Background
==========

The Human immunodeficiency virus (HIV) pandemic continues to spread in the population making HIV infection one of the most important public health crises in the world \[[@B1]\]. Globally, about 33.3 million persons were estimated to be infected with HIV/AIDS in 2010, of these, 22.5 million (68%) are in sub Saharan Africa and about 3 million alone in Nigeria. This makes it the country with the second highest burden of HIV and AIDS in the world after South Africa \[[@B1]\]. The current prevalence rate of HIV in Nigeria as at 2010 based on the sentinel surveillance is 4.1%. Cross River State were the study was conducted currently has the 9th highest prevalence (7.1%) in the country as at 2010 and is found in the South-south geopolitical zone of Nigeria \[[@B2]\].

In the absence of a cure, antiretroviral therapy (ART) has remained the only available option that offers the possibility of dramatically reducing HIV/AIDS-related morbidity and mortality, while improving the status of PLHIV. It has proved effective in reducing viral load, improving immune function, \[[@B3]\] and improving the quality of life of PLHIV \[[@B3],[@B4]\]. However, successful long-term treatment of HIV requires strict adherence to the Highly Active Antiretroviral Therapy (HAART) regimen \[[@B3],[@B5],[@B6]\]. This is especially important in countries such as Nigeria where PLHIV make up 10% of the global burden of HIV/AIDS \[[@B1]\] and about 1.5 million require treatment \[[@B7]\]. Adherence level of at least 95% and above has been considered appropriate to achieve therapeutic success, \[[@B8]-[@B11]\] as this maintains optimal viral suppression as demonstrated by Paterson and colleagues \[[@B11]-[@B13]\]. Failure to observe sustained desired adherence threshold has been associated with dire consequences such as treatment failure, disease progression and emergence of drug resistant HIV/IADS strains \[[@B14],[@B15]\].

With the realization of the central role played by adherence in the success of HIV/AIDS treatment, several studies conducted in various parts of the world including reviews have reported non-adherence rates ranging from 50% to 80% in different contexts \[[@B9],[@B10],[@B16]\]. However, in reality adherence rates are often lower than 95% \[[@B11]\] and rates of adherence from previous studies conducted in Nigeria have ranged from as low as 44% being adherent \[[@B17]\] to more than 95% from different parts of Nigeria \[[@B18]\]. Most of the previous reports were carried out with fewer PLHIV being on treatment restricted access to ARV drugs unavailability and payment for ARV medications were heavily subsidized.

With wide spread awareness of HIV/AIDS, expansion of treatment and prevention programs that have increased ART access to previously un-served and underserved populations in Nigeria coupled with provision of free ART services, \[[@B19]\] there is a need for implementation of continuous monitoring and evaluation mechanisms for adherence, This is of great importance especially because the key to the success of ART programmes and prevention of treatment failures is hinged on consistently high adherence levels. Scaling up of ARVs alone is definitely not the answer when adherence inconsistencies are not tackled. Therefore, the first step to solving this problem is to assess the determinants of adherence to HAART which may differ across geopolitical zones of the country with their unique characteristics of culture, religion, educational status and health seeking behaviours. The objectives of the present study were to determine the prevalence of adherence to HAART and identify factors associated with adherence.

Methods
=======

The study was conducted at the President's Emergency plan for AIDS Relief (PEPFAR) clinic now the Specialist treatment clinic of the University of Calabar Teaching Hospital. The Hospital was selected as a centre for the implementation of the President's Emergency plan for AIDS Relief (PEPFAR) by the United States Agency for International Development (USAID) in June 2005. It has since been responsible for the provision of care and support services for PLHIV as well as one of the major centres where PLHIV both in Cross River and other neighbouring states receive anti retroviral therapy. The patient population is about 4,000, of which more than 2,000 are on treatment. The clinic is run under three units. The paediatric adult and the Prevention of Maternal to Child transmission (PMTCT) clinics.

Study population
----------------

The study population comprised of 411 HIV positive clients who were enrolled and had commenced HAART in UCTH from October 2011- December 2011. They were made of 129 males and 282 females. Participants were consecutively recruited over the study period till the desired sample size was attained. All PLHIV on HAART were eligible to participate except those that satisfied the exclusion criteria. These criteria included PLHIV below 18 years of age, who were attending the clinic but had not commenced HAART, terminally ill patients and pregnant women. The inclusion criteria adopted for the study included consenting out patients diagnosed and confirmed to be HIV positive, at least 18 years of age and had been on HAART for 3 months.

