Introduction
Self-perception of side-effects has already been shown to be associated with short-term non-adherence to highly active antiretroviral therapies (HAART) [1,2]. Long-term toxicity of HAART, such as lipodystrophy syndrome and other metabolic complications [3-6], is also likely to affect patients' adherence. The APROCO cohort of French HIV-infected patients started on a protease inhibitor-containing antiretroviral therapy gave us the opportunity to study the impact of patients' perceptions of lipodystrophy on failure to maintain adherence in the long-term.
Methods
Among the 811 patients who were enrolled in the APROCO cohort between May 1997 and June 1999, a total of 500 had completed self-administered socio-behavioural questionnaires at both four (M4) and twenty months (M20) follow-up visits (response rate, 61.7%). No significant differences were found between these 500 respondents and the 311 non-respondents in terms of age, sex, employment, education, plasma HIV RNA, CD4 cell counts and clinical stage at initiation of HAART (M0).
Adherence measurement at M4 and M20 was based on five different questions accordingly to the methodology established by the AIDS Clinical Trial Group [7]. Patients were classified as adherent only if they concordingly declared: 100% intake of their prescribed daily number of pills for each drug included in their HAART regimen during the 4 days prior to the visit; having 'totally' taken their prescribed doses of HAART, never having taken their whole daily doses of drugs in a unique intake, and never having modified the prescribed schedule during the same 4-day period; finally, not having skipped a dose during the last week-end prior to the visit.
Results
At first visit after initiation of HAART (M4), 277 patients (55.4%) did fulfil these five conditions and were classified as adherent; they were more likely to have undetectable HIV RNA (59.4% versus 41.6%; Chi-squared test P = 0.008). Clinical and psycho-socio demographic characteristics of these 277 initially adherent patients are described in Table 1. Among them, about one-third (n = 83; 30.0%) failed to maintain adherence to HAART at M20. A majority of the 277 initially adherent patients (76.2%) declared at least one of the following symptoms at M20. The most frequently reported symptoms were 'change in the body shape' (50.5%) and 'bigger belly or wider waist' (46.9%). Non-adherent patients at M20 were more likely to report these two symptoms (60.2% versus 46.4%; Chi-squared test;P = 0.03; 55.4% versus 43.3%;P = 0.06); they were also more likely to report breast enlargement (`bigger breast') (26.5% versus 13.4%;P = 0.008). No significant differences in reports of the six other symptoms (`slimmer legs', 'slimmer arms', 'veins on the legs more visible', 'hollow cheeks', 'slimmer buttocks', or 'accumulation of fat in the neck') were found between those who maintained adherence at M20 and those who failed to do so. Overall, non-adherent patients at M20 tended to report a higher number of lipodystrophy-related symptoms than those who maintained adherence (Table 1).
For 218 out of the 277 patients, standardized data about medical diagnosis of lipodystrophy syndrome (report by consulting physician of at least one of the following symptoms: cheek atrophy, neck hypertrophy including buffalo neck, breast enlargement, atrophy of upper limbs, atrophy of lower limbs, waist size increase, buttock atrophy, phlebomegaly, hypertrophy of subscapular region) [4] were also available at M20. Among the 162 of these 218 patients who reported at least one symptom, 75.9% had medically diagnosed lipodystrophy concordantly, whereas only 30.4% of the 56 patients who did not report any symptom were diagnosed with lipodystrophy (Chi-squared test, P < 0.001). Medical diagnosis of lipodystrophy was more frequent among non-adherent patients at M20 (71.4%) than among those who maintained adherence (61.3%), although this difference did not reach statistical significance (Chi-squared test, P = 0.16).
Even after multiple adjustment by logistic regression for other variables related to adherence failure at M20 in univariate analysis (P ≤ 0.25), number of self-reported lipodystrophy-related symptoms was significantly associated with failure to maintain adherence at M20 (Table 1). When patients' report of 'change in the body shape' was introduced in the model alternatively to total number of lipodystrophy symptoms, this item remained significant (adjusted odds ratio, 1.80; 95% CI, 1.1-3.1).
