The recent case of a child being cured of HIV in Missisippi is a new dawn in AIDS research. Avantika Bhuyan speaks to medical experts to gauge the implications of this development
March 3, 2013. The whole world sat up in amazement as news came in about a functional cure that had been achieved for an HIV-infected infant in Mississippi. All eyes were focused on a team of researchers from Johns Hopkins Children's Center, the University of Mississippi Medical Center and the University of Massachusetts Medical School as they presented the case report in Atlanta at the 20th Conference on Retroviruses and Opportunistic Infections. Nearly 13 days have lapsed since the announcement was first made and already doctors are hard at work, interpreting and reinterpreting implications of the case.
While, on a medical front, this research may pave way to eliminating infection in children, but on a more humane level it represents hope to millions across the world infected with HIV. Doctors are hopeful that this particular baby will have great chances for a long and healthy life. "This baby will not need antiviral medication while her viral load remains below level of detection," says Hannah Gay, University of Mississippi Medical Center Associate Professor of Pediatrics, who treated this particular baby.
Many people are wondering what a functional cure really means. The report breaks it down: in contrast to a sterilising cure which is a complete eradication of all viral traces from the body, a functional cure occurs when viral presence is so minimal that it remains undetectable by standard clinical tests, yet discernible by ultrasensitive methods. Only one case of sterilising cure has been witnessed so far when Timothy Ray Brown was treated with a bone marrow transplant for leukemia in a surgery conducted in 2007. "The bone marrow cells were taken from a donor with a rare genetic mutation of the white blood cells that rendered some people resistant to HIV," mentions the report that was presented in Atlanta. However, it is not feasible to replicate this treatment model for the millions infected with HIV globally, thus making the Mississippi cure all the more significant.
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"Our next step is to find out if this is a highly unusual response to very early antiretroviral therapy (ART) or something we can actually replicate in other high-risk newborns," said Johns Hopkins Children's Center virologist and lead author of the report, Deborah Persaud, at the conference. She is also the scientific chair of the HIV Cure Committee of the International Maternal, Pediatric Adolescent AIDS Clinical network, a consortium of researchers and institutions that was critical in spearheading the earliest clinical trials of mother-to-child transmission and early treatment of infants 15 years ago.
However, the investigating team would like to add a word of caution to patients who feel that a magic cure has been achieved that can immediately rid them of consistent ART spread across a lifetime. "One thing I would like to emphasise is that prevention is better than cure. And I need people to understand that we don't have a magic pill yet and it will be years that we have a cure that we can apply consistently. Until careful investigation has been conducted and it has been proven that cure can be achieved in other children, it is vitally important that patients who are currently on therapy remain on their drugs. It is far too early for anyone to try stopping effective therapy just to see if the virus comes back," says Gay.
Scientists at India's National Aids Research Institute (NARI) too believe that there are miles to go before this cure can be replicated for a vast majority of people. "It is important that Indian pediatricians should not over-interpret the findings and use it in their practice to manage HIV-exposed babies as of now. A single case of cure should only stimulate researchers to undertake further studies and not be considered as a standard of care for management of HIV exposed children," says R Paranjape, director, NARI.
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According to the National AIDS Control Organisation (in technical report, India HIV estimates 2012), it is estimated that about 142,000 (range: 111,000 to 183,000) children were living with HIV infection in 2011. It is believed that of these, 34 per cent children are already receiving ART, while 86,000 of them may be requiring ART. So, as Paranjape maintains, that this functional cure will be of minimal use to those children who are already infected and are living with HIV infection that they acquired from their infected mothers. "Longer follow up of this particular baby will be required to understand the full implications. Furthermore, these findings have very little implication to the adult situation as of now," he says.
THE LANDMARK CASE
According to the report presented by the investigative team at CROI, the infant underwent remission of HIV infection after receiving ART therapy within 30 hours of birth. The prompt administration of antiviral treatment led to the infant's cure by halting the formation of hard-to-treat viral reservoirs or dormant cells responsible for re-igniting the infection in most HIV patients within weeks of stopping therapy.
