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Introduction

The human immunodeficiency virus pandemic has an interesting history laden with stigma, politics, and myths. In June, 1981, the U.S. Centers for Disease Control and Prevention (CDC) informed health care providers that it had identified a cluster of cases of rare Pneumocystis pneumonia, caused by the organism is Pneumocystis jirovecii.¹ (The naming of this organism and the infection have changed over time. Initially, this organism was called Pneumocystis carinii and the infection referred to as Pneumocystis carinii pneumonia or PCP. WHO updated the organism's name to distinguish it from Pneumocystis varients that infect other animals. Some now refer to this infection as PJP, and PCP generally refers to Pneumocystis pneumonia. ²) Usually, only people with failing or impaired immune systems developed Pneumocystis pneumonia.

This small outbreak was noteworthy because the men were all homosexual, leading researchers to call it Gay-Related Immune Deficiency or GRID. That nomenclature was short-lived because epidemiologists quickly determined that in the cases that followed—and many did— approximately half of affected individuals weren't gay. Many of them developed Kaposi's sarcoma, a very rare cancer. By 1982, CDC changed the syndrome's name to acquired immunodeficiency syndrome (AIDS). Patients who developed AIDS were plagued with rare infections seen only in the immunocompromised, yet they had none of the usual factors associated with immunodeficiency (e.g. they weren't taking corticosteroids, being treated for cancer, elderly, pregnant, transplant recipients, or compromised by chronic conditions). Why people were developing these "opportunistic infections" was a mystery.³

In 1983, scientists at the Pasteur Institute in France discovered the virus that causes AIDS. An American team confirmed the discovery a year later, although the 2 groups called the virus by different names. In 1986, the French and American researchers agreed to a new, consistent term: human immunodeficiency virus (HIV). Its impact in the early years was disturbing. By 1984, 3,064 American had been diagnosed with AIDS and 1,292 had died.³

From its name, it's clear that HIV is a human virus, and 2 types of HIV (HIV-1 and HIV-2) infect humans. Scientists believe that both of these viruses originated from chimpanzees and monkeys and "jumped" to humans. No one is certain how this happened. HIV-1 is more virulent than HIV-2, and causes most HIV infections globally. Although CDC believed that HIV was a new condition in 1981, researchers have identified HIV-1 in plasma samples taken from people who died as early as 1959 and estimate that globally, 31 people had died of AIDS before then. While the current epidemic is about 36 or 37 years old, it's likely that HIV has been around for a long time and probably started around 1930.^3,4

The prognosis associated with HIV was grim in the early days of the epidemic. Over time, better diagnostic testing and new treatments have brightened the outlook for people living with HIV (PLWH). PLWH who are diagnosed, start treatment early, and adhere to their mediations well can expect to live almost as long as others. By 2020, 70% of PLWH will be 50 years of age or older.^5,6

HIV Today

More than 1.1 million American adults are living with HIV, yet 15% of infected individuals are unaware that they are infected.⁷ HIV infection and AIDS remain obstinate health problems in the United States and other countries around the world. Since the peak of the epidemic in the mid- 1980s, the number of new HIV infections in the US has been reduced from approximately 130,000 per year to 37,600 per year.⁶ Even with the large fall in number of infections over time, the estimated number of new HIV infections continues to be elevated, particularly among gay and bisexual men, people who inject drugs, and members of certain minority populations.⁸

Tracking Transmission, Reducing Risk

Once researchers identified HIV as the causative virus, they determined it is a bloodborne virus. From there, its risk factors for transmission became clear (see Table 1). HIV can be found at low concentrations in infected individuals' saliva, tears and urine, but transmission from these fluids is negligible. It is also present in sexual fluids, and can be transmitted during sex.⁹

