Cures are grabbing the headlines these days. So when studies were presented with great fanfare pointing to a 180-degree turnaround in HIV—once considered 100% fatal and all the way to functional cure or remission—it's no surprise that they get a lot of attention.
Several weeks ago, the so-called functional cure of the presumably HIV-infected baby from rural Mississippi hit. Two weeks later, French researchers published a paper suggesting that as many as 15% of carefully selected and followed adults with HIV may one day safely go off medication, putting the virus into remission.
Since these stories broke, scientists and HIV advocates have taken a step back to see what they really mean, offering a far more nuanced perspective than early news reports offered. What follows is a review of the research and a snapshot of how people with HIV and the science and medical community see it.
The HIV-Infected Baby Functional Cure
"What appears to be clear is that the baby, born to a woman with HIV in rural Mississippi, who was not getting antiretroviral therapy during her pregnancy, came to the attention of doctors at birth," David Margolis, MD, UNC Chapel Hill and the Collaboratory of AIDS Researchers for Eradication of Cure, told Windy City Times.
Essential facts in the story are as follows:
- During the mother's pregnancy, the mom had not been tested for HIV, , she was not on antiretroviral treatment, and she was not getting prenatal care.
— At birth, routine HIV tests found that the baby had HIV DNA and HIV RNA plasma.
— Two days after birth, HIV tests were repeated and confirmed, with sequencing showing that the virus genetically matched the mother's virus. Tests of the mother and baby were repeated numerous times.
— Early aggressive antiretroviral therapy with AZT/3TC/Nevirapine began 31 hours after birth for the first week of life.
— Antiretroviral therapy was continued for 18 months, when the mother stopped treating the baby, and the mother dropped out of care. Only extremely low levels of HIV were found.
— The child was again tracked at about 2 years of age, finding a negligible amount of HIV RNA in plasma and a few dozen copies of HIV DNA in blood, but other HIV tests were negative.
"A key point," noted Margolis, "is that the drugs were given with full-dose twice a day nevirapine—as if the baby was presumed to be infected—not the lower dose that would have been given to the baby in perinatal prevention protocol."
The case was presented at the 20th Conference on Retroviruses and Opportunistic Infections or CROI in Atlanta. As one of the largest international scientific meetings on retrovirus infections, CROI newsbreaks get a lot of attention. Margolis acknowledged: "Yes, there is a general problem talking about an HIV cure, yet at the same time, we do use terms, in sound bites, that we hear, but don't understand."
Dazon Dixon Diallo, founder and president of SisterLove, Inc. in Atlanta, Ga., said that extrapolating from this case is difficult. "We cannot generalize from one case," she said. "All we can say is something is possible."
Diallo also felt that "no perinatal infections should be happening in an age of universal HIV testing, prenatal care, and access to therapy in the United States." She views the study differently: more as a failure of the healthcare system to treat this woman and her baby than as a scientific advance.
"Last year, in Georgia, we had 11 perinatal transmissions in Georgia," said Diallo. "That is not acceptable." ¨
Linda Meredith told WCT: "Cure is a powerful word. It shouldn't be tossed around in HIV or cancer or other chronic and potentially life-ending disease. But Obama and Clinton issued a document last year at the International AIDS Conference hyping the beginning of the end of AIDS. I suppose this is one of the things they can hang their hats on as their own 'Proof of Concept'."
Michelle Lopez, longtime HIV activist in Brooklyn, also found the "cure" talk disconcerting. "I had friends who were calling me, some still struggling with their own diagnosis, but it sounded like such hype."
Yet what really infuriates Lopez is that youth HIV infections are going up enormously, but cure gets played up big. To the extent that prevention and testing remain invisible, too many people get infected.
HIV-Positive Women, HIV-Positive Moms
In addition, Lopez has plenty of reason to be angry. "The system failed me," she said. Lopez had a baby at St. Vincent's Hospital in New York City in 1990, which was known as one of the nation's hospitals with one of the highest caseloads of HIV+ men. Even though she got prenatal care and had insurance, Lopez was never offered an HIV test. She gave birth to a daughter, who had repeated infections. Nine months after her daughter was born, Lopez and her daughter were diagnosed with HIV at a community health center. She asks: "How did I fall through the cracks?"
But Lopez' anger reflects how HIV research in pregnant women lagged behind. "We didn't begin testing everyone who is pregnant until 1994, when the results of AZTG 076 ( www.aidsmap.com/AZT-in-pregnancy/page/1730608/ ) came in," said Mike Saag, MD, director of the Center for AIDS Research at the University of Alabama at Birmingham. In the early years of the AIDS epidemic, the focus was largely on gay men. The AZTG 076 trial tested AZT, also known as zidovudine or Retrovir, as the first antiretroviral medicine for its effectiveness in preventing HIV perinatal transmission. The trial revealed that 8% of women taking transmitted HIV to their newborns, in comparison with 25% of moms on placebo.
"What really got lost here is that the mom had no prenatal care," said Mike Saag, MD, director of AIDS Research at the University of Alabama at Birmingham, and past-chair of the HIV Medicine Association of the Infectious Diseases Society of America.
Saag founded one of the largest HIV clinics in the Deep South. When the functional cure story surfaced, "nobody had a clue what we are up against. There are still instances where pregnant women don't get prenatal care [in the Deep South] and therefore the women are not tested for HIV." He continued: "In this case, after she delivered, the mom either dropped out of care because she had a long way to travel or there was some dysfunction in her life that prevented her from staying retained in care."