Discussion
Various studies have found an association between viral suppression due to HAART and the development of lipodystrophy, one possible explanation being that adequate adherence results in bigger exposure to antiretroviral drugs which may imply a higher probability of long-term side-effects [8,9]. Our study among patients who were initially adherent to HAART establishes a significant statistical association between patients' subjective perceptions of lipodystrophy symptoms and failure to maintain adherence.
It must be noted that, although a good relationship was found between these patients' perceptions and physicians' report of symptoms, the association between the medical measurement of lipodystrophy and adherence failure did not reach statistical significance. This may be due to some lack of statistical power in our sample of respondents where complete behavioural and medical data were available. This may also be due to the fact that patients' self-assessment of symptoms differ from physicians' estimations of side-effects [10,11] and that the same side-effect may have a different impact on perceptions and behaviours according to patients' individual and group characteristics [12].
Of course, relationships between occurrence of lipodystrophy, adherence behaviour and virological effectiveness of HAART need further investigations, carried out in larger samples of patients, followed during a longer period of time, and with more systematic cross-validation between self-reports and other methods of measurement [13] than in the present study.
Socio-behavioural research has, however, established that factors which interfere with initial adoption of a behaviour may partly differ from those who play a role in long-term sustaining of this behaviour [12]. It is therefore not surprising that initially adherent patients who experience lipodystrophy syndrome may be particularly vulnerable to adherence failure. Medical and psycho-social interventions aimed at early recognition of this syndrome and promoting continuation of adherence among affected patients are clearly needed.
Acknowledgements
We thank the patients who participated in this study.
References
1. Catz SL, Kelly JA, Bogart LM, Benotsch EG, McAuliffe TL. Patterns, correlates, and barriers to medication adherence among persons prescribed new treatments for HIV disease. Health Psychol 2000, 19: 124-133.
2. Duran S, Spire B, Raffi F. et al. Self-reported symptoms after initiation of protease inhibitor in HIV-infected patients and their impact on adherence to HAART. HCT 2001, 2: 38-45.
3. Carr A, Samaras K, Burton S. et al. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS 1998, 12: F51-F58.
4. Carr A, Samaras K, Thorisdottir A, Kaufmann GR, Chisholm DJ, Cooper DA. Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor- associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study. Lancet 1999, 353: 2093-2099.
5. Polo R, Verdejo J, Martinez-Rodriguez S, Madrigal P, Gonzalez-Munoz M. Lipoatrophy, fat accumulation, and mixed syndrome in protease inhibitor- naive HIV-infected patients. J Acquir Immune Defic Syndr 2000, 25: 284-286.
6. Heath KV, Hogg RS, Chan KJ. et al. Lipodystrophy-associated morphological, cholesterol and triglyceride abnormalities in a population-based HIV/AIDS treatment database. AIDS 2001, 15: 231-239.
7. Chesney MA, Ickovics JR, Chambers DB. et al. Self-reported adherence to antiretroviral medications among participants in HIV clinical trials: the AACTG adherence instruments. Patient Care Committee & Adherence Working Group of the Outcomes Committee of the Adult AIDS Clinical Trials Group (AACTG). AIDS Care 2000, 12: 255-266.
8. Kotler DP, Rosenbaum K, Wang J, Pierson RN. Studies of body composition and fat distribution in HIV-infected and control subjects. J Acquir Immune Defic Syndr Hum Retrovirol 1999, 20: 228-237.
9. Martinez E, Mocroft A, García-Viejo M. et al. Risk of lipodystrophy in HIV-1 infected patients treated with protease inhibitors: a prospective cohort study. Lancet 2001, 357: 592-598.
10. Macquart-Moulin G, Viens P, Bouscary M. et al. Discordance between physicians' estimations and breast cancer patients' self-assessment of side-effects of chemotherapy: an issue for quality of care. Br J Cancer 1997, 76: 1640-1645.