Table 1. Risk Factors for HIV Infection
Route of Transmission	Facts to Note
Sexual route	Most HIV infections are acquired through unprotected sex. Occurs when infected sexual secretions of 1 partner come into contact with the rectal, genital or oral mucous membranes of another.
Blood or blood product route (including illicit injection drug use)	Accounts for infections in intravenous drug users; also people with hemophilia, blood transfusion recipients, and blood product recipients in developing nations but not developed nations. Associated with reuse of needles in healthcare settings in developing nations Rarely, follows needlestick injury in health care workers People who give and receive tattoos, piercings, and scarification procedures may be at risk
Mother-to-child transmission	Occur in utero during the last weeks of pregnancy and at childbirth in 25% of cases where the mother is HIV-infected and preventive steps are not taken Antiretroviral therapy to achieve an undetectable viral load reduces the risk to less than 1%; patients who do not reach viral suppression can undergo Cesarean section to reduce transmission risk. Breast feeding also presents a risk of infection for the baby
Source: 9

To be completely safe, sexually active individuals should try to determine the status of their partners and take steps to protect themselves. They should also know their own status to protect their partners. Condoms, dental dams, or other latex barriers can prevent the spread of HIV, as can avoiding rough sex or other activities that might cause bleeding. Polyurethane (plastic) or polyisoprene (synthetic rubber) condoms are good options for people with latex allergies, but plastic condoms break more often than latex condoms. Natural membrane (such as lambskin) condoms have small holes in them, so they don't block HIV and other STDs. CDC recommends using water- or silicone-based lubricants to lower the chances that a condom will break or slip during sex. CDC advises against oil-based lubricants (for example, petrolatum, shortening, mineral oil, massage oils, body lotions, and cooking oil) with latex condoms because they can weaken the condom and cause it to break. PLWH or at risk for infection can also use pre-exposure prophylaxis or PrEP (discussed below).⁹

Individuals who use injection drugs are at elevated risk for HIV if they frequently use drug paraphernalia after someone with HIV has used it. Using drugs also increases the likelihood of engaging in risky sex. Individuals who continue to inject drugs can lower their risk in several ways. Ideally, they would use only new, sterile needles and drug paraphernalia and use sterile water to prepare their drugs each time they inject themselves. Many communities have needle exchange programs that provide new needles and drug paraphernalia, and some pharmacies may sell needles without a prescription. If injection drug users are unable to obtain key clean supplies each time they inject, they should never share needles or drug paraphernalia. They can clean used needles with bleach, although this is not entirely effective. They also need to clean their skin before they inject, and avoid contamination with other people's blood.⁹

Individuals who use injection drugs should also dispose of needles safely using a sharps container. Health care provider should encourage these individuals to schedule HIV testing annually. They might also consider using pre-exposure prophylaxis (PrEP, discussed below). Health care provider should also counsel these individuals to avoid having sex if they are high, and using condoms consistently when they do have sex.⁹

Workplace Protections

The same infection control procedures that protect health care providers from other infectious agents protect them from HIV. Consider this: HIV and hepatitis B are transmitted the same way (although HIV is much less infectious than hepatitis B). Standard precautions (see Table 2) minimize risk of HIV infection by preventing parenteral, mucous membrane, and broken skin exposures to blood borne pathogens.

Table 2. Examples of Universal Precautions

Assume all blood, body fluids, secretions, excretions (except sweat), non-intact skin and mucous membranes contains transmissible infectious agent Apply to all patients in any setting in which health care is delivered Avoid touching others unless necessary Know and use good hand hygiene Wash hands using soap and water and plenty of friction and rinsing Wear a clean pair of gloves that fit correctly when contact with infectious agents is possible; remove them carefully to prevent contamination Wear gown, mask, eye protection, or face shields, depending on the potential exposure Use (and promote) safe injection practices Use safety needles Dispose of sharps in puncture-proof containers Do not re-cap, bend or break needles Do not overfill sharps containers Handle equipment or items likely to have been contaminated with infectious body fluids carefully (e.g. wear gloves for direct contact, properly clean and disinfect or sterilize reusable equipment before use on another patient)

Source: 10

Health care providers who experience a needlestick injury should seek care from their occupation health provider and be treated with post-exposure prophylaxis, or PEP. In fact, anyone who has had a possible exposure (e.g. a sexual assault, unprotected sex, needle-sharing) can take advantage of PEP. Patient must start PEP within 72 hours of a possible HIV exposure. Several 28-day drug regimens have been approved to deliver PEP.^11,12

Pre-exposure prophylaxis (PrEP)

