Development and validation of the WebAd-Q Questionnaire to monitor adherence to HIV therapy

Transcription

1 Rev Saude Publica. 2018;52:62 Origial Article Developmet ad validatio of the WebAd-Q Questioaire to moitor adherece to HIV therapy Felipe Campos Vale I, Erai Tiaraju de Sata-Helea II, Maria Altefelder Satos I, Waia Maria do Espirito Sato Carvalho I, Paulo Rossi Meezes III, Caritas Relva Basso I, Mariliza Herique Silva IV, Aa Maroso Alves I, Maria Ies Battistella Nemes III I Uiversidade de São Paulo. Faculdade de Medicia. Programa de Pós-Graduação em Medicia Prevetiva. São Paulo, SP, Brasil II Uiversidade Regioal de Blumeau. Departameto de Medicia. Programa de Pós-Graduação em Saúde Coletiva. Blumeau, SC, Brasil III Uiversidade de São Paulo. Faculdade de Medicia. São Paulo, SP, Brasil IV Cetro de Referêcia e Treiameto em DST e Aids do Estado de São Paulo. São Paulo, SP, Brasil ABSTRACT Correspodece: Felipe Campos Vale Av. Dr. Araldo, adar São Paulo, SP, Brasil felipecvale@gmail.com Received: Ju 30, 2017 Approved: Sep 22, 2017 How to cite: Vale FC, Sata-Helea ET, Satos MA, Carvalho WMES, Meezes PR, Basso CR, et al. Developmet ad validatio of the WebAd-Q Questioaire to moitor adherece to HIV therapy. Rev Saude Publica. 2018;52:62. Copyright: This is a ope-access article distributed uder the terms of the Creative Commos Attributio Licese, which permits urestricted use, distributio, ad reproductio i ay medium, provided that the origial author ad source are credited. OBJECTIVE: To preset the developmet ad validatio of the WebAd-Q Questioaire, a self-report istrumet to moitor adherece to atiretroviral therapy i HIV/AIDS ceters i Brazil. METHODS: The WebAd-Q is a electroic questioaire that has three questios about the use of atiretrovirals i the last week. It was costructed from iterviews ad focus groups with 38 patiets. Its validity was tested i a study with a sample of 90 adult patiets o atiretroviral therapy for at least three moths. We used electroic moitorig bottles, pill coutig, ad self-report iterview to compare adherece. The WebAd-Q was aswered o the sixtieth day, twice, with at least oe hour of iterval. The viral load of the patiets was obtaied from the service records. We have aalyzed the agreemet betwee the aswers to the WebAd-Q, the associatios, ad the correlatios with viral load ad performace compared to other measures of adherece. RESULTS: Amog the ivited patiets, 74 (82.2%) aswered the WebAd-Q. No difficulties were reported to aswer the questioaire. The average aswer time was 5 mi 47 sec. The set of three questios of the WebAd-Q obtaied agreemet of 89.8%, with Kappa of 0.77 (95%CI ). The o-adherece aswers of the WebAd-Q were associated with detectable viral load. We obtaied moderate viral load correlatios with the o-adherece scale accordig to the WebAd-Q. For the three questios of the WebAd-Q, patiets with o-adherece aswers were also reported as less adheret accordig to the other measures of adherece. CONCLUSIONS: The WebAd-Q aswered all the issues cosidered relevat i the validatio of questioaires, was well uderstood by patiets, was associated with viral load, ad obtaied good agreemet ad good performace compared to the other measures. The feasibility aalysis of its implemetatio still depeds o a atioal study o its applicability. DESCRIPTORS: Ati-HIV Agets, supply & distributio. HIV Ifectios, drug therapy. Medicatio Adherece. Surveys ad Questioaires, utilizatio. Validatio Studies. 1

2 INTRODUCTION The success of atiretroviral therapy (HAART) for HIV/AIDS heavily depeds o timely diagosis 1, adequate treatmet, ad high patiet adherece to therapeutic regimes 2. I Brazil, amog the estimated 781,000 persos livig with HIV (PLHIV) i 2014, 649,000 (83.1%) were diagosed. Amog the diagosed PLHIV, 405,000 (62.4%) received atiretroviral therapy from the Brazilia Uified Health System (SUS). Approximately 88% of the persos o HAART had a udetectable viral load b. The curret Brazilia cliical treatmet protocol a recommeds the use of HAART i all adults with positive serology for HIV, eve without immuological impairmet 3. Brazil adopts the goal of UNAIDS, which proposes that coutries should achieve by 2020: 90% of the estimated PLHIV diagosed; 90% of the persos diagosed o HAART; 90% of the persos o HAART with udetectable viral load c. Efforts to achieve these goals should progressively icrease the umber of persos o HAART i the coutry, which will require a expaded respose from the SUS. Today, treatmet is performed i approximately 971 SUS ceters of differet sizes ad istitutioal cofiguratios 4,5. I