Adherence
There is a new HIV epidemic worldwide and 44% of these new infections are occurring in people from racial minorities and marginalized groups, including gay men, bisexual men, drug users, sex workers, transgender individuals, adolescents, and their partners. Even though new infections are declining globally, they remain substantially higher amongst younger populations. Mr. George Johnson wrote an open letter to physicians in the United States in an article in Vice Media regarding the treatment of black and latinx HIV infected patients saying, “We continue to see a chasm between patients from marginalized communities and those who are responsible for our treatment and long-term care. With everything from daunting signage to doctors’ inaccurate presumptions, there are concrete reasons as to why the HIV healthcare system is losing marginalized patients.” The reason why this problem is so significant is because doctors and health systems struggle to engage these groups and provide appropriate services to at-risk youth and marginalized people. Even though the rate at which HIV infection in these populations rise, healthcare systems cannot engage with them enough to increase adherence of PrEP and decrease the overall prevalence of infection.
In the United States, among men who have sex with men, the CDC reports 26,753 cases of HIV infection in 2015, and 26,844 cases in 2016. In 2016, gay and bisexual men accounted for 67% (26,844) of all HIV diagnoses and 82% of diagnoses among males aged 13 and older. Among all gay and bisexual men who received an HIV diagnosis in the United States, African-Americans accounted for the highest number (10,226; 38%), followed by Hispanics/Latinx (7,689; 29%) and Whites (7,392; 28%). Other races/ethnicities accounted for 1,537 (6%) diagnoses among gay and bisexual men. Black and latinx populations had the highest rates of HIV infection from 2011 to 2016 with a combined total of 740,184 compared to whites with 439,998. In 2017, male-to-male sexual contact was the most prevalent means of transmission for HIV infection with the total number being 25,748. Also in 2017, 16,694 African-Americans were diagnosed with HIV compared to 10,049 Whites and 9,908 Hispanics/Latinx. Those between the ages of 25-29 also saw an increase of HIV infection from 7,692 in 2015 to 8,030 in 2016. The region of the United States with the highest rates of HIV infection is the South, with 20,588 cases. The most widely acceptence HIV prevention therapy is PrEP. Pre-exposure Prophylaxis (PrEP) is an oral pill, composed of antiretrovirals–tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC), taken daily to prevent HIV infection. In 2016, among 32,853 (41.9%) PrEP users, 68.7% were white, 11.2% were African American or black, 13.1% were Hispanic, and 4.5% were Asian. Although black men and women accounted for approximately 40% of persons with PrEP indications, this study found that nearly six times as many white men and women were prescribed PrEP as were black men and women. The problem is that there is a gap between races of effective PrEP in America.
Pre-exposure prophylaxis (or PrEP) is used when people at very high risk for HIV take medicines daily to lower their chances of getting infected. This preventative regimen works in over 90% over users to prevent HIV infection, and is particularly prescribed to at-risk populations including gay men, bisexual men and injecting drug users. Condom use, in addition to PrEP, substantially decreases the rate of HIV infection. Understanding the pharmacology of PrEP is critical for clinicians to know its effectiveness. Standard PrEP treatment includes a once-daily 300mg dose of TDF and 200 mg dose of TDF/FTC. TDF and FTC are nucleoside analog reverse transcriptase inhibitors (NRTIs) that are phosphorylated to form a pharmacologically active diphosphate and triphosphate anabolites. A unique feature of these NRTIs is the long half-life and “pharmacologic forgiveness”, meaning it lasts in the bloodstream for a longer period of time without degrading, and may be less impacted by drug-to-drug or food-to-drug interactions. The efficacy of these drugs may be reduced in patients already infected with HIV due to drug resistance. Fortunately, there has not been serious side effects associated with PrEP use. In a clinical trial led by Dr. Jared Beaton, MD, PhD, only a small amount of users (10%) experienced gastrointestinal side effects (nausea) that lasted for a short period of time. TDF has been associated with renal complications, however, the clinical trial found no increased risk of renal complications in healthy HIV-uninfected people. FTC and TDF quickly emerged as viable and practical PrEP agents based upon safety and tolerability from studies in HIV-infected subjects, potential cost-effectiveness, penetration into target tissues and expected HIV resistance profile, if HIV infection were to occur during PrEP use. In addition, these agents have favorable pharmacological characteristics that allow for once daily and potentially less frequent dosing, and theoretical effectiveness during periods of missed doses.
