One Shot or Two? Necessity of COVID-19 Vaccination Among People Living with HIV and/or Chronic Liver Disease

At the time of this writing, the United States’ Food and Drug Administration (FDA) has provided Emergency Use Authorizations (EUAs) to 3 COVID-19 vaccines, with Novavax’s product potentially leading the race to become the fourth. While some have fretted over “which vaccine” is “the best”, governors and clinicians have resoundingly adopted a simple answer: “which ever vaccine you can get”. While President Biden has pushed to expand eligibility to all adults in the US by May 1st, as we’re all too familiar with in patient advocacy, eligibility does not necessarily equate to access and, in this respect, demand still vastly outstrips vaccine supply domestically.

The debate on who should get a vaccine and when began well before the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations in December 2020. ACIP’s recommendations focused primarily on constructing an ethical model based on hospitalizations and mortality, with an eye toward those performing duties most necessary to meet the health care demands of the moment. Ultimately, outside of this job-based prioritization, ACIP gave top priority via age-based allocation and then ascertaining those at-risk for these outcomes based on pre-existing conditions. Most states adopted some version of these prioritized populations. The debate on the efficacy of this model continues to rage on – what about those in marginalized communities more impacted by COVID-19 than more affluent communities? What about younger people with comorbidities? Which health conditions should be prioritized?

Regardless of where one’s local government falls on this debate, evidence catalogued by the CDC indicates a very real need for people living with HIV and those with chronic liver diseases to seek a vaccine as readily as possible as these cohorts are at increased risk for complications related to a COVID-19 infection. Studies have found PLWH experiencing an acute COVID-19 infection may see as much as 50% drop in CD4 T-cells compared to their historical levels, a condition known as lymphopenia – of which, is also an indicator for severe COVID-19 and protracted recovery or death. Additionally, the same study found key clinical metrics used to measure inflammation were similarly increased among PLWH. Another study out of Wuhan, examining people with chronic, yet controlled Hepatitis B infections may see a reactivation of viral activity and/or potentially face significant progression of liver cirrhosis during and after a COVID-19 diagnosis. Another study found SARS-CoV-2 may target certain cells in the bile tract and cause focused damage to the systems serving a person’s liver, with another study suggesting the need for health care providers to emphasize liver repair post COVID diagnosis.

While Janssen ensured PLWH were enrolled in phase 3 clinical trials for their product, none of the currently authorized products included solid organ transplant recipients in their trials. While the American Society of Transplantation notes COVID-19 vaccine administration recommendations for solid organ transplant recipients remains the same as other vaccines (either completed at least 2 weeks prior to transplant or initiated at least 1 month after transplant). Which may pose a problem according to a study published in March showing transplant recipients having received the first shot in the series mounted an antibody response just 17% of the time. While antibody responses are not necessary to confer immunity, they are the leading indication of an immune response. The authors of this study will be seeking to answer that question later this year.

Furthermore, additional research is needed in assessing post-acute COVID-19 infections and the implications of “long COVID”. Most research at this moment on long-COVID is tied to assessing symptom presentation and frequency of health care needs. However, there is a minor bit of information regarding organ function post-hospitalization with COVID-19 – none of it is “good news”. In particular, people experiencing chronic liver diseases were almost 2 times as likely to experience “major adverse events” after being released from the hospital due to COVID-19.

All of this information culminates with a sense of urgency some states are heeding in expanding vaccine access “ahead of schedule” to include people living with HIV or specific programming targeted to provide vaccines to these communities.

Brandon Macsata, CEO of ADAP Advocacy Association, recently penned a blog addressing any hesitancy among people living with HIV around getting their vaccines: “Vaccines are an important element of the journey, along with proven public health strategies (i.e., wearing masks, remaining social distant, washing hands). For the HIV-positive community, it is even more important for us to do our collective part to protect ourselves, as well as the people around us. Get your Covid-19 vaccine!”

With the CDC’s guidance on prioritizing our communities in vaccination schemes, I couldn’t agree more.

