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Print version ISSN 1807-5932

Clinics vol.63 no.2 São Paulo  2008 



Difficulties reported by hiv-infected patients using antiretroviral therapy in brazil



Mark Drew Crosland GuimarãesI; Gustavo Machado RochaI, II; Lorenza Nogueira CamposI; Felipe Melo Teixeira de FreitasI; Felipe Augusto Souza GualbertoI; Ramiro d’Ávila Rivelli TeixeiraI; Fábio Morato de CastilhoI

IDepartment of Preventive and Social Medicine, Faculty of Medicine, Federal University of Minas Gerais - Belo Horizonte/MG, Brazil
IIEduardo de Menezes Hospital, Minas Gerais State Health Department - Belo Horizonte/MG, Brazil.




OBJECTIVE: To describe the degree of difficulty that HIV-infected patients have with therapy treatment.
INTRODUCTION: Patients’ perceptions about their treatment are a determinant factor for improved adherence and a better quality of life.
METHODS: Two cross-sectional analyses were conducted in public AIDS referral centers in Brazil among patients initiating treatment. Patients interviewed at baseline, after one month, and after seven months following the beginning of treatment were asked to classify and justify the degree of difficulty with treatment. Logistic regression was used for analysis.
RESULTS: Among 406 patients initiating treatment, 350 (86.2%) and 209 (51.5%) returned for their first and third visits, respectively. Treatment perceptions ranged from medium to very difficult for 51.4% and 37.3% on the first and third visits, respectively. The main difficulties reported were adverse reactions to the medication and scheduling. A separate logistic regression indicated that the HIV-seropositive status disclosure, symptoms of anxiety, absence of psychotherapy, higher CD4+ cell count (> 200/mm3) and high (> 4) adverse reaction count reported were independently associated with the degree of difficulty in the first visit, while CDC clinical category A, pill burden (> 7 pills), use of other medications, high (> 4) adverse reaction count reported and low understanding of medical orientation showed independent association for the third visit.
CONCLUSIONS: A significant level of difficulty was observed with treatment. Our analyses suggest the need for early assessment of difficulties with treatment, highlighting the importance of modifiable factors that may contribute to better adherence to the treatment protocol.

Keywords: AIDS. Treatment. Patient Perception. Adherence. Modifiable Factors.




Antiretroviral therapy (ART) has brought important benefits to HIV-infected patients, such as increased survival, better quality of life, significant reduction in the incidence of opportunistic infections and lower costs related to ambulatory care and hospitalization.1,2,3 The Brazilian National STD/AIDS Program of the Ministry of Health has guaranteed universal and free access to ART since 1996.4 Patients diagnosed in that year had a median survival three times longer than those diagnosed in 1995, clearly indicating the benefits of ART.5 The clinical goals of HIV treatment and care, including maximizing survival and improving quality of life, are optimally accomplished only through a high-level of adherence to ART and, consequently, a durable suppression of the HIV viral load.6 Non-adherence has become a common cause of therapy failure, with failure rates varying from 7.0% to 43.0% in different health care settings worldwide.7-14 Factors potentially associated with non-adherence include characteristics related to the antiretroviral regimen (e.g., complexity of therapy, pill burden, food requirements, adverse reactions), a patient’s perception of the treatment, the interference of ART in a patient’s daily life, symptoms of AIDS and level of education, among others.8-15 However, there are few published epidemiologic studies that investigate the difficulties reported by patients initiating antiretroviral therapy, and to our knowledge, none in Brazil. Patients may feel emotionally unprepared for treatment due to a lack of understanding and/or belief in ART, leading to increased difficulties with everyday treatment management.16-17 Identifying and understanding the difficulties that arise in the beginning of treatment may help prevent further episodes of non-adherence and potentially increase long-term adherence with sustainable clinical benefits and improvement in patient quality of life.16,17 The present study aimed to describe the degree of difficulty with ART reported by HIV-infected patients in public AIDS reference centers using two cross-sectional analyses issued subsequent to the beginning of treatment (after one and seven months). In addition, we explored potential factors associated with such difficulties, including sociodemographic, psychosocial, clinical and health care-related variables.




