Cases of rare pneumonias and cancers in otherwise healthy gay males puzzled CDC during the summer of 1981. Uncertainty and fear quickly spread as similar illnesses indicative of severely compromised immune systems were soon identified among injection drug users, infants, and blood product recipients.1 AIDS soon became a household acronym, and in May 1983, the causative agent now called HIV was first reported in Science.1
In the 30 years since, this once-mysterious virus has become perhaps the most rigorously researched infection in the history of modern medicine. The health care world has witnessed the evolution of a global pandemic and the remarkable shift from palliative care to chronic disease management, prevention strategies, and promising scientific breakthroughs.
Mary Cavanaugh-Byers, ACRN, CCM, RN, a recently retired HIV nurse case manager, recalling how the course of this deadly disease changed during her career, commented, “How great it was to see a dear friend take that first Crixivan [indinavir—Merck] dose; help patients kick their pneumonia, grow stronger, and return to work; receive an invitation to a wedding and not a funeral; and see the joy a baby brings to its mother. Even for patients with an AIDS diagnosis, we can now offer hope instead of hospice.”
HIV has emerged as one of the most controversial, stigmatized, and politicized health conditions, due in part to its primary modes of transmission: sexual, parenteral, and mother-to-child.2 Today, more than 60% of persons acquire the virus via male-to-male sexual contact and 25% from injection drug use.3 Other subpopulations disproportionately affected include black and Hispanic/Latino patients, who account for 44% and 21% of HIV diagnoses but only 12% and 16% of the U.S. population, respectively.3
With improved survival and stable incidence rates, the number of people living with HIV has climbed to more than 1.1 million, of which nearly one-fifth are undiagnosed.3,4 Fortunately, AIDS-related deaths appear to have peaked in 1995, falling to an estimated 15,529 in 2010. This decrease can be attributed to a number of factors, most notably the expansion of antiretroviral therapy (ART).2
HIV requires a host cell to replicate and targets CD4 receptors found on T-helper lymphocytes.2 Shortly after infection, rapid viral replication causes a sharp drop in CD4 T-cells, and 50% to 70% of patients with HIV experience acute retroviral syndrome (ARS).2 Although some patients do seek medical attention, ARS is rarely identified as it presents similarly to other self-limiting viral infections such as mononucleosis or influenza.5
Typically within 3 weeks to 6 weeks, the patient’s immune system responds by developing antibodies that slow viral replication and allow partial CD4 T-cell rebound.2 The immune system will often suppress the viral load to relatively low levels, leading to an asymptomatic latent period for a median of 10 years.2 The disease will continue to progress during this time, however, as the virus replicates and CD4 counts gradually deteriorate.2,5 Eventually, most patients experience constitutional symptoms, such as weight loss and fatigue, and are rendered unable to resist life-threatening infections caused by opportunistic organisms.2
A patient’s CD4 count, as a measurement of the immune system’s status, is the strongest predictor of disease progression and survival. This value also guides recommendations for initiating ART and opportunistic infection prophylaxis.6 A patient is diagnosed with AIDS if the CD4 count drops below 200 cells/mm3 or specific health conditions, such as esophageal candidiasis, develop.2 Viral load tests of HIV RNA measure the number of viral copies per mL of plasma.5 Values below the assay’s lower limit of detection are said to be “undetectable,” although the virus is still present.6 Resistance testing is a powerful tool that helps clinicians detect viral mutations that may alter drug efficacy and lead to HIV resistance to certain antiretrovirals.
Treatment with a combination of antiretrovirals, optimally consisting of at least three active medications from at least two drug classes, is referred to as highly active antiretroviral therapy (HAART). More than 20 unique agents with six distinct mechanisms of action are currently available, but HAART typically consists of a dual-nucleoside reverse transcriptase inhibitor (NRTI) backbone combined with a ritonavir-boosted protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), integrase strand transfer inhibitor (INSTI), or CCR5 antagonist.6
Antiretroviral therapy guidelines from the U.S. Department of Health and Human Services recommend treatment for all patients with HIV and designate four preferred regimens in ART-naive patients (see Table 1). The strength of these recommendations and their supporting evidence vary with pretreatment CD4 count and transmission risk; more information may be found in the complete guidelines.
