Human immunodeficiency virus (HIV) is a single-stranded RNA retrovirus that when untreated, possesses insidious effects against the body’s immune system, specifically the CD4 T-lymphocyte cells. Prolonged infection and a reduction of one’s CD4 count below 200 cells per cubic millimeter, defined as acquired immunodeficiency syndrome (AIDS), can lead to severe immunosuppression and resultant opportunistic infections.

In the United States, an estimated 1.1 million people are living with HIV, including approximately 162,500 people that are undiagnosed.1 Although no cure currently exists, the advent of antiretroviral therapy (ART) in the mid-1990s significantly reduced HIV-associated morbidity, mortality, and transmission.2 Here is a review of HIV/AIDS with a particular focus on counseling points and essential information to know as a pharmacist:

Prevention
HIV is primarily transmitted through 3 modes: sexual transmission, parenteral transmission, and perinatal transmission. Thus, there are many available strategies to effectively prevent HIV transmission. The CDC recommends abstinence, limiting one’s number of sexual partners, proper use of condoms with every sexual encounter, and never sharing needles.3 For patients who are HIV-positive, adherence to HIV medications is critical to maintaining adequate viral suppression, consequently reducing the risk of both vertical and horizontal transmission. Pre-exposure prophylaxis (or PrEP) can also be offered to patients at very high risk for HIV from sex or injecting drugs. Currently, emtricitabine/tenofovir disoproxil fumarate (Truvada, Gilead) is the only FDA-approved therapy for PrEP. Patients should be counseled to take this medication daily and to maintain regular visits and testing as instructed by their health care provider (HCP).

Treatment
There are now more than 40 FDA-approved antiretroviral (ARV) medications categorized within 7 mechanistic classes. These 7 classes include the nonnucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs), integrase strand transfer inhibitors (INSTIs), a fusion inhibitor, a C-C chemokine receptor type 5 antagonist, and a CD4 post-attachment inhibitor. In addition, there are 2 drugs, ritonavir and cobicistat, that are used solely as pharmacokinetic (PK) boosters/enhancers to improve the PK profiles of other ARV medications.

Current guidelines recommend that the initial ARV regimen for a treatment-naïve patient include 2 NRTIs in combination with an INSTI, boosted PI, or NNRTI. Certainly, selection of an initial regimen should be individualized based on virologic efficacy, potential adverse effects, childbearing potential and use of effective contraception, pill burden, dosing frequency, drug-drug-interactions, comorbid conditions, cost, access, and resistance test results.2 Because much of this information is based on clinical trial data, remember that guideline recommendations are always subject to change and are quickly adapting to the growing number of agents available. In the last 6 years alone, there have been 9 guideline updates.2

Adherence
Medication adherence is an essential component of HIV treatment as it reduces the risk of drug resistance, treatment failure, and HIV transmission. Previous studies have shown 40–60% of patients being less than 90% adherent, which is concerning as adherence also seems to decrease over time.4  Historically, near-perfect adherence (>95%) has been required to prevent resistance and to obtain full viral suppression.5,6 Single-tablet regimens, as opposed to multi-tablet regimens, are thought to improve overall adherence rates, although definitive data is limited.

Nevertheless, patients should be counseled on the use of effective strategies including pill boxes, alarms, reminders, paper or electronic medication diaries, and/or support groups. Family and friends can also be great supports although one must remain sensitive to the confidentiality and privacy of patients. Lastly, patients should be encouraged to maintain honest and open communication with their health care providers. Only with transparency and trusting patient-provider relationships can HCPs help address the concerns and needs of the patient.

Safety (Adverse effects, monitoring)
While newer ARV regimens are generally associated with fewer side effects than those in the past, adverse and intolerable side effects of ART remain a primary reason for switching or discontinuing therapy, as well as for medication nonadherence. Medication adverse effects exist on a spectrum and can range from mild rashes and GI upset to more serious effects such as hypersensitivity, metabolic disturbances, cardiac conduction abnormalities, and nephrotoxicity. In addition, as the life expectancy of patients on ART increases, there has been an added focus from solely avoiding early ARV-related toxicities to avoiding complications in the long term as well.2 Patient comorbidities and concomitant medications should be carefully evaluated and patients should be encouraged to continually address their concerns at each followup visit. 

Drug-Drug Interactions
Drug-drug interactions (DDIs) between ARV medications and concomitant medications are common as many ARV medications are potent cytochrome P450 3A4 enzyme inhibitors, inducers, or both. In addition, PK interactions can occur anytime during the medication’s absorption, metabolism, or elimination phase, leading to decreased or increased drug exposure.2

A good rule of thumb is to always screen for DDIs and to consider monitoring for therapeutic efficacy. Common agents responsible for DDIs include acid-reducing agents, polyvalent cations/anions, and potent inhibitors/inducers of the cytochrome P450 system, p-glycoprotein, or uridine diphosphate glucuronosyltransferase (UGT) enzyme. Patients should be advised to alert their pharmacist and HCPs of any changes or additions in their concomitant medications, including complementary and alternative therapies.

Conclusion
HIV treatment continues to advance and evolve over time. Therefore, it is prudent for pharmacists to stay current with these therapies and prevention strategies, as they are well-positioned to educate and support patients in their illness.
 
Alvin B. Oung, PharmD, BCACP is a clinical assistant professor at the University of Wyoming School of Pharmacy in Laramie, WY. 

References
  1. Centers for Disease Control and Prevention. Estimated HIV incidence and prevalence in the United States, 2010–2016. HIV Surveillance Supplemental Report 2019;24(1). http://www.cdc.gov/hiv/library/reports/hiv-surveillance.html. Published February 2019. Accessed June 1, 2019.
  2. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Department of Health and Human Services. Updated October 2018. http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed June 1, 2019
  3. Centers for Disease Control and Prevention. HIV Basics: Prevention. Updated January 2019. https://www.cdc.gov/hiv/basics/prevention.html. Accessed June 1, 2019.
  4. Bartlett JA. Addressing the challenges of adherence. J Acquir Immune Defic Syndr. 2002; 29 Suppl 1:S2-10.
  5. Paterson DL, Swindells S, Mohr  J, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med. 2000;133(1):21-30
  6. Smith RJ. Adherence to antiretroviral HIV drugs: how many doses can you miss before resistance emerges? Proc Biol Sci. 2006; 273(1586):617-624.