Pre-exposure prophylaxis is a medication strategy to keep healthy people who are at high risk of acquiring HIV from becoming infected. The US Public Health Service (PHS) recommends evaluating all adults for risky sexual or injection drug behaviors and offering PrEP as an additional preventive measure. FDA has approved only 1 PrEP medication regimen: tenofovir disoproxil fumarate plus emtricitabine in a fixed-combination tablet that is administered once daily. FDA approved PrEP for use in combination with safer sex practices in specific high-risk adults. These may include^13,14:

• HIV-negative men who have sex with men and who are at high risk of sexually transmitted HIV-infection
• HIV-negative members of discordant couples (sex partners in couples where 1 partner has HIV infection and the other does not)
• HIV-negative individuals who use condoms inconsistently or not at all; have previous confirmed sexually transmitted diseases (STDs); exchange sex for commodities; people who have injected drugs in the past 6 months and have shared needles or drug paraphernalia or been in drug treatment in the past 6 months; are alcohol-dependent; or are incarcerated.

All patients who receive PrEP must visit their prescribing clinicians at least every 3 months to be retested and evaluated for signs or symptoms of acute infection. For this reason, prescriptions for PrEP can be filled for only 3 months. At the testing visit, the prescriber will write a new prescription or authorize refills for the next 3 months. At least every 6 months, the prescriber will need to evaluate the patient's kidney function and test for STDs. Annually, the prescriber will need to discuss whether to continue PrEP with the patient.^13,14

Viral Lifecycle as a Basis for Treatment

The goals of managing HIV/AIDS are to slow progression of the infection, reduce opportunistic infections (OIs), prolong survival, improve quality of life, and prevent transmission.¹⁵ Current HIV treatment approaches capitalize on the way the virus infects the cell. HIV is a retrovirus; it must infect a cell to reproduce (or make copies of itself).¹⁶ Clinicians measure how many copies of HIV are circulating in a patient's blood using a test called the viral load. They monitor viral load carefully to ensure that treatment is working.¹⁷

HIV's main target is the CD4 lymphocyte cell, also called a T-cell or CD4 cell. T-cells are the immune system's key player in its ability to fight infection. However, as HIV infects more and more T-cells, it gradually disables the immune system. If the infection is untreated, it eliminates the body's immune defenses entirely. With waning defenses, the infected individual experiences infections that healthier people are able to fight successfully.¹⁶ Clinicians monitor patients' CD4 cells using a test called the CD4 count. People with normal immune defenses generally have CD4 counts of 800 cells/mm³ or more. Once the CD4 count falls below 200 cells/mm³, patients are diagnosed with AIDS. An interesting point is that as the CD4 count falls, OIs develop rather predictably and clinicians use the CD4 count to determine when they should start antimicrobial prophylaxis or increase monitoring for opportunistic infection.¹⁵ Table 2 demonstrates at what CD4 count clinicians can expect to see specific opportunistic infection develop.¹⁸

Table 2. Relationship between CD4 cell count and Opportunistic Infection
T cell count
Any CD4 count in PLWH	Increased risk of developing Streptococcus pneumoniae infection Pulmonary tuberculosis Herpes zoster Oropharyngeal candidiasis (thrush)
<200 cells/mm3	Start prophylaxis to prevent pneumocystis pneumonia using co-trimoxazole, dapsone, atovaquone, or pentamidine Increased risk of developing miliary/extra pulmonary tuberculosis
<150 cells/mm3	Start prophylaxis for histoplasmosis in areas where histoplasmosis is common using an antifungal drug Risk for Candida yeast infections and Coccidioides fungal infection increase significantly
<100 cells/mm3	Start prophylaxis if patient is positive for previous toxoplasma exposure using trimethoprim/sulfamethoxazole Increase risk of developing Cryptosporidium parasite infection and Candida esophagitis
< 50 cells/mm3	Risk for Mycobacterium avium complex (MAC) and Cytomegalovirus (CMV) increase significantly Patient will need to start prophylaxis for MAC with azithromycin or clarithromycin
Source: 18

Seven HIV drug classes act on the various phases of the HIV lifecycle (see Table 3). HIV enters the cells, reproduces, and exits the cell in a predictable way. To enter human cells, HIV uses proteins embedded in its outer membrane to bind with receptors located on the target cell membrane. Entry inhibitors work at this step. Once it binds, the HIV membrane fuses with (or becomes part of) the T-cell membrane, and lets the content of the HIV virus—which is single-stranded RNA particles—enter the cell's cytoplasm.¹⁶ Fusion inhibitors work at this step.

