HIV Under Castro

In 1983, Fidel Castro attended a presentation by Dr. Gustavo Kouri at Cuba's Institute of Tropical Medicine. Kouri was speaking on dengue fever and malaria, both common and perilous tropical diseases, to a room otherwise overfull of doctors, researchers, and military personnel. As he finished, Kouri recalls in his book AIDS: Confessions to a Doctor, all eyes fell not on Kouri but Castro. There was a long silence, and finally Castro asked, "Gustavo, what are you doing to keep AIDS from entering Cuba?"

Somewhat taken aback by this non-sequitur, Kouri admitted that the medical community knew strikingly little about the disease. The first case of AIDS recognized in the United States was only two years earlier, and the doctor could not even tell the comandante whether the disease was a bacteria, fungus, or virus.

This however did nothing to temper Fidel's seriousness when speaking about the subject. As he allegedly told the doctor on that day, just two years before the first case of HIV would be reported in the Pearl of the Antilles, "I think it will be the epidemic of this century. And it's your responsibility, Gustavo, to stop it becoming a major problem here."

Kouri took Fidel's order seriously. In 2015, with an overall infection rate of 0.2 percent, Cuba has the lowest infection rate in the Caribbean, a region of the world that has become particularly ravaged by the virus, second only in its average infection rate to sub-Saharan Africa. But, despite Cuba's general success in its long struggle to contain the spread of HIV, it has noticed a relative surge in infection rates in recent years, which culminated last January in a research paper announcing that a rare hyper-aggressive strain of HIV known as CRF19 was spreading on the island.

The paper understandably drew the attention of news outlets the world over, inaugurating a reporting frenzy on Cuba's "new epidemic strain of HIV virus" which would allegedly kill patients within three years of contraction. Cuba seemed like an odd place for an HIV super-strain to develop. Puzzled, I decided to pay a visit to Dr. Vivian Kourí, the lead author of the paper in the question and one of Cuba's most prominent virologists, to find out just what the emergence and spread of this virus means for the future of HIV/AIDS in the country.

Kourí works in the microbiology branch of the Institute for Tropical Medicine Pedro Kourí (IPK) in Havana, her lab being a part of what basically amounts to the Cuban equivalent of the United States' Centers for Disease Control. She is the third generation of Kourís to take up residence at the IPK, the center having been founded by her grandfather in 1937 and Kourí's father having served as the Institute's director for over three decades until his passing in 2011.

Dr. Kourí's work studying the rapid progression of CRF19 to AIDS that eventually lead to the aforementioned paper began back in 2009, when she was contacted by Anne-Mieke Vandamme, a prominent HIV/AIDS researcher at the University of Leuven in Belgium. Vandamme proposed that the two apply for a grant that would allow them to study the resistance and rapid progression of this particular recombinant strain of HIV, the only reported cases of which have come from the Cuban isle.

Although their formal partnership only began six years ago, Kourí and her colleagues at the IPK have been aware of CRF19's existence since 1999, the year the first instance was documented by a team of Spanish and Cuban researchers among a group of HIV patients sampled in 1997.

"We have had this strain for a long time, it's certainly not new," Kourí told me. "It is a recombinant form of three kinds of HIV-1 virus (A, D and G) and these three viruses are supposed to have African origin."

What makes CRF19 so noteworthy is that unlike many other strains of HIV, those who contract it are likely to see a rapid progression to AIDS, usually occurring within three years. Rapid progression has previously been associated with the combination of the various subtypes of the virus (particularly recombinants of subtypes A and D). These HIV subtype cocktails tend to result from having sex with multiple infected partners.

As Kourí explains, there were 95 patients sampled in the study and those patients were subdivided into three groups: 52 who exhibited rapid progression to AIDS (progressing from HIV-free to AIDS inside of three years), 21 non-AIDS patients (those who remained AIDS-free after at least three years following seroconversion, or the point when the antibody can become detectable in the patient's blood), and 22 patients in the chronic-AIDS group (those who were diagnosed with AIDS more than three years after seroconversion). The median age of the patients was 33 years old and, according to the study, the patients primarily consisted of white males from Havana.

When a patient becomes infected with HIV through sexual contact, the virus typically anchors itself to a protein known as as CCR5 that's located on the membranes of cells typically found in muscosa. It first binds to the CD4 receptor until it is able to find the CCR5 co-receptor. This binding sequence triggers the fusion of the membranes of the host cell and virus, allowing the latter to infect the former. After entry the virus begins a process of replication which typically ends with the destruction of the cell and the release of new viruses.

After several years of replication, the virus can accumulate mutations which make it possible for it to switch its binding to the co-receptor CXCR4. This switching of co-receptors marks the point at which the patient's progression to AIDS becomes much more rapid, for reasons that are not quite known. What is known, however, is that the use of the CXCR4 coreceptor tends to be associated with a higher viral load and significantly lower T-Cell count in the infected patient.

