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Adherence to Highly Active Antiretroviral Therapy


The human immunodeficiency virus (HIV) is a life-threatening retrovirus that progressively destroys the body's immune system. Acquired immune deficiency syndrome (AIDS) is the disease state resulting from infection with HIV. Deaths are usually due to secondary infections such as pneumonia or tuberculosis rather than the HIV infection itself.

HIV is prevalent worldwide, and the number of newly infected people continues to rise. More than 6,500 new HIV infections occur every day, and more than 2 million deaths are associated with HIV annually. 1 An estimated 25 million deaths have occurred since the onset of the epidemic in the mid-1980s.

The HIV virus replicates over many months to years. The amount of replicated virus in the blood is known as the viral load. The strength of the body's immune system is measured by the cluster of differentiation cell count (CD4).1,2 A patient is diagnosed with AIDS when his or her CD4 count is below 200 cells/mm3. If replication of the HIV virus is suppressed and the CD4 count is maintained above 200, the patient's ability to maintain a strong immune system is prolonged. This leads to a longer lifespan and a better quality of life.2


Treatment for HIV

Highly active antiretroviral therapy (HAART) suppresses viral replication and is an essential tool in the management of patients with HIV. The goal of treatment with HAART is to prevent AIDS and fatal secondary infections, thus prolonging life. 3,4 Since 1996, the success of HAART has changed HIV from a fatal virus to a treatable chronic illness.5

In recent years, additional pharmacologic treatments have become available. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) are newer components of HAART that prevent the breakthrough of drug-resistant virus.6 As of fall 2013, the FDA had approved 35 antiretroviral medications for use in the United States.

Many factors can affect the ability of HAART to suppress viral replication. These include drug regimen, laboratory monitoring and inadequate adherence to therapy.7 A qualitative study by Beusterien et al8 found that a major problem contributing to inadequate adherence is the complexity of medication regimens. Newer HAART medications offer reduced pill counts, reduced dosing frequency and fixed-dose combinations of medications. Beusterien stated that patients on fixed-dose combinations reported greater than 95% adherence and improved patient satisfaction.


Importance of HAART Adherence

The major determinant of HAART therapy success is sustained optimum adherence.9 Several studies have determined that an adherence rate of greater than 95% is necessary to achieve therapeutic success and decrease the risk of suppression failure and viral resistance.9-11 A study by Stephenson12 further demonstrated the necessity of strict adherence. This study found that among patients who were 95% adherent, a viral suppression rate of 81% was achieved. However, among patients who were 80% to 90% adherent, only half achieved successful viral suppression.12

It can be challenging to achieve high rates of adherence with HAART because the therapy requires multiple, expensive medications with complex dosing regimens. Many patients have poor tolerability to medication interactions and side effects. As many as half of patients who receive a prescription for HAART fail to take their medication in accordance with dosing, timing and dietary instructions.8 A concern about newer HAART regimens is that the longer half-lives may lead to drug resistance if they are suddenly discontinued.13

A review by Atkinson and Petrozzino6 found that improved clinical outcomes, based on measures of virologic response to HAART, could be attributed to two factors: improved antiviral medications and a greater focus on factors affecting treatment adherence. Improved medications have reduced viral breakthrough by relaxing the strict and complicated dosing regimens, reducing side effects and improving medication tolerability.

The study identified predictors of nonadherence and divided them into clusters. Clinical predictors (cluster 1) such as high baseline viral load, possibly a result of prior nonadherent behaviors, can be carried forward into future treatment. Comorbid predictors (cluster 2), such as anxiety or drug and alcohol abuse, consistently predict nonadherent behavior. This is because the treatment regimen requires high levels of organization and discipline, which are frequently undermined by coexisting psychosocial conditions.6


Barriers to HAART Adherence

Multiple barriers prevent long-term adherence to HAART. A review of the current HIV/AIDS literature reveals that four significant barriers are life stressors,4 alcohol abuse,14 declining cognitive function15 and the patient-provider relationship.5

Life Stressors. Consideration of life stressors is important when developing a plan of care for patients with HIV. A longitudinal investigation by Bottonari et al4 sought to determine if life stress, depression and inadequate coping negatively influence HAART adherence. The investigation concluded that life stress, whether from acute life events (such as death of a family member, divorce or loss of employment) or from chronic stress (such as dealing with a chronic disease) correlated positively with decreases in treatment adherence. Additionally, life stress was more strongly associated with a decrease in adherence in patients diagnosed with depression. Coping style did not have an effect on treatment adherence.4 This study suggests that providers should assess all HIV-positive patients for stress and depression. Clinicians should utilize appropriate depression screening tools and treatments and be especially alert to episodic life stress that may result in a lapse in treatment adherence.

Alcohol Abuse. Alcohol abuse is important when formulating treatment plans. Azar et al14 conducted a systematic review of the impact of alcohol use disorders on HIV treatment outcomes, adherence to HAART and healthcare utilization. The researchers found that alcohol abuse was strongly associated with increased risk-taking behaviors such as IV drug use, unprotected sex and sex with multiple partners. These behaviors can result in decreased adherence to HAART and increased HIV transmission. The study found that alcohol abuse resulted in a delay in HIV diagnosis, a decrease in healthcare utilization, a higher risk for hepatitis C infection, an acceleration of cognitive decline, a higher prevalence of mental illness, and an increase in mortality.14

Alcohol and drug use should be assessed at every visit. Steps must be taken to decrease or discontinue substance use in patients on HAART. Providers must be familiar with community resources for treating alcohol and drug abuse, so that they can make appropriate referrals and provide sufficient support for patients.

