As new therapies for HIV/AIDS extend many patients' lives, pharmacists are well situated to help them manage the disease
Approximately 1.2 million people in the United States are living with human immunodeficiency virus (HIV), according to the Centers for Disease Control and Prevention (CDC). Of these, 20% are unaware of their HIV status - and of the fact that they will be responsible for 50% of all new cases of the disease.
Over the next 20 years, another 1.2 million new HIV infections are estimated to occur, with a lifetime cost of $450 trillion. The current rate of disease progression is simply unsustainable.
Of the individuals who are aware of their HIV status, only half remain in care, meaning that they see their healthcare providers and receive antiretroviral (ARV) agents when indicated. In 2011, there were approximately 32,000 new diagnoses of acquired immunodeficiency syndrome (AIDS) in the United States, according to CDC. (http://www.cdc.gov/hiv/statistics/basics/index.html)
The management of HIV/AIDS has seen unparalleled progress in a relatively brief time. In approximately 30 years, our knowledge of the disease and development of treatment options have transformed a diagnosis of HIV from a terminal disease with a short life expectancy to a chronic disease with a longer life expectancy. Yet despite the investment in research and development, and despite the tremendous strides that have been made, only one out of every four persons living with HIV achieves viral suppression.
As we continue to progress in our management of the disease, pharmacists have the opportunity to help alleviate the burden associated with HIV. Pharmacists, especially those practicing in the community, can be valuable members of interdisciplinary teams; the can assist in identifying the estimated 236,400 patients unaware of their status, linking them to specialty care, reducing the likelihood of medication errors, and ensuring medication adherence, thus having a positive effect on patients’ CD4 counts and HIV RNA.
Relatively speaking, HIV is a fairly young disease. Although unconfirmed, it is assumed that the most common HIV strains made the jump from chimpanzee to human sometime in the late 19th or early 20th century.
One of the more common theories connected with its origin is the “Hunter Theory,” which suggests transmission through zoonosis, the transmission of an infection from an animal to a human. In this case, chimpanzees infected with simian immunodeficiency virus (SIV) transmitted the virus when a hunter was bitten or cut, exposing the hunter to SIV, which mutated into HIV. The virus is thought to have made its way to the United States by way of Haiti sometime in the late ’60s or early ’70s.
In 1981, the CDC published a report detailing accounts of five previously healthy homosexual males in their late 20s to mid-30s, presenting with Pneumocystis carinii pneumonia (PCP, now Pneumocystis jiroveci) in the Los Angeles area. Although it couldn’t have been known at the time, this report marked the beginning of the HIV/AIDS epidemic in the United States. In September 1982, the CDC officially coined the term “acquired immunodeficiency syndrome (AIDS).” (The timeline accompanying this article indicates other major events in the history of HIV/AIDS.)
No treatment options were available until March 1987, when zidovudine (Retrovir), a nucleoside reverse transcriptase inhibitor (NRTI), became the first ARV agent to win FDA approval. The NRTIs were the only drug class available until ritonavir (Norvir) and indinavir (Crixivan), the first protease inhibitors (PI), were approved in March 1996.
After approval of the PIs, delavirdine (Rescriptor), the first non-nucleoside reverse transcriptase inhibitor (nNRTI), received FDA approval in April 1997. In 2003, the first fusion inhibitor was approved, followed by the CCR5 antagonists and integrase inhibitors (InSTI) in 2007. With the approval of Stribild last year, which includes elvitegravir (a novel InSTI) with a pharmacokinetic enhancer and two NRTIs, there are 24 different ARV agents, among six different drug classes, currently approved and available for the treatment of HIV.
Approximately 216,000 individuals unknowingly living with HIV are responsible for almost 50% of new infections. One way to reduce the burden of new HIV infections is by identifying those with previously unknown HIV-positive status and linking them to care. It has been well documented that if a patient is receiving therapy, the risk of transmission is decreased. At present two organizations offer recommendations on HIV screening: the CDC and the U.S. Preventive Services Task Force (USPSTF).
In the past, their guidelines recommended that patients classified as “high-risk” should be regularly screened. However, as of April 2013, both sets of guidelines now suggest that everyone between the ages of 15 and 65 years should be screened. The availability of these tests has expanded beyond physicians’ offices and emergency rooms into community pharmacies and even into at-home testing.
The primary set of treatment guidelines used in the United States was published by the Department of Health and Human Services (HHS) and endorsed by the CDC. The guideline authors meet on a monthly basis to determine whether updates or amendments to the guidelines are needed.
With the 2012 and 2013 updates, HHS has made significant changes to its treatment recommendations. Previously, the recommendation was to wait to initiate therapy until patients’ CD4 counts fell below 200 cells/mm3. This recommendation has now changed, as more evidence has shown that earlier initiation has resulted in better patient outcomes and decreased transmission rates. (See Figure 1 for the most recent HHS recommendations on when to initiate therapy.)
