For Concepts Writer Only

Running Head: NEUROCOGNITIVE PROBLEMS CAUSED BY ARV THERAPY

1

Grant Proposal: Neurocognitive Problems Caused by Anti-Retroviral Therapy

LaShawn Tubman

PSY: 625

Teresa Barttrum

October 15, 2018

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1. Barttrum

Barttrum, Psy. D. [Teresa

Barttrum]

NEUROCOGNITIVE PROBLEMS CAUSED BY ARV THERAPY

2 Background

Anand et al., (2010) note that the manner in which HIV drugs affects the brain has been a

difficult subject to understand this has been a recent focus of most researches. They also note that

the blood-brain barrier allows small HIV drug molecules to penetrate into the Cerebrospinal fluid

although large compounds are blocked (Anan et al., 2010). Some of the HIV medications that

cross the blood-brain barrier include non-nucleoside reverse transcriptase inhibitors such as

efavirenz, nevirapine, and delavirdine, nucleoside reverse transcriptase such as zidovudine,

tenofovir, and abacavir, protein inhibitors such as ritonavir, lopinavir and indinavir among others

(Carter, (2007). Therefore, HIV patients who use drugs that are able to cross the blood-brain

barrier as listed are a high risk of cognitive impairment as compared to those using drugs that

have a low BBB penetration.

Individuals who are HIV positive suffer neurocognitive impairment barely 5 months after

the initiation of HAART. The rates of deaths and suffering have reduced significantly since the

availability of treatment in the year 1996 (Cysique & Brew, 2009). This is attributed to the fact

that ARVs are capable of decreasing the viral load in CSF and blood thus a reduction in the

incidences of neurologic diseases associated with HIV (Nightingale, et al., 2014). However,

close to a fifth of this population face cognitive dysfunction in the forms of confusion, loss of

memory, inability to pay attention, personality changes, anxiety, and depression. As supported by

Awori et al., (2018), this increases the difficulty in diagnosing the co-existence of other

conditions such as underlying psychiatric issues more so depression, substance abuse, and

alcoholism.

Winston, et al. (2013) notes that, even in countries where HAART is readily available, people

stiff suffer from HIV associated dementia. Although dementia associated with HIV is rarely

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1. Anand

see in-text formatting for four

authors in first use [Teresa

Barttrum]

2. Cerebrospinal

does not need capitalized

[Teresa Barttrum]

3. barrier

(BBB) [Teresa Barttrum]

4. HAART.

which is what? [Teresa

Barttrum]

NEUROCOGNITIVE PROBLEMS CAUSED BY ARV THERAPY

3 diagnosed today, there exists a lot of evidence that HIV medications significantly affect people’s

brains and can easily be noted through psychological and neurological testing (Ghate, et al.,

2015). Several medications used in the management of HIV such as efavirenz, zidovudine, and

abacavir cause symptoms of neurocognitive issues since they are able to penetrate the blood-

brain barrier resulting to problems in memory, thinking, mood, physical function, and

coordination (Ances & Clifford, 2008). In the mild form where the symptoms are unnoticed and

undetectable by an individual, it is referred to as asymptomatic neurocognitive impairment. In

instances where moderate symptoms are experienced, it is called mild neurocognitive disorder

(Cysique, et al., 2009). In the most severe forms, the most noticeable neurocognitive problems

that patients develop include: difficulty to pay attention for a long period of time, weakened

reflexes, anxiety, and feelings of hopelessness and sadness, difficulty to learn new tasks and poor

memory (Borjabad, et al., 2011).

Significance

According to the World Health Organization, patients diagnosed with HIV/AIDS without

ARV therapy are twice more likely to develop neurocognitive problems. Similarly, those

receiving ARV therapy are also at risk of neurocognitive problems (Watkins & Treisman, 2015).

With continued advancement in treatments and therapy so does the adverse and side effects of

HIV/AIDS medications. This study will be essential in identifying the relationship that exists

between HIV medications and the neurocognitive state of patients under HIV/AIDS treatment. It

will inform clinical decision making on the possible precautionary measures that healthcare

providers should take to maintain the cognitive function of patients taking specific ARV drugs.

