Aids cure BABY!

What we can learn from the Mississippi miracle

As the hope and excitement generated by the chance-breakthrough at the University of Mississippi that ‘functionally’ cured a child of its HIV-infection continue to reverberate across the world, it’s time to look at some key take-aways.

What does it mean for millions of people living with HIV and millions more who are at risk of contracting HIV, particularly tens of thousands of unborn children?
Is a cure on the horizon? If not, does it at least provide new insights to prevention?
Does it offer greater tools to public health specialists to protect people who are at heightened risk such as sex workers, gay men and transgender people?

What does it say about the importance of anti-retroviral treatment (ARV) that has dramatically transformed the AIDS-landscape of the world, including the developing countries?
Significant enough, the Mississippi miracle has some answers for all of these. They may not be perfect and finite, but they do offer some interesting cues and evidence than can strengthen existing knowledge and possibilities of clinical exploration.

Let’s start with the most proximate: prevention of mother-to-child transmission of HIV.
Since the instinctive paediatrician at Mississippi deviated from the standard guidelines of ARV on infants which resulted in “curing” the child, it will certainly call for a review of the existing WHO guidelines.

At present, under three possible options, a child born to an HIV-positive mother is prescribed only one of two common and old ARVs (Nevirapine or AZT), whereas the paediatrician prescribed a full course of three ARVs that HIV-positive people take lifelong.

Whether in an organised way or not, this successful experiment might prompt many others to follow suit. There is no dearth of similar clinical settings in sub Saharan Africa and countries such as India where doctors might desperately repeat this practice to save a few lives. If the resultant clinical data can establish the replicability of the Mississippi results, it will certainly call for a revision of guidelines for not only prevention of HIV among infants, but perhaps – for the first time – also for possible cure.

We don’t know yet if we are being hyper-optimistic because such is the magic of the word ‘cure’ in HIV. However, the development certainly underscores and amplifies the immense importance of treatment as prevention, as well as the need to hit hard early.

Two types of treatment are used for prevention of HIV – one: a prophylactic (preventive) dose of ARVs for people who suspect exposure to the virus, sexually or otherwise (e.g. need pricks); and two, a regular dose of ARVs for people who are at higher risk of HIV, such as gay men.

In the first, people who have had unprotected sex with a person who is confirmed to be HIV-positive are advised a 28-day course of ARV. This is similar to the after-pill for preventing pregnancy.
This dosage should begin soonest after exposure, but not later than 72 hours. The premise is that if started immediately after exposure, ARVs will prevent the virus from establishing and replicating in the body. The initial rate of replication of the virus is high and it is when the prophylactic should try to hit hard.

There is no way of knowing if it is really working because one doesn’t know if a person dodged the HIV-bullet by sheer chance or because of the prophylactics. All HIV-exposures do not lead to infection, and in fact only very few do. However, it is of great psychological significance, and perhaps is working as well because the results have been good.

The Mississippi experience will certainly strengthen this practice because what cured the child of the virus was the potent combination of three drugs and the timing of its administration. The paediatrician in fact repeated the old adage in AIDS-treatment of hitting hard early. The hard-hitting three drug combo would have blocked the viral replication from different fronts, compared to a single drug.

The same principle of early attack is the science behind the daily dose of ARVs taken by gay men to keep themselves free of HIV despite their high-risk sexual behaviour. A multi-national clinical trial in 2010, in which gay men were administered Truvada, a remarkable once-a-day single pill, showed a 44% reduction of HIV-risk compared to men who did not take the drug. People who had higher rate of adherence had better results.

However, a similar study conducted among sex workers, a group at very high risk of HIV-infection, in three African countries didn’t yield promising results and was called off early. The jury is still out on why it worked among gay men and not among high risk women. Perhaps better adherence, better peer-support and motivation in gay men compared to poor sex workers, or perhaps different science altogether.

Therefore, at least on two counts, the life-affirming experience of the Mississippi child corroborates the importance of starting early and starting right. Perhaps, it should also encourage scientists to revive prevention-as-treatment trials among sex workers as well.
Starting early places enormous responsibility on governments and others as well.

In the context of the Mississippi child, the question is how early is early? and the answer: As early as one is infected.
For it to work, people at high risk of infection need to undergo HIV-tests regularly and voluntarily. In the developing countries such as India, majority of the infected people do not know that they are infected till they fall seriously ill.

Therefore, countries need to do more on early diagnosis and testing. This entails reliable infrastructure that goes all the way to the PHCs, and much greater awareness and social conditions that encourage testing. It’s a tall order even for rich countries, but that should be the ideal that countries such as India should strive for, if it has to make use of emerging scientific knowledge.

Another significance of the Mississippi child is the effectiveness of ARVs – even the old ones. The drugs that the Mississippi paediatrican used were in fact very old and dirt-cheap – Zidovudine, Lamivudine and Nevirapine. Of these, Nevirapine has some issues, but the other two are mainstay drugs that most begin their treatment with.

While the old ARVs still work, the news ones are magic. The single combo pills such as Truvada (2004) and Atripla (2006) that had dramatically transformed medication for HIV are available as cheaper generic copies in India. Then there are recent drugs such as Complera and Stribild, still controlled by MNCs, which can further improve the treatment outcome.