What did 2009 contribute to the HIV field?

Brigitte Autran, Editor of AIDS
Special Editorial   

When celebrating World AIDS Day, our first thought is of the global scale of the pandemics and of the therapeutic issues. In developing countries, the past years brought increasing access to first line low-cost antiretroviral drugs. Results came out in 2009 with successful prevention of mother to child transmission in spite of the fact that AIDS is controlled in less than a fourth of the infected patients. But 2009 also meant the emergence of virus resistance to first and sometimes second line ART. What was easily predictable from experience in the developed countries indeed occurred despite adherence to treatment of the majority of the patients. A major debate early this year dealt with the question of virus monitoring in developing countries. Emergence of drug resistance underlines the fact that CD4 count monitoring is not enough. Installing virology facilities and providing medical training in order to efficiently monitor viral loads and virus genotypes is an urgent necessity. Ensuring continuous access to novel drugs in the developing world is even more essential.

In contrast with this tough reality, 2009 was a very optimistic year for clinicians and patients, with access to the last generations of antiviral drugs, though no major novel molecule showed up this year. Simply, the promises of the 2007/08 breakthroughs, i.e. the integrase inhibitors and the anti-CCR5, held true in 2009, and the generalized use of extremely potent drug combinations is rewarded by very rapid, profound and sustained virus control. Not only are 80% of patients now treated in developed countries but, even more importantly, HIV remains undetectable in more than 80% of them, even when using lower and lower thresholds of detection. This success also means less virus resistance, provided adherence to treatment is maintained. Is this at last the taming of the shrew? As always in the history of HIV and AIDS, successes bring back old chimeras: treatment alleviation and HIV eradication. Treatment simplification might become an option, though it should maintain similar efficacy, and 2010 might tell us whether such ideal regimens exist. Another option might be treatment intensification if one wants to test the concept of eradication, although 2009 showed none of these new drugs substantially affect the HIV reservoirs. Nevertheless, one of the most appealing novelties was the first case suggesting HIV elimination after a bone-marrow graft from a donor bearing a homozygous D32 deletion of the CCR5 gene. This achievement reinforces the value of drugs blocking HIV entry and opens the way for new creative therapeutic strategies attempting at exhausting the virus reservoirs.

Were there major breakthroughs in the pathophysiology of HIV/AIDS? Immune activation is now well recognized as a major mechanism of HIV pathogenesis. In 2009, with immune deficiency being prevented, cardiovascular diseases or accelerated senescence appeared as two major complications of the HIV infection itself, occurring before initiation of ART. Increasing evidence from several human genome wide analyses ascertained the critical role played by some genetic polymorphisms in the durable HIV control observed in LTNPs or Elite Controllers. No magic novel gene was discovered, but the good old HLA ones! If these immune response genes are key in HIV control, does this mean HIV should be controlled sooner or later by a vaccine? 2009 might say so. After the multiple disillusions of the 25-year-long quest for an HIV vaccine, a first, though modest, signal came out last October: 30% protection conferred by a prime-boost vaccination regimen in 16,000 human volunteers (Phase III) trial in Thailand. Words of caution should be raised, however, when one realizes that 30% protection means 51 versus 74 infections only, while no correlates of protection were observed yet. What can we learn from this? Continuing the quest for an HIV vaccine is even more worthy than ever.

Brigitte Autran
Laboratoire "Immunité et Infection" INSERM-U945,
Hôpital Pitié-Salpêtrière, Université Pierre et Marie Curie, Paris, France
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