisler R, Liou S, Servoss J, et al. Incidence of hepatotoxicity and mortality in 21 adult antiretroviral treatment trials ACTG Liver Diseases Focus Group. 1st International AIDS Society Conference on HIV Pathogenesis and Treatment, Buenos Aires, Argentina, 2001. Abstract 43.
22 . Hitti J, Frenkel LM, Stek AM, et al. Maternal toxicity with continuous nevirapine in pregnancy: results from PACTG 1022. J Acquir Immune Defic Syndr (2004) 36:772–6.[CrossRef][Web of Science][Medline]
23 . Stern JO, Robinson PA, Love J, et al. A comprehensive hepatic safety analysis of nevirapine in different populations of HIV infected patients. J Acquir Immune Defic Syndr (2003) 34(Suppl_1):S21–33.[CrossRef][Web of Science][Medline]
24 . Badia X, Podzamczer D, Garcia M, et al. A randomized study comparing instruments for measuring health-related quality of life in HIV-infected patients. AIDS (1999) 13:1727–35.[CrossRef][Web of Science][Medline]
25 . Burgoyne R, Rourke S, Behrens D, et al. Long-term quality of life outcomes among adults living with HIV in the HAART era: the interplay of changes in clinical factors and symptom profile. AIDS Behav (2004) 8:151–63.[CrossRef][Web of Science][Medline]
26
.
Burgoyne R, Saunders D. Quality of life among urban Canadian HIV/AIDS clinic outpatients. Int J STD AIDS (2001) 12:505–12.
27 . Carrieri P, Spire B, Duran S, et al. Health-related quality of life after 1 year of highly active antiretroviral therapy. J Acquir Immune Defic Syndr (2003) 32:38–47.[Web of Science][Medline]
28 . Cunningham W, Shapiro M, Hays R, et al. Constitutional symptoms and health-related quality of life in patients with symptomatic HIV disease. Am J Med (1998) 104:129–3.[CrossRef][Web of Science][Medline]
29 . Murri R, Ammassari A, Fantoni M, et al. Disease-related factors associated with health-related quality of life in people with nonadvanced HIV disease assessed using an Italian version of the MOS-HIV health survey. J AIDS Hum Retrovirol (1997) 16:350–6.[Medline]
30 . Lorenz KA, Cunningham WE, Spritzer KL, et al. Changes in symptoms and health-related quality of life in a nationally representative sample of adults in treatment for HIV. Qual Life Res (2006) 15:951–8.[CrossRef][Web of Science][Medline]
31 . Preau M, Leport C, Salmon-Ceron D, et al. Health-related quality of life and patient-provider relationships in HIV-infected patients during the first three years after starting PI-containing antiretroviral treatment. AIDS Care (2004) 16:649–61.[CrossRef][Web of Science][Medline]
32
.
Saunders D, Burgoyne R. Evaluating health-related wellbeing outcomes among outpatient adults with human immunodeficiency virus infection in the HAART era. Int J STD AIDS (2002) 13:683–90.
33 . Vogl D, Rosenfeld B, Breitbart W, et al. Symptom prevalence, characteristics, and distress in AIDS outpatients. J Pain Symptom Manage (1999) 18:253–62.[CrossRef][Web of Science][Medline]
34
.
Wachtel T, Piette J, Mor V, et al. Quality of life in persons with human immunodeficiency virus infection: measurement by the medical outcomes study instrument. Ann Intern Med (1992) 116:129–37.
35 . Wu A, Rubin H, Mathews W, et al. A health status questionnaire using 30 items from the medical outcomes study. Med Care (1991) 29:786–98.[Web of Science][Medline]
36 . Burgoyne R, Renwick R. Social support and quality of life over time among adults living with HIV in the HAART era. Soc Sci Med (2004) 58:1353–66.[CrossRef][Web of Science][Medline]
37 . De Boer JB, Sprangers MA, Aaronson NK, et al. The feasibility, reliability and validity of the EORTC QLQ-C30 in assessing the quality of life of patients with a symptomatic HIV infection or AIDS. Psychol Health (1994) 9:65–77.[CrossRef][Web of Science]
38 . Lubeck DP, Fries JF. Changes in health status after one year for persons at-risk for and with HIV infection. Psychol Health (1994) 9:79–92.[CrossRef][Web of Science]
39 . Lubeck DP, Fries JF. Assessment of quality of life in early stage HIV-infected persons: data from the AIDS time-oriented health outcome study (ATHOS). Qual Life Res (1997) 6:494–506.[CrossRef][Web of Science][Medline]
40 . Revicki DA, Wu AW, Murray MI. Change in clinical status, health status, and health utility outcomes in HIV-infected patients. Med Care (1995) 33:AS173–82.[Web of Science][Medline]
41 . Scott-Lennox JA, Mills RJ, Burt MS. Impact of zidovudine plus lamivudine or zalcitabine on health-related quality of life. Ann Pharmacother (1998) 32:525–9.[Abstract]
42 . Tsevat J, Solzan JG, Kuntz KM, et al. Health values of patients infected with human immunodeficiency virus. Med Care (1996) 34:44–57.[CrossRef][Web of Science][Medline]
43 . Wu AW, Rubin HR, Mathews WC, et al. Functional status and well-being in a placebo-controlled trial of zidovudine in early symptomatic HIV infection. J Acquir Immune Defic Syndr (1993) 6:452–8.[Web of Science][Medline]
44
.