11. Fontaine A, Larue F, Lassauniere JM. Physicians' recognition of the symptoms experienced by HIV patients: how reliable? J Pain Symptom Manage 1999, 18: 263-270.
12. Dunbar J. Predictors of Patient Adherence: Patient Characteristics. The Handbook of Health Behavior Change. New-York: Springer; 1990.
13. Liu H, Golin CE, Miller LG. et al. A comparison study of multiple measures of adherence to HIV protease inhibitors. Ann Intern Med 2001, 134: 968-977.
14. Fuhrer R, Rouillon F. La version Française de l'échelle CES-D. Description and translation of the auto-evaluation scale (in French). Psychiatrie et Psychobiologie 1989, 4: 163-166.
Appendix
The APROCO study group
Scientific Committee
Steering Committee. Principal Investigators: C. Leport, F. Raffi. Methodology: G. Chêne, R. Salamon. Social Sciences: J.-P. Moatti, J. Pierret. Virology: F. Brun-Vézinet, H. Fleury. Pharmacy: G. Peytavin. Other members. D. Costagliola, P. Dellamonica, C. Katlama, L. Meyer, M. Morin, D. Sicard, A. Sobel, F. Vincent-Ballereau.
Events Validation Committee
M. Dupon, V. Le Moing, B. Marchou, T. May, P. Morlat, A. Waldner-Combernoux.
Observers
F. Agid, F. Bourdillon, J.-F. Delfraissy, J. Dormont, J.-Y. Lacut, Y. Souteyrand, J.-L. Vildé.
Study group on metabolic complications
J.M. Bard, A. Basdevant, J. Capeau, G. Chêne, C. Coussieu, M. Krempf, C. Leport, F. Raffi, W. Rozenbaum, M. Savès.
Monitoring and statistical analysis
C. Alforo, C. Barennes, V. Cailleton, C. Deveaud, C. Droz, G. Dupouy, S. Duran, S. Dutoit, J. L. Ecobichon, C. Egouy, S. Gautier, C. Germain, C. Jadand, V. Journot, R. Lassalle, S. Lawson-Ayayi, L. Latour, V. Le Moing, C. Lewden, B. Masquelier, W. Nouioua, G. Palmer, E. Pereira, S. Roloff, V. Rondé-Oustau, A. Sangue, M. Savès, M. Souville, B. Spire, R. Winelm.
Promotion
Agence Nationale de Recherches sur le Sida (ANRS, Action Coordonnée no 7).
Clinical centres (coordinators)
Amiens (Prof. Schmit), Angers (Dr Chennebault), Belfort (Dr Faller), Besançon (Dr Estavoyer, Prof. Laurent, Prof. Vuitton), Bordeaux (Prof. Beylot, Prof. Lacut, Prof. Le Bras, Prof. Ragnaud), Bourg-en-Bresse (Dr Granier), Brest (Prof. Garré), Caen (Prof. Bazin), Compiègne (Dr Veyssier), Corbeil Essonnes (Dr Devidas), Créteil (Prof. Sobel), Dijon (Prof. Portier), Garches (Prof. Perronne), Lagny (Dr Lagarde), Libourne (Dr Ceccaldi), Lyon (Prof. Peyramond), Meaux (Dr Allard), Montpellier (Prof. Reynes), Nancy (Prof. Canton), Nantes (Prof. Raffi), Nice (Prof. Cassuto, Prof. Dellamonica), Orléans (Dr Arsac), Paris (Prof. Bricaire, Prof. Caulin, Prof. Frottier, Prof. Herson, Prof. Imbert, Dr Malkin, Prof. Rozenbaum, Prof. Sicard, Prof. Vachon, Prof. Vildé), Poitiers (Prof. Becq-Giraudon), Reims (Prof. Rémy), Rennes (Prof. Cartier), Saint-Etienne (Prof. Lucht), Saint-Mandé (Prof. Roué), Strasbourg (Prof. Lang), Toulon (Dr Jaubert), Toulouse (Prof. Massip), Tours (Prof. Choutet). Cited Here...
© 2001 Lippincott Williams & Wilkins, Inc.