Key figures leading the fight against HIV discussed the status of the elusive HIV cure. Chaired by Prof Linda-Gail Bekker, Chief Operations Officer at the Desmond Tutu HIV Foundation, the speakers discussed why we need an HIV cure, is a cure possible and what that cure might look like.
The landscape of the disease has changed significantly since it first appeared in the 20th century where an HIV infection was a death sentence surrounded with stigma. Today, the story is very different: 18.2 million people are on antiretroviral therapy (ARTs) and AIDS-related deaths have declined by 45%. An HIV-positive person who takes their ARTs effectively has a similar life expectancy to an HIV-negative person.
Why we need an HIV Cure
Prof Sipho Dlamini, associate professor at the UCT/Groote Schuur’s Division of Infectious Disease & HIV Medicine, Department of Medicine, thinks that these numbers can be even better and a cure might be the way forwards. The ARTs we have now are significantly better than ten years ago, however, not everyone who needs ARTs receive them, pill fatigue makes people bored of taking drugs everyday and ARTs are a lifetime expense.
When it comes to the number of HIV-positive people on treatment, Prof Dlamini comments that “The global average is still less that 50%,” and with 2 million new HIV infections globally this unarrested growth needs to be addressed. A once-off cure would nip this infection at the source.
There is no doubt that HIV treatment has improved. The first ARTs, whilst preventing HIV, had a lot of unpleasant side effects. Nombeko Mpongo, AIDS activist and counsellor, spoke of her own experience with HIV after she was infected with HIV after being gang-raped on her way to work. On top of the trauma of her experience, she had to battle stigma around the disease, sham advice from the government and had no access to ARTs.
Today, ARTs are a daily pill that, if taken consistently, give patients a similar life expectancy to that of an HIV-negative person. Advice used to be that HIV-infected people had to wait until their cell count fell below 250 before they could take ARTs, however, now ARTs are prescribed immediately after infection. Mpongo celebrates that she is able to live a normal life, something that ARTs have given her. However, it is still tiring taking a daily pill, although she commented that she used to have to take three pills a day.
Is an HIV Cure possible?
There have been 70 million cases of HIV and only one cured case. Prof Carolyn Williamson, Prof Carolyn Williamson, Head of Division of Medical Virology & of the Institute of Infectious Disease and Molecular Medicine (IDM), said that “It gives us hope that there will one day be a cure, but we have unfortunately been unable to repeat the miracle.” Naturally, a lot of research is going into this cure.
It is difficult to cure HIV because it affects a certain type of immune cell called a T cell. HIV integrates with the T cell’s genetic material, ‘becoming one’ with the cell. Prof Williamson explains that “Drugs that we have only ‘see’ infected cells or actively multiplying viruses. HIV, however, can get into ‘resting’ T cells and lies dormant.” There are no signals for the drugs or immune system to detect, so HIV can’t be destroyed. ARTs suppress HIV, but as soon as a patient stops taking them, the virus springs back.
One intermediate step to a full cure might be remission. This is where HIV is still in the body but the virus hides in the body for a period of time. Examples were seen in the Mississippi baby, who had ARTs very early in life and went into remission after stopping ARTs for a few years. However, the HIV eventually came back. There is also a 10 year old South African child in remission, diagnosed with HIV from birth. The ARTs were taken away at 10 months and the child is clinically asymptomatic. However, with careful study, symptoms of the virus‘ presence can be found.
The Berlin Patient
Timothy Ray Brown is one in 70 million. Brown states the “I was infected with HIV when the only treatment was AZT [an ART with multiple side effects]. Then I was diagnosed with acute myeloid leukaemia [cancer of the blood and bone marrow].” A stem cell transplant from a very specific donor cured his HIV and sent his leukaemia into remission. These donor cells had a rare variation of a gene called CCR5-delta32, the gene that HIV normally attaches to in an infection. However, this variant is resistant to HIV. After the stem cell transplant, Brown’s body reset so that this rare gene variant was integrated with his DNA and HIV could no longer infect his cells.
It was confirmed that Brown no longer had HIV, even in reservoirs that are difficult to sample, but after intensive tests, including a brain biopsy, Brown was confirmed free from HIV. Prof Williamson added that “If you can get the material you can detect very low amounts of virus, but the virus can be found in different reservoirs and can be very difficult to sample.” Brown’s brain biopsy was very unusual in this regard and was only performed under the pretense of searching for leukaemia cells.
Brown’s situation is unique. Stem cell transplants are not a viable, commercial HIV cure; the procedure is very risky, expensive, it would be difficult to farm enough stem cells from suitable donors and HIV-positive people can manage the virus with ARTs. That, and the transplant does not always work.
Click here for Brown’s incredible story in more detail.
Strategies for an HIV cure?
Dr Wendy Burgers, Associate Professor in the Division of Medical Virology, Department of Pathology, University of Cape Town, asks “How do we get disease-free and drug-free remission?” There are several strategies to either ridding the body of HIV or the symptoms of HIV.
- Stem cell transplantation – As described in ‘The Berlin Patient’, Stem cell transplantation is very dangerous, expensive and doesn’t always work. The main issue here is safety.
- Early treatment – Treating the virus fast can lead to a smaller HIV reservoir so there is less virus hidden in the body. However, many people do not have access to treatment early.
- Shock and kill – The name to describe waking up the silent reservoir cells containing HIV and destroy them. Whilst seemingly counter-intuitive, the idea is to apply a drug that activates latent HIV cells to produce virus so that every single one of those activated cells can be destroyed, thus destroying the reservoir. Drugs that reverse HIV’s latency have been identified. The next challenge is to find drugs that can destroy HIV-infected cells and not normal, healthy cells.
- Lock and block – Opposite to ‘Shock and Kill’, ‘Lock and Block’ deeply locks HIV in its reservoir so they can never be reactivated.
- Vaccine – Researchers want similar results in a vaccine to the HIV resistant people with the CCR5 gene mutation. A vaccine would give the body a marker to identify and destroy HIV cells
A safe, affordable and scalable cure has not yet been found. Dr Burgers points out “these experiments are done under extremely controlled conditions, so it is extremely important to continue to take ARTs everyday for the rest of the patient’s life in order to live a life as long as someone without HIV.”
The symposium was an excellent space to get the run down on the what, where and how of the HIV cure. Whilst one man has been cured, it still looks like scientists are a long way from developing a safe cure that can be made for the millions of people with HIV. In the meantime, antiretroviral therapy
Written by Caroline Reid