this cotext, i additio to the essetial moitorig of adherece i the idividual cliical follow-up 6, it is urget to treat adherece from a programmatic poit of view 5,7, that is, as a idicator of the performace of health ceters. For health teams, the moitorig of the rate of adherece of patiets is aother proxy measure of the quality of care 8,9, thus servig as a idicator of the outcome of itervetios focused o promotig adherece 5,7. However, there is o cosesus i the literature o a gold stadard for measurig adherece to HAART. There are differet methods of measuremet, such as self-report, pill coutig, pharmacy records, ad electroic moitorig devices. Each method has advatages ad disadvatages, which vary accordig to the cotext ad the desired objectives 7,10,11. a Miistério da Saúde (BR), Secretaria de Vigilâcia em Saúde, Departameto de DST, Aids e Hepatites Virais. Bol Epidemiol Aids DST. 2015[cited 2016 Aug 11];4(1). Available from: br/pt-br/pub/2015/boletimepidemiologico-hivaids-2015 b Miistério da Saúde (BR), Secretaria de Vigilâcia em Saúde, Departameto de DST, Aids e Hepatites Virais. Protocolo clíico e diretrizes terapêuticas para o maejo da ifecção pelo HIV em adultos. Brasília (DF); 2013 [cited 2016 Aug 11]. Available from: tdf/pub/2013/64484/pcdt_ adulto_ pdf?file=1&type= ode&id=64484&force=1 c Joit Uited Natios Programme o HIV/AIDS : a ambitious treatmet target to help ed the AIDS epidemic. Geeva: UNAIDS; 2014 [cited 2016 Aug 11]. Available from: uaids.org/sites/default/files/ media_asset/ _e_0.pdf Self-reports as questioaires structured for iterviews or self-completio are commoly used to measure adherece, both i observatioal studies ad i the collectio of iformatio from health ceters, give their operatioal simplicity, low cost, ad possibility to address several dimesios of adherece 12. I order to moitor adherece, self-report questioaires must preset a adequate balace betwee psychometric, theoretical, ad pragmatic properties 13. Psychometric properties are related to the reliability ad accuracy of the measure, icludig the mitigatio of iformatio biases (such as memory or desirable respose biases) 14,15. These properties are usually tested by measures of validity, reliability, ad acceptability. Although there is o stadardizatio of the validatio methods, questioaires should geerally cosider validity i relatio to a cliical outcome measure (costruct validity) ad i relatio to other measures of adherece (criterio validity) 16. The theoretical properties ivolve the iterpretatio give to the measure ad the adaptatio of the istrumet to its purpose. O the other had, pragmatic properties are those that eable the implemetatio of the istrumet: low cost, o-itrusive, ca repeat the measure over time, self-applied, fast i the collectio ad orgaizatio of aswers 13. I Brazil, the methods used to measure adherece to HAART are usually o-specific ad depedet o the idividual iitiative of professioals. The lack of a stadardized resource prevets the routie ad homogeeous moitorig of the rates of adherece i health ceters ad hiders the evaluatio of the results of activities aimed at improvig adherece 17. Frequetly, oly the cliical outcome is moitored by measurig the viral load, which, however, does ot allow the detailig of what difficulties may be occurrig i the itake of the medicatio. Although the medicatio give is accompaied by the Logistic Medicatio Cotrol System (SICLOM), the use of this system is still predomiatly operatioal ad ot always aimed at moitorig adherece. To date, there are o self-report questioaires validated for routie use i SUS ceters that assist PLHIV. 2

3 This study presets the developmet ad validatio of the web versio of a self-report istrumet to moitor the average rates of the adherece to HAART i health ceters: the Web Adherece Questioaire (WebAd-Q). METHODS The WebAd-Q Questioaire was developed ad tested i a study performed betwee 2008 ad The istrumet was proposed based o literature review ad the previous experiece of the research team i assessig the adherece of persos livig with HIV ad other chroic diseases. Ispired by a self-report questioaire previously developed by the team to measure adherece to drug therapy for hypertesio 18, the WebAd-Q has bee specifically adapted to evaluate the adherece to HAART. The WebAd-Q was developed to evaluate adherece at the collective level, that is, to provide average rates of adherece for maagemet use i HIV/AIDS ceters ad i operatioal research studies. The costructio of the questioaire sought to respect the followig attributes: evaluate the mai compoets of the act