Video report by ITV News Correspondent Libby Wiener
The prime minister said he's "optimistic that over the medium-term" vaccines for Covid-19 and mass testing will "help areas to come down the tiers".
When asked if he could be "honest" about areas moving down tiers in the next few weeks, Mr Johnson said "it is true that it's going to be tough for a while", but he added that "there really is the prospect" of restrictions being eased in some areas.
Tiers will be reviewed weekly, with the first review taking place a fortnight after lockdown ends, on Wednesday December 16.
Many backbench Tories are furious about the PM's move to put 99% of England into Tier 2 or 3 after lockdown ends on December 2.
It means indoor mixing between households indoors will effectively be banned for more than 55 million people - the vast majority of the country.
But Mr Johnson defended the tier system, saying the tough measures are essential to reduce the spread of coronavirus.
He acknowledged how many people felt "frustrated" - particularly if they were in an area with low infection rates.
"I know it is frustrating for people when they are in a high-tier area when there is very little incidence in their village or their area. I totally understand why people feel frustrated," he said during a visit to a public health laboratory in Wiltshire.
"The difficulty is that if you did it any other way, first of all you'd divide the country up into loads and loads of very complicated sub-divisions - there has got to be some simplicity and clarity in the way we do this.
"The second problem is that, alas, our experience is that when a high-incidence area is quite close to a low-incidence area, unless you beat the problem in the high-incidence area, the low-incidence area, I'm afraid, starts to catch up."
Only the Isle of Wight, Cornwall and the Isles of Scilly – accounting for little more than 1% of England’s population – face the lightest Tier 1 coronavirus restrictions.
Large swathes of the Midlands, North East and North West are in the most restrictive Tier 3, which accounts for 41.5% of the population, or 23.3 million people.
The majority of authorities – including London – will be in Tier 2, which will cover 57.3% of the country, or 32 million people.
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Out of those areas to go into Tier 3, only eight of 119 have reported a rise in cases.
Sir Graham Brady, chairman of the influential 1922 Committee of Conservative MPs, said the decision would make it “harder” to push the measures through Parliament.
The tier system will be put to a vote in the Commons on Tuesday and there's the prospect that up to 70 Tory MPs - members of the Covid Research Group - could reject the PM's proposals.
The prime minister is almost certain to win the vote, but he may have to rely on the backing of Labour MPs.
Some MPs were left angered after seeing their areas escalated up two tiers compared to their status before the November lockdown.
Former cabinet minister Liam Fox and John Penrose, husband of NHS Test and Trace boss Baroness Dido Harding, criticised the move to place their North Somerset constituencies into Tier 3, having previously only been in Tier 1.
They said the reason used – due to the amount of workers in the area who commute to Bristol which has seen a recent spike in Covid-19 cases – "isn’t right or fair".
In Kent there was dismay at putting the whole county into Tier 3 when there were discrepancies in the infection rate across the area.
Mr Johnson said he was forced to use the tough measures because the incidence of coronavirus is "still really pretty high".
"It's about 1 in 80/85 people in this country have it," he added.
"I totally understand why people frustrated, I get that."
What can you do in each tier from December 2? The new rules in England at a glance:
Tier 1: Up to six people can meet indoors or outdoors. Pubs and restaurants can open, with last orders at 10pm and closing at 11pm.
Tier 2: No mixing indoors, apart from support bubbles. Up to six people can meet outdoors. Pubs and restaurants can open, with last orders at 10pm and closing at 11pm - but alcohol can only be served with a substantial meal.
Tier 3: No mixing indoors. People can only meet outdoors in limited places such as parks and public gardens. Pubs and restaurants must close, with the exception of takeaway sales.
In all tiers, non-essential shops, gyms, hairdressers and personal care services can open. People in all tiers to work from home where they can do so. Full details on what you can do in each tier here.