In addition to its recommendations related to CD4 counts, HHS recommends earlier initiation of antiretroviral therapy (ART) as a step toward decreasing transmission rates. This recommendation is grounded in concern for public health.
Once the decision is made to initiate therapy, the guidelines offer specific treatment options. The HHS guidelines recommend a potent ARV combination therapy for initial treatment (Figure 2). Generally, a potent ART regimen consists of two NRTIs, plus either one nNRTI, a ritonavir-boosted PI, or an InSTI (Figure 3).
The patient’s lifestyle and desire to initiate medications should be at the center of any treatment-related decisions. HIV/AIDS differs from most chronic disease states, in that there are no proven nonpharmacologic therapies for its treatment. Antiretroviral agents are responsible for the extended life expectancy and decreased transmission rates.
It is imperative that patients taking ARV medications remain adherent. While an adherence rate of 80% is generally acceptable for other disease states such as diabetes or hypertension, this is not the case with HIV/AIDS. Patients must be at least 95% adherent with their ART in order to prevent development of resistance and transmission of the disease, according to a 2000 report published by the Annals of Internal Medicine (Paterson DL and colleagues).
There are now combination products such as emtricitabine/tenofovir (Truvada; Gilead Sciences) or lamivudine/zidovudine (Combivir; GlaxoSmithKline) that give patients their NRTI “backbone.” In addition, there are three full-regimen combination products that come in once-daily single-pill regimens (Stribild, Gilead Sciences; Atripla, Gilead Sciences/Bristol-Myers Squibb; Complera, Gilead Sciences).
Even though the regimens have become simpler and the pill burden has decreased, patient adherence should be emphasized and positively reinforced with every patient interaction.
While the past 20 years have seen major developments in the area of treatment, recently there have been significant breakthroughs, and the foreseeable future is likely to bring more.
In July 2012, emtricitabine /tenofovir (Truvada) was given an additional indication for use in pre-exposure prophylaxis (PrEP). With this new indication, HIV-negative patients will have a pharmacologic option for prevention of virus transmission from a sero-positive partner.
The introduction of dolutegravir (ViiV Healthcare) will bring a new once-daily InSTI with a clean side-effect profile to the market. This could become the preferred agent in that class of medications.
There is ongoing research into NRTI-sparing regimens, which may help decrease long-term side effects.
On the subject of vaccines for prevention of HIV infection, the trials have been relatively disappointing thus far. That is not to say that a vaccine will never happen, but it is further down the line.
The search for a functional cure that would make medication therapy no longer necessary has been energized recently by the cases of the Berlin patient who became virus-neutral following a complete bone-marrow transplant and the baby in Mississippi who achieved similar status after receiving immediate treatment once the infection was discovered. Although their circumstances are different, both of the patients appear to have been functionally cured.
From decreasing the pill load to preventing serious interactions and strengthening adherence, pharmacists are key influences when it comes to improving the lives of patients and supporting public health.
In addition to the public health benefits, there also is a significant business case to be made for pharmacies to focus on HIV management. HIV medications cost, on average, $2,000 to $5,000 per month and can run as high as $27,000 per year. Patients living with HIV may also spend more onn over-the-counter products and complementary therapies; they may also visit the pharmacy more often.
Community pharmacists can take simple measures to attract and assist patients living with disease. One option is to offer in-depth, MTM-style meetings with HIV patients. By providing education along with a medication review, pharmacists may discover underlying issues of nonadherence and prevent medication-related issues in the future.
Another way to attract patients living with HIV is to provide compliance packaging that addresses their complex regimens and comorbid conditions, such as cardiovascular disease and diabetes. In this connection, pharmacists can use packaging systems typically employed by assisted living facilities to improve adherence.
Finally, pharmacists can also implement adherence reporting for physicians who prescribe ART. Pharmacies that have implemented this simple strategy have reported increased numbers of HIV-related prescriptions coming in from satisfied physicians.
In relative terms, the understanding and treatment of HIV/AIDS have come a long way over the past 30 years. There is still a long way to go, as treatment shifts from dealing with a terminal illness to managing a chronic disease with multiple comorbidites, such as cardiovascular disease and diabetes.
To help maximize therapeutic benefits, medication experts must be integral members of the team. Pharmacists have a relationship with their patients that other healthcare providers do not, and they are in a position to significantly affect disease-state management. Rated among the most accessible and trusted healthcare professionals, pharmacists have access to the complete medication profile, including OTC medications; they can identify drug-drug interactions or medication errors; and they are aware of the degree to which patients adhere to their medications.
As the stigma of HIV continues to fade, pharmacists will capitalize on the opportunity to help HIV patients, improving at the same time the pharmacy’s bottom line.