Study design
------------

A cross-sectional analytical study aimed at documenting the level of adherence among PLHIV on HAART was conducted between October 2011- December 2011.

Data collection instrument
--------------------------

This consisted of an interviewer administered semi-structured questionnaire which was divided into sections to collect relevant information on socio-demographic data, medical profile including treatment experiences at health facility of respondents. Adherence to HAART in the previous seven days of the interview was measured by self-report. The questions were adopted from The Brief Medication Questionnaire self-report tool for screening adherence and barriers to adherence \[[@B20]\]. The degree of adherence from patient self-reporting was estimated using the following formula: \[[@B21]\]

$$\begin{array}{l}
{\%\ {Adherence}\ {over}\ {last}\ 7\ {days}} \\
{\quad = \frac{\#{doses}\ {should}\ {have}\ {taken}‒\#{missed}\ {doses} \times 100\%}{\#{Doses}\ {should}\ {have}\ {taken}}} \\
\end{array}$$

Then, the percentage of adherence to the antiretroviral was estimated by the average of adherence to the drugs. For the purpose of this study a score of 95% and above represented good adherence and less than 95% was rated as having poor/suboptimal adherence.

Data analysis
-------------

Data were analyzed using SPSS for windows version 19.0. Descriptive and inferential statistical tests were employed. These included bivariate (chi-square) and multivariate (logistic regression) analysis to determine correlates or predictors of adherence. Descriptive statistics (frequencies, proportions, means and standard deviation to summarize variables while Inferential statistics (chi square Test) was used to test the significance of association between categorical variables and level of significance was set at 5%. Logistic regression analysis was used to identify the predictors of adherence to HAART in the study population. Variables entered into the logistic model were those which had earlier been significantly associated on bivariate analysis at 10% significance derived. Predictors were determined at 5% significance.

Ethical clearance and consent
-----------------------------

The ethical Committee of the University of Calabar Teaching Hospital reviewed and approved the study procedures and data collection instruments.

Results
=======

Four hundred and eleven eligible respondents receiving HAART at the PEPFAR clinic UCTH were studied. The mean age of respondents was 35.7 ± 9.3 years. The largest proportion of the PLHIV 171 (41.6%) were in the age group 25-34 years, followed by 136 (33.1%) in the 35 to 44 age group. The majority of those interviewed were female; 68.6% and currently married 51.8%. More than a third 39.7% had attained at least secondary education and 38.4% were of the skilled non manual occupational group. Also majority 85.9% resided within the state and 67.4% earned less than the minimum wage in Nigeria (\<*N*19,000) monthly which is equivalent to \$118.75. Almost all (99.8%) respondents interviewed were Christians (Table [1](#T1){ref-type="table"}). The Medical profile of respondents interviewed (Table [2](#T2){ref-type="table"}) revealed that more, 183 (44.5%) had been on HAART for more than 24 months. The median duration on HAART was 24 months (range 3--192 months). More than half of the study population 226 (55%) had encountered side effects since the commencement of HAART and majority 273 (66.4%) were not using any form of herbal treatment alongside their antiretroviral medications. Furthermore, a little over two-thirds of the respondents 282 (68.6%) were on at least 2 pills per day and a vast majority 386 (93.9%) perceived their health status as improved since their commencement on HAART. A few respondents 49 (11.9%) of the study population reported paying for services at the treatment site.

###### 

**The Socio**-**demographic characteristics of study participants** (**n** = **411**)

    **Characteristics**                  **Frequency**    **Percentage**
  ------------------------------------- ---------------- ----------------
    **Age group(years)**                                         
    \<25                                       31              7.5
    25-34                                     171              41.6
    35-44                                     136              33.1
    45-54                                      53              12.9
    \>55                                       20              4.9
    **Sex**                                                      
    Male                                      129              31.4
    Female                                    282              68.6
    **Marital status**                                           
    Single                                    126              30.7
    Married                                   213              51.8
    Divorced                                   36              8.8
    Widowed                                    36              8.8
    **Educational status**                                       
    None                                       19              4.6
    Primary                                    66              16.1
    Secondary                                 163              39.7
    Post secondary                            163              39.7
    **Occupation**                                               
    Professional/managerial/technical         126              30.7
    Skilled manual                             41              10.0
    Skilled non-manual                        158              38.4
    Unskilled/unemployed/retired               86              20.9
    **Religion**                                                 
    Christianity                              410              99.8
    Islam                                      1               0.2
    **Place of residence**                                       
    Within Cross river                        353              85.9
    Outside Cross river                        58              14.1
    **Average monthly income**                                   
    \<*N*19,000                               277              67.4
    ≥*N*19,000                                134              32.6
    **Median(range)**                    7000(0--5,000)          