ad the process of takig medicatio; have high sesitivity for o-adherece; mitigate the socially desirable respose ad memory biases; ad be easily uderstadable ad feasible for the routie services of the SUS. The aswer to the questioaire is aoymous, as the purpose of the questioaire is ot to evaluate idividual adherece, but rather to allow health ceters to periodically obtai the rates of adherece for all patiets or groups of patiets. The WebAd-Q is desiged to provide self-aswers o a computer, accessible via the Iteret d or offlie, cotaiig multimedia resources ad automatically geeratig a database of aswers of restricted access. It is formatted as a iteractive cartoo, which asks three questios about the use of medicatios i the last seve days. The texts were audio recorded so that the questioaire could be both read ad heard by the respodets. Based o ours istructios, a web desiger produced three alterate desigs for the images ad screes, from which we chose two: oe with a female image ad oe with a male image. The two drawigs, as well as the writig of the questios, were aalyzed i two phases by voluteer patiets from two health ceters with iterviews i the waitig room ad focus groups. For this stage of developmet of the istrumet, we defied a itetioal sample of 38 patiets, from both sexes, differet social strata, educatio level, ethic groups, ad differet therapeutic regimes, who are moitored at the STD/AIDS Referece ad Traiig Ceter of the State of São Paulo (CRT-DST/AIDS-SP) ad at the Cliic of Medical Specialties of São Berardo do Campo (SAE-SBC). The operatio of the aswer system ad the database was tested at CRT-DST/AIDS-SP. Based o the cosultatios made, the research team istructed the fial desig ad supported the web desiger i the desig of the applicatio. The patiets showed preferece for the female versio of the mai character. The speeches of the characters were recorded by actors, guided by the research team. d The questioaire is available at: www2.fm.usp.br/webad-q. For access, the code 1999 must be used. The WebAd-Q begis with a itroductio to the questioaire made by the character Coquetel, which explais the procedures of the questioaire ad esures the cofidetiality of the participat. The, the character Silvia appears, a patiet who is i a health ceter where she wet to get her medicatio. Silvia itroduces herself, commets that sometimes she has difficulty takig her medicatio, ad asks the respodet three questios: 1) Ad you? I the last seve days, did you take ay medicatio from your cocktail outside the time appoited by your doctor? ; 2) I the last seve days, did you stop takig ay medicatio from your cocktail? ; 3) I the last seve days, did you take more or less pills from your cocktail? (Figure). 3

4 I the last 7 days, have you take ay of your regime drugs at times other tha those scheduled by your doctor? Yes No I do ot kow/ I do ot recall I the last 7 days, have you failed to take ay of your regime drugs? Yes No I do ot kow/ I do ot recall I the last 7 days, have you take less or more pills of ay of your regime drugs? Yes No I do ot kow/ I do ot recall Figure. Screes of the questios of the WebAd-Q questioaire with the character Silvia. Possible aswers for each questio are: No (adherece aswer), Yes or I do t kow/i do t remember (o-adherece aswers). I additio to the measures for each idividual questio, we costructed a scale of o-adherece of four categories, takig ito accout all three questios: 1) o o-adherece aswer, 2) oe o-adherece aswer, 3) two o-adherece aswers, ad 4) three o-adherece aswers. For the validity study, we ivited 90 adult patiets o HAART for at least three moths at the SAE-SBC, which is a health ceter that moitored approximately 800 persos o HAART at the time of data collectio. The calculatio of the sample size had sesitivity of 80%, precisio of 10%, ad prevalece of adherece of 70% as parameters. Patiets were ivited accordig to a coveiece sample, accordig to the order of arrival i the ceter, from August to October Patiets who agreed to participate siged a iformed coset ad were istructed to use a special Medicatio Evet Moitorig System (MEMS) bottle for 60 days, whose lid has a microprocessor that is activated whe ope, recordig the date, time, ad duratio of the opeig. Participats were asked to use the MEMS for the medicatio with the highest 4