Once those viral particles are inside the cell, the host cell's innate mechanisms dissolve the viral particles' coating. The HIV RNA uses its own enzymes including reverse transcriptase to create a double-stranded molecule of viral DNA; these are not whole HIV virions, but pieces of DNA. Reverse transcriptase inhibitors work at this step.¹⁶

The viral DNA slips into the host cell's nucleus, releases the enzyme integrase, and becomes integrated into the host's DNA.¹⁶ Integrase inhibitors work at this step. Once HIV is incorporated into the host DNA, it will remain there for the remainder of the host cell's life. At this stage, we call this DNA a provirus. The provirus serves as a template to create new viral RNA. This process is called transcription, and it creates multiple proteins that are building blocks needed to create new, whole viral units. Next, the new viral RNA is used to synthesize viral protein and enzymes that assemble into new viral particles.¹⁶

Once transcription occurs, the new RNA moves out of the cell nucleus and back into the cytoplasm. At this point, the viral proteins are in fairly large pieces, and they need to use an enzyme called protease to cut the big pieces into small pieces that can be used to build new virions. The protease inhibitors work at this step.¹⁶

If the cell is able to successfully create the small pieces, they move to the cell's outer membrane, accumulate, and assemble, creating a "bud" on the cells membrane. Host cell proteins cut the viral bud, releasing new viral particles that move along looking for other cells to infect. Currently, we have antivirals that work at every step of the process except terminal budding and release.¹⁶

Table 3. Available Antiretroviral Drugs
Fusion or Entry Inhibitors work at the cell membrane	Reverse Transcription Inhibitors work in the cytoplasm	Integrase Inhibitors work in the cell nucleus	Protease Inhibitors work in the cytoplasm
Fusion Inhibitor   • Enfuvirtide (ENF, T-20)   Chemokine coreceptor  5 (CCR5) Inhibitor   • Maraviroc (MVC)	Nucleoside Reverse Transcriptase Inhibitor (NRTIs/nRTIs)   • Abacavir (ABC)   • Didanosine (ddI)   • Emtricitabine (FTC)   • Lamivudine (3TC)   • Stavudine(d4T)   • Tenofovir alafenamide   • Tenofovir disoproxil fumarate (TDF)   • Zidovudine (AZT, ZDV) Nonnucleoside reverse transcriptase inhibitor (NNRTIs)   • Efavirenz (EFV)   • Etravirine (ETR)   • Nevirapine (NVP)   • Rilpivirine (RPV)	Integrase Strand Transfer Inhibitors (INSTIs)   • Bictegravir   • Dolutegravir (DTG)   • Elvitegravir (EVG)   • Raltegravir (RAL)	Protease Inhibitors (PIs)   • Atazanavir (ATV)   • Darunavir (DRV)   • Fosamprenavir (FPV)   • Indinavir (IDV)   • Lopinavir (LPV)   • Nelfinavir (NFV)   • Ritonavir (RTV)   • Saquinavir (SQV)   • Tipranavir (TPV)
Pharmacokinetic enhancer (PKE)   • Cobicistat (COBI)
Source: 15 Antiretrovirals highlighted in green represent DHHS-recommended drugs for an initial treatment of HIV infection (always used in combination; never used alone) Antiretrovirals highlighted in red are not recommended in initial ART. Source: DHHS Guidelines. https://aidsinfo.nih.gov/guidelines

Current antiretroviral agents work at various stages in the HIV replication cycle. The specific types of drugs include the following:

