Cured: How the Berlin Patients Defeated HIV and Forever Changed Medical Science

  • Nathalia Holt
Dutton: 2014. 9780525953920 | ISBN: 978-0-5259-5392-0

In the 30 years since HIV was identified as the cause of AIDS, antiretroviral treatment has changed the infection from a death sentence to a chronic, manageable disease. Now, treatment is lifelong but often consists of just a tablet a day; resistance to the drugs is rare; and side effects are infrequent. However, the virus integrates into the patient's DNA and becomes silenced, in what is known as latency, and no tools have yet been found to eliminate it. When the antiretrovirals are stopped, infectious virus re-emerges.

Timothy Brown was cured of HIV after a bone-marrow transplant for leukaemia. Credit: Polaris/Eyevine

But since at least 2009, a cure for HIV has been widely accepted as possible, thanks to a handful of reported cases. Members of this select group are functionally cured, often in unusual circumstances: the virus is detectable at low levels, but is under control without antiretrovirals. Now, in Cured, Nathalia Holt — an immunologist who has done groundbreaking research on gene therapy as a cure strategy — traces the fascinating cases of two people who have effectively vanquished HIV.

The Berlin patients, both diagnosed in the city, are 'Christian' (not his real name), and Timothy Brown, an American. Cured covers their personal stories and the science that their cases inspired, as well as the scientific and political history of HIV.

Christian, Holt tells us, was functionally cured after receiving antiretroviral treatment and a fairly toxic cancer drug, hydroxyurea, within days of infection. Brown was cured of HIV after a bone-marrow transplant for leukaemia; the donor lacked the CCR5 receptor, which normally ushers HIV into human cells, and so was naturally resistant to the virus. Both cases were reported in The New England Journal of Medicine (NEJM), in 1999 and 2009 respectively.

The cases are similar in many details, as Holt relates. Both men were diagnosed in the mid-1990s — when infection with HIV heralded a real prospect of early death. Both were cared for at some time by the same dedicated family doctor, Heiko Jessen. Both had access to life-saving antiretrovirals. Both their identities were initially hidden. And both cases became the focus of media stories claiming that a cure had been found, even though the treating physicians had carefully avoided using that word in interviews.

The Berlin patients also highlight the often vicious and competitive nature of science — rife with big egos, high stakes and a reluctance to brook unexpected findings from outsiders. Much of the innovation in how they were managed came from two unknown German physicians: Jessen and Gero Hütter, Brown's haematologist, who tested unconventional treatments outside formal clinical trials. The big science, which demanded an analysis of how much virus was left and why it was under control, was driven largely by well-known US investigators. The tensions between the two cultures are telling.

Jessen, for example, ended up as fourth author of the 1999 NEJM paper on Christian's case; as Holt explains, he no longer works with any of his US-based collaborators. Hütter's initial submission to NEJM was rejected, and his presentation of Brown's case at the 2008 Conference on Retroviruses and Opportunistic Infections in Boston, Massachusetts — the premier meeting for HIV scientists — was largely ignored. In Holt's view, it was only when the American Foundation for AIDS Research started to take an interest that Hütter engaged well-recognized names, and NEJM eventually accepted his paper.

More importantly, the Berlin patients' cases have inspired new scientific ideas. We still do not know what led to either cure. Many researchers think that Christian is probably an 'elite controller', one of the 1% of people with HIV whose genetic make-up gives them an effective immune response to the virus. So he may have controlled his virus at the outset. However, his case raised the possibility that very early treatment could reduce or prevent the formation of long-lived reservoirs, as was demonstrated last year in 14 people with HIV in the VISCONTI (Viro-Immunological Sustained Control after Treatment Interruption) study in France. Christian's case also revealed the importance of the role of the T-cell immune response in controlling the virus — a major stimulus to HIV vaccine development.

With Brown, was the cure a reaction of the donor marrow against his immune system, a process called graft-versus-host disease? Was it down to the intensive conditioning treatment he received before the transplant? Or was it that the donor marrow was CCR5-negative? A promising treatment based on eliminating CCR5 using gene therapy was developed in a mouse model by a team including Holt, and is now being tested in clinical trials.

I enjoyed the book but I do have quibbles. Holt's discussions can be dense and detailed. Her interviews, which tend to focus on US-based leaders in HIV science, make it seem as if little discovery was being led from elsewhere, even though there have been significant contributions from many other countries, not least France, where the initial discovery of the virus was made. This is an important book, nevertheless.

Although the Berlin patients' case reports are anecdotes, they convinced a sceptical scientific world that a cure was possible, and inspired lines of enquiry and investment. On World AIDS Day 2013, US President Barack Obama announced that his administration would give an extra US$100 million to research towards a cure. Most importantly, the cases belong to a significant handful that is giving hope to millions of people living with HIV.