Chan K, Revicki DA. Changes in surrogate laboratory markers clinical endpoints health-related quality of life in patients infected with the human immunodeficiency virus. Eval Health Prof (1998) 21:265–81.
45 . Cohen C, Revicki DA, Nabulsi A, et al. A randomized trial of the effect of ritonavir in maintaining quality of life in advanced HIV disease. AIDS (1998) 12:1495–502.[CrossRef][Web of Science][Medline]
46 . Low-Beer S, Chan K, Wood E, et al. Health related quality of life among persons with HIV after the use of protease inhibitors. Qual Life Res (2001) 9:941–9.[CrossRef][Web of Science]
47 . Revicki DA, Moyle G, Stellbrink HJ, et al. Quality of life outcomes of combination zalcitabine-zidovudine, saquinavir-zidovudine and saquinavir-zalcitabine-zidovudine therapy for HIV-infected adults with CD4 counts between 50 and 350 per cubic millimeter. AIDS (1999) 13:851–8.[CrossRef][Web of Science][Medline]
48 . Weinfurt KP, Willke RJ, Glick HA, et al. Relationship between CD4 count, viral burden, and quality of life over time in HIV-1-infected patients. Med Care (2000) 38:404–10.[CrossRef][Web of Science][Medline]
49 . Zinkernagel C, Ledergerber B, Battegay M, et al. Quality of life in asymptomatic patients with early HIV infection initiating antiretroviral therapy. AIDS (2000) 13:1587–9.[CrossRef][Web of Science]
50 . Nieuwkerk PT, Gisolf EH, Colebunders R, et al. Quality of life in asymptomatic- and symptomatic HIV infected patients in a trial of ritonavir/saquinavir therapy. AIDS (2000) 14:181–7.[CrossRef][Web of Science][Medline]
51 . Nieuwkerk PT, Gisolf EH, Reijers MH, et al. Long-term quality of life outcomes in three antiretroviral treatment strategies for HIV-1 infection. AIDS (2001) 15:1985–91.[CrossRef][Web of Science][Medline]
52
.
Rabkin JG, Ferrando SJ, Lin S, et al. Psychological effects of HAART: a 2-year study. Psychosom Med (2000) 62:413–22.
53 . Lubeck DP, Bennett CL, Mazonson PD, et al. Quality of life and health service use among HIV-infected patients with chronic diarrhea. J Acquir Immune Defic Syndr (1993) 6:478–84.[Medline]
54
.
Wachtel T, Piette J, Mor V. Quality of life in persons with human immunodeficiency virus infection: measurement by the medical outcomes study instrument. Ann Intern Med (1992) 116:129–37.
55 . Tramarin A, Parise N, Campostrini S, et al. Association between diarrhea and quality of life in HIV-infected patients receiving highly active antiretroviral therapy. Qual Life Res (2004) 13:243–50.[CrossRef][Web of Science][Medline]
56 . Snijders F, DeBoer JB, Steenbergen B, et al. Impact of diarrhoea and faecal incontinence on the daily life of HIV-infected patients. AIDS Care (1998) 10:629–37.[CrossRef][Web of Science][Medline]
57 . Rachlis A, Gill CJ, Baril J, et al. Effectiveness of step-wise intervention plan for managing nelfinavir-associated diarrhea: a pilot study. HIV Clin Trials (2005) 6:203–12.[CrossRef][Web of Science][Medline]
58 . Volberding P. The impact of anemia on quality of life in human immunodeficiency virus-infected patients. J Infect Dis (2002) 185(Suppl 2):S110–S114.[CrossRef][Web of Science][Medline]
59 . Collins E, Wagner C, Walmsley S. Psychosocial impact of the lipodystrophy syndrome in HIV infection. AIDS Read (2000) 10:546–50.[Medline]
60 . Dukers H, Stolte I, Albrecht N, et al. The impact of experiencing lipodystrophy on the sexual behaviour and well-being among HIV-infected homosexual men [Letter]. AIDS (2001) 15:812–3.[CrossRef][Web of Science][Medline]
61 . Oette M, Juretzko P, Kroidl A, et al. Lipodystrophy syndrome and self-assessment of well-being and physical appearance in HIV-positive patients. AIDS Pat Care (2002) 16:413–7.[CrossRef]
62
.
Power R, Tate H, McGill S, et al. A qualitative study of the psychosocial implications of lipodystrophy syndrome on HIV positive individuals. Sex Transm Infect (2003) 79:137–41.
63 . Blanch J, Rousaud A, Martinez E, et al. Impact of lipodystrophy on the quality of life of HIV-1-infected patients. J Acquir Immune Defic Syndr (2002) 31:404–7.[Web of Science][Medline]
64 . Paton N, Earnest A, Ng Y, et al. Lipodystrophy in a cohort of human immunodeficiency virus-infected Asian patients: prevalence, associated factors and psychological impact. Clin Infect Dis (2002) 35:1244–9.[CrossRef][Web of Science][Medline]
65 . 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) 14:981–90.[CrossRef][Web of Science][Medline]
66 . Guaraldi G, Orlando G, Murri R, et al. Quality of life and body image in the assessment of psychological impact of lipodystrophy: validation of the Italian version of assessment of body change and distress questionnaire. Qual Life Res (2006) 15:73–8.
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