Current Approaches to Treating HIV

Often, pharmacists look for shortcuts so they can remember complex information or update outdated learning, a technique that most pharmacists learn and refine while they are in pharmacy school. But when it comes to treatment of HIV, there are few shortcuts that address the large number of medications and different treatment regimens that are needed to treat patients.

Between 1988 and 1995, more than 75% of individuals with HIV died from AIDS-related causes. With a better understanding of how this virus works and better pharmacotherapy, there has been a tremendous change. Between 2005 and 2009, only 5% of patients with HIV died from AIDS-related causes. The basic principle employed to treat patients who have HIV is that they need to take antivirals that attack the virus at different stages in the cell. Available agents (see Table 1) attack HIV at specific areas:

• The fusion inhibitors prevent the virus from attaching to the cell wall.
• The nucleoside reverse transcription inhibitors and the non-nucleoside reverse transcription inhibitors work in the cytoplasm.
• The integrase strand transfer inhibitors decrease integration of HIV into the host cell's DNA.
• The protease inhibitors work after the HIV exits the host's cell nucleus, and clip viral proteins into pieces.

Since the first antiretroviral medication was marketed (zidovudine in 1987), research has shepherded 27 additional antiretrovirals to market. Research has demonstrated the agents, and specifically, which combinations, reduce HIV’s viral load most effectively. Looking at the table, pharmacists will see that there are a handful of medications for an initial treatment (highlighted in green) and then use the fusion inhibitors and CCR5 inhibitors for patients whose viruses become resistant. Many of the older agents (zidovudine, didanosine, zalcitabine, stavudine) are used only rarely because the newer agents have fewer adverse effects and better effectiveness. Pharmacists should note that cobicistat is a pharmacologic enhancer with no anti-HIV activity that inhibits liver enzymes that would otherwise metabolize HIV medications. It increases serum levels of the HIV antiviral and allows clinicians to use lower doses and reduce the likelihood of adverse effects. It is most frequently used with darunavir, atazanavir, and elvitegravir.

Table 1. Available Antiretroviral Drugs

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)

• Delavirdine (DLV)

• Efavirenz (EFV)

• Etravirine (ETR)

• Nevirapine (NVP)

• Rilpivirine (RPV)

Protease Inhibitors (PIs)

• Atazanavir (ATV)

• Darunavir (DRV)

• Fosamprenavir (FPV)

• Indinavir (IDV)

• Lopinavir (LPV)

• Nelfinavir (NFV)

• Ritonavir (RTV)

• Saquinavir (SQV)

• Tipranavir (TPV)

Integrase Strand Transfer Inhibitors (INSTIs)

• Dolutegravir (DTG)

• Elvitegravir (EVG)

• Raltegravir (RAL)

Fusion Inhibitor

• Enfuvirtide (ENF, T-20)

C-C chemokine receptor type 5 (CCR5) Inhibitor

• Maraviroc (MVC)

Pharmacokinetic enhancer (PKE)

• Cobicistat (COBI)

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

Today's approach to HIV infection most often employs a combination of protease inhibitors (usually darunavir boosted with ritonavir), or integrase inhibitor class 2 nucleoside reverse transcription inhibitors. Table 2 describes the regimens that newly diagnosed patients are most likely to start.

Table 2. Recommended Initial Regimens for HIV-infected Individuals

Integrase Strand Transfer Inhibitor-Based Regimens and Combination Product Names

Generic description of regimen

Brand name of combination products

Dolutegravir/abacavir/lamivudine—only for patients who are HLA-B*5701 negative

Triumeq

Dolutegravir plus either tenofovir disoproxil fumarate/emtricitabine or tenofovir alafenamide/emtricitabine

Tivicay Truvada or Tivicay Descovy

Elvitegravir/cobicistat/tenofovir alafenamide/emtricitabine

Genvoya

Elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine

Stribild

Raltegravir plus either tenofovir disoproxil fumarate/emtricitabine or tenofovir alafenamide/emtricitabine

Isentress Truvada or Isentress Descovy

Protease Inhibitor-Based Regimens:

Darunavir/ritonavir plus tenofovir disoproxil fumarate / emtricitabine or tenofovir alafenamide/emtricitabine

Prezista/Norvir Truvada or Prezista/Norvir Descovy

With early treatment and adequate adherence, many patients are able to reach a point of undetectable viral load. This reduces the risk of transmission to other people to almost zero. Contributing to a greater likelihood of reducing viral load is the fact that today, individuals with HIV don't struggle with the enormous pill load they faced in the 1990s. Many patients can take 1 or 2 tablets daily, which significantly improves adherence, and can reach a point where their viral load is undetectable.

In addition to better drugs for HIV itself, there is also a greater understanding of how to treat opportunistic infections; the biggest strides have been made in treatment of drug-resistant tuberculosis.

Officials with the United Nations believe that with coordinated global efforts, the AIDS epidemic could cease by 2030. The biggest barriers to eradication of HIV will be complacency and nonadherence.

Many tools are available to help pharmacists provide better care to patients with HIV. A good reference site is the AIDS Education & Training Center (AETC; https://aidsetc.org/). This site has a number of medication tools and tables that pharmacists can use to simplify dosing, patient counseling, and drug interactions. They also offer a table of medications that patients should avoid when they are on HIV antivirals.

Combinations of drugs—often known as the HIV cocktail—have greatly reduced the likelihood of progression to AIDS and transmission of the virus to others. Pharmacists have an integral role in counseling patients about transmission prevention, testing, early treatment, medication adherence, and how pharmaceuticals improve quality and length of life.

Reference

Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed May 27, 2017.