• Fusion or entry inhibitors: These medications prevent the virus from binding to cell receptors or fusing with the cell membrane. The sole entry inhibitor, maraviroc, is also known as a chemokine coreceptor 5 (CCR5) inhibitor. It is taken by mouth as a tablet or oral solution, and its most common adverse effects are upper respiratory tract infections, cough, pyrexia (fever), rash, and dizziness. The single fusion inhibitor is enfuvirtide. It is an injectable antiviral, and its most common side effects are local injection site reactions, diarrhea, nausea, and fatigue. Neither of these medications are first-line therapies for HIV.¹⁵
• The reverse transcription inhibitors block the action of reverse transcriptase and prevent the virus from producing genetic material capable of infecting the host's genome. Two reverse transcriptase inhibitor classes are currently available: the Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) and Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs). The most common adverse effects associated with the NRTIs include lactic acidosis and lipodystrophy, although these are now rare with currently recommended agents. The most common adverse effects associated with the NNRTIs are rash and liver toxicity. One NNRTI, nevirapine, is used rarely because of the risk of hepatotoxicity; female gender and higher CD4 + cell counts at initiation of therapy place patients at increased risk.¹⁵
• The integrase inhibitors prevent integrase from effectively adding the viral genes to the host DNA. The most common side effects associated with integrase inhibitors are insomnia, headache, dizziness, nausea, and fatigue.¹⁵
• The protease inhibitors prevent viral protease from cutting up the long HIV proteins. The most common side effects associated with protease inhibitors are lipodystrophy (especially hump on the base of the neck or bony face, although these are rare with currently recommended agents) hypertriglyceridemia, hyperglycemia, osteoporosis, and kidney stones. It's important to know that 1 protease inhibitor, ritonavir, interacts with several other protease inhibitors and increases their level in the blood. Many antiretroviral combinations include ritonavir for this reason; it "boosts" the level of other protease inhibitors so patients can take a less medication, but obtain the same effect.¹⁵

A critical point to remember when dealing with HIV medications is that many of the names are very similar, and health care providers who practice in HIV often have a bad habit of using abbreviations (which are listed in Table 3, and should not be used).^19-21 In addition, manufacturers have created and marketed combination products that make it easier for PLWH to take their medications. The large number of products adds to the confusion. Pharmacy employees should always check and double check the brand and generic names to avoid medication errors. The University of California, San Francisco sponsors a web site called HIV InSite that offers a number of charts to help health care providers find information quickly. It links to a page that provides several charts that cover drugs (e.g. single tablet regimens, individual drug classes and located here https://www.poz.com/drug_charts/hiv-drug- chart?utm_campaign=301_Redirect&utm_source=aidsmeds). It is a handy reference to check and double check prescriptions, minimizing confusion and errors. It also include photos of the tablet or capsule, which is helpful.^22,23

Targeting single steps in the HIV viral replication process doesn't work very well. Targeting multiple sites in the viral lifecycle is necessary to suppress viral resistance formation. This is why highly effective antiretroviral therapy (HAART) uses medication combinations.¹⁵ In addition, researchers have been able to identify something called a pharmacologic enhancer. The enhancer, called cobicistat, has no anti-HIV activity itself but inhibits liver enzymes that would otherwise metabolize HIV medications. It increases serum levels of certain HIV antivirals when giving concurrently, and allows clinicians to use lower doses and reduce the likelihood of adverse effects. It is most frequently used with darunavir, atazanavir, and elvitegravir.¹⁵

In the United States, we currently use the Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV to design treatment protocols for most PLWH.¹⁵ The guidelines are comprehensive, and cover a large number of clinical situations. Pharmacy technicians should note that the website aidsinfo.nih.gov is a central repository for all guidelines related to HIV, including guidelines for children and pregnant women among others. It also includes additional information about HIV infection.