5 umber of doses or pills of their atiretroviral prescriptio, as well as ope the bottle oly whe takig the pills. They were also istructed to retur to the health ceter after 30 ad 60 days brigig the MEMS bottle. The MEMS bottle allows us to costruct two measures of adherece: MEMS dose of seve days (doses take, calculated by the umber of opeigs of the bottle i relatio to the umber of prescribed doses; we cosidered adheret patiets with % of doses take) ad MEMS time of seve days (doses take at the correct time, calculated by the umber of opeigs of the bottle i a time iterval of 15 miutes for more or less tha prescribed i relatio to the umber of doses ad time of the prescriptio; we cosidered adheret patiets with % of doses take at the correct time iterval). We also couted the pills give to the patiets at the begiig of the study, after 30 days, ad after 60 days. The patiets were istructed to retur o the thirtieth ad sixtieth day with the pills ot take, recorded as retured. We made a percetage measure o o-adherece by the umber of pills retured i relatio to the umber of pills supplied. The idividual who retured 5% or more of the supplied pills was cosidered o-adheret. O the thirtieth day, the participats reported their adherece to a traied iterviewer usig a previously tested self-report questioaire 19. After guidace, the patiet was asked to recall the last three days ad to idetify the medicatio, time, ad amout take each day. We calculated the measure of adherece by the percetage of pills take i relatio to the total of pills prescribed. We cosidered adheret the idividual who report takig 95% or more of the pills prescribed. The results of the viral load of each patiet were collected routiely i the SAE-SBC. I this ceter, viral load tests are requested from all patiets i the follow-up every four moths. For each patiet, we aalyzed the result of the viral load test closest to the aswer to the WebAd-Q, collected before or after aswerig the questioaire. As a mathematical resource to calculate the viral load log, we used the uit to express idividuals with udetectable viral load. For the aalysis of the social, demographic, ad cliical data of the participats, we calculated the absolute ad relative frequecies ad the respective 95% cofidece itervals (95%CI) of the qualitative variables, ad the medias, meas, ad respective stadard deviatios of the cotiuous variables. The WebAd-Q was aswered by the patiets at the ed of the sixtieth day of research, i a specific room for this purpose, after receivig istructios from previously traied health professioals. We asked patiets to aswer to the WebAd-Q twice, with a miimum iterval of oe hour, i order to estimate the test-retest agreemet usig the Kappa idex. We calculated the results of the WebAd-Q ad the other measures of adherece, with 95%CI. I summary, o the thirtieth day, the patiets performed electroic moitorig of doses ad time, couted the pills, ad aswered the self-report questioaire with the iterviewer. O the sixtieth day, they agai performed the electroic moitorig ad pill coutig ad respoded to the WebAd-Q. At the ed of the study, we obtaied the measure of viral load closest to the aswer to the WebAd-Q, collected routiely i the ceter. We tested the associatios betwee detectable viral load ad the aswers to the WebAd-Q, with 95%CI (p < 0.05). We used the Spearma coefficiet to aalyze the correlatio betwee the scale of o-adherece of the WebAd-Q ad the viral load log, accordig to the viral load measure closest to the aswer to the questioaire. I additio to total correlatio, we tested correlatios for differet groups of respodets, accordig to the distace betwee the date of the aswer to the WebAd-Q ad the date of viral load collectio: up to seve days, from seve to 30 days, more tha 30 days. We compared the aswers for each questio of the WebAd-Q with the other measures of adherece usig the Ma-Whitey test. 5

6 RESULTS Of the 90 ivited patiets, 74 (82.2%) aswered the WebAd-Q questioaire. The average follow-up time i the study was 60.7 days [stadard deviatio (SD) of six days]. Amog those who did ot aswer the questioaire, there were two (2.2%) refusals ad 14 (15.6%) drop-outs. Table 1 presets the sociodemographic ad cliical data of the patiets who completed the study. We observed a higher proportio of male participats, mea age above 45 years, high proportio of ie years or more of educatio, log treatmet time, reports of previous o-adherece ad adverse reactios, ad low proportio of persos who regularly use alcohol ad drugs. Amog the 74 participats i the study, four (5.4%) reported difficulty i usig MEMS, which resulted i the loss of iformatio for MEMS dose ad MEMS time i the last seve days. Two participats (2.7%) did ot complete the self-report iterview. Altogether, 17 patiets (23.0%, 95%CI ) had a detectable viral load (> 40 copies/ml) i