A flurry of excitement over a claimed "functional cure" for HIV opened the 20th Conference on Retroviruses and Opportunistic Infections (CROI) here in Atlanta. But questions remain about some of the details of what happened with the young girl, and even if it proves to be true, it is likely to have little immediate or widespread effect in daily care.
The case study involved a girl born prematurely at the University of Mississippi to a mother who was infected with HIV but did not know it. Because the mother had a high viral load at the time of delivery, and likelihood of transmission of the virus increases as viral load increases, the physician decided to test the infant for HIV and started her within 30 hours of birth on combination therapy.
The viral load test came back showing 20,000 copies of HIV. That strongly suggests she became infected in the womb and not at delivery, which is another point of high risk for mother to child transmission. While the RNA test for the virus showed that it was replication competent, there was no reason at the time to run a test used only in research and not in clinical practice to show if the virus was capable of infecting cells. A significant portion of HIV RNA has defects that leaves it incapable of infecting cells.
The infant remained on antiretroviral drugs for 18 months and then mother and daughter stopped going to clinic. They reappeared four months later and the girl had not been on therapy for much of that time. The doctors took a blood sample to measure her viral load but it was below the 20 copy level that they used.
That is when researchers from Johns Hopkins University stepped in. They used ultrasensitive tests to look for the virus but could not find it the first or subsequent times that they looked. "We were unable to detect replication competent virus," said lead author of the study Deborah Persaud. "We believe that perhaps the initiation of very early antiretroviral therapy prevented the formation of viral reservoirs in CD4 t-cells."
The child is two-and-a half years old now and apparently free from infection.
But questions remain. Was the initial viral load test accurate or was there some mix up in processing or record keeping? And was the virus capable of infecting cells? There is no stored blood sample so there is no way to answer those questions definitely.
"The question is whether the HIV DNA [detected by the study] is junk DNA or replication competent DNA." said Scott Hammer a researcher a Columbia University and vice chair of the conference. "Or is this an example of an elite controller and the baby would have cleared the virus without drugs."
Elite controllers are less than 1% of those who become infected. Their immune system has one or more unusual variations that are capable of controlling HIV infection for long periods of time, up to several decades, at very low levels and without clinical symptoms of disease.
There was much initial skepticism around the first person cured of AIDS, Timothy Ray Brown, first known only as the "Berlin patient." He underwent chemotherapy for lymphoma and a bone marrow transplant to rebuild his immune system. The doctor secured a transplant match that contained a rare variation — the delta32 mutation for the CCR5 cell receptor — known to naturally confer resistance to HIV infection. It took several years of monitoring for people to become convinced that Brown had been cured.
Even if this child does prove to be cured, the immediate impact on care for people will be small because most pregnant women receive care for their HIV to prevent transmission of the virus to their child. Fewer than 50 infants a year in the US acquire HIV infection around the time of birth, said Kevin Robert Frost, who heads up amfAR (American Foundation for AIDS Research). The shortfall is not in the science but in the delivery of care.
The same can be said of mother to child transmission of HIV in the rest of the world. The tools are there to virtually eliminate such transmission; often what is lacking is the healthcare infrastructure and the political will to implement those programs.
Prevention
The news was less encouraging when it comes to using pills or microbicide gels to prevent the acquisition of HIV by women. The VOICE study enrolled 5029 primarily young single women in Africa. The complex trial had five groups and participants received either a vaginal microbicide gel containing tenofovir that was to be applied a short time prior to having sex, a daily pill of tenofovir, or Truvada, which contains tenofovir and another antiretroviral drug, or a placebo version of the gel or pill.
The gel groups in the study were stopped early when it became apparent that it would not offer any protection. The other groups continued to the end of the study, but neither of the pills proved to be protective. Tenoforvir pills had proven effective in some earlier PrEP (pre-exposure prophylaxis) studies.
"None of the products were efficacious in preventing HIV acquisition in women," said Jeanne Marrazzo, a researcher from the University of Washington who participated in the study. When they looked at stored samples to measure drug concentrations in the blood, only about 30% were using the products frequently enough to be detected in their blood. "The bottom line is that the women were not using the product."
Stigma around HIV medications appears to be a major reason why the young women were not taking the drug, she said. Others have suggested that perhaps the women were giving or selling the drug to people who were already infected.
"A long acting product would be great because it reduces the barrier to having to do something every day, if women want that product," according to Marrazzo. The monthly birth control injection Depo-Provera is popular with some women because it provides discretion that a pill might not offer, added Sharon Hillier, a leading HIV prevention researcher at the University of Pittsburgh. It would be good to develop a similar long-lasting option for HIV prevention.