###### 

**Medication**/**treatment variables including treatment experiences** (**n** = **411**)

    **Characteristics**                                                        **Frequency**      **Percentage**
  ------------------------------------------------------------------------- -------------------- ----------------
    **Duration of treatment(months)**                                                                    
    \<12                                                                            120                29.2
    12-24                                                                           108                26.3
    \>24                                                                            183                44.5
    **Median duration of treatment(range)**                                  **24(3**--**192)**          
    **Encountered side effects**                                                                         
    Yes                                                                             226                55.0
    No                                                                              185                45.0
    **Herbal use**                                                                                       
    Yes                                                                             138                33.6
    No                                                                              273                66.4
    **Number of pills/day**                                                                              
    ≤2                                                                              282                68.6
    3-4                                                                             112                27.3
    \>4                                                                              17                4.1
    **Presence of opportunistic infection**                                                              
    Yes                                                                              32                7.8
    No                                                                              379                92.2
    **Paid for ART services**                                                                            
    Yes                                                                              49                11.9
    No                                                                              362                88.1
    **Perceived health status as improved   since commencement of HAART**                                
    Improved                                                                        386                93.9
    No improvement                                                                   25                6.1
    **Perceived health rating**                                                                          
    Excellent                                                                        39                9.5
    Very good                                                                       253                61.6
    Good                                                                             92                22.4
    Fair/poor                                                                        27                6.6
    **Transportation cost to Health facility**                                                           
    \<*N*1000                                                                       275                66.9
    ≥*N*1000                                                                        136                33.1

Prevalence of adherence to HAART in the study population showed that more than half (59.9%) of the respondents' attained 95% adherence to prescribed HAART regimen. The main reasons cited for missing or skipping doses among respondents who missed their medications included being busy (43.8%), simply forgetting (31.1%), depression (20%), frequent travelling (14.8%) and inconvenient timing for medications schedule (12.7%). This is represented in Figure [1](#F1){ref-type="fig"}.

![Reasons for missing/skipping medications.](1471-2334-13-401-1){#F1}

Factors associated with adherence on bivariate analysis (Tables [3](#T3){ref-type="table"} and [4](#T4){ref-type="table"}) were; Being resident outside Cross river state, 42 (72.4%) was significantly more likely to adhere to HAART compared with 204 (57.8%) being resident within the state (p \< 0.05). Similarly other significant correlates of adherence included obtaining free ART services, perceived health status as excellent/good and paid more than *N*1000 on transportation to the health care facility (p \< 0.05) (Table [4](#T4){ref-type="table"}). The predictors of adherence to HAART amongst PLHIV accessing treatment in PEPFAR clinic UCTH were non use of herbal remedies, obtaining free ART services, perceived improvement in health status, and reduced pill load. Participants not using herbal remedies were more likely to adhere to their prescribed doses compared with those using herbal remedies. Similarly obtaining free ART services, taking not more than two pills per day, and a perceived improvement in health following the commencement of HAART than those who paid for ART services, took more than 2 pills per day, and who reported their perceived health status as not improved. This is presented in Table [5](#T5){ref-type="table"}.