the exam with the closest date. Table 2 shows the measures of o-adherece obtaied by the WebAd-Q questioaire ad the other methods. The aalysis of all three questios of the WebAd-Q showed a total of 49 (66.2%; 95%CI ) patiets with oe or more o-adherece aswer. Regardig the measures for each questio separately, the proportio of o-adherece was greater for questio 1 (time). I relatio to the o-adherece scale, we ca observe decreasig proportios for each category of the scale, that is, as the umber of o-adherece aswers icreases. I relatio to the other measures, the proportio of o-adherece was higher for MEMS time, followed by MEMS dose, pill coutig, ad self-report. Table 1. Sociodemographic ad cliical characteristics of the participats who completed the study o the validatio of the WebAd-Q. ( = 74) Variable, % or average Stadard deviatio Male Average age (years) Years of educatio a > Average time of diagosis (moths) Average time o HAART (moths) b Report of adverse reactio Report of prior iterruptio of the HAART Use of tobacco Use of ijectable drugs Itake of alcoholic beverage Do ot drik Less tha oce a week Weekly or more Use of marijuaa Do ot use Less tha oce a week Weekly or more Use of cocaie Do ot use Less tha oce a week Weekly or more WebAd-Q: Web Adherece Questioaire; HAART: atiretroviral therapy a Excluded or igored: = 3 (4.1%). b Excluded or igored: = 1 (1.4%). 6

7 The average time to aswer the WebAd-Q questioaire was 1 mi 53 sec (SD = 1 mi 53 sec). There was o statistically sigificat differece i the time to aswer the questioaire betwee patiets with adherece or o-adherece aswers, cosiderig all three questios (p = 0.272). No patiet reported difficulties i aswerig o the computer. Of the total umber of participats, 59 (79.7%) aswered the questioaire twice. I the test-retest, the aswers for the set of three questios of the WebAd-Q obtaied agreemet of 89.8%, with Kappa of 0.77 (95%CI ). Table 3 shows the statistically sigificat associatios betwee detectable viral load ad o-adherece aswers. The media distace betwee the aswer to the WebAd-Q ad viral load collectio was 88 days, with a iterquartile rage of 91 days. The correlatio betwee viral load log ad o-adherece degree was moderate (r = 0.476, p < 0.001), with icreasig tred accordig to the proximity of the date of viral load collectio: r = (p = 0.074) for a distace of up to seve days, r = (p = 0.122) for a distace from seve to 30 days, ad r = (p = 0.001) for a distace greater tha 30 days. Table 4 presets the compariso of the aswers for each questio of the WebAd-Q with the other measures of adherece. All measures were cosistet with the aswers obtaied by the WebAd-Q. That is, i all measures used, whe there was a statistically sigificat differece, the media adherece was higher for patiets with adherece aswers, accordig to the three questios of the WebAd-Q. Questio 2 had the best performace, showig statistically sigificat differeces betwee patiets with adherece or o-adherece aswers for all measures used, except for PC of 60 days. Table 2. Results of o-adherece, accordig to the WebAd-Q ad other methods. Measure Result % 95%CI Questios of the WebAd-Q ( = 74) No-adherece to time (Q1) No-adherece to medicatio (Q2) No-adherece to dose (Q3) Scale of o-adherece ( = 74) No o-adherece aswer o-adherece aswer o-adherece aswers o-adherece aswers Electroic moitorig ( = 70) MEMS of dose of 7 days MEMS of time of 7 days Pill coutig ( = 74) PC of 30 days PC of 60 days Iterview ( = 72) Self-report of 3 days WebAd-Q: Web Adherece Questioaire; PC: pill coutig Table 3. Associatios betwee detectable viral load ad aswers to the WebAd-Q. ( = 74) Measure Detectable viral load % OR (95%CI) p Q1 Time Adherece No-adherece ( ) Q2 Medicatio Adherece No-adherece ( ) < Q3 Dose Adherece No-adherece ( ) Total WebAd-Q: Web Adherece Questioaire 7

8 Table 4. Compariso betwee the three questios of the WebAd-Q ad the other measures of adherece. Q1 (time) Q2 (medicatio) Q3 (dose) Medidas Adherece media (mi.; max.) No-adherece media (mi.; max.) p Adherece media (mi.; max.) No-adherece media (mi.; max.) p Adherece media (mi.; max.) No-adherece media (mi.; max.) p PC 30 (32.3; 107) (52.2; 103.5) (32.3; 107) (52.2; 103.5) (32.3; 107) (56.3; 103.5) PC (64.4; 130.4) (50.6; 125) (50.6; 130.4) (70.6; 125) (64.4; 130.4) 63 (50.6; 123.2) SR (67; 200) 28 (17; 156) (67; 200) 46 (17; ) (17; 200) (17; ) MEMS D7 (43; ) (0; ) (0; ) (29; ) (29; ) 60 (0; ) MEMS T7 93 (0; ) (0; ) (0; ) (29; ) (0; ) (0; ) WebAd-Q: Web Adherece Questioaire; PC 30: pill coutig of 30 days; PC 60: pill coutig of 60 days; SR: