Clues to a possible cure for AIDS

On July 22nd the week-long 25th International AIDS Conference kicked off in Munich. Though these gatherings are no longer the war councils they were in the epidemic’s early days—for the strategy to defeat HIV is now pretty much settled—there remains much fighting to be done.

In a report released as the conference started, UNAIDS, the United Nations agency that deals with the disease, said that almost 40m people are now infected. There were 1.3m new infections in 2023, and 630,000 HIV-related deaths. But those numbers are down from 2.1m and 1.3m respectively in 2010. That year is the baseline for calculating the drop of 90% in annual new infections and HIV-related deaths, which experts reckon would end AIDS as a public-health threat. The hope is to reach this target by 2030. On current trends that seems unlikely. But the numbers are, mostly, heading in the right direction.

Because sub-Saharan Africa has been the worst-hit part of the world, most effort has been concentrated there. This has paid off. New infections there since 2010 have fallen by 56%. Partly as a consequence, UNAIDS’s figures say that for the first time since the epidemic began more new infections occurred outside this part of the world than in it. Another contributor to the shift, however, was that in three areas—Latin America; eastern Europe and central Asia; and the Middle East and north Africa—new infection rates rose.

Although no cure currently exists, AIDS can nonetheless be ended. This depends on two steps: treating those already infected and preventing transmission to those who are not. Targets help, if only to clarify objectives. For treatment, UNAIDS promulgates the easy-to-remember formula “95-95-95”. This translates to an aspiration that 95% of those infected are aware of the fact, that 95% of this group are taking antiretroviral drugs to suppress their infections, and that in 95% of those so treated (ie, 86% of those infected), the treatment is successfully suppressing their viral load. Across the world the “treatment trilogy” is an encouraging 86-89-93, with 30.7m people estimated to be on antiretroviral drugs.

Crucially—and this is where treatment and prevention are linked—people taking antiretroviral drugs in the way the doctor ordered have negligible viral loads and so are unlikely to pass the infection on. This state of affairs, known in the field as U=U (undetectable=untransmissible), gives a constellation of preventive approaches (such as condoms, microbicidal vaginal rings and various prophylactic drug regimes) a better chance of working.

Using drugs for pre-exposure prophylaxis, commonly called PrEP, is a particularly promising approach. Some 3.5m people around the world already take Truvada or Descovy, the first PrEPs to be approved. But these are pills which provide only short-term protection, so must be swallowed regularly. Longer-term cover comes from an injection.

The first injectable PrEP was cabotegravir, made by ViiV Healthcare and approved by America’s Food and Drug Administration (FDA) in 2021. This gives protection for two months, and a trial in Uganda showed it was more popular than pills. The second is lenacapavir, from Gilead Sciences, which also makes Truvada and Descovy. The meeting coincided with the publication of complete results from PURPOSE-1, a trial of this in South Africa and Uganda. PURPOSE-1, which began in 2021 and involved 5,300 women, showed it gave 100% protection for six months. This is seen as a real breakthrough, and activists called on Gilead to make it available cheaply.

On the question of a cure, some news announced just before the conference caused particular interest. This was the revelation of the seventh known individual to reach apparently permanent remission from HIV infection after a bone-marrow transplant to treat leukaemia. Bone marrow is the source of the immune system’s CD4 T-cells, which are attacked by HIV. So, in a few cases where a leukaemia patient was also HIV-positive, surgeons deliberately sought a donor who had a mutation in the gene for a T-cell surface protein called CCR5 (which the virus uses to enter those cells), in the hope of curing two diseases for the price of one. That’s because HIV finds it difficult to infect T-cells of people with mutated CCR5 proteins.

What is special about the latest case, that of an anonymous individual known as the second Berlin patient (the first, Timothy Brown, was treated in Germany’s capital in 2007), is that the donor had inherited this mutation from only one parent, meaning half the relevant protein molecules in her bone marrow were unmutated and thus remained HIV-friendly. Moreover, news of the second Berlin patient comes after a yet-more-puzzling case reported last year from Geneva, in which the donor had completely normal CCR5 proteins.

Surprise twist

All this suggests that something more complex is going on. Sharon Lewin, president of the International AIDS Society, which organises the meeting, is a leading light in the search for a cure for AIDS. She suspects that, in the patients who have been cured, preparations for transplant intended to kill the existing marrow, and also the immune response of the new marrow to remaining old marrow, are shrinking the reservoirs in which HIV hides and giving the CCR5 mutation a helping hand.

Such reservoir-shrinkage, by means of special drugs, is something she is already investigating. Combined with infusions of T-cells genetically engineered to disrupt CCR5, it might form the basis of a cure. ■

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