###### 

**Distribution of socio**-**demographic characteristics**, **of the study participants by their ART adherence pattern**

  **Characteristics**                  **Good adherence**   **Poor adherence**   **Significance**
  ----------------------------------- -------------------- -------------------- -------------------
  **Age (years)**                                                                         
  ≤35                                      137(58.3)             98(41.7)            p = 0.46
  \>35                                     109(61.9)             67(38.1)        *x*^**2**^ = 0.55
  **Sex**                                                                                 
  Male                                      78(60.5)             51(39.5)            p = 0.864
  Female                                   168(59.6)            114(40.4)        *x*^**2**^ = 0.02
  **Marital status**                                                                      
  Married                                  133(62.4)             80(37.6)            p = 0.27
  Not married                              113(57.1)             85(42.9)        *x*^**2**^ = 1.23
  **Level of Education**                                                                  
  None                                      11(57.9)             8(42.1)                  
  Primary                                   36(54.5)             30(45.5)             p= 0.47
  Secondary                                 94(57.7)             69(42.3)        *x*^**2**^ = 2.54
  Tertiary                                 105(64.4)             58(35.6)                 
  **Residence**                                                                           
  Within Cross river                       204(57.8)            149(42.2)          **p = 0.035**
  Outside Cross river Herba                 42(72.4)             16(27.6)        *x*^**2**^ = 4.43
  **Occupation**                                                                          
  Professional managerial/Technical         80(63.5)             46(36.5)                 
  Skilled manual                            23(56.1)             18(43.9)             p= 0.74
  Skilled non manual                        94(59.5)             64(40.5)        *x*^**2**^ = 1.24
  Unskilled/unemployed/retired              49(57.0)             37(43.0)                 
  **Average monthly income**                                                              
  ≤ N19,000                                163(58.8)            114(41.2)             p=0.55
  \>N19,000                                 83(61.9)             51(38.1)        *x*^**2**^ = 0.36

###### 

**Distribution of Medical profile**/**treatment experiences of the study participants by their ART adherence pattern**

    **Characteristics**                            **Good adherence N = 246 Frequency (%)**   **Poor adherence(N = 165)Frequency (%)**     **Significance**
  ----------------------------------------------- ------------------------------------------ ------------------------------------------ -----------------------
    **Use of Herbal remedies**                                                                                                                      
    Yes                                                            74(53.6)                                   64(46.4)                         p = 0.07
    No                                                            172(63.0)                                  101(37.0)                     *x*^**2**^ = 3.36
    **Number of pills/day**                                                                                                                         
    ≤**2**                                                        161(57.1)                                  121(42.9)                         p = 0.091
    \>2                                                            85(65.9)                                   44(34.1)                     *x*^**2**^ = 2.85
    **Opportunistic infections**                                                                                                                    
    Yes                                                            18(56.2)                                   14(43.8)                         p = 0.665
    No                                                            228(60.2)                                  151(39.8)                       *x*^2^ = 1.88
    **Paid for ART services**                                                                                                                       
    Yes                                                            21(42.9)                                   28(57.1)                   **p** = **0**.**01**
    No                                                            225(62.5)                                  137(37.8)                     *x*^**2**^ = 6.69
    **Rating of Perceived Health**                                                                                                                  
    Excellent/good                                                238(62.0)                                  152(39.4)                   **p** = **0**.**01**
    Fair/poor                                                      8(29.6)                                    19(70.4)                     *x*^**2**^ = 10.1
    **Perceived health status**                                                                                                                     
    Improving                                                     234(60.6)                                  152(39.4)                         p = 0.21
    Not improving                                                  12(48.0)                                   13(52.0)                     *x*^**2**^ = 1.56
    **Encountered side effects**                                                                                                                    
    Yes                                                           126(55.8)                                  100(44.2)                         p = 0.061
    No                                                            120(64.9)                                   65(35.1)                     *x*^**2**^ = 3.52
    **Cost of transportation to health centre**                                                                                                     
    \<*N*1000 (\$ 6.25)                                           154(56.0)                                  121(44.0)                   **p** = **0**.**023**
    \>*N*1000 (\$ 6.25)                                            92(67.6)                                   44(32.4)                     *x*^**2**^ = 5.14
    **Duration on HAART(months)**                                                                                                                   
    \<24                                                          116(60.1)                                   77(39.9)                         p = 0.864
    ≥24                                                           130(59.6)                                   88(40.4)                      *x*^2^ = 0.029