This analysis is part of a prospective concurrent study conducted at two public health referral centers in a large metropolitan city in Brazil. The objective of the main project was to estimate the incidence of non-adherence to ART among patients initiating treatment and the factors associated with it. Briefly, eligibility criteria were serologic-confirmed HIV infection; no prior history of antiretroviral use; age over 18 years old (or 16 years old for pregnant women); having had one’s first antiretroviral regimen dispensed in one of the centers and voluntarily participation consent. Patients were interviewed after first receiving medication (baseline interview), and subsequently in the first, fourth and seventh month of follow-up. The project was approved by the Ethical Committee Board of both participating centers and the Federal University of Minas Gerais (ETIC 106/99).

Exposure and event measurements

Data were collected using a pre-tested semi-structured questionnaire consisting of closed and short open-ended questions. Face-to-face interviews were conducted by trained research personnel in private rooms. Sociodemographic (e.g., gender, age, schooling, income), behavioral (e.g., disclosure of HIV-seropositive status, condom use and alcohol and injection drug use), health services and clinical characteristics (e.g., difficulty of access to services, embarrassment, understanding of medical orientation) were obtained during baseline interviews, while data on ARV use (e.g., difficulties with the treatment, prescribed regimens, change in regimen, pill burden, adverse reactions and adherence) were obtained from each follow-up interview. Additionally, the CDC clinical classification18 and CD4+ T-lymphocyte count were obtained from medical charts during the study period. Symptoms of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale during the baseline interview.19 Disclosure of one’s HIV-seropositive status was self-reported and defined as having communicated an HIV positive result to a close acquaintance such as a relative, friend or sexual partner.

For the current analysis, the outcome measurement (i.e., the difficulty of antiretroviral therapy use) was assessed in a cross-sectional approach at the first (first month) and third (seventh month) visits. We used only these visits as points of comparison because the time between the first and second visits was brief. Patients were asked to classify the degree of difficulty of their treatment at each visit as very high, high, medium, low, or very low and to justify their choice. The reported reasons were classified as problems associated with adverse reactions, scheduling, pill burden, emotional status, adaptation, social interactions, health care service, organoleptic properties of the drugs or dietary interference.

Data analysis

Descriptive analysis was conducted for the reported difficulties while crude associations were assessed by chi-square test. The degree of difficulty was categorized as a dichotomous variable, comparing all values falling between medium and very high difficulty to those in the range of low to very low difficulty, due to power considerations. The magnitude of the associations between putative risk factors and the degree of difficulty with treatment was estimated by the odds ratio (OR) with a 95% confidence interval (95% CI). The independent effect of potential exposure variables was assessed by multivariate analysis using logistic regression for each visit. All variables with p-values equal to or less than 0.20 obtained in the univariate analysis were used to begin multivariate modeling. A backward deletion strategy was applied, and those variables with p-values equal to or less than 0.05 remained in each of the final models. Goodness of fit was evaluated using the Hosmer-Lemeshow test,20 while the SAS System® and EGRET for Windows®, were used for data analysis, and Paradox® was used for data storage.



Of the 406 participants enrolled in the study, 362 (89.2%) patients returned for the first and 218 (53.7%) for the third visit after initiating ART. Twelve and nine patients did not classify the degree of difficulty of their treatment in the first or third visits, leaving 350 (86.2%) and 209 (51.5%) patients for analysis, respectively. No difference was observed when comparing the two visits for most variables, although there were fewer participants in the third visit. Descriptive data indicated that, for both visits, most participants were male, younger than 35 years old, and had less then 8 years of schooling, a low individual monthly income and no health insurance (Table 1). While more than half of the sexually-active participants reported always using condoms in the last month, fewer patients reported alcohol or injection drug use for both periods. Similarly, most patients had disclosed their HIV-seropositive status to relatives or friends while fewer participants declared embarrassment during clinic visits, reported some difficulty of access to the health service or were receiving psychotherapy. Clinical markers indicated high proportions of patients with lower CD4+ T-lymphocyte count (< 200 cells/mm3) or with CDC clinical classification B or C. Protease inhibitors were commonly prescribed, while a reasonable proportion of patients reported more than four adverse reactions or had a low understanding of their prescription’s medical orientation.