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NEUROCOGNITIVE PROBLEMS CAUSED BY ARV THERAPY

4 References

Anand, P., Springer, S. A., Copenhaver, M. M., & Altice, F. L. (2010). Neurocognitive

Impairment and HIV Risk Factors: A Reciprocal Relationship. AIDS and Behavior, 14(6), 1213–

1226.

Ances, B. M., & Clifford, D. B. (2008). HIV-Associated Neurocognitive Disorders and the

Impact of Combination Antiretroviral Therapies. Current Neurology and Neuroscience

Reports, 8(6), 455–461.

Awori, V., Mativo, P., Yonga, G., & Shah, R. (2018). The association between asymptomatic

and mild neurocognitive impairment and adherence to antiretroviral therapy among people living

with human immunodeficiency virus. Southern African Journal of HIV Medicine, 19(1),

674.

Bhatti, A. B., Usman, M., & Kandi, V. (2016). Current Scenario of HIV/AIDS, Treatment

Options, and Major Challenges with Compliance to Antiretroviral Therapy. Cureus, 8(3), 515.

Borjabad, A., Morgello, S., Chao, W., Kim, S.-Y., Brooks, A. I., Murray, J., Volsky, D. J.

(2011). Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues

of Patients with HIV-1-Associated Neurocognitive Disorders. PLoS Pathogens, 7(9),

e1002213.

Cysique, L. A., Vaida, F., Letendre, S., Gibson, S., Cherner, M., Woods, S. P., llis, R. J. (2009).

Dynamics of cognitive change in impaired HIV-positive patients initiating antiretroviral

therapy. Neurology, 73(5), 342–348.

Carter M., (2007). Cognitive impairment common in people with HIV on antiretroviral therapy. In

Robertson KR et al. The prevalence and incidence of neurocognitive impairment in the HAART

era. AIDS 21: 1915 – 1921, 2007

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NEUROCOGNITIVE PROBLEMS CAUSED BY ARV THERAPY

5 Cysique L.A., & Brew B. J., (2009). Neuropsychological functioning and antiretroviral

treatment in HIV/AIDS: a review. Neuropsychol Rev. 2009; 19:169–185.

Ghate, M., Mehendale, S., Meyer, R., Umlauf, A., Deutsch, R., Kamat, R., Marcotte, T.

(2015). The effects of anti-retroviral treatment initiation on cognition in HIV-infected individuals

with advanced disease in Pune, India. Journal of Neurovirology, 21(4), 391–398.

Kenedi, C. A., & Goforth, H. W. (2011). A systematic review of the psychiatric side-effects of

Efavirenz. AIDS and Behavior, 15(8), 1803-1818

Mwesigire, D. M., Wu, A. W., Martin, F., Katamba, A., & Seeley, J. (2015). Quality of life in

Patients treated with first-line antiretroviral therapy containing nevirapine or efavirenz in

Uganda: a prospective non-randomized study. BMC Health Services Research, 15292.

Nightingale, S., Winsto, A., Letendre, S., Michael, B. D., McArthur, J. C., Khoo, S., & Solomon,

T. (2014). Controversies in HIV-associated neurocognitive disorders. The Lancet.

Neurology, 13(11), 1139–1151.

Saylor, D., Dickens, A. M., Sacktor, N., Haughey, N., Slusher, B., Pletnikov, M., & McArthur,

J. C. (2016). HIV-associated neurocognitive disorder — pathogenesis and prospects for

treatment. Nature Reviews. Neurology, 12(4), 234–248.

Winston, A., Arenas-Pinto, A., Stöhr, W., Fisher, M., Orkin, C. M., Aderogba, K., for the

PIVOT Trial Team. (2013). Neurocognitive Function in HIV Infected Patients on Antiretroviral

Therapy. PLoS ONE, 8(4), e61949.

Watkins, C. C., & Treisman, G. J. (2015). Cognitive impairment in patients with AIDS –

Prevalence and severity. HIV/AIDS (Auckland, N.Z.), 7, 35–47.

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