HTB: no. 6 – plus HIV and COVID-19 (1 June 2021)

This issue contains continued coverage from both the excellent BHIVA/BASHH – with many summary reports – conference and CROI.

But for most of 2021 there has been a move in our COVID-19 reports from potential treatments to the impact of the vaccines, including, this week, the UK approval of the Janssen vaccine.

Effective treatments are still just as desperately needed of course – and treatment research still continues. This issue includes links to a new review of ivermectin.

But the high efficacy of the vaccines has focused management of the pandemic by working towards maximum vaccine coverage, as quickly as possible.

Vaccine efficacy is complex. So far, all authorised vaccines generate both humoral and cellular responses.

Estimates of vaccine efficacy are still mainly based on results from large phase 3 studies. But in this issue we include several reports on people who were not generally included in these studies but who are showing antibody responses limited protection from vaccines.

• People older than 80 (also reported in the previous issue)

• People with severe immune suppression, including people with solid organ transplants.

France has responded by already offers a third vaccine dose (though low CD4 count and HIV are not included) in the hope that this might generate higher antibody titres, similar to approaches with some other vaccines.

But without data we currently do not know whether these concerns will affect HIV positive people who have a very low CD4 count. We report on a small US study showing lower antibody responses followiing the firt dose, but it is response after the second dose that counts. And we need data on a broad range of lower CD4 counts, and in people with detectable viral load, and at higher ages etc etc.

So while limited data showing good vaccine responses in people on ART with a good CD4 count, there is no evidence of protection in the most at risk group, defined by BHIVA as having a CD4 count < 50 cells/mm3.

As a result, BHIVA helpfully continue to recommend caution to reduce risk of infection in the higherst risk grousp. BHIVA have also formally requested that a low CD4 count should be included in the UK criteria for a third vaccine dose, if this programme is approved, possibly in the Autumn.

On a population level, vaccine programmes also edge towards high enough uptake to reach herd immunity. Estimated targets for herd immunity to control a national epidemic range from 60% to upwards of 85%.

As this issue of HTB went to virtual press, this level in the UK is around 35%. So although 36 million people have received at least once vaccine, generating partial protection, just over 20 million have received two shots. This makes the UK one of the countries with the highest vaccine covers.

Both daily cases and mortality have also dropped but this is still under lock down restrictions. What happens as lock down relaxes in uncertain, especially with the new B.1.617 variants.

Of serious concern, we report cases of COVID -19 in care home residents who have had two vacciines doses, but where vaccination of staff needs to be universal. Although the vaccines still provided population protection, two of these residents progressed to severe COVID-19 and died.

More optimistically, women during pregnancy, also not included in studies (although pregnancy occurred) are showing similar immunogenicity to women who are not pregnant. And more than 10,000 pregnancies have been reported without concern in women who received vaccines.

These perspectives, of course, depend on living in a country that has access to vaccines.

Early access to vaccines almost exclusively went to high-income countries, including the UK and the US, who were able to preorder large supplies. These countries also had sophisticated surveillance programmes that were able to capture the association with extremely rare blot clots.

Most of the rest of the world, including through the international COVAX programme are currently only expecting much lower vaccine coverage during 2021, sometimes only 3% to 20%, with projections that some countries will not achieve herd immunity until 2023.

The historic US administrations support for patent waiver on these vaccines – largely due to activist pressure for global access – will help, but this also needs the transfer of expertise to rapidly be able to produce them.

The block in manufacturing capacity desperately needs generic companies to be included in production – and this includes not only protection from patent restrictions, but also technology transfer and support from originator companies. Vaccines are more complex than antiretrovirals.