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mutations in the gene encoding the ccr5 receptor prevent hiv (blue) from entering immune cells. image credit: national institutes of health

lenacapavir may soon be available as a preventive drug. image source: nature website

our reporter liu xia

in july this year, scientists reported the world's seventh hiv "cured" person.

aids is acquired immunodeficiency syndrome, which is caused by infection with the human immunodeficiency virus (hiv). in 1981, the world's first aids patient was discovered in the united states. since then, countless scientists have devoted themselves to the battle between humans and aids, and have worked hard to create various "weapons" - cocktail therapy, stem cell transplantation, vaccine prevention, etc., laying a solid foundation for the prevention and treatment of the disease.

according to a recent report on the website of the british journal nature, despite the continuous good news in the field of aids treatment, most therapies can only inhibit the replication of hiv in the human body, but cannot completely eliminate it, because hiv can integrate its own genome into the host dna. humans still have a long way to go before they can truly cure aids.

stem cell transplantation is not universal

antiretroviral therapy (art, cocktail therapy) is currently the standard treatment for aids. however, this therapy also has many hidden dangers: it cannot eradicate hiv; patients must take medication for life, and once the medication is stopped, the virus will come back and cause reinfection; some patients will experience strong toxic side effects; and the cost of treatment is high.

to realize the dream of curing aids, scientists have developed a variety of strategies, among which stem cell therapy has attracted much attention.

at the 25th world aids conference held in july this year, scientists from charité university hospital and other institutions reported that a german man infected with hiv had no hiv virus detected in his body for nearly six years after receiving a stem cell transplant without receiving art treatment, and was confirmed to be "cured." previously, scientists had reported six "cured" aids patients.

all seven patients achieved similar results through a bone marrow stem cell transplant. the cells they received contained a mutation that prevented the expression of ccr5, a protein that hiv uses to enter human cells.

sharon levine, director of the peter doherty institute for infection and immunity in australia, pointed out that although stem cell transplantation is excellent in clearing hiv, it is not universal. currently, the treatment is only effective for 7 people, and all of them have cancer that requires bone marrow transplantation. in addition, this treatment is invasive and may cause complications.

sharon lewin, president of the international aids society, also said previously that these "cured" cases have no direct clinical significance, but the related cases can provide a reference for exploring other potential treatment approaches.

targeted therapy is still being tested

nature reported that although the above stem cell therapy is beyond the reach of most aids patients, its success has led to the development of gene therapy targeting ccr5. scientists are also actively developing gene therapy targeting hiv, bringing new hope for curing the disease.

the british magazine new scientist reported in march that scientists from the university of amsterdam in the netherlands successfully eliminated hiv from infected cells using crispr gene editing technology.

in addition, scientists have proposed other treatment options, including effectively controlling or eliminating the hiv reservoir. this reservoir is full of hiv-infected cells. but these cells do not produce viral particles, causing the immune system to "turn a blind eye" to them. however, after the patient stops art treatment, these cells will be reawakened. methods targeting this reservoir include enhancing the patient's immune response, awakening and attacking dormant infected cells in it. professor sun caijun of sun yat-sen university once vividly called it "luring the snake out of the hole and then killing the virus", or letting the virus in it dormant forever.

levin said that most of the above therapies have not yet passed phase i or phase ii clinical trials, and "it is too early to say whether they are effective."

despite this, there have been a lot of progress in long-term treatments in the past few years. previously, regulators in several countries gave the "green light" to the combination therapy of cabotegravir and rilpivirine. patients receiving this therapy are injected every two months to control the virus. in 2022, regulators approved lenacapvir, which only needs to be injected once every 6 months, bringing more convenience to patients.

vaccine development faces challenges

rama rao amara, an immunologist at emory university in the united states, pointed out that scientists hope to develop a vaccine that can neutralize multiple hiv strains. however, hiv genome mutations can lead to a high diversity of strains, causing many pharmaceutical giants and well-known institutions to fail in this journey.

the development of hiv vaccines has been progressing continuously, and one of the important tasks is to develop an immunogen that can induce broadly neutralizing antibodies. in two papers published on august 30 in the journal science immunology, scientists reported an immunogen, gt1.1, which can produce potent broad-spectrum neutralizing antibodies targeting hiv in macaques. currently, scientists are conducting phase i clinical trials on this immunogen.

scientists at the scripps research institute in the united states published a paper in the journal nature communications in april last year, saying that the new hiv vaccine they developed showed significant virus neutralization ability in preclinical trials.

pre-exposure prophylaxis (prep) is critical to curbing the spread of hiv. studies have shown that oral prep can reduce the risk of hiv infection by about 99%. in 2021, the u.s. food and drug administration approved cabotegravir for preventive use. lenacapavir may also soon be available as a prep drug. a study published in july reported that more than 2,000 young women participating in the study successfully prevented hiv infection by injecting lenacapavir twice a year.

despite the bumpy road, countless scientists are still forging ahead in the hope of finding a cure for aids.