Studies have proven the effectiveness of PrEP in preventing HIV. However, there are other barriers that can hinder marginalized populations from accessing this treatment. In the United States, young, black or hispanic men-who-have-sex-with-men (MSM) have the highest incidences of HIV infection, yet they are among the fewest users of PrEP. An online survey was completed by black, hispanic, and white HIV-infected men between the ages of 18 and 24 years old regarding sexual behavior, healthcare access, and previous PrEP use and only 3.4% of the 2,297 respondents used PrEP. PrEP use was associated with higher levels of education, greater healthcare access, and having a primary care physician (PCP). Additional multivariable analysis was performed showing that older MSM, blacks, hispanics, those with fewer years of education, and southwestern US residents were less likely to have access to proper healthcare. This data confirms the disparities in PrEP adherence among races in America, and more opportunities must be made for these marginalized populations to have access to PrEP. Drug resistance is fair consideration in analyzing the effectiveness of PrEP for users. Drug resistance occurs when a virus develops a mutation that makes it resistant to antiviral drug therapy. In a randomized trial of PrEP users, only 2% of TDF or FTC drug-resistant infections had resistance. No adverse effects are associated with TDF or FTC use. They are generally safe antiviral compounds, however, some side effects associated with first-time use can be present in some PrEP users then subside after a month. These side effects include gastrointestinal disturbances such as abdominal pain, nausea, vomiting or diarrhea.
An important factor in the successful implementation of PrEP and decreasing the prevalence of HIV infection in marginalized populations is adherence. Some social determinants of HIV transmission include poverty, education, housing, income, and insurance. PrEP research and implementation has been most successful among MSM of a higher educational and socioeconomic status, yet there are still many barriers that keep minority populations from access to PrEP resources. One particular study analyzed theses barriers for Latinx population living in the U.S. through an ecosocial lens. Kathleen Page and colleagues described structural barriers to healthcare for immigrant populations that can decrease adherence, including lack of health insurance, ineffective patient-provider communication, low health literacy, and limited English proficiency. Many southern states, with high latinx populations, lack medicaid expansion and limited health insurance coverage. Foreign-born individuals are eligible for health insurance coverage under the ACA only if they are naturalized citizens or have been permanent residents for more than five years, and temporary immigrants or those without documentation are ineligible for coverage. These are examples of how PrEP is inaccessible to many latinx individuals who could benefit, and may be at elevated risk as recent immigrants. PrEP should be accessible to all at-risk populations to decrease the prevalence of HIV infection. Increased awareness is also an important factor that can increase adherence. Omar Martinez conducted a qualitative study which assessed the awareness of PrEP amongst spanish-speaking MSM in New York City and found that most of them have not even heard about PrEP. One of the reasons Latinx populations have not taken PrEP was due to unawareness or inaccessibility to healthcare.
Many challenges arise for preventing HIV infection, which are recognized by the CDC. One of them being that 1 in 6 gay and bisexual men with HIV are unaware they have it. Since they don’t know they have it, they continue to transmit the infection to their partners. Additionally, most gay and bisexual men have anal sex without using condoms and don’t take PrEP which increase transmission. The CDC also notes that homophobia, stigma, and discrimination place gay and bisexual men at risk for many physical and mental health problems that can affect their ability to seek preventative health care services. Finally, as noted previously with the Latinx population, socioeconomic factors are a critical challenge in PrEP use amongst racial and sexual minorities. These socioeconomic factors include lower income and educational levels and higher rates of unemployment and incarceration. In order to combat these disparities, the CDC funds state and local health departments to increase surveillance and prevention efforts. This research supports the conclusion that PrEP use remains low for at-risk populations due to many challenges. The incidence of HIV infection in at-risk populations will continue to remain high unless these challenges are addressed. Healthcare providers are critical for implementation and adherence of PrEP among all populations, however, black and hispanic MSM may not even have access to a physician due to their disproportionately lower socioeconomic status.
Current preventative measures being researched that can make the most impact for populations high-risk for HIV infection include an HIV vaccine. If HIV vaccination therapy is successful, preliminary studies have predicted a worldwide decline of HIV infection from 1.7 million currently, to 257,000 by 2070. Only six human HIV efficacy trials have been conducted using Vax003, Vax004, Step, Phambili, HVTN 505, and RV144, yet the RV144 trial conducted in Thailand was the only trial with the lowest HIV incidence. The efficacy was 60% but eventually dropped to 31%. These results show that the goal of producing HIV vaccines warrants more research before such vaccine can be available to the public. Combination therapy has been an alternative treatment measure that was explored with PrEP and HIV vaccine candidates. Ted Ross and colleagues performed combination research by applying DNA vaccine SIVmac239 Gag intramuscularly, with FTC and TDF drugs orally to rhesus macaques and observed 87.5% efficacy. No clinical trials have been conducted. PrEP is the standard for HIV prevention due to the lack of effective HIV vaccination or combination therapy. In order to decrease the epidemic of HIV infection amongst high-risk populations, there must be an increase in adherence to PrEP. PrEP remains an effective means for preventing HIV infection in at-risk populations.