Medications enable the management of HIV.
Introduction
Throughout history, illnesses, diseases, and plagues have devastated humanity, eradicating thousands, even millions of people. The infamous Black Death nearly destroyed Europe in the 14th century, taking 50 million lives.1 The recent Ebola outbreak in West Africa claimed almost 11,300 lives.2 AIDS is a deadly disease caused by HIV that has claimed the lives of more than 34 million individuals since the first cases appeared in the early 1980s.3

AIDS is a chronic, incurable disease that attacks the body’s ability to defend itself against infection and cancer. Untreated, HIV may progress to AIDS. Management of HIV is, however, now possible. New advancements in pharmacologic therapies and the promotion of safer behaviors aid in the prevention of the disease. HIV no longer means certain death for the affected patient. Pharmacists can assist patients in taking appropriate measures to prolong their lives.

Epidemiology
Currently, more than 1.2 million Americans are living with HIV. According to AIDS.gov, “almost 1 in 8 (12.8%) are unaware of their infection.”3 HIV infection rates have stabilized to an estimated 50,000 new cases every year. Homosexual, bisexual, and other men who have sex with men (MSM) collectively make up the group most affected by HIV.4 MSM represented approximately 63% of all new infections in 2010.4

As of 2010, 84% of newly diagnosed cases of HIV in women were primarily attributed to heterosexual sexual contact and 16% to injection drug use.4 African Americans and Hispanic Americans are disproportionately affected by HIV/ AIDS, with 44% and 21% of newly diagnosed cases of HIV in 2010, respectively.4

Although there are disparities among the groups affected by this disease, the overall message is optimistic. New HIV infections are no longer on the rise, proving that prevention methods and community awareness are effective. However, the steady incidence of new HIV infections every year shows that our work is far from finished.

Pathophysiology
There are 2 types of HIV, subtypes 1 and 2. HIV-1 is the predominant form of the virus worldwide, while subtype HIV-2 primarily affects people in West Africa.5 HIV in both subgroups affects the CD4+ lymphocytes, decreasing immunity and increasing the risk of opportunistic infections and cancers.6 Two glycoproteins, glycoprotein 120 and glycoprotein 41, allow HIV attachment to the surface of the CD4+ cell.7 Interactions between the virus and chemokine co-receptors (CCR5 and CXCR4) trigger irreversible conformational changes to the receptors.7 Fusion of the membranes takes place, prompting the viral core to release itself into the CD4+ cell and allow HIV RNA the opportunity to replicate.7

Reverse transcriptase is a unique enzyme HIV uses to create viral DNA from HIV RNA.7 A major reason HIV/AIDS is difficult to treat is that reverse transcription allows for numerous errors, yielding multiple mutations of each DNA strand, thereby promoting resistance.6 Following the creation of HIV DNA, the viral enzyme integrase integrates HIV DNA into the host CD4+ cell’s DNA.7 The viral DNA then continues to replicate. This replication creates more HIV DNA, which can then be transcribed into HIV RNA and translated into HIV proteins.7 HIV virions are cleaved by protease and bud from the cell surface and infect other CD4+ cells.7 Infected CD4+ cells have a significantly shorter half-life than uninfected cells, impeding the body’s ability to fight against infection.6

Table 1: HIV Medication Classes
  Drug Name (abbreviation; brand name) Notes
NRTIs Abacavir (ABC; Ziagen)
Lamivudine (3TC; Epivir)
Didanosine (ddl; Videx)
Emtricitabine (FTC; Emtriva)
Stavudine (d4t; Zerit)
Tenofovir (TDF; Viread)
Zidovudine (AZT; Retrovir)
Associated with lactic acidosis and lipodystrophy. HLA-B*5701 testing should be done before use of abacavir.13
NNRTIs Delavirdine (DLV; Rescriptor)
Efavirenz (EFV; Sustiva)
Etravirine (ETR; Intelence)
Nevirapine (NVP; Viramune)
Rilpivirine (RPV; Edurant)
Associated with rash and lipid disorders that may require discontinuation, drug switch, or use with lipid-lowering agents.13
Protease Inhibitors Atazanavir (ATV; Reyataz)
Darunavir (DRV; Prezista)
Fosamprenavir (FPV; Lexiva)
Indinavir (IDV; Crixivan)
Lopinavir/ritonavir (LPV/RTV; Kaletra)
Nelfinavir (NFV; Viracept)
Ritonavir (RTV; Norvir)
Saquinavir (SQV; Invirase [hard-gel capsule]; Fortovase [soft-gel capsule])
Tipranivir (TPV; Aptivus)
RTV is a booster agent for other protease inhibitors. Class is associated with gastrointestinal effects, lipohypertrophy, glucose intolerance, and lipid disorders. Protease inhibitors are often used in regimens for patients who fail a prior regimen.13,14
Integrase Inhibitors Raltegravir (RAL; Isentress)
Dolutegravir (DTG; Tivicay)
Elvitegravir (EVG; Vitekta)
Raltegravir is associated with rhabdomyolysis and myopathy, and resistance to the drug develops easily.13
CCR5 Receptor Antagonists (Entry Inhibitors) Maraviroc (MRC; Selzentry) A tropism test is required prior to administration. Associated with a slightly increased risk of heart attack, abdominal pain, hepatotoxicity and other adverse events.13
Fusion Inhibitors Enfuviritide (ENF; Fuzeon) Used in treatment-experienced patients, although not commonly. It is the only subcutaneous HIV medication. Associated with neutropenia and increased risk of pneumonia.13
CCR5 = C-C chemokine receptor 5; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside/nucleotide reverse transcriptase inhibitors. 




