ABSTRACT

1. ABSTRACT Compliance to Anti-Retrovirals: The Impact of Adherence-Enhancers on Patients .Muko KN, Meiburg A, Shu EN, Chick S Institution: Catholic Health Services, Bamenda Cameroon.P.O. BOX 82 CAMERON Problem Statement: Adherence (compliance) to anti-retroviral (ARV) medication is an essential factor for therapeutic success and for favourable clinical outcomes. Some studies have identified low adherence and associative factors among patients. The adherecents (adherence-enhancers) cited here refer to attributes that may directly increase compliance to ARVdrugs. Objectives: To assess the impact of adherecents on compliance in patients taking anti-retroviral drugs.Study Design: Cohort controlled study. Non-randomized, utilizing qualitative data from self-reported questionnaires.Setting: Primary treatment centre for HIV/AIDS using patient records. Regional hospital providing health care services to a polulation of over 170.000 people. Study Population: One hundred and sixty six patients divided in two groups of eighty-three (study and control group) were involved in the study carried out between November 2002 and July 2003. Inclusion criteria were all patients in the institution willing to take part in the survey whose CD4 counts were less than 600 at the time of the commencement of study. Exclusion criteria was those who had been on treatment for less than 3 months or had been recently transferred to the institution within the previous three months, and those whose CD4 count was less than 50 . Seventy-nine of the study group and seventy-six of the control group completed the study. Intervention: Adherence-enhancers utilized in the study for a period of six months included provision of free drugs for opportunistic infections, free laboratory monitoring (except CD4 counts), voluntary counseling and testing (VCT) for relations of victims, and active involvement of at least two relatives of victims in care management.Outcome Measures: 1) Percentage of patients who a) missed taking their drugs; b) stopped taking drugs; c) followed precautions and advice in both groups. 2) Average changes in level CD4 cell counts. Results: Results show that the use of self-reported adherence is as accurate as CD4 counts. Adherence was significantly higher (P<0.001) with patients in the study group compared with those in the control group. Patients perceived that involvement of relatives in management and provision of free VCT to relatives had a greater impact on adherence than provision of free drugs for opportunistic infections and free laboratory investigations. Conclusion: Adherence-enhancers could be a useful tool to improve compliance in patients on anti-retrovirals. Most useful may be those targetting socio-cultural factors militating against taking of anti-retrovirals Funding body:Inter Care/Njinikom Project Hope

2. INTRODUCTION HIV/AIDS poses a formidable challenge to policy makers over the world today. Nowhere is the problem as crucial as in sub-saharan countries where infection rates as high as 30% amongst adults have been recorded.(1) In recent years, major advances have been made in the care of HIV/AIDS patients, particularly in antiretroviral treatment which have dramatically improved survival and quality of life. Lately increased efforts to provide greater access to Highly Active Antiretroviral Therapy(HAART) is resulting in increased availability of cheaper generic products to patients in sub-saharan Africa. Unlike treatment for other chronic diseases, achieving the full benefit of HAART requires an extremely high level of adherence to potent antiretroviral combinations. This is often difficult to achieve given the high pill burdens, drug interactions and adverse events associated with treatment. Furthermore, treatment-related toxicities, a high prevalence of metabolic complications with unknown consequences in the future affect adherence to these medications. Other multiple factors that have been shown to be related to adherence include gender, racial/ethnic distribution, age, personality traits, education, alcohol use and others.(2) A consequence of poor adherence is low therapeutic drug levels leading to HIV replication and increased drug resistance .

3. Non-adherence thus poses an immediate threat to individuals who develop resistant forms of the virus as well as a public health threat if those individuals pass on treatment-resistant forms of the virus. The aim of providing and maintaining therapeutic benefit necessitates that clinicians develop and employ practical and relevant strategies to support antiretroviral adherence. Such strategies have been employed in treatment of tuberculosis in Haiti(3).These adherent-enhancers(adherecents) have been shown to lead to increased therapeutic success . The Republic of Cameroon with a 12% prevalence rate has been making concerted efforts to provide HAART to HIV/AIDS victims.The Cameroonian government has ensured the availability of HAART at $1/day for patients at over a dozen pilot treatment centres in the country.In addition to the cost of the drugs, patients pay for laboratory tests,drugs for opportunistic infections and also the cost of managing side effects.Unlike other settings were treatment with HAART is being carried out, the cost of therapy was shown to be the prime factor militating against adherence in one of the affiliated HIV/AIDS treatment centres (Njinikom). It is located in a rural area in the North West province of Cameroon with over 65% of the population (mostly subsistent farmers) living on less than $1/day.The community with the help of a British N.G.O(Inter Care) have put in place an HIV/AIDS prevention/care/treatment programme.The paper reports on an intervention to increase adherence amongst patients on HAART in this centre.

4. METHODS A focus group discussion was held with all the prescribers(4),half of the counselors(8)(all of whom had been randomly assigned numbers and those with even numbers selected),half of the patients support group(PLWHA)(20) who were all on HAART and had been selected using the same format as the counselors.The focus group discussion identified four major factors that militate against adherence which could be easily addressed as; a)stigma b)patients forgetting to take medication c)cost of associated medication(for opportunistic infections, to mitigate/alleviate/ treat side effects of antiretroviral) d)inadequate information e)cost of laboratory investigations. Between November2002 and July 2003,patients who were qualified for treatment with HAART(with normal values for basic organ tests i.e.. Liver,kidney etc ) and who indicated an ability for contineous payment for antiretroviral therapy were recruited for the study.All the patients (166) met the following criteria; a)were above 18years, b)CD4 lymphocyte counts of <600cells/ul, c)had been taking antiretrovirals for at least 3 months d)were not living alone.Patients were allocated numbers and separated into two groups based on odd and even numbers.In addition to the approval from the health service ethical committee,the purpose of the study was explained to the patients and their consent obtained .

