Why We Need mRNA Vaccines in Africa, and For All Who Are Immunocompromised

Larry Corey, MD

The HIV pandemic, and COVID-19 pandemic, are intersecting.

The relationship between the two conditions is creating an epidemiological synergy that is starting to translate into additional misery for humankind.

If we can better understand this phenomenon, we can think more clearly about how to better protect the most vulnerable populations among us – people with HIV, and millions of others who are immunocompromised. We have seen overlapping epidemics before, and can draw from that experience.

Let’s start with HIV. Individuals living with HIV have a degree of immunosuppression which varies based on their therapy and disease course. If the disease course is well controlled and fully virologically suppressed on antiretroviral therapy, there is evidence to believe that these patients are at a normal risk of acquiring and controlling COVID-19, much like others in their families and communities.

This analogy is partially accurate in that those living with HIV can, because of their medicines, have obesity, diabetes, and increased lung disease, which are all predispositions or comorbidities associated with severe COVID-19.

Importantly, there are subsets of persons living with HIV, including those who are immune deficient with low T cell counts, those with viremia due to drug-resistant HIV viral strains, those not receiving or not taking antiretroviral therapy; and the many millions we know are living with undiagnosed HIV infection, including those recently infected.

These persons are subject to acquire persistent, prolonged COVID-19 infection, akin to organ transplant recipients and severely immunosuppressed cancer patients.  

There are many causes of immune deficiency, but in many countries, HIV infection is among the most common.

A recent case report by Karim et al. from South Africa, the country with the largest percentage of the population living with HIV of any country, described a case of HIV infection in a person who had very low CD4 counts due to resistant virus and a lack of compliance who developed COVID-19. Over a period of 200 days, this patient—who was ambulatory, living in the community, and without serious symptoms—shed COVID-19. The person had mild illness early on, which is why they were observed, and because of HIV, follow-up care ensued. The investigators had samples from the patient, and they shed COVID-19 at high titers, showing the development of multi-mutational changes in the virus over time. Mutational changes that essentially recapitulated the Beta variant, which has 9 to 11 different mutational changes from the original ancestral strain.

This is a single case, but it’s important because it illustrates a broader issue at work in our communities.

Individual patients living with HIV and compromised immune systems who have this prolonged shedding pattern can result in the kind of mutational changes that lead to germination and spread of variants of concern.

This case is illustrative because it’s not rare. Out of the estimated 38 million people living with HIV worldwide, South Africa alone has more than 16 million. In South Africa, that means one out of every four of its 65 million people are living with HIV.

So okay, the two epidemics are intertwined, what’s the concern? The concern is that these people will suffer more serious COVID-19 cases and that they may serve as the potential unwitting source of super-spreading events of new variants through household and community contacts.

As the greatest population of persons living with HIV is in sub-Saharan Africa, where vaccination rates are currently less than 2% of the populace, this continual reservoir of variant generation is and should be of concern to all of us. We need to recognize that we do not have a demonstrably effective vaccine against COVID-19 among persons living with HIV. People with immunocompromised profiles weren’t included in the well-controlled vaccine studies of the past year, when speed of enrollment was of the essence (see June 29 article in Timmerman Report).

While we lack comprehensive data, we have good reason to be concerned about vaccine efficacy in immunocompromised groups. The data that we have from the Novavax study in South Africa showed absolutely no efficacy against COVID-19. In the Ensemble Johnson & Johnson (J&J) study, too few cases were acquired to adequately evaluate the effectiveness of the one-dose J&J vaccine. And in the Moderna trial, no cases of COVID-19 were reported in the 150 HIV+ recipients who received vaccination. The reason for the lack of efficacy of the Novavax vaccine is puzzling and worrisome, as the post-vaccination binding antibody titers were well above natural infection and in the range associated with reasonable efficacy (median 33,000).

So, what’s going on here? The answer is, I don’t know the reason for lack of effectiveness, but I do know that the mRNA vaccines offer the most immediate solution to this major hole in the public health control of COVID-19 variants.

The data suggest that we need to take our most potent vaccines—mRNA or perhaps two doses of the J&J vaccine or a heterologous “mix-and-match” prime-and-boost with one of the vaccines being an mRNA vaccine—into areas of the world where there is HIV.

We need to urgently take steps to evaluate if our best vaccine regimens are able to effectively prevent acquisition of COVID-19 in all persons living with HIV, but especially among those with uncontrolled HIV.

This is the kind of urgent, heavy lifting that only the US government can do in an emergency.

The tale of these two intersecting epidemics needs a better ending than what we—as a global community—are currently creating. The Delta variant epidemic is rapidly illustrating that chasing variants is not a successful strategy. The Delta variant has swept through countries like the UK, Israel, and South Africa in four to eight weeks and is approaching the predominant variant in the United States at a speed that even with RNA technologies, we cannot keep up. Our approach must be to slow down the generation of these rapidly doubling super-spreading micro-epidemics of infection among unvaccinated persons.

The equation today among those unvaccinated individuals is not whether you will get COVID-19 infection but when you will get it. Slowing it down requires our best vaccine strategies. It’s certainly not too late. But we need both studies and implementation of our most potent vaccines and vaccine regimens to be applied to all of our immunosuppressed populations, the largest of which is HIV, for us to have a globally effective strategy.

Dr. Larry Corey is the leader of the COVID-19 Prevention Network (CoVPN ) Operations Center, which was formed by the National Institute of Allergy and Infectious Diseases at the U.S. National Institutes of Health to respond to the global pandemic and the Chair of the ACTIV COVID-19 Vaccine Clinical Trials Working Group. He is a Professor of Medicine and Virology at University of Washington and a Professor in the Vaccine and Infectious Disease Division and past President and Director of Fred Hutchinson Cancer Research Center.

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