What About Us? Reflections on What the Global Covid-19 Vaccine Means to HIV

A year ago, the world turned its eyes to a justifiably disparate race to find any possible treatment, cure, or prophylactic for COVID-19. The collective experience was familiar to veterans of the fight against HIV – though, for some, the feeling was tinged with dulling hope and cynicism. Afterall, the first HIV vaccine trial began in 1987. A near 35 years later and we’ve yet to find an effective and safe protective vaccine.

The COVID-19 effort spurred extraordinary and sometimes bizarre theories, with journalists soaking up non-peer-reviewed pre-prints with the abandon of a starving person. From theories on hormone replacement therapies to reduce blood clotting risks to the now-infamous hydroxychloroquine episodes to convalescent plasma to repurposing our own antiretroviral therapies, many, if not most, of these failed the test of time. Something HIV advocates and researchers are all too familiar with. As a result of the pressure and need, the Trump Administration initiated one of the largest scale federal research funding initiatives in history: Operation Warp Speed, promising to deliver a vaccine for the novel coronavirus in record time.

The resulting skepticism was understandable. Previously, the fastest any modern vaccine had been developed was about 5 years, with the current mumps vaccine. The difference this time, though, was vaccine tools that had failed elsewhere, in the fights against cancer, Ebola, and other diseases, had provided us the opportunity to “practice” for such an incident – expanding the unused tools in the toolbox as it were. Included among these was a near 50 year old theoretical approach, using messenger RNA to teach our bodies how to fight this new pathogen. Moderna and Pfizer did indeed produce such a product in December 2020.

While the world praised these developments, HIV also took an exception to the announcements. We’ve been waiting nearly 40 years for the same technological miracle. With more than 75 million known transmissions, approximately 32 million having died from AIDS related complications, and 38 million people currently living with HIV, since the start of our pandemic, it’s understandable to ask “what about us?” Where was this “warp speed” effort in 1995 when AIDS was the leading cause of death among 25-44 year-olds in the United States?

It’s important to note: coronaviruses and HIV are two very different types of viruses. Coronaviruses maintain a greater integrity in their reproduction processes and HIV’s “copy writers” are known for making “mistakes”, developing mutations and resistance to medications. As such, coronaviruses “mutate” at a much slower rate than HIV. Despite the very warranted concerns on SARS-CoV-2 variants, most vaccine products coming to market are showing promise in beating back these emerging threats. Whereas HIV is also known to “hide” viral reservoirs within a person’s body – merely waiting to be activated, thwarting certain progress.

Still, technology moves forward and hope springs eternal. Moderna has already announced intentions to use mRNA vaccine technology to produce more accurate vaccines for influenza, personalized vaccines for certain cancers, and HIV. Scribbs Research has also recently announced a phase I trial utilizing “germline targeting” technology to stimulate the exact B-cell responses for a body to develop HIV neutralizing anti-bodies.
Additionally, in a remarkable find, Abbott has recently identified an extraordinary occurrence of elite controllers, those with HIV antibodies but no or undetectable viral load without the use of antiretroviral therapies, in the Democratic Republic of Congo (DRC). With a prevalence of 2.7-4.3%, as opposed to 0.1-0.2% elsewhere in the world, researchers believe this population provides us an opportunity to investigate what is essentially a natural occurring immunity to HIV, something medicine doesn’t currently understand well enough to replicate. Abbott was able to identify this population through surveillance activities, as its screening tools are used in about 60% of the world’s blood supply donations, where information gathered is also used to identify emerging diseases – in particular “new” strains of HIV and viral hepatitis. Abbott’s findings state this occurrence of elite controllers is extends as far back as 1987, prior to the advent of antiretroviral therapies, at “similarly elevated levels”.

Regardless of the promise (read: hope) of a protective or therapeutic vaccine for HIV, any effective product is bound to face the same persistent issues of equity COVID vaccines are currently facing. From trial design by and inclusion of the most affected communities to equitable distribution outside of western countries, we absolutely run the risk of perpetuating existing global health disparities. Manufacturers, governments, and researchers will need to better align their actions with our moral and ethical obligations in order to truly end HIV for all, instead of just some.