Zephyr Foundation

In an abstract published online ahead of print today in the Journal of Virology, International HIV Controller Study collaborators characterized genetic signatures in the CD4 T-cells of an "unselected" cohort of elite controllers to further elucidate underlying immunological and virological mechanisms of HIV-1 control. Genetic profiles of the majority of elite controllers were similiar to patients on antiretroviral therapy, although different from HIV-1 negative persons. However, in a smaller proportion of elite controllers, an alternative genetic pattern was observed that was indistinguishable from that of HIV-1 negative persons, and different from individuals on highly active antiretroviral medications. Significantly higher CD4 T-cell counts and smaller levels of HIV-1 specific CD8+ T-cell responses were measured in this sub-group of elite controllers. who did not significantly differ from other elite controllers in respect to viral loads and HLA class I alleles. This study team concludes that the data identify a "specific subgroup of elite controllers whose immunological and gene expression characteristics approximate those of HIV-1 negative persons."
Abstract Accessed 12/22/10, at: http://jvi.asm.org/cgi/content/abstract/JVI.01846-10v1

Commentary from Nature Medicine
Full article is freely available at Nature Medicine
 

HIV/AIDS remains one of humanity's greatest challenges. Since 1981, it has claimed over 25 million lives and is

currently responsible for over 2.5 million new infections worldwide each year1. Although progress has been made in

preventing new HIV infections and in lowering the annual number of AIDS-related deaths through comprehensive

prevention programs and increased access to antiretroviral therapy, the number of people living with HIV—now over 33

million—continues to grow¹. Currently, only two out of five people who need treatment receive it, and even this modest

level of progress in treatment is in jeopardy, as the availability of donor funds plateaus or declines². Whereas universal

access to treatment is an ambitious goal, the annual accrual of newly infected individuals who require treatment

testifies to the urgent need for more effective prevention strategies. Vaccines are the primary public health intervention

for dozens of infectious diseases worldwide; they are easy to administer and yield lasting effects. As one of the most

powerful tools for preventing infection against other infectious diseases, a safe, effective, accessible HIV vaccine is

therefore one of our greatest priorities—and one of science's greatest challenges.

The unique ability of HIV to evade and suppress the immune response, its extraordinary genetic diversity, the

properties of its envelope glycoprotein and the ability to establish systemic infection within days and to induce

dysfunction and death of the immune cells needed to mount a protective response have posed unprecedented

challenges for vaccine development³. Nonetheless, although a highly effective HIV vaccine remains elusive, we have

never been closer to the target. Among the most visible achievements of the past five years were the results of RV144,

the trial conducted in Thailand, that showed that a poxvirus-protein prime-boost combination provided modest (31%)

protection against HIV acquisition⁴. These results represent the first-ever demonstration of any level of efficacy in

preventing HIV acquisition in humans by a vaccine. Although many questions remain, the results of the RV144 trial

have brought renewed energy to the field and created a new lens through which to evaluate future priorities and set

strategic directions.

There have been other key advances in HIV vaccine research over the past five years. They include a growing

understanding of the role of the mucosa as a barrier to sexually transmitted HIV infection⁵, descriptions of the earliest

immunological responses in humans after acute HIV infection⁶, the demonstration that HIV infection in humans is

usually initiated by one or a very small number of founder viruses^{7, 8}, the development of computational algorithms to

inform the design of unique mosaic immunogens to address the challenge of viral sequence diversity by achieving

maximum epitope coverage while preserving natural antigen expression and processing⁹, new insights into the

immunological and genetic basis for the ability of some people to control the virus or prevent virus acquisition (socalled

'elite controllers' and 'exposed but uninfected persons', respectively)^{10, 11}, the first proof of substantive simian