According to the researchers, those infected with CRF19 noticed a tendency for the virus to switch from the CCR5 to CXCR4 coreceptor very early on, perhaps even right from the start, which accounts for the abnormally rapid progression from HIV to AIDS. This observation thus raises the obvious and crucial question: What prompts the CRF19 strain to either forego anchoring to CCR5 entirely, or to switch so quickly from the CCR5 to the CXCR4 co-receptor after the initial infection?

The research team noticed that in those infected with CRF19, the rapid progression to AIDS tended to coincide with a higher than average Rantes count, which assesses the prevalence of a molecule that typically alerts the body's immune system to fight against infections. In what turns out to be a cruel and ironic twist, the over prevalence of this molecule in a patient may actually be to blame for the rapid progression from HIV to AIDS—in other words, the overabundance of Rantes molecules is a classic and potentially deadly case of "too much of a good thing."

"When Rantes binds to CCR5, this signals to the immune cell that there is a need for defense," explained Vandamme. "The same CCR5 molecule functions as co-receptor for HIV. When a lot of Rantes molecules are produced to fight infection, most CCR5 receptors are occupied [and] that reduces the opportunity of HIV to anchor itself to the cell through the CCR5 co-receptor. When CCR5 is unavailable, the virus that survives is the one that uses CXCR4. Many aspects are still unclear, so this is just a hypothesis."

According to the team's hypothesis, in addition to exhibiting an above average number of Rantes molecules, patients infected with CRF19 tend to carry a high viral load, which implies high replication rates. The more the virus replicates, the more opportunities it has to mutate and since CCR5 co-receptors are blocked by the patient's Rantes molecules, those mutations which allow the virus to anchor directly to CXCR4 are ultimately favored in the genetic lottery.

The real danger inherent in CRF19 is its capacity for rapid progression, which means that patients infected by the virus may develop AIDS before realizing they have even contracted the virus, severely limiting their opportunities for treatment and the recovery of their immune system. Indeed, a significant number of the patients sampled in the study had tested negative for HIV only a year prior to their diagnosis with AIDS.

In this sense, Cuba's unparalleled approach to diagnosis and treatment may be exactly what the doctor ordered, so to speak, helping to prevent this rare and aggressive strain of HIV from becoming a true epidemic on the island.

HIV was first discovered in Cuba in 1985 among soldiers recently returned from Africa. Part of what has allowed the country to maintain an infection rate that is roughly a third of the United States' was a policy put in place by Fidel Castro requiring those who were found to be infected to live out the remainder of their lives in state-run sanatoriums.

Although these institutions were decried by the likes of Dr. Jonathan Mann, the World Health Organization's first AIDS director who, according to the New York Times, referred to Cuba's sanatorium network as a collection of "pretty prisons," the ethically questionable policy was undoubtedly effective. According to the same Times article, from 1986 to 1990, fewer than 150 new HIV diagnoses were made annually and the number of Cubans living with HIV/AIDS today stands at a mere 14,000 out of Cuba's total population of 11 million.

While wildly effective in preventing an HIV/AIDS epidemic on the island, the compulsory cloistering of HIV/AIDS patients into sanatoriums had some unintended consequences; e.g., patients who chose to self-inoculate with the virus so that they could live in the relative luxury of the sanatoriums rather than the harsh material conditions of the Cuban streets. The forced sequestering of HIV/AIDS patients officially ended in 1993, but the Cuban government is far from giving up its struggle against HIV/AIDS and sanatoriums are still an option for infected Cubans who can voluntarily enroll in one of the three remaining institutions in the country.

According to both Kourí and Vandamme, the primary reason for Cuba's post-sanatorium success in combatting HIV/AIDS is largely thanks to a robust (and free) primary health care system and the introduction of intensive HIV education at early ages.

"In the Cuban society, it is accepted as normal to regularly perform an HIV test," said Vandamme. "For example, teenagers go for testing at school with their entire class and they make no big deal of it. They consider it kind of fun."

These opinions are buoyed by Kourí. "We have a free system for health, great primary care, and a lot of prevention strategies," she said. "For example, when we have one [HIV/AIDS] patient, the epidemiological group tries to do contact tracing and to test people who may have had sexual contact with the patient. I think strategies like these are important to early diagnosis. We still have late-diagnosis patients of course, but most of the patients are not late."

As both Drs. Kourí and Vandamme point out, these strategies have clearly been effective and continue to help Cuba make large strides in tempering the HIV/AIDS epidemic on the island. Most recently, the World Health Organization announced that Cuba was the first country in the world to end mother-to-child HIV transmission, suggesting that an end to the global HIV/AIDS epidemic is in fact possible.

Despite this promising news, Cuba continues to struggle in other areas: Its infection rate has been slowly climbing over the past few years, as has the infection rate of CRF19. These figures are relative, of course, and Cuba is still miles ahead of the competition in terms of containing and treating its HIV/AIDS patients. For this reason, Vandamme cautions against blowing the issue out of proportion, like many news agencies did when the story about the CRF19 epidemic first broke.

"I do think the 'outbreak' was sensationalized because our report was only the first report of CRF19 as a fast progressing virus," Vandamme said. "Such reports need to be confirmed by independent studies before the public is being scared by media. However, now there will be more vigilance towards this strain, which is indeed needed."

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