self-report of 3 days; MEMS D7: electroic moitorig of the dose of 7 days; MEMS T7: electroic moitorig of itake time of 7 days Ma-Whitey test. DISCUSSION This study aalyzed the validity of a self-admiistered questioaire to measure adherece to atiretroviral therapy i care ceters for PLHIV, ad we observed high levels of test-retest agreemet ad good agreemet betwee the aswers ad other idicators of adherece. The associatios betwee the aswers to the WebAd-Q ad viral load suggest cosistecy of the measures of the questioaire for each questio idividually. The scale of o-adherece obtaied by the WebAd-Q had moderate correlatio whe compared to the cliical outcome evaluated by the viral load, which is similar to that obtaied by other self-report HIV questioaires 20,21. Furthermore, cosiderig the icreasig tred of this correlatio accordig to the greater proximity of the aswer to the date of viral load collectio, the results suggest that the scale of o-adherece proposed is also theoretically cosistet. The scale seems to fit the purpose of the follow-up, as it provides health professioals with a umerical ad sythetic measure of o-adherece for all patiets, which helps i the idetificatio of the most frequet types of o-adherece ad provides subsidies for compariso, replaig, ad evaluatio of strategies. This study used several measures of o-adherece, ad it obtaied differet results for this measure, from 25% i the three-day self-report iterview to 69% i the seve-day electroic moitorig measure that icluded time. This variability is expected, sice differet istrumets evaluate differet aspects of medicatio itake. The electroic moitorig records the opeig of bottles ad the pill coutig records the umber of pills ot take. The self-report records the pills take accordig to the iformatio give by the patiet. All these methods are subject to reliability problems: the opeigs of the bottle may ot match the pills take, pills may be discarded, memory o the pills take may fail, ad the aswer of the patiet may be iflueced by the iterviewer or the eviromet 22. I a systematic review, Simoi et al. 21 have show that self-report questioaires to measure adherece to HAART have their performace evaluated maily by comparig them with the cliical outcome, measured by viral load: 78% of the studies icluded i this review compared the viral load, with sigificat associatios i most cases, although without uiformity i the parameters used for the detectio of viral load (detectio limit). Approximately 35% of the studies compared other measures of adherece, such as electroic moitorig ad pill coutig. Oly 22% compared viral load with aother cocurret measure. Oe of the coclusios of the study is that the evaluatios of self-report questioaires lack methodological stadardizatio. 8

9 Give this diversity, the validatio of the WebAd-Q sought a expaded scope, based o the compariso with both viral load ad differet types of cocurret measure. Sice there is o gold stadard established ad the compariso with the cliical outcome was satisfactory, we uderstad that the criterio (or cocurret) validity by compariso with other methods caot be evaluated similarly as i studies o the accuracy of diagostic tests. Thus, if the various methods evaluate differet dimesios of adherece, we have to uderstad the compariso as a overall idicator of cosistecy betwee the measures obtaied. This study showed that the groups of patiets who provided o-adherece aswers to the WebAd-Q were also cosidered less adheret by the other methods. The questioaire esures the aoymity of the respodets, miimizig the desirable respose bias. Although the research eviromet requires iformed coset, the high o-adherece results obtaied suggest that patiets were comfortable to admit that they did ot take or that they chaged the dose of their medicatio. e Miistério da Saúde (BR), Secretaria de Vigilâcia em Saúde. HIV Aids Bol Epidemiol Aids IST jaju [citado 31 ja 2018];5(1). Available from: aids.gov.br/system/tdf/ pub/2017/65093/boletim_aids_ iteret_1.pdf?file=1&type=ode &id=65093&force=1 f The applicability study resulted i the two doctoral theses listed below. The respective articles metioed have bee submitted for publicatio: - Carvalho WMES. Avaliação da aplicabilidade de um istrumeto para aferição da adesão do paciete ao tratameto atirretroviral os serviços do Sistema Úico de Saúde que assistem pessoas vivedo com HIV [thesis]. São Paulo: Faculdade de Medicia da Uiversidade de São Paulo; Satos MA. O papel dos serviços de saúde a adesão do paciete ao tratameto atirretroviral do HIV/Aids: associações etre medidas de