Overall, 51.4% (n=180) patients found their treatment to be of medium to high difficulty in the first visit while this rating frequency dropped to 37.3% (n=78) in the third visit (Table 2). Adverse reactions were the main reason reported (33.3%), followed by complex scheduling (23.9%), among those reporting medium to high degree of difficulty in the first visit. Less frequent reasons were those associated with emotional status (9.4%), social interaction (7.2%), pill burden (6.7%), health care service (6.1%) and the organoleptic properties of the drugs (5.6%). On the other hand, adverse reactions only accounted for 19.2% and scheduling became the foremost difficulty by the third visit (37.2%). Among those with less difficulty with the treatment overall, the main reason reported was scheduling, while there was an increase in treatment adaptation over time (23.5% and 32.1%, for the first and third visits, respectively) (Table 2).



Univariate analysis indicated similar proportions of patients with increased difficulty with treatment across age, schooling, income, condom, alcohol or injection drug use, for both visits. Although more patients reported a change in regimen in the first visit, this was not associated with greater difficulty with treatment (data not shown). On the other hand, at the first visit, an increased degree of difficulty (p-value < 0.05) was found for those who disclosed their HIV-seropositive status, reported embarrassment during clinic visits, had a higher CD4+ T-lymphocyte count (> 200 cells/mm3), presented moderate to severe symptoms of anxiety, had > 4 adverse reactions and had experienced a longer time period between the first HIV medical visit and the first antiretroviral prescription (> 3 months). Borderline significance was observed for difficulty of access to services, psychotherapy attendance and being clinically asymptomatic (Table 3). Fewer factors were statistically associated (p-value < 0.05) with difficulty with treatment in the third visit, including higher CD4+ T-lymphocyte counts (> 200 cells/mm3), ARV antiretroviral regimen with protease inhibitor, daily pill burden (> 7 pills), use of other medication, > 4 adverse reactions and low understanding of medical orientation. It should be noted that women had more difficulties with treatment in the third visit, although this result is only of borderline significance (p=0.068).



Adjusted OR with 95% CI are shown in Table 4. Because women showed a statistically-independent borderline association during the third visit (p=0.081), we decided to retain this variable in the final model of each visit for comparison purposes. HIV-seropositive status disclosure, > 4 adverse reactions reported, presence of symptoms of anxiety and absence of psychotherapy were independently associated with the degree of difficulty in the first visit while CDC clinical category A, pill burden (> 7 pills), use of other medication, > 4 adverse reactions reported and low understanding of one’s medical orientation were associated with difficulties during the third visit, in addition to gender.




By using several simple questions, we were able to assess patient perception of difficulties related to initial ART. We chose to compare visits at two separate, cross-sectional time points due to power considerations, despite the known limitation of cross-sectional designs with regard to causal inferences. However, we should emphasize that no difference was observed with regard to non-participation rates and most variables were similarly distributed between the two periods. In addition, patients at these centers represented approximately 90% of all reported AIDS cases during the study period for the region.

Notably, a high proportion of patients indicated a high degree of difficulty in the beginning of treatment (51.4%). Health care-related variables seem to have played a more important role in the first visit, while treatment and clinical characteristics were more prominent in the third visit. Although most sociodemographic variables were not statistically associated with our outcome of interest, women tended to report more difficulties, but only for the third visit, and this with borderline significance. This is corroborated by other data indicating that women may have higher rates of non-adherence21 or a poorer quality of life.22 Because of the need to cope with their partners’ and/or children’s treatment, women often fail to adhere to their own treatment, which may partially explain the finding from the third visit.23

Factors related to health care providers are crucial for patients initiating ART therapy, including compliance to regular clinic visits, counseling, availability of support services and a multidisciplinary approach. A complete understanding of the complexity of the regimen, side effects and scheduling, among other concerns, may help patients deal with their medication with less difficulty. In addition, earlier access to care and counseling before actual ART may help prepare patients for long-term treatment effects and reinforce the need for high adherence. As shown, patients with a longer time between their initial medical visit and their antiretroviral prescription and those who reported embarrassment were more likely to have increased difficulties with the treatment in the first visit, although these results did not remain in the final statistical model. Factors such as irregular medical visits, discontinuation of their clinical follow-up24 and poor health professional-patient relationships25,26 may indirectly explain such findings. In addition, particularly related are the lack of psychotherapy and the presence of moderate-to-severe symptoms of anxiety, which were also associated with increased difficulty in the first visit. This may clearly indicate the lack of adequate psychiatric counseling by trained professionals in these services before treatment started, as shown in other studies27.