In the past, we used the patient's CD4 count to determine when to start antiretroviral therapy. Today, our guidelines indicate that patients should begin antiretroviral treatment as soon as they are diagnosed with HIV infection^.15 Starting HIV treatment early lowers the risk of a variety of HIV-related illnesses. It dramatically reduces the chance of passing HIV to an HIV-negative sexual partner. In addition, many newer HIV medications are more effective, easier to take, and have fewer side effects. Once patients begin antiretroviral therapy for HIV infection, they must continue taking antiretrovirals for the remainder of their lives. Patient should only stop antiretroviral therapy if they experience significant or life-threatening side effects, and they should only stop under medical supervision.¹⁵

The current guidelines recommend combining an integrase inhibitor with 2 nucleoside reverse transcriptase inhibitors for most people with HIV.¹⁵

• Dolutegravir/tenofovir/emtricitabine
• Elvitegravir/cobicistat/tenofovir/emtricitabine
• Raltegravir/tenofovir/emtricitabine
• Dolutegravir/abacavir/lamivudine if HLA-B*5701 negative

Table 3 highlights these medications in green. One problem with HIV infection is that the virus is smart. If patients are started on effective antiviral regimens, and if they are completely adherent, it's very likely that patients will reach a point of undetectable viral load. However, if they are nonadherent to their medications, the virus is able to mutate into forms that can circumvent the medication. Once again, the patient's viral load will increase. This is called developing resistance. Once resistance develops, patient will need to undergo drug-resistance testing, which is a blood test used to see which other antivirals should still be effective. They will need to switch to a different medication regimen. Table 3 also highlights medications that should be reserved for treatment if the patient's virus becomes resistant in red.¹⁵

Pharmacy staff can help patients remain adherent in a number of ways, and often, the pharmacy technician is the person who is a primary contact. Refill reminders are important, and many pharmacy software programs can send automatic reminders by phone or mail when refills are due. Some patients may have difficulty paying for their antiretrovirals. If this is the case, pharmacy staff can link them to prescription assistance programs. Simply asking patients if they need help with adherence can open communication about adherence devices (pill boxes, blister packing, etc), and technicians can let patients know if delivery services are available when transportation is a problem. Last, some patients find that mail order pharmacies are less nimble than local pharmacies. If that is the case, pharmacy technicians can explore how patients can opt-out of mail-order delivery.²⁴

Growing Concerns: Aging Patients and Drug Interactions

Until recently, prescribers were most concerned about selecting the best antiviral treatment for PLWH, and because most HIV-infected individuals were young, they had fewer concerns about medications for other conditions. However, statisticians estimate that 75% of individuals with HIV will be 50 years or older by 2030 and 84% of PLWH will have at least 1 comorbidity. As they age, they may develop other chronic conditions that require medication.

Consider this: older individuals with HIV are^25,26

• twice as likely to develop cardiovascular disease than the general population
• at 4 times the risk of developing diabetes
• 3 times more likely to fracture a bone
• as likely to develop chronic kidney disease as people who have diabetes.
• more likely to develop liver disease, especially if they are co-infected with hepatitis B or C is or drink alcohol regularly or to excess
• at higher risk of neurocognitive impairment than others

Early, aggressive treatment with ART, followed by careful screening for age-associated comorbidities can help PLWH stay healthy. Older PLWH also need polypharmacy management to ensure that they avoid drug interactions and adverse effects.²⁷ Many PLWH experience dyslipidemia associated with NNRTI- and protease inhibitor-based regimens and take statins, so this is an area of particular concern.²⁷ Many older PLWH will also need anticoagulation, and the newer anticoagulants may be preferred over warfarin primarily based on convenience. However, apixaban and rivaroxaban are CYP3A4 and P-gp substrates, and dabigatron and edoxaban are P- gp substrates. This heightens the need to monitor for drug interactions.²⁷

Antiretrovirals have numerous drug interactions, which can be definite, probable, or possible. Differentiating between the various levels of interactions is critical. The most probable drug interactions include the following^15,28:

• PDE5 inhibitors (sildenafil, tadalafil, and vardenafil used for erectile dysfunction) and PIs or cobicistat
• Fluticasone and PIs or cobicistat
• Methadone and certain PIs or NNRTIs
• Rifamycins (rifampin, rifabutin) and PIs, NNRTIs, cobicistat, or maraviroc
• Specific combinations of HIV agents (eg, certain PIs or integrase inhibitors with NNRTIs, maraviroc with PIs or NNRTIs, tenofovir with atazanavir)
• Statins with PIs or cobicistat
• St. John's wort and cobicistat

