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.714 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.815 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.1617 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 ) .
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 .
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
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 .
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 ) .
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 .
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
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 / mm ) 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 / mm ) , 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/ mm ) , 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
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 .
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.21,2830 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 .
 objectiveto describe the degree of difficulty that hiv - infected patients have with therapy treatment.introductionpatients perceptions about their treatment are a determinant factor for improved adherence and a better quality of life.methodstwo 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.resultsamong 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.conclusionsa 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 . 