adesão e características orgaizacioais dos serviços do Sistema Úico de Saúde que assistem pessoas vivedo com HIV [thesis]. São Paulo: Faculdade de Medicia da Uiversidade de São Paulo; Carvalho WMES, Nemes MIB, Satos MA, Vale FC, Basso CR, Sata Helea ET. Feasibility of a self-report web-based questioaire to moitor patiets adherece to atiretroviral therapy: a qualitative study o the health providers perspective. Submitted for publicatio. - Satos MA, Nemes MIB, Sata Helea ET, Basso CR, Vale FC, Carvalho WMES, et al. Moitorig self-reported adherece to atiretroviral therapy i public HIV care facilities i Brazil: a atioal cross-sectioal study. Submitted for publicatio. The study showed the good pragmatic properties of the WebAd-Q: patiets reported o difficulties i aswerig it; the average time to aswer it was 5 mi 47 sec, which is short cosiderig that the questioaire has a itroductio ad ackowledgmets at the ed; ad the database is easily fed with aswers, which dismisses the use of typists ad ca be cosulted ad shared olie. The purpose of the WebAd-Q was to develop a maagerial istrumet for health ceters, with the provisio of averages for the o-adherece of a group of patiets i a autoomous, stadardized, aoymous, ad routie way. This would ot be possible with a istrumet that required a log time from patiets ad professioals, or if it were too complex to be aswered ad aalyzed. That is why we chose the self-reported computer questioaire, similar to the istrumets used i other studies o adherece to HAART 15,23. The developmet of the istrumet together with patiets was fudametal i this aspect, sice it esured that respodets had friedly ad iterestig graphic elemets ad questios. These attributes were show by several patiets already i the first tests of the WebAd-Q i a large HIV/AIDS ceter, the CRT-DST/AIDS-SP, where a very diverse populatio aswered the questioaire i a real-life eviromet. This study had limits regardig sample loss durig the two moths of the study, especially regardig the use of electroic moitorig bottles. Some of the drop-outs may also be related to difficulties i the use of MEMS, previously reported i the literature 24. I future studies, prior traiig of participats to facilitate the hadlig of bottles could miimize the umber of losses. Although the rate of aswers to the questioaire remaied above 82%, the decrease i sample umber reduces the statistical power of the study. This may have hidered the observatio of statistically sigificat results, particularly i relatio to the compariso with other measures, which yielded some borderlie results, but still eough for the criterio validity. Aother limit to be cosidered is that, i the cotext of the study, the cocomitat use of differet methods to measure adherece, together with viral load collectio i the routie of the health ceter, may have geerated greater attetio ad care from the patiets i relatio to the medicatio take, reducig possible memory biases whe aswerig the WebAd-Q. Regardig the sociodemographic characteristics of the participats, we ca observe the profile of users of a public health ceter i a medium-sized city i the state of São Paulo, which does ot ecessarily correspod to the profile of PLHIV i Brazil. For example, we ca observe that the study participats preseted a higher educatio level i relatio to the average profile of Brazilias livig with HIV, accordig to data from the last epidemiological bulleti o HIV/AIDS e. I view of this limitatio, the use of the WebAd-Q i the routie of the SUS was later tested i a applicability study coducted i a atioal sample of HIV ceters from differet regios of the coutry, which will be addressed i future publicatios f. 9

10 The WebAd-Q is a multidimesioal questioaire that icludes takig all medicatios at the times ad doses prescribed durig the last week, with good reliability, patiet friedly, ad feasible for routie applicatio i health ceters. Therefore, i this validatio study, the WebAd-Q showed adequate properties for the moitorig of the rates of o-adherece to HAART. The feasibility of its implemetatio i the routie of HIV ceters will be aalyzed i a atioal study, coducted after this study, which will seek to reflect the heterogeeity both of the persos uder treatmet i the coutry ad the characteristics of the health ceters that treat them. REFERENCES 1. Grageiro A, Escuder MM, Meezes PR, Alecar R, Castilho EA. Late etry ito HIV care: estimated impact o AIDS mortality rates i Brazil, PLoS Oe. 2011;6(1):e Simpso SH, Eurich DT, Majumdar SR, Padwal RS, Tsuyuki RT, Varey J, et al. A meta-aalysis of the associatio betwee adherece to drug therapy ad mortality. BMJ. 2006;333(7557): Nachega JB, Uthma OA, Del Rio C, Mugarevo MJ, Rees H, Mills EJ. Addressig the Achilles Heel i the HIV care cotiuum for the success of a test-ad-treat strategy to achieve a AIDS-free geeratio. Cli Ifect Dis. 2014;59 Suppl 1:S Nemes MIB, Alecar TMD, Basso CR, Castaheira ERL, Melchior R, Alves MTSSB, et al. Avaliação de serviços de assistêcia ambulatorial em aids, Brasil: estudo comparativo 2001/2007. Rev Saude Publica. 