389its victims. Although long-term survival has increased by aggressive therapy with
combination of antiviral agents, all HIV-infected persons are at risk for illness and
death from opportunistic infections and neoplastic complications as a consequence
of the inevitable manifestations of AIDS.
There are two variable factors in HIV/AIDS: how people respond to the HIV and
how HIV responds to drugs. These should be taken into consideration. Personalized
management of HIV/AIDS means use of the most rational and effective approach in
which one method could be effective in several variants of the disease.
Decoding the Structure of an Entire HIV Genome
HIV, like the viruses that cause infl uenza, hepatitis C and polio, carries its genetic
information as single-stranded RNA rather than double-stranded DNA. The HIV
RNA genome is very large, composed of two strands of nearly 10,000 nucleotides
(building blocks) each. The information encoded in DNA is almost entirely in the
sequence of its nucleotides. But the information encoded in RNA is more complex;
RNA is able to fold into intricate patterns and structures. These structures are cre-
ated when the ribbon-like RNA genome folds back on it to make 3D objects.
The structure of an entire HIV-1 genome at single nucleotide resolution using
SHAPE, a high-throughput RNA analysis technology, has been published (Watts
et al. 2009 ). The genome encodes protein structure at two levels. In addition to the
correspondence between RNA and protein primary sequences, a correlation exists
between high levels of RNA structure and sequences that encode inter-domain loops
in HIV proteins. This correlation suggests that RNA structure modulates ribosome
elongation to promote native protein folding. Some simple genome elements previ-
ously shown to be important, including the ribosomal gag-pol frameshift stem-loop,
are components of larger RNA motifs. The authors also identifi ed organizational
principles for unstructured RNA regions, including splice site acceptors and hyper-
variable regions. These results emphasize that the HIV-1 genome and, potentially,
many coding RNAs are punctuated by previously unrecognized regulatory motifs
and that extensive RNA structure constitutes an important component of the genetic
code. The study opens the door for further research, which could accelerate the
development of antiviral drugs.
Genetics of Human Susceptibility to HIV Infection
Humans are not equal in terms of susceptibility to infection to HIV, or in the rate of
disease progression. This is evidenced by the identifi cation of individuals that
remain seronegative despite of multiple exposures to HIV-infected partners, and by
the existence of the so called “long-term progressors”. Elite controllers’ are rare
HIV-infected individuals who are able to spontaneously control HIV replication
without medication, maintaining viral loads that are consistently below the limits of
detection by currently available commercial assays. Studies of elite controllers may
Personalized Management of Viral Infections