Pharmacy technicians should note that 1 of the most significant drug interactions listed involves a supplement (St. John's wort). Many PLWH—approximately 67%—take supplements and over-the-counter medications that can and do interact with antivirals.²⁹ The clinical implications of using complementary and alternative (CAM) with antiretrovirals include the following²⁹:

• Calcium carbonate and ferrous fumarate have the potential to cause treatment failure when given with the INSTIs (elvitegravir, dolutegravir, raltegravir).
• Cat's claw and evening primrose oil inhibit CY3A4. These CAMs have the potential to cause treatment failure in patients who are taking protease inhibitors, NNRTIs, or INSTIs. Evening primrose oil is also a CYP 2D6 inhibitor.
• Gingko biloba, milk thistle, St. John's wort, and vitamin C induce CYP3A4 and have the potential to cause treatment failure in patients who are taking protease inhibitors, NNRTIs, or INSTIs.
• Zinc sulfate, a chelating agent, can also cause treatment failure in patients who are taking protease inhibitors, NNRTIs, NRTIs, or INSTIs.

Technicians are often the first person to see that PLWH are purchasing supplements or OTC products. Using CAM is not wrong, but PLWH need to use them carefully. In particular, pharmacy technicians should notify the pharmacist if PLWH purchase proton pump inhibitors and products that reduce stomach acid as they may decrease the effectiveness of many HIV medications.³⁰

With age, PLWH are more likely to develop cancer, which has been a problem for the HIV population since the epidemic began. Here too, drug interactions are a primary concern when patients need chemotherapy.³¹ Table 4 describes good resources to find information about antiretroviral drug interactions.

Table 4. Drug Interaction Web Sites for HIV Medications
Web Site and Link	What to Expect
HIV Drug Interactions University of Liverpool http://www.hiv-druginteractions.org/	Intuitive interaction checker that groups interactions by severity using colored headers Has a smart phone app
HIV InSite University of California, San Francisco http://arv.ucsf.edu/insite?page=ar-00-02	Offers 3 ways to search for interactions: by antiretroviral drug, by interacting drug, or by interacting drug class
AIDSinfo U.S. Department of health and Human Services https://aidsinfo.nih.gov/	Contains comprehensive charts for each antiviral class

Florida Omnibus AIDS Act

Sadly, many people and organizations have discriminated against or ostracized PLWH. PLWH have experienced difficulty in the workplace, in their search for housing, and during medical treatment. Acknowledging this, the Florida legislature passed the Florida Omnibus AIDS Act in 1988 and has amended it repeatedly. It regulates HIV testing and requires clinicians to hold all information about HIV status strictly confidential. By emphasizing confidentiality, the Act encourages people to undergo HIV testing, prevents coercive testing, and prevents discrimination based on viral status.³²

It requires health care providers to take specific steps when ordering HIV tests³²:

• Secure oral or written informed consent from the patient
• Confirm preliminary test results (either positive or negative) before informing the patient
• Make a good faith attempt to notify patients of their results
• Inform the patient about available medical services, the importance of notifying sexual contact(s), and HIV transmission prevention
• Maintain confidentiality during communication of HIV test results to third parties (including county health departments)
• Follow unique confidentiality requirements and exemptions stipulated in state law

This law is based on the principles of informed consent. Health care providers who test patients must inform the patient orally or in writing that they plan to conduct an HIV test and that the patient may refuse testing. Discreet informed consent for HIV testing is unnecessary if the patient has provided consent for ongoing general medical care requiring HIV testing. Providers must almost always obtain consent for incompetent, incapacitated, or minor patients from a parent or legal guardian.²⁵ However, Florida allows non-emancipated children younger than 18 years of age to receive diagnosis and treatment of STDs (including HIV) without parental consent.³³ HIV testing does not require parental consent; in fact, the statute forbids providers from discussing the testing with parents, even if an opportunity arises that might let them (e.g. the parent has a question about billing or similar matters).