###### 

Binary logistic regression analysis of predictors for good adherence

    **Independent Variable**                        **Odds ratio**   **95%confidence interval**    **p-value**
  ------------------------------------------------ ---------------- ---------------------------- ---------------
    **Use of herbal remedies**                                                                           
    No                                                   1.83                1.22- 2.72           **0**.**003**
    Yes                                                   1                                              
    **Paid for ART services**                                                                            
    Yes                                                  0.46                0.25- 0.87           **0**.**017**
    No                                                    1                                              
    **Pill number**                                                                                      
    ≤2 pills/day                                         1.84                1.25-2.72            **0**.**002**
    \>2 pills/day                                         1                                              
    **Description of perceived   health status**                                                         
    Improving                                            3.11                1.58-6.11            **0**.**001**
    Not improving                                         1                                              
    **Residence**                                                                                        
    Outside Cross river                                  0.76                0.40-1.47                0.42
    Within Cross river                                    1                                              
    **Encountered side effects**                                                                         
    Yes                                                  0.92                0.65-1.29.               0.61
    No                                                    1                                              
    **Transportation costs**                                                                             
    \<*N*1000 (\$ 6.25)                                  0.76                0.50-1.16                0.20
    ≥*N*1000 (\$ 6.25)                                    1                                              

Discussion
==========

The present study aimed to contribute towards addressing gap in knowledge regarding the prevalence and factors associated with treatment adherence among a representative sample of PLHIV accessing treatment site in Cross River State Nigeria.

The self reported adherence reported in the present study was 59.9%. This finding was comparable with other studies done in Nigeria and other African setting, \[[@B21]-[@B23]\] but slightly higher than earlier reports by Ilyasu and colleagues in Kano (Northern Nigeria), \[[@B18]\] Nwauche and colleagues (Southern Nigeria) and a study done in Kenya, who reported adherence levels of 54.5%. 49.2%and 43.2% respectively. However adherence level reported in this study was lower than seen in other studies \[[@B22],[@B24]-[@B26]\]. Our current findings showed that about two fifths of patients interviewed were non adherent both in terms of dose adherence and timing. Emphasis should therefore be placed on adherence to HAART especially during counselling sessions as this is required for optimal clinical response and complete viral suppression.

The major reasons cited by participants for missing doses included; operating a busy schedule and simply forgetting medications. These two reasons though related to one another have been cited by several studies as the main risk factors for suboptimal adherence \[[@B21],[@B23],[@B27]-[@B29]\]. Another important reason given by respondents for skipping or missing medications which is note worthy was feeling depressed. Approximately a fifth of the study population indicated feeling depressed as a reason for poor adherence to medications. This was similar to findings conducted in USA in 2010 where patients with symptoms of depression had higher rates of suboptimal adherence \[[@B30]\]. Issues bothering around stigma and discrimination, personality traits, fear of being discovered, lack of social support, and poorer health outcomes may contribute strongly to emotional non-adjustment to HIV/AIDS, depression and loss of interest in ones treatment. This would ultimately result in poor adherence to medications amongst PLHIV.

Most socio-demographic characteristics such as age, sex, marital status, educational attainment did not significantly affect adherence levels amongst our study population. This corroborates the findings of some authors \[[@B17],[@B28],[@B31],[@B32]\] but refutes the findings of others were certain socio-demographic variables were associated with being adherent to HAART \[[@B24],[@B33]\].

Medication adherence was found to be significantly associated with non use of Traditional herbal medicines. The effect of the use of herbal remedies in addition to HAART was noted in this study. Non herbal use was demonstrated as a significant predictor of adherence in this study. This finding is in agreement with a study conducted in Ilorin, (south western Nigeria) were the use of herbal medicines was a major risk factor for non adherence \[[@B34]\] and a study done in South Africa by Peltzer et al. which demonstrated non use of herbal remedies as a major facilitator of adherence \[[@B26]\]. The reason respondents may consider using herbal remedies could be attributable to the fact that some patients may gradually be losing faith in their anti-retrovirals which most are aware does not provide a cure and are opting for herbal remedies. Secondly, the proliferation of alternative healers and a claim on the media by traditional medicine practitioners of an instant cure for HIV infection may cause some to abandon their treatment.

Pill burden also significantly affected adherence in the present study. Respondents on more than two pills per day were less likely to adhere to their treatment compared to those on at least two pills per day. This finding was also identified as a significant predictor of adherence in a study done by Falang and colleagues in Jos \[[@B25]\] and Sow et al. in Senegal \[[@B35]\] where pill burden was reported to have a strong impact on adherence. Similarly, in India Cauldbeck et al. demonstrated that patients who attained 100% adherence took fewer pills \[[@B36]\]. This could be attributable to the fact that these patients probably because of their busy schedules may have been unable to incorporate their drugs schedule into their daily schedule or may be developing pill fatigue. Reducing pill load as well as dosing schedules to once or twice daily has been found to be associated with better adherence \[[@B25]\].