Additionally, the way the functional cure story was covered, specifically the invisibility of the HIV+ mom may be more reflective of how HIV+ women feel about how they are judged, and it is pretty disempowering. Linda Meredith pointed out: "The way this story ran, people only see potential babies, not the mother." She questioned whether one possible explanation is "knee-jerk sexism towards HIV-positive women in general."
Very few stories in the press had anything to say about the mom in the story—just the baby. Mary Lucey, learned that she was HIV-positive in 1989, during her pregnancy. Lucey's daughter was born with HIV. She's not convinced views of women with HIV have progressed very far since she was pregnant.
HIV-pregnant women are not written about much in the mainstream press and stigma is strong. Clearly, patient privacy must have been a concern in presenting the case, but Meredith said that HIV+ women should be part of the story with their point of view taken seriously in treatment considerations. When the mom is out of the story, it fuels looking at the mom as irresponsible. "We are asking pregnant women, for the sake of the child, to choose treatments that we might not have chosen, that may be toxic," she explained.
That's why it is great news that on Monday, April 15, EMPOWERED, a new campaign, is being launched around women and HIV/AIDS featuring Alicia Keys; former White House Senior Advisor Valerie Jarrett; Rep. Barbara Lee, co-chair of the Congressional HIV/AIDS Caucus; and experts from Kaiser and AIDS United to discuss the impact of HIV on women and women's role in affecting change. Sister Love, Inc. will have a live Webcast on its site.
Moving Ahead
Weeks after the presentation, WCT spoke with Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. Fauci was careful to stress that this was only "a single case" and that it is "not a cure."
"What this raises is whether we should carefully re-examine how we treat babies," said Fauci. "We need to examine whether giving aggressive treatment at birth is better than post-exposure prophylaxis for six weeks, [which is now standard of care for babies born to children born to HIV-positive moms]." The trial would be in poorly resourced countries, where many HIV-infected children are born, according to Fauci.
That may not seem immediately relevant to people living with HIV in the United States. Few babies are born with HIV in the United States and standard protocols call for HIV testing of all pregnant women, treatment with antiretroviral therapy during pregnancy, and postexposure prophylaxis for the baby around birth and for 6 weeks.
However, it's possible that if prompt aggressive regimen (within 30 hours of birth) proves effective, it might ultimately spare HIV+ parents repeat testing of newborns in the weeks following birth of the baby, as well as spare them anxiety.
An HIV Cure in Adults?
Just as the baby story was beginning to fade, on March 14, the Public Library of Science's journal PLOS Pathogens published a study showing that long-term remission was possible in adults under certain conditions:
— In the study, antiretroviral treatment was started early enough (within 10 weeks of infection), when the HIV virus is establishing itself in the body.
— It was continued for about 3.5 years, with close monitoring and supervision.
— In the study, a subset of patients were able to have their antiretroviral medications safely withdrawn after 3.5 years, and were followed for an average of 7.5 years off the medications.
— None of these individuals were considered "natural elite controllers," which are people for whom the virus doesn't take hold. They were treated early and aggressively because the virus did take hold.
— Those who were able to go off treatment were called "elite controllers."
Research is Preliminary
Nobody should look at this study and go off their HIV medications, agreed everyone WCT interviewed for this story.
Fauci told WCT: "This is definitely not any kind of a new treatment paradigm for adults with HIV. After a few years and further clinical study, we may be able to make recommendations, but it is definitely not a license for anyone to stop treatment."
"These people became post-treatment controllers because of early aggressive therapy," said Margolis. "The finding is interesting and needs more follow-up. I am not convinced that this finding will pan out over time," he added. Margolis also took issue with the study design, which was not prospectively collected, the gold standard in research studies. Additionally, he pointed out that "quite a lot of patients didn't convert," meaning that it's a bit early to put hopes on this as a functional cure.
Saag put it this way: "In my practice, I start everyone with acute infection on antiretroviral therapy, but I don't think we know enough to stop it in anyone. Several studies of treatment interruption have found precipitous, dangerous increases in HIV replication when treatment is interrupted in most people." Saag pointed out that only 15% of patients were able to avoid viral rebound, hardly a calling card for discontinuing treatment.
One area where this study may prove valuable is in vaccine development. Since the study pointed to an immune response, it's possible that if the immune system can be primed and activated to prevent, as well as control infection, it could lead to new directions in vaccine development, Saag explained.
Ensuring Community Health
These studies may yield new avenues for better prevention and treatment of HIV, but many advocates questioned whether people with HIV are being left out in the cold.
Diallo said: "Where was the role of prenatal care and treating per protocol when the HIV baby story came out? A lot of that got missed." Novel treatment and cure make for big headlines, but "we really need to double down on prevention," Diallo added.
"Tracking and following that one child, what was the cost of that?" added Diallo. What she'd like to see—and what is happening today is empowering women and teens to take steps to prevent HIV in the first place.
Meredith raised other issues. "Poor people, people of color are still in the same predicament that they were in, 25 years ago," she said. In fact, it's probably getting worse with Medicaid cuts and threats to ADAP [AIDS Drug Assistance Program] funding.
"This kind of work doesn't help those people," Meredith added. It's ludicrous that people are at risk of getting their medications right now." That's a story that simply isn't sexy for mainstream media, but one that needs to be out there.
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