HIV testing consists of 2 phases: an on-site preliminary test followed by a confirmatory test with greater accuracy. Florida defines preliminary test results as "an antibody or antibody-antigen screening test, such as the immunosorbent assays, or a rapid test approved by the United States Food and Drug Administration." Many health care providers use rapid testing because it produces preliminary results in as few as 20 minutes. (These rapid tests have been available for sale at retail pharmacies for many years, and these rules do not apply to patient self-testing at home.). Florida requires health care providers to conduct confirmation tests in most circumstances before disclosing the results. This prevents unnecessary emotional pain or alarm from false positive results (reporting an uninfected patient as infected). Yet, providers may share positive preliminary test results before confirmation testing in certain circumstances. Testing providers may share results with personnel experiencing a significant exposure, patients possibly harmed by delays in care, or in accordance with FDA labeling. The Omnibus AIDS Act defines a significant exposure as blood, infected body fluid, or patient-derived infective material exposure on or through the skin or mucous membranes. The FDA-approved labeling on retail rapid testing products explains how to disclose the results. Providers should ensure patients understand the testing is preliminary and document the reasoning for premature notification in the medical record.³²

Providers should teach patients with positive test results how to seek medical and support services, notify partners, and prevent HIV transmission. Provider should teach patients how to prevent HIV transmission even if the test is negative. Testing personnel or facilities must notify the local county health department of positive test results within 2 weeks. Informing the county without notifying the patient first is only appropriate if a patient is lost to follow-up such as leaving an emergency department against medical advice before receiving their positive test results. The local health department will then contact the patient.³²

Licensed health care providers and facilities that fail to obtain informed consent may be disciplined by the state. Punishments can include a letter of reprimand, suspension or loss of license, and fines.³⁴ Facilities and providers cannot force patients into testing, admission to a licensed facility, or to receive a facility's or provider's licensed services. If patients refuse testing, health care provider can withhold treatment appropriate only in HIV-positive patients.

Penalties for disclosing test results inappropriately include misdemeanor or felony charges. A confidentiality breach is a first-degree misdemeanor and malicious, purposeful, dissemination of STD test results is a third-degree felony. The felony is reserved for those "who knew or should have known the nature of the information and maliciously, or for monetary gain, disseminates this information" with persons other than a physician, nurse, or law enforcement personnel. This statement explicitly mentions only 2 health care professions but applies strictly to actions taken maliciously or for monetary gain. Providers may share HIV test results with others on a need-to- know basis consistent with HIPAA and state privacy statutes.³⁴

Exceptions to the informed consent requirement include if the patient is^32,35,36:

• Mandated by court order consistent with Omnibus AIDS Act
• Monitored for clinical progress with known HIV-positive status
• Pregnant: testing is nearly mandatory because the patient must opt-out of testing. Providers must inform the patient they will administer a HIV test but the pregnant patient does NOT need to consent. This is only the first half of informed consent. Personnel should document the opt-out, in writing, in the medical record.
• Convicted of prostitution or of procuring another to commit prostitution, inmates before prison release, or subject to a medical examiner examination. Providers may test certain populations for STDs, including HIV, without their consent in the interest of public health.
• Sexual battery victims requesting testing of the defendant in their case but the results must be disclosed to the victim and defendant only
• Experiencing a bona fide emergency requiring test results for diagnosis or effective treatment and the patient is unable to consent. Personnel should not use this reason to avoid obtaining informed consent when possible.
• Likely to finds the results detrimental (a concept called therapeutic privilege); the testing provider(s) must document exigent circumstances in the medical record supporting the withholding of results
• Part of epidemiological research consistent with institutional review boards without disclosure of test subject's identity to researchers or public
• Donating certain kinds of tissues or organs
• Source of significant exposure to medical or non-medical personnel with testing cost borne by personnel or personnel's employer (including exposure caused by an expired patient)
• An infant after a reasonable attempt to contact patient's parents has been unsuccessful (medical record must document reason for lack of consent); the parent must be informed of results upon contact. Note an infant is incapable of consenting to treatment.

Conclusion

As the years have passed, our ability to treat (but not cure) HIV infection has improved. It has extended the normal life expectancy for PLWH. Experts indicate these improvements stem from more effective treatments that are simpler and better tolerated. In the pharmacy, that means staff needs to be watchful when PLWH visit. Pharmacy staff needs to make sure patients receive effective antiviral combinations, and watch for drug interactions with other prescribed drugs and products that can be purchased without a prescription.

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