Clinical- and treatment-related factors were found to be barriers for good adherence. Although adverse reactions remained statistically significant in both visits, they were more common in the first visit and indicated a stronger early effect of treatment. They were also more commonly cited as the main reason for difficulty with treatment in the first relative to the third visit, at rates of 33.3% and 19.2%, respectively. This is consistent with the literature, which indicates that adverse effects are related to a decrease in the quality of life and low adherence among HIV-treated patients.21,28-30 However, ART is a dynamic phenomenon, which changes over time, as patients tend to adapt their daily routine to regimen scheduling and more readily learn how to identify and deal with side effects.31 As shown, better scheduling and easier adaptation were the most common reasons reported by those patients with low to very low difficulty in the third visit (34.4% and 32.1%, respectively). However, pill burden, the inclusion of regimens with protease inhibitor and the additional use of other medications over time are factors which also tend to create more difficulties. Additionally, it should be noted that poor understanding of medical orientation remained a predictor of difficulties only for the third visit. This may indicate that, even if adequately counseled when beginning treatment, long-lasting and sustained good levels of information may not be feasible if routine counseling and reminders by health professionals are not continuously received by patients. Finally, the association of a higher CD4+ cell count and the asymptomatic patient designation (CDC classification A) with increased difficulties may reflect a lower perception of these patients with regard to the need for treatment, and thus a lower threshold for dealing with the daily burden of ART regimens.

Findings from these analyses suggest the need for early assessment of factors associated with increased difficulties and therefore the need to identify patients who are at a greater risk of lower adherence before starting treatment. Health care professionals and AIDS referral services must develop focused interventions to address modifiable factors such as compliance with medical visits, counseling, improved physician-patient relationships and better ARV orientation to achieve immediate and sustainable adherence.



1. Walensky RP, Paltiel AD, Losina E, Mercincavage LM, Schackman BR, Sax PE, et al. The survival benefits of AIDS treatment in the United States. J Infect Dis. 2006;194:11-9.        [ Links ]

2. Freedberg KA, Losina E, Weinstein MC, Paltiel AD, Cohen CJ, Seage GR, et al. The cost effectiveness of combination antiretroviral therapy for HIV disease. N Engl J Med. 2001;344:824-31.        [ Links ]

3. Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998;338:853-60.        [ Links ]

4. Programa Nacional de DST/AIDS. Legislação sobre DST e AIDS no Brasil. Brasília: Ministério da Saúde; 2000.        [ Links ]

5. Marins JR, Jamal LF, Chen SY, Barros MB, Hudes ES, Barbosa AA, et al. Dramatic improvement in survival among adult Brazilian AIDS patients. AIDS. 2003;17:1675-82.        [ Links ]

6. Lucas GM. Antiretroviral adherence, drug resistance, viral fitness and HIV disease progression: a tangled web is woven. J Antimicrob Chemother. 2005;55:413-6.         [ Links ]

7. Nemes MIB, Carvalho HB, Souza MFM. Antiretroviral therapy adherence in Brazil. AIDS 2004;18(Suppl. 3):S15–S20.         [ Links ]

8. Walsh JC, Sherr L, Adherence Strategy Group. An assessment of current HIV treatment adherence services in the UK. AIDS Care. 2002;14:329-34.        [ Links ]

9. Andreo C, Bouhnik AD, Soletti J, Bertholon DR, Moatti JP, Rossert H, et al. Non-compliance in HIV infected patients, supported by a community association. Sante Publique. 2001;13:249-62.        [ Links ]

10. Oyugi JH, Byakika-Tusiime J, Charlebois ED, Kityo C, Mugerwa R, Mugyenyi P, et al. Multiple validated measures of adherence indicate high levels of adherence to generic HIV antiretroviral therapy in a resource-limited setting. J Acquir Immune Defic Syndr. 2004;36:1100-2.        [ Links ]

11. Duran S, Spire B, Raffi F, Walter V, Bouhour D, Journot V, et al. and the APROCO Cohort Study Group. Self-reported symptoms after initiation of a protease inhibitor in HIV-infected patients and their impact on adherence to HAART. HIV Clin Trials. 2001;2:38-45.        [ Links ]

12. Mehta S, Moore RD, Graham NMH. Potential factors affecting adherence with HIV therapy [Editorial review]. AIDS. 1997;11:1665-70.        [ Links ]

13. Fogarty L, Roter D, Larson S, Burke J, Gillespie J, Levy R. Patient adherence to HIV medication regimens: a review of published and abstract reports. Patient Educ Counsel. 2002;46:93-108.        [ Links ]