Table 1. HHS recommendations for therapy in treatment-naive patients
ART is recommended for all patients with HIV to reduce the risk of disease progression.
ART is recommended for all patients with HIV for the prevention of transmission of HIV.
Patients starting ART should be willing and able to commit to treatment and understand the benefits and risks of therapy and the importance of adherence (AIII).
Note: Recommendations are rated on a scale of A for strong, B for moderate, and C for optional; evidence is rated on a scale of I for data from randomized controlled trials, II for data from well-designed nonrandomized trials or observational cohort studies with long-term clinical outcomes, and III for expert opinion.
Abbreviations used: ART, antiretroviral therapy; HHS, U.S. Department of Health and Human Services; INSTI, integrase strand transfer inhibitor; NNTRI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.
Source: Reference 6.
Therapy success relies on a collaborative, interdisciplinary approach with regimens tailored based upon drug efficacy, toxicity, interactions and resistance, adherence potential, and patient comorbidities. If clinical or psychosocial barriers arise, ART may be briefly deferred until resolution and the patient better understands the short- and long-term implications of treatment and lifelong adherence.6
Despite a relatively crowded ART marketplace, resistance concerns and pressure to simplify regimens continue to fuel the demand for new therapies. Most recently, GlaxoSmithKline submitted dolutegravir, a second-generation INSTI studied in a fixed-dose combination with abacavir and lamivudine, to FDA in December 2012; it was granted priority review in February 2013.
Other recently submitted HIV medications include cobicistat and elvitegravir, a dedicated cytochrome P450 3A inhibitor (pharmacokinetic booster) and INSTI, respectively. FDA approved these two agents, emtricitabine, and tenofovir as part of the combination product Stribild (Gilead) in August 2012. The agency denied approval for cobicistat and elvitegravir as individual products in April 2013, however, due to deficiencies in quality testing procedures. At present, no additional unique agent is close to market.
As the development of novel HIV therapies narrows, advocates have increased their focus on preventive strategies. In April 2013, the U.S. Preventive Services Task Force published expanded HIV screening guidelines encouraging all persons aged 15 years to 65 years and high-risk adolescents and older adults to undergo testing at least once.7 “High risk” individuals include men who have sex with men and injection drug users, as well as those who have unprotected intercourse; have sexual partners who have HIV, are bisexual, or are injection drug users; or exchange sex for money.7 These updates align with previous CDC guidelines encouraging HIV testing as a component of routine medical care. The Affordable Care Act, which incorporates this recommendation into its preventive services mandate, will require insurers to cover the costs of these tests, which should reduce the percentage of undiagnosed persons living with HIV in the United States.8
Meanwhile, transmission prevention efforts have experienced both advancements and new challenges. The largest ongoing HIV vaccine trial featuring U.S. study centers, the HIV Vaccine Trials Network 505 clinical trial, was discontinued in April 2013 after a safety review board found a lack of evidence supporting the vaccine’s ability to prevent infection and reduce viral load.9 Persons at increased risk, such as those with an HIV-infected partner, can still effectively reduce their infection risk through the FDA-approved pre-exposure prophylactic (PrEP) regimen of once-daily emtricitabine/tenofovir (Truvada) in combination with safe sex practices.10
Despite advancements in ART, significant improvements in the outlook for patients with HIV on a national scale will largely rely on the success of the National HIV/AIDS Strategy (NHAS), a program enacted in 2010 to reduce HIV incidence and health disparities while increasing access to care and optimizing health outcomes.11 NHAS was designed with a collaborative, stepwise initiation plan requiring the orchestration of information and resources by state and federal governments. By 2015, NHAS goals include reducing new HIV infections by 25%, increasing newly diagnosed patients referred to clinical care within three months by 20%, and increasing the percentage of black and Hispanic/Latino patients and gay and bisexual men with undetectable viral loads by 20%.11
With approximately 2 years remaining to reach these goals, it is still too early to measure the program’s success. It is clear, however, that NHAS has led to positive initiatives in both rural and urban communities. HIV educational programs, expanded screening services, and enhanced data collection and sharing are just a few of the NHAS efforts that will augment the resources of communities that struggle to serve indigent HIV populations. As the care for all patients with HIV continues to improve, the NHAS vision of a nation with equal access to comprehensive and affordable health care becomes clearer, as does the long-term goal of a world free from HIV.