A series of tests showed progressively diminishing viral presence in the infant's blood, until it reached undetectable levels 29 days after birth. The infant remained on antivirals until 18 months of age, at which point the child was lost to follow-up for a while and, the researchers say, stopped treatment.
Ten months after discontinuation of treatment, the child underwent repeated standard blood tests, none of which detected HIV presence in the blood. Test for HIV-specific antibodies - the standard clinical indicator of HIV infection - also remained negative throughout.
The current treatment for both children and adults infected with HIV follows a consistent administration of antiretroviral drugs. The cost of these medicines varies in children and adults depending on the dose and the drug that one uses to treat. "The overall cost of treating a child with ART (average of all age groups) to the government is about Rs 8,000 per patient per year whereas the overall cost of ART for all adults is about Rs 6,500 per patient per year," explains Dr Paranjape. This cost has come down drastically from the Rs 40,000 that one had to shell out for antiretroviral drugs per month till 1997-98. "Now with Indian pharma companies supplying drugs to 70 per cent of the world, it has become cheaper for them to produce medicines at low costs," says R Gangakhedkar, a scientist with NARI.
These are exciting times for doctors and scientists working in the field of HIV/AIDS as the past five years have witnessed several scientific breakthroughs which have helped numerous people across the world. "The major breakthroughs have been to scale up treatment so that 8 million people who need it are now able to access life-saving therapy. There is still progress to be made, however, as there are still 7 million people in urgent need of treatment who are not receiving it. So we are working hard to make sure that by 2015 all of the 15 million people in need of treatment will have access to medicine," says Geneva-based Michel Sidibé, executive director of the Joint United Nations Programme on HIV/AIDS (UNAIDS) and Under-Secretary-General of the United Nations.
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According to him, a second breakthrough has been the clear proof that treatment is an effective way to prevent transmission of HIV, so that the more people take to ART consistently, the fewer new infections will occur. "The costs of HIV treatment have also fallen greatly for the first line treatment, which once cost thousands of dollars per month and now costs around $100 per year. Nonetheless, the success of the scale-up means that the funding needed to produce and deliver the medicines is still considerable and second and third line treatments are still much too expensive,' he explains.
Former NBA star Magic Johnson, who announced his infection in 1991, stands as testament to the fact that the sooner you get medication the easier it is to live a long and healthy life. "If ART is taken irregularly, then it can lead to drug resistance. HIV can be treated very effectively if people have access to treatment and take the medicine properly." says Sidibé.
In fact, modeling studies reveal that a 30-year-old HIV infected individual can survive up to 75-years if he or she does not have hepatitis infection, or so claim scientists from NARI. This institute, which has been fundamental to several breakthroughs in AIDS research, spends close to Rs 3 to 5 crore on HIV treatment research annually.
NARI was perhaps the first independent international "Clinical Trial Unit" recognised among resource-limited countries by the National Institutes of Health, USA due to its past performance in HIV research. A path-breaking research, sponsored by NIH, in which NARI helped in the enrolment of over 10 per cent couples, gave HIV discordant couples a sigh of relief and encouraged them to stay together. "Prior to this, most couples, especially those whose wives were HIV positive, used to seek separation," points out Gangakhedkar.
A separate study showed that HIV-infected women were more likely to develop cancer cervix rapidly. Research at NARI also proved that HIV led to premature ageing and early incidence of events such as high cholesterol, heart attacks and certain kinds of cancers. "Thus, we have started treating every individual as ten years older than his chronological age. Preventive treatment to reduce the incidence of these conditions is vital among HIV infected individuals," he says. These patients are put on baby dose of aspirin at the earliest. They are advised to walk for at least 30 minutes a day and are asked to reduce intake of fatty or high carbohydrate diet. "With the decline in social stigma to HIV due to antiretroviral therapy, advise to have a positive attitude towards life has become easy to follow," he concludes.