2013;47(1): Nemes MIB, Castaheira ERL, Sata Helea ET, Melchior R, Caraciolo JM, Basso CR, et al. Adesão ao tratameto, acesso e qualidade da assistêcia em Aids o Brasil. Rev Assoc Med Bras. 2009;55(2): Rocha GM, Machado CJ, Acurcio FA, Guimarães MDC. Moitorig adherece to atiretroviral treatmet i Brazil: a urget challege. Cad Saude Publica. 2011;27 Supl 1:S Nemes MIB, Sata Helea ET, Caraciolo JMM, Basso CR. Assessig patiet adherece to chroic diseases treatmet: differetiatig betwee epidemiological ad cliical approaches. Cad Saude Publica. 2009;25 Supl 3:S Chalker JC, Adualem T, Gitau LN, Ntagaira J, Obua C, Tadeg H, et al. Measurig adherece to atiretroviral treatmet i resource-poor settigs: the feasibility of collectig routie data for key idicators. BMC Health Serv Res. 2010;10: Ross-Dega D, Pierre-Jacques M, Zhag F, Tadeg H, Gitau L, Ntagaira J, et al. Measurig adherece to atiretroviral treatmet i resource-poor settigs: the cliical validity of key idicators. BMC Health Serv Res. 2010;10: Chesey MA. The elusive gold stadard. Future perspectives for HIV adherece assessmet ad itervetio. J Acquir Immue Defic Sydr. 2006;43 Suppl 1:S Wright EC. No-compliace or how may auts has Matilda? Lacet. 1993;342(8876): Simoi JM, Frick PA, Pataloe DW, Turer BJ. Atiretroviral adherece itervetios: a review of curret literature ad ogoig studies. Top HIV Med [cited 2016 Aug 11];11(6): Available from: Garfield S, Clifford S, Eliasso L, Barber N, Wilso A. Suitability of measures of self-reported medicatio adherece for routie cliical use: a systematic review. BMC Med Res Methodol. 2011;11: Nieuwkerk PT, Oort FJ. Self-reported adherece to atiretroviral therapy for HIV-1 ifectio ad virologic treatmet respose: a meta-aalysis. J Acquir Immue Defic Sydr. 2005;38(4): Bagsberg DR, Brostoe A, Hofma R. A computer-based assessmet detects regime misuderstadigs ad oadherece for patiets o HIV atiretroviral therapy. AIDS Care. 2002;14(1):

11 16. Berg KM, Arste JH. Practical ad coceptual challeges i measurig atiretroviral adherece. J Acquir Immue Defic Sydr. 2006;43 Suppl 1:S Caraciolo JMM, Sata Helea ET, Basso CR, Souza RA, Silva MH, Adão VM, et al. Atividades para melhoria da adesão à TARV em serviços de saúde do SUS o estado de São Paulo, Saude Soc. 2009;18 Supl 2: Sata Helea ET, Nemes MIB, Eluf-Neto J. Desevolvimeto e validação de questioário multidimesioal para medir ão-adesão ao tratameto com medicametos. Rev Saude Publica. 2008;42(4): Nemes MIB, Carvalho HB, Souza MF. Atiretroviral therapy adherece i Brazil. AIDS. 2004;18 Suppl 3:S Arste JH, Demas PA, Farzadega H, Grat RW, Gourevitch MN, Chag CJ, et al. Atiretroviral therapy adherece ad viral suppressio i HIV-ifected drug users: compariso of self-report ad electroic moitorig. Cli Ifect Dis. 2001;33(8): Simoi JM, Kurth AE, Pearso CR, Pataloe DW, Merrill JO, Frick PA. Self-report measures of atiretroviral therapy adherece: a review with recommedatios for HIV research ad cliical maagemet. AIDS Behav. 2006;10(3): Wilso IB, Carter AE, Berg KM. Improvig the self-report of HIV atiretroviral medicatio adherece: is the glass half full or half empty? Curr HIV/AIDS Rep. 2009;6(4): Bagsberg DR, Brostoe A, Chesey MA, Hecht FM. Computer-assisted self-iterviewig (CASI) to improve provider assessmet of adherece i routie cliical practice. J Acquir Immue Defic Sydr. 2002;31 Suppl 3:S Ailiger RL, Black PL, Lima-Garcia N. Use of electroic moitorig i cliical ursig research. Cli Nurs Res. 2008;17(2): Fudig: Departmet of STD, AIDS, ad Viral Hepatitis of the Health Surveillace Departmet of the Miistry of Health (Project TC 90/2008 Developmet of Istrumets for the Evaluatio of Patiet Adherece to Atiretroviral Treatmet i the SUS). Authors Cotributio: Desig ad plaig of the study: ETSH, CRB, MIBN. Collectio, aalysis, ad iterpretatio of the data: FCV, ETSH, MAS, WMESC, PRM, CRB, MHS, AMA, MIBN. Preparatio or review of the study: FCV, ETSH, MAS, WMESC, PRM, CRB, MHS, AMA, MIBN. All authors have approved the fial versio of the study ad assume public resposibility for its cotet. Coflict of Iterest: The authors declare o coflict of iterest. 11