Self reported improved health status was significantly associated with adherence amongst our study population. The odds of adherence among those who rated their health status as improved was three times compared to those who perceived their health as not improved. This study was in agreement with another study \[[@B37]\] where staying healthy was a key motivator of adherence to treatment. In contrast to our findings, Olowookere and colleagues in south western Nigeria reported that feeling good/healthy, were risk factors for non-adherence. They further reported that most patients tend to abandon treatment once there was an improvement in their health \[[@B21],[@B23]\].

Obtaining free treatment at ART clinics was a significant predictor of adherence to treatment. Respondents who didn't pay for obtaining ART services were two times better adherers compared to those who paid for services. This was in keeping with studies done in the south western part of Nigeria, \[[@B33]\] and another study done in Botswana when cost were removed as a barrier, adherence was predicted to increase from 54% to 74% \[[@B11]\]. Financial constraints among respondents were a major deterrent to adherence as observed in this study. Although drugs were given free of charge in most health facilities offering ART services, patients are still required to pay some user fees at health facility e.g. opening of folders, certain laboratory investigations and treatment of opportunistic infections. In addition there are some indirect costs these patients bear e.g. cost of transportation to the health care facility. Non-payment of services at every HAART clinics should be enforced and providing free treatment for opportunistic infections will also go a long way in improving adherence.

Certain limitations of this study should be recognized. The cross-sectional nature of the survey did not allow for inferences to be drawn as to causal relationship among variables. The use of self report medication adherence to assess medication adherence was a limitation in this study since participants had to recall their medication adherence in the previous week. Concerted efforts were made to reduce recall bias by limiting recall of medication to 7 days prior to the study which was in itself a limitation because of the possibility that subjects would either over- or underestimated their adherence to HAART. This was further worsened by the inability to corroborate patient self- report of adherence with viral loads and CD4 responses because of financial and logistic constraints of frequent laboratory monitoring. This was because restricted access to patient's folders.

Conclusion
==========

This study showed that medication adherence rate was low among PLHIV accessing treatment in UCTH Calabar, Nigeria. It is also obvious that there are barriers to adherence therefore efforts should be targeted and assessed for each patient so that appropriate adherence enhancing interventions can be undertaken. The authors therefore recommend that non-payment of services at every ART clinics and provision of free treatment should also include opportunistic infections and required investigations. This will go a long way in improving adherence. Also the focus during counselling sessions should discourage the use of traditional herbal remedies alongside HAART which has been seen to affect adherence in the present study. In addition, curtailing the activities of Alternative medical practitioners in the country claiming to have found a cure for HIV/AIDS would be of immense help. Pharmaceutical companies involved in manufacture of ARVs should ensure that all recommended ARV regimens should consist of not more than two pills per day.

Abbreviations
=============

AIDS: Acquired immune deficiency syndrome; ART: Antiretroviral therapy; HAART: Highly active antiretroviral drugs; HIV: Human Immunodeficiency virus; PEPFAR: President's Emergency plan for AIDS Relief; PMTCT: Prevention of Maternal to Child transmission; PLHIV: People living with HIV/AIDS; UCTH: University of Calabar Teaching Hospital; USAID: United States Agency for International Development.

Competing interests
===================

The authors declare that they have no competing interests.

Authors\' contributions
=======================

OA conceived, designed and coordinated the study, she carried out statistical analysis and drafted the manuscript; OE contributed by means of her competence and experience in reviewing the manuscript critically for its intellectual content and also participated in the conception and design of the study. IO and OA participated in the design of the study, questionnaire and critically reviewed the manuscript. All authors read and approved the final manuscript.

Pre-publication history
=======================

The pre-publication history for this paper can be accessed here:

<http://www.biomedcentral.com/1471-2334/13/401/prepub>

Acknowledgements
================

The authors would like to thank the staff of the President's Emergency plan for Aids Relief (PEPFAR) clinic in the department of Family Medicine, University of Calabar Teaching Hospital for the support and assistance during the collection of data.
