The Growing Importance of Hepatitis Co-Infection among Persons Living with HIV

The Growing Importance of Hepatitis Co-Infection among Persons Living with HIV

Because of shared routes of transmission, co-infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) is common among PLWH, contributing significantly to liver-related morbidity and mortality in this population.^81-83 Even with virologic suppression via ART, PLWH continue to have evidence of immune deficiency, dysregulation, and activation that may contribute to increased risk and severity of non-AIDS comorbidities, including the liver disease associated with viral hepatitis.^84-88 HBV and HCV may each lead to cirrhosis and hepatocellular carcinoma and, in both cases, co-infection with HIV accelerates progression to these end-stage manifestations of disease.^89-94

Worldwide, HBV is the leading cause of chronic liver disease and is estimated to be responsible for 620,000 deaths per year.^95,96 In the United States and Western Europe, 6-14% of PLWH are also chronically infected with HBV.⁸¹ The risk of liver-related mortality increases eight-fold in the setting of HIV/HBV co-infection compared to HIV mono-infection and all-cause mortality is increased beyond the mortality rate of either infection alone.⁹⁷ Drugs with activity against both HIV and HBV—such as tenofovir, lamivudine and emtricitabine—are effective at reducing HBV viral load, but patients treated with these drugs remain at risk of developing end-stage liver disease and its complications.⁹⁸

In the United States, Europe and Australia, approximately 20-30% of PLWH are also chronically infected with HCV.^81-83 Although spontaneous recovery from HCV infection occurs in 20%-30% of people without HIV, clearance occurs in only 5-15% of people co-infected with HIV.^99-102 Clinical manifestations of liver failure secondary to HCV such as ascites, encephalopathy and esophageal varices are all more common in the presence of HIV co-infection and contribute to increased morbidity among HIV/HCV co-infected patients as compared to HIV mono-infected patients.^103-105 HCV is also associated with extrahepatic complications such as renal disease, cardiovascular disease, diabetes, and neuropsychiatric disorders.^106-110

Because it is such a common comorbidity among PLWH, viral hepatitis is quickly emerging as one of the most important contributors to morbidity and mortality in this population. As the HIV-infected population in the United States continues to age, diseases that are traditionally associated with HIV, like pneumocystic pneumonia and Kaposi sarcoma, are likely to play a diminishing role in morbidity and mortality among PLWH. Chronic illnesses such as liver disease, renal disease, and cardiovascular disease will play an increasingly important role in influencing overall health and healthcare needs among PLWH.

Failures of Healthcare in the United States for Persons Living with HIV

In 2009, 81.1% of PLWH in a nationally representative sample had health insurance, including 40.3% with Medicaid, 30.6% with private health insurance, and 25.7% with Medicare.¹¹¹ Furthermore, among PLWH diagnosed from May 2004-April 2009, 37% reported a lapse in insurance coverage during the previous 12 months and this lapse was independently associated with delays in initiation of life-saving ART as compared to persons with continuous coverage.¹¹² The distribution of third-party payors among PLWH is very different from that observed in the general U.S. population, in which 63.9% of persons were privately insured, 15.7% had Medicaid, and 14.1% had Medicare in 2009.¹¹³ These differences are driven largely by the fact that HIV disproportionately affects individuals with lower socioeconomic status. In 2009, 43.8% of PLWH had household incomes at or below federal poverty guidelines.¹¹¹

Health insurance coverage is highly correlated with overall health. People with health insurance are more likely than those who are uninsured to use preventive services and enjoy better clinical outcomes, including lower risk of mortality.^114-117 Among PLWH, health insurance coverage is associated with a greater likelihood of sustained virologic suppression, lower use of acute care services, and decreased risk of developing clinical AIDS.^118-120

Even among PLWH who are insured, underinsurance may remain an issue. For example, in order to receive prescription drug coverage through Medicare, individuals must opt to enroll into the Medicare Part D program, which requires payment of a separate premium. These plans have complex schedules of cost-sharing tiers, deductibles and co-payments that may each leave patients with significant healthcare costs. Most plans also have coverage gaps, commonly referred to as “doughnut holes,” wherein the insurer covers a portion of medication costs up to a certain annual allowance. After reaching this allowance, individuals are responsible for the full cost of prescription drugs until Medicare catastrophic prescription coverage kicks in and again starts covering such expenses. The existence of “doughnut holes” in Medicare prescription drug plans can cost insured PLWH thousands of dollars, creating a precarious situation for low-income patients who may not always be able to afford medications and are living with a disease that requires strict medication adherence.¹²¹

Since passage of the Ryan White Comprehensive AIDS Resources Emergency (CARE) Act in 1990, federal and state governments have provided financial support to deliver HIV care, medications and social services that were not otherwise available to uninsured and underinsured low-income PLWH. In 2012, $2.4 billion was allocated from the federal budget to support the Ryan White HIV/AIDS Program.¹²² This included over $1 billion allocated to AIDS Drug Assistance Programs (ADAPs) that are administered separately by each of the 50 states, the District of Columbia, the Commonwealth of Puerto Rico, the U.S. Virgin Islands, American Samoa, the Federated States of Micronesia, Guam, the Northern Mariana Islands, Republic of Palau and the Republic of the Marshall Islands. These programs provide medications—principally antiretrovirals—to low income, uninsured, and underinsured PLWH who would otherwise not have access to these life-saving medications. Additional state contributions and drug rebates brought the total budget for these programs to over $2 billion in 2012 and 2013.¹²³ ADAPs are designed to be a “payer of last resort,” to be relied upon when all other avenues for acquiring medications are exhausted. Despite significant spending, ADAP budgets still often fell short of demand. From 2008 to 2013, it was not uncommon for state programs to have waiting lists, forcing ADAPs to limit formularies and ration drugs.^122,124 It was not until November 11, 2013, that ADAP waiting lists were finally cleared and all eligible patients enrolled, largely owing to an influx of emergency funding from the federal government that began in 2010.¹²³

Even with all eligible patients enrolled in ADAPs, coverage gaps exist. Individual states determine whether to contribute to ADAPs, how much to contribute, what drugs to include on formularies, and what patient characteristics determine eligibility for these programs. In 2013, 16 of 51 ADAPs reporting data did not receive any state contributions.¹²³ In 2010, only Massachusetts, New Jersey, New York and Pennsylvania included guideline-based medications for diabetes, hypertension, dyslipidemia, and smoking cessation on their ADAP formularies; thirteen states listed no drugs for any of these chronic comorbidities on their formularies.¹²⁵ This is despite the fact that treatment for each of these could reduce the prevalence of cardiovascular disease, which is disproportionately common among PLWH as compared to the general population and accounts for about a quarter of all deaths.^67,69,126

The U.S. government spends a considerable amount of money on specialized programs for the support of HIV-related healthcare. These programs are unlike those afforded to any other disease. Still, the system falls short of meeting the increasing healthcare needs of a growing, aging, and largely underinsured HIV-infected population.