HIV update - 19th September 2019

CRISPR gene editing

For the first time, researchers have used a type of gene editing called CRISPR to try to treat a person infected with HIV. They managed to engineer stem cells that are immune to HIV and transplant them into a man living with HIV and leukaemia (a blood cancer). The gene-edited cells survived in the man’s body for more than a year without causing detectable side-effects, but didn’t reduce the amount of HIV in his blood.

The research was inspired by the case of Timothy Ray Brown, the ‘Berlin patient’ who appears to have been cured of HIV after a stem cell transplant from a donor who had a rare genetic mutation. The donor did not have CCR5 receptors (which HIV usually uses to gain entry to a cell) on their immune system cells, making the donor resistant to HIV infection. After the transplant, Brown appears to be resistant to HIV too.

Chinese scientists took stem cells from a normal donor (someone who does not have this genetic mutation) and used gene editing to remove the CCR5 receptors. This was difficult to do and only 18% of the cells were successfully edited.

Their patient was a 27-year-old man who had been diagnosed with HIV and leukaemia and needed a stem cell transplant. After chemotherapy and the transplant, his leukaemia went into remission. The transplant of edited cells does not appear to have done the man any harm, but it has not resulted in a lowering of viral load or a remission of HIV. The man stopped his HIV treatment for a few weeks and his viral load increased rapidly, so he went back onto HIV treatment.

Scientists are excited about this case because the man is doing well more than a year and a half later (there are some concerns about the safety of CRISPR gene editing) and because up to 8% of his stem cells continue to have the CCR5 mutation. This shows that gene-edited cells can persist in the body.

For gene editing to have more impact on HIV, it would need to be possible to engineer a larger number of cells without CCR5 receptors. And for more of them to survive in the body.

But this study provides a proof of concept to inspire researchers working towards an HIV cure.

For more information, read NAM's page 'The search for an HIV cure'.

Kidney disease

Although impaired kidney function is not very common in people doing well on HIV treatment, it occurs more often than in people who don’t have HIV, a Danish study shows.

In general, kidney problems are more common in people over the age of 50. They are also more common in people of black or Asian ethnicity. Conditions that make kidney problems more likely include diabetes, high blood pressure, raised cholesterol, drug use, heavy drinking, hepatitis B and hepatitis C.

In people living with HIV, a low CD4 count or a high viral load raise the risk. But the Danish researchers were particularly interested in looking at the risk of impaired kidney function in people with HIV who were generally at low risk. Their study only included people who were white, had an undetectable viral load, did not have hepatitis C and had never injected drugs. Each person living with HIV was compared with four people of the same age and sex in the general population.

They found that 3.7% of people with HIV had impaired kidney function (a glomerular filtration rate – GFR – below 60). This compared with 1.7% of people in the general population. The researchers say that the increased risk of kidney disease in people living with HIV was comparable to that of people living with diabetes.

The risk of kidney disease increases as you get older. But it seemed to do so to a greater extent in people with HIV in this cohort.

But no specific HIV-related factor was associated with a higher risk of kidney problems. This includes taking the anti-HIV medication tenofovir disoproxil fumarate, which other studies have found to be associated with kidney problems.

For more information, read NAM's page 'Chronic kidney disease and HIV'.

Falls in new HIV diagnoses

There’s good news from several wealthy countries about falling HIV diagnoses:

• Diagnoses are continuing to fall in England, down to their lowest level since the year 2000. They fell by 28% between 2015 and 2018. But 43% of people are still diagnosed at a late stage of infection.

• The annual number of new HIV diagnoses in San Francisco has dipped below 200, falling to its lowest level since the early 1990s. Figures for the quality of medical care are good.

• Cases of recently acquired HIV are falling in France.

It’s thought that these are the result of combination prevention – more frequent testing, prompt initiation of HIV treatment for those who are diagnosed, most people with HIV having an undetectable viral load, pre-exposure prophylaxis (PrEP) and continued condom use.

One group of American researchers have tried to estimate how much difference PrEP makes, on top of the rest of the package. They say that cities with the highest rates of PrEP use in at-risk people had nearly 16% fewer diagnoses than the cities with the lowest rates.