14. Souza-Jr PRB, Szwarcwald CL, Castilho EA. Delay in introducing antiretroviral therapy in patients infected by HIV in Brazil, 2003-2006. Clinics. 2007;62:579-84.        [ Links ]

15. Reynolds NR, Testa MA, Marc LG, Chesney MA, Neidig JL, Smith SR et al and Protocol Teams of ACTG 384, ACTG 731 and A5031s. Factors influencing medication adherence beliefs and self-efficacy in persons naive to antiretroviral therapy: a multicenter, cross-sectional study. AIDS Behav. 2004;8:141-50.        [ Links ]

16. Veinot TC, Flicker SE, Skinner HA, McClelland A, Saulnier P, Read SE, et al. "Supposed to make you better but it doesn’t really": HIV-positive youths’ perceptions of HIV treatment. J Adolesc Health. 2006;38:261-7.        [ Links ]

17. Perez RI, Bano JR, Ruz MAL, Jimenez AA, Prados MC, Liano JP, et al. Health-related quality of life of patients with HIV: impact of sociodemographic, clinical and psychosocial factors. Qual Life Res. 2005;14:1301-10.        [ Links ]

18. Centers for Disease Control and Prevention, 1993. Revised classification system for HIV infection and expanded surveillance case definitions for AIDS among adolescents and adults. MMWR. 1992;41(RR-17):1-19.        [ Links ]

19. Zigmond AS and Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67:370-6.        [ Links ]

20. Hosmer DW and Lemeshow S. Applied logistic regression. New York: John Wiley & Sons; 1989. p.304.        [ Links ]

21. Bonolo PF, Cesar CC, Acurcio FA, Ceccato MG, Padua CA, Alvarez J, et al. Non-adherence among patients initiating antiretroviral therapy: a challenge for health professionals in Brazil. AIDS 2005; 19 (suppl 4): S5-S13.        [ Links ]

22. Mrus JM, Williams PL, Tsevat J, Cohn SE, Wu AW. Gender differences in health-related quality of life in patients with HIV/AIDS. Qual Life Res. 2005;14:479-91.        [ Links ]

23. Hackl KL, Somlai AM, Kelly JA, Kalichman SC. Women living with HIV/AIDS: the dual challenge of being a patient and caregiver. Health Soc Work. 1997;22:53-62.        [ Links ]

24. Arici C, Ripamonti D, Maggiolo F, Rizzi M, Finazzi MG, Pezzoti P, et al. Factors associated with the failure of HIV-positive persons to return for scheduled medical visits. HIV Clin Trials. 2002;3:52-7.        [ Links ]

25. Roberts KJ. Physician-patient relationships, patient satisfaction, and antiretroviral medication adherence among HIV-infected adults attending a public health clinic. AIDS Patient Care STDS. 2002;16:43-50.        [ Links ]

26. O’Brien MK, Petrie K, Raeburn J. Adherence to medication regimens: updating a complex medical issue. Med Care Rev. 1992;49:435-54.        [ Links ]

27. Campos LN, Bonolo PF, Guimarães MDC. Anxiety and depression assessment prior to initiating antiretroviral treatment in Brazil. AIDS Care. 2006;18:529-36.        [ Links ]

28. Eriksson LE, Bratt GA, Sandstrom E, Nordstrom G. The two-year impact of first generation protease inhibitor based antiretroviral therapy (PI-ART) on health-related quality of life. Health Qual Life Outcomes. 2005;3:32.        [ Links ]

29. Abel E, Painter L. Factors that influence adherence to HIV medications: perceptions of women and health care providers. J Assoc Nurses AIDS Care. 2003;14:61-9.         [ Links ]

30. Ammassari A, Murri R, Pezzotti P, Trotta MP, Ravasio L, De Longis P, et al. Self-reported symptoms and medication side effects influence adherence to highly active antiretroviral therapy in persons with HIV infection. J Acquir Immune Defic Syndr. 2001;28:445-9.         [ Links ]

31. Remien RH, Hirky AE, Johnson MO, Weinhardt LS, Whittier D, Le GM. Adherence to medication treatment: a qualitative study of facilitators and barriers among a diverse sample of HIV+ men and women in four US cities. AIDS Behav. 2003;7:61-72.        [ Links ]



Received for publication on 31/08/07
Accepted for publication on 09/11/07

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