Treatment
Treatment methods for HIV/AIDS target the steps of HIV pathophysiology that involve the progression of the disease. There are currently 6 different medication classes used in the treatment of HIV/AIDS: nucleoside/ nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase inhibitors, fusion inhibitors, and entry inhibitors.

NRTIs act as false nucleosides or nucleotides, causing reverse transcriptase to create defunct HIV DNA strands.8 NNRTIs are similar to NRTIs in their effects on HIV.9 PIs prevent the enzyme protease from cleaving HIV DNA proteins into new HIV virions.10 Integrase inhibitors disrupt the integration of HIV RNA into host-cell DNA.6 Entry inhibitors bind to the CCR5 protein on the CD4+ cell to prevent the HIV from binding.11 Fusion inhibitors also block the entry of HIV into CD4+ cells by inhibiting membrane fusion.12 Further information regarding the medications in each class can be found in Online Table 1 and Table 2.

Conclusion
A pharmacist can improve affected patients’ health care by optimizing pharmacologic therapy tailored to each patient. Tailoring care ensures that patients receive a regimen suited to their daily lives. The optimization of drug therapy will promote patient adherence to their drug regimens, minimize adverse reactions, and decrease drug resistance. Pharmacists can help patients with assistance programs to aid in the purchase of costly medications. The Ryan White HIV/AIDS Program, Medicare, and Medicaid provide patients additional care access.17 Pharmacists play a vital role in the pharmacological management of patients with HIV/AIDS, helping them to live longer, healthier lives.


Jerry Barbee, Jr, PharmD, BCPS, is a clinical pharmacist at HCA West Florida Hospital. Hollie Fletcher, PharmD, is a clinical pharmacist at HCA West Florida Hospital. Jarah Yates is a 2016 PharmD candidate at the Florida Agricultural and Mechanical University.

References
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  2. The Economist data team. The toll of a tragedy. The Economist website. www.economist.com/blogs/graphicdetail/2015/07/ebola-graphics. Published July 8, 2015. Accessed August 6, 2015.
  3. U.S. statistics. AIDS.gov website. www.aids.gov/hiv-aids-basics/hiv-aids-101/statistics/. Revised December 2, 2014. Accessed August 6, 2015.
  4. Osmond DH. Epidemiology of HIV/AIDS in the United States. University of California, San Francisco HIV InSite website. http://hivinsite.ucsf.edu/InSite?page=kb-01-03. Published March 2003. Accessed August 6, 2015.
  5. HIV strains: types, groups and subtypes. AVERT website. www.avert.org/hiv-types.htm. Accessed August 6, 2015.
  6. McCutchan JA. Human immunodeficiency virus (HIV) infection [professional version]. Merck Manuals website. www.merckmanuals.com/professional/infectious-diseases/human-immunodeficiency-virus-hiv/human-immunodeficiency-virus-hiv-infection. Updated August 2013. Accessed August 6, 2015.
  7. Simon V, Ho DD, Abdool KQ. HIV/AIDS epidemiology, pathogenesis, prevention, and treatment. Lancet. 2006;368(9534):489-504.
  8. Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). Aidsmeds.com website. www.aidsmeds.com/archive/NRTIs_1082.shtml. Updated June 4, 2015. Accessed August 6, 2015.
  9. Non-nucleoside reverse transcriptase inhibitors (NNRTIs). Aidsmeds.com website. www.aidsmeds.com/archive/NNRTIs_1612.shtml. Updated June 4, 2015. Accessed August 6, 2015.
  10. Protease inhibitors (PIs). Aidsmeds.com website. www.aidsmeds.com/archive/PIs_1068.shtml. Updated January 21, 2015. Accessed August 6, 2015.
  11. Attachment and entry inhibitors. Aidsmeds.com website. www.aidsmeds.com/archive/EIs_1627.shtml. Updated September 16, 2011. Accessed August 6, 2015.
  12. FUZEON: mechanism of action. Fuzeon website. www.fuzeon.com/Fuzeon/hcp-mechanism_of_action.do. Accessed August 6, 2015.
  13. Reust CE. Common adverse effects of antiretroviral therapy for HIV disease [corrected version appears at www.aafp.org/afp/2011/0615/p1443.html]. Am Fam Physician. 2011;83(12):1443-1451.
  14. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Updated April 8, 2015. Accessed August 6, 2015.
  15. Currently approved drugs for HIV: a comparative chart. Aidsmeds.com. www.aidsmeds.com/articles/DrugChart_10632.shtml. Updated March 10, 2015. Accessed August 6, 2015.
  16. Cobicistat. AIDSinfo drug database website. https://aidsinfo.nih.gov/drugs/536/cobicistat/0/patient. Accessed August 6, 2015.
  17. Addressing the cost of care. Aids.gov website. www.aids.gov/hiv-aids-basics/just-diagnosed-with-hiv-aids/find-care-and-treatment/addressing-cost-barriers/. Updated May 1, 2015. Accessed August 6, 2015.