Updated July 28, 2015.

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Since the earliest days of the HIV epidemic, scientists have regularly observed HIV-infected individuals who did not progress to AIDS and were able to maintain stable CD4 counts and low-to-undetectable viral loads without treatment, often for decades.

In more recent years, as the HIV sciences have begun to advance considerably, a number of medical interventions have appeared to have had the same (or similar) effect on people with known HIV infection—even so much as apparently “clear” the virus entirely from their bodies.

What we have learned—and continue to learn—from these individuals may one day provide scientists with the insights needed to potentially reverse the course of HIV infection or eradicate HIV altogether.

Here is a brief overview of the groups or individuals who have “cheated” HIV and helped propel HIV sciences forward:

Stephen Crohn, "The Man Who Can't Catch AIDS"

Stephen Crohn, who was dubbed "The man who can't catch AIDS" by the U.K's Independent newspaper, was found to have had an anomaly called a "delta 32" mutation on CCR5 receptors of his CD4 cells, the mutation of which effectively prevents HIV from entering target immune cells. Crohn first came to the attention of Dr. Bill Paxton of the Aaron Diamond AIDS Research Center in 1996 after tests revealed no signs of infection despite having had multiple sexual partners, all of who died of AIDS. The mutation has since been identified in less than 1% of the population.

The discovery of the so-called "CCR5-delta-32" mutation led to the development of both the CCR5 inhibitor-class drug, Selzentry (maraviroc) and a stem cell transplant procedure used to "functionally cure" HIV patient Timothy Ray Brown in 2009 (see below).

Born in 1946, Crohn committed suicide on August 23, 2013 at the age of 66.

One in 500 People with HIV  

As surprising as it might seem, one in 500 people with HIV are classified as "long-term non-progressors" (LTNPs), roughly defined as being able to maintain high CD4/CD8 T cell counts for more than 15 to 20 years without the use of antiretroviral drugs. Within this group is a rarer subset called "elite controllers" who are able to sustain viral loads of less than 50 copies/mL throughout the course of infection. It is estimated that there are 1,500 elite controllers in the U.S.

In studying these groups since the mid-1990s, we have begun identify some of the mechanisms by which viremic control is achieved. Among the discoveries is a genetic mutation in the FUT2 gene, which has been found to occur in 10-20% of Europeans and is believed to confer a protective association against heterosexual HIV infection. The anomaly was first noted in 2000 among a group of female Senegalese sex workers who appeared to have an innate resistance to HIV.

A number of other genetic characteristics have since been identified in LTNPs, including one associated with the production of certain classes of human leukocyte antigens (HLAs), known to exert control over HIV.

Timothy Ray Brown, "The Berlin Patient"

Timothy Ray Brown, also known as "the Berlin Patient," is the first person believed to have been "functionally cured" of HIV.

Born in the U.S., Brown was given a bone marrow transplant in 2009 to treat his acute leukemia. Doctors at Charité Hospital in Berlin, Germany selected a stem cell donor with two copies of the CCR5-delta-32 mutation, known to confer to HIV resistance. Routine tests performed soon after the transplant revealed that the HIV antibodies had decreased to such as to suggest the complete eradication of the virus from his system.

While Brown continues to show no signs of HIV, two subsequent stem cell transplants conducted by doctors at Brigham and Women's Hospital failed to achieve similar results, with both patients experiencing viral rebound after 10 and 13 months of undetectable tests. These patients were not transplanted with the Delta 32 mutation, however.

"Donor 45"

In 2010, a gay African American man known simply as "Donor 45" was found to possess a powerful HIV neutralizing antibody called VRC01 by researchers at the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases (NIAID).

What was particularly compelling about the discovery was the fact that VRC01 is able to bind to 90% of all global strains of HIV, effectively blocking infection even as the virus mutates. Due the high genetic diversity of HIV, most defensive antibodies are unable to achieve this level of action.

The discovery helped broaden research into the stimulation of broadly neutralizing antibodies, which may one day prevent or slow disease progression without the use of antiretroviral drugs.

Subsequent research in 2011 identified two HIV-infected Africans with similar VRC01 antibodies.  

The Visconti Cohort

In  April 2013, the story of a Mississippi baby "functionally cured" of HIV captured world headlines. The child, given given antiretroviral therapy at the time of birth, was reported to have been cleared of the virus and "functionally cured" of HIV. While the baby would ultimately experience viral rebound in 2014, setting back claims of any such cure, there remained suggestions that early drug intervention may have its benefits by preventing HIV from hiding in many of the latent reservoirs of the body.

Following on the heels of the Mississippi baby case was a report from France in which 14 out of 70 patients in the on-going Visconti Study were said to be able to maintain fully suppressed viral loads without treatment after having been prescribed antiretrovirals within ten weeks of infection.

In each of the cases, treatment was stopped prematurely by the patient. Of the 14 able to maintain persistent viral suppression (some for up over seven years), CD4 counts increased from an average of 500 to 900 cells/mL while viral loads dropped from 500,000 to less than 50 cells/mL. Further research is being conducted to ascertain whether other factors, genetic or virological, contributed to the results.

The study helped bolster the argument for a "test and treat" strategy, wherein early treatment may correlate to greater viral control. Whether early intervention can actually reverse infection—as some had suggested with the Mississippi baby case—remains largely in doubt. Most authorities are now suggesting that "sustained remission" is a more appropriate term, given the setbacks in earlier "functional cure" cases.

French Teen's Remarkable HIV Remission

In July 2015, French scientists again announced a case of sustained HIV transmission, this time in a 18-year-old girl who had been able to sustain viral suppression for 12 year without antiretroviral therapy. Like the Mississippi baby before her, the teenager was provided combination therapy at the time of birth, which she was prescribed over the course of five years—often with incidences of viral rebound due to poor HIV drug adherence.

In the fifth year, her parents pulled her from the research program and terminated therapy altogether. When they returned a year later, they and the researchers were surprised to find that the child had an undetectable viral load, something the girl has been able maintain since.

Further investigation aim to identify the mechanisms, genetic or otherwise, for such controls in both the French teen and her adult counterparts in the Visconti cohort.

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