Cognitive Function. A decline in cognitive function or change in mental status may also play a part in decreased long-term adherence to HAART. HIV infection can lead to cognitive compromise ranging from mild changes in processing speed to severe dementia.15 Memory impairment, motor slowing, psychomotor slowing and attention deficits have all been observed in patients living with HIV.

In a 4-year study, Becker et al15 sought to find out if a decline in cognitive functioning would correspond with decreased HAART adherence. The study confirmed that a decline in cognitive functioning resulted in a drop in adherence rates. Participants were measured for changes in adherence over 6 months and were classified as either cognitively impaired or normal. Adherence rates declined over time in both the cognitively impaired and normal groups, but the cognitively impaired group showed a greater decline in adherence and a sharper decline over time. Greater decreases in adherence were also noted for learning and memory deficits specifically. This makes sense considering the complexity of the HAART regimen.15

By establishing baseline cognitive function and conducting regular reassessment, providers may be able to detect changes in cognition and identify patients at risk for poor adherence. The mini mental status exam is one example of a tool utilized by providers to detect changes. If changes are noted, early interventions could then be implemented to assist with adherence.

Patient-Provider Relationship. The relationship between provider and patient is an important factor in adherence to treatment regimens.3 Adherence issues may arise when trust in medication regimens and healthcare providers has not been established. Data from the Never in Care Project,16 conducted in Indiana, New Jersey, New York City, Philadelphia and the state of Washington, found that respondents sometimes believed HIV care and medications might be harmful or unnecessary. Some respondents expressed the belief that starting on medications too early might result in the need for more toxic medications later, or set the stage for resistance in the virus over time. Others did not trust the effectiveness of the medication. One patient commented that people who took HAART "told me they got sicker . and they died anyway."

These findings demonstrate how important it is to educate patients about HAART medications. This qualitative study showed why it is important for providers to establish a relationship of trust with HIV patients. They should provide consistent information while listening to the concerns of the patient.

In a literature review by Horstmann et al,5 retention of patients in treatment programs was a significant problem contributing to nonadherence to HAART. Retention was measured according to the number and frequency of missed appointments and the use of healthcare resources at regular intervals. The review revealed a positive association between missing appointments and poor adherence to HAART. It also determined that the number of missed appointments significantly predicted the progression of viral loads and CD4 counts to levels diagnostic for AIDS. Retaining HIV infected patients in care has the added potential benefit of lowering health care costs by improving patient outcomes, thereby reducing doctor and emergency department visits. Another stated benefit of retaining patients in care is the opportunity to counsel patients about preventive healthcare and to reduce transmission-risk behaviors.5 An ongoing patient-provider relationship founded in trust, honesty and mutual respect is essential to retain patients and to increase adherence to HAART.


Work Together

The steady rates of new infections and the mortality associated with HIV make it likely that every primary care provider will come in contact with more than one HIV-positive patient. HAART has been successful at prolonging and improving the lives of these patients. In the primary care setting, screening and assessment for barriers to adherence should address psychosocial stress, alcohol abuse, cognitive function and improving the patient-provider relationship. By assessing, acknowledging and addressing these barriers, healthcare providers may be able to improve adherence to HAART. While specialty care clinics bear the primary responsibility for the management of HIV and AIDS, all healthcare providers must work together to end the devastation of this disease.


Katherine Gardner is a family nurse practitioner at The Urology Clinic in Athens, Ga. Seth Lee is a family nurse practitioner at The Minute Clinic in Dacula, Ga. Sharon Chalmers is a family nurse practitioner who is the graduate coordinator for the nursing program at the University of North Georgia in in Dahlonega. The authors have completed disclosure statements and report no relationships related to this article.



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2. PubMed Health. AIDS: Acquired Immune Deficiency Syndrome.

3. Beer L, et al. Medication-related barriers to entering HIV care. AIDS Patient Care And STDs. 2012;26(4):214-221.

4. Bottonari KA, et al. A longitudinal investigation of the impact of life stress on HIV treatment adherence. J Behav Med. 2010;33(6):486-495.

5. Horstmann E, et al. Retaining HIV-infected patients in care: Where are we? Where do we go from here? Clin Infect Dis. 2010;50(5):752-761.

6. Atkinson M, Petrozzino J. An evidence-based review of treatment-related determinants of patients' nonadherence to HIV medications. AIDS Patient Care STDs. 2009;23(11):903-914.

7. Shah B, et al. Adherence to antiretroviral therapy and virologic suppression among HIV-infected persons receiving care in private clinics in Mumbai, India. Clin Inf Dis. 2007;44(9):1235-1244.

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10. Paterson DL, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med. 2000;133(1):21-30.

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12. Stephenson J. AIDS researchers target poor adherence. JAMA. 1999;281(12):1069.

13. Sahay S, et al. Optimizing adherence to antiretroviral therapy. Indian J Med Res. 2011;134(6):835-849.

14. Azar MM, et al. A systematic review of the impact of alcohol use disorders on HIV treatment outcomes, adherence to antiretroviral therapy and health care utilization. Drug Alcohol Depend. 2010;112(3):178-193.

15. Becker BW, et al. Longitudinal change in cognitive function and medication adherence in HIV-infected adults. AIDS Behav. 2011;15(8):1888-1894.

16. Fagan JL, et al. Understanding people who have never received HIV medical care: a population-based approach. Public Health Rep. 2010;125(4):520-527.












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