5. To one group, patients were encouraged to involve close relations in the management of the illness which entailed disclosing his/her status to at least two member of the family with whom he/she is living and joining the support group of people living with HIV/AIDS.In turn some drugs for opportunistic infections and treatment of side effects (which had been previously identified by the FGD)were provided free of charge to members of this group alongside subsequent laboratory monitoring services apart form subsequent CD4 cell counts.An initial baseline CD4 count was taken for all participants.In addition “follow-up counselors” who were mostly reverend sisters were assigned to members of this group and either visited them at home or made appointments with them at the hospital premises at least once in a month.These services were not provided to the other group principally as a result of inadequacy of resources.History, laboratory data was prospectively recorded for a 7 month period between November 2002 to July 2003 .This was done alongside a pretested questionnaire design to elicit information with respect to number of pills missed,discontinuation of therapy for at least 1 week, adherence to 5 mainadvices/precautions.Adherence was defined as number of pills taken over those prescribed, number of advices/precautions(out of 5 key ones) followed.Non-adherence was defined as being below 80% for above parameters or those who had stopped taking drugs for at least 1 week. The time point for data collection were 1) at every refill visit for drugs which was on a monthly basis b)at every CD4 count test which took place every six months.

6. OBJECTIVES The objectives of the study were to identify factors that could improve on the uptake of antiretrovirals and evaluate the impact of these factors on adherence. Study questions included Which are the factors that militate against adherence to antiretrovirals? What is the impact of interventions aimed at addressing these factors on adherence?

7. DEMOGRAPHIC DATA OF RESPONDENTS STUDY GROUP CONTROL GROUP Age(years) median 38 37 mean 34 33 min/max 18-59 18-61 Sex (male/female) 49/34 47/36 Income >$2/day 43 48 Above 7years formal education 61 65 Marital status(married/single/widowed) 41/23/19 39/24/20

8. ADHERENCE AND TREATMENT DURATION

9. FIG II MEAN INCREASES IN CD4 CHANGES AFTER MONTHS Mean CD4 increases Patients baseline CD4 ranges

10. A majority of the respondents were subsistent farmers 73% of whom earn less than $2 a day.This implies that fewer people would be able to afford HAART at $1/day(which is the cost in Cameroon).More males can afford for HAART than female because of a higher income earning capacity.A majority(68% were literate. Respondents identified factors that militate against adherence as stigma (67%),cost treatment(63%),feeling of being well(39%), side effects(18%). As shown in fig I adherence slowly increased with duration of treatment for both groups. This was for the parameter for missed dose and precautions/advice. However a greater increase in adherence was observed for the study group.With time some patients stopped taking the drugs as a result of cost, side effects and feeling of being treated. This was more prominent in the control group. Increased adherence correlated with increases in CD4 counts as shown in fig II. The increase was more significant(p>0.001) with the study group .A greater increase in mean CD4 was observed for the patients with lower baseline CD4 than those with higher CD4. Patients responded that active participation of relations/friends had the greatest impact(52%), compared to continuous follow up counseling(20%)free palliative drugs(20%)and free laboratory test(8%). Four patients died,two moved and five completely discontinued treatment.

11. IMPLICATIONS/CONCLUSIONS To maximize the potential of each drug and drug combination, targeted efforts to increase and maintain excellent adherence in the real-world clinical setting are essential, and are second in importance only to the more widespread availability of HAART .Provision of increased access to HAART without addressing the factors that militate against compliance does not address the issue of treatment of HIV/AIDS. In Africa, the most afflicted continent,the greatest resource for treatment is the external family system. Thus patients whose income cannot pay for HAART are supported by relations. Unfortunately most patients do not benefit from this resource because of stigma. The paper has shown that stigma can be addressed by involving relations of the victims in management.In addition , involvement of relations will increase provision of HAART to spouses of victims who hitherto may not be aware of the status of their spouse.Furthermore a greater involvement of relations leads to an increased uptake similar to the Direct Observational Therapy (DOT) for tuberculosis. A lot of attention is presently being focused on a reduction in the cost of drugs at the detriment of other allied services. In the Cameroonian case, the cost of laboratory services, transportation, treatment of side effects far outweighs the fixed cost of antiretrovirals.Increased access and availability of these services will increase adherence to HAART.

12. Continuous provision of “follow up” counseling ensures that recent information on management is provided to the patient, his/her queries and other needs are immediately addressed and other support services are provided.Patients stopped taking medication because they felt better(in some cases they thought they had been treated), or as a result of side effects. Clarifying such issues is vital for therapy. In some cases, the side effects were mostly cosmetic which did not necessitate discontinuation of therapy, information which could have been provided by counselors.Unfortunately this calls for a great deal of manpower for counseling services. The theoretical basis for improving adherence exists, but more substantial research is required. The paper has shown that factors that may increase adherence may not be clinically related. This is crucial in settings were socio-cultural factors have a great deal to play as it is the case in Africa.A closer look at these adherecents is needed to increase a favourable uptake of HAART.