Page 20 - AIDSBK23C

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Phylogenetic studies can identify genetic clusters of HIV-1 env genes, which are known
as subtypes, or clades, that have arisen along with progression of the AIDS epidemic worldwide.
The V3 loop amino acid sequences of these genetic variants influence HIV phenotype and
immune response.[91] Thus, the biologic properties of HIV can vary with the subtype. This is
possible even within a single HIV-infected person, where variants of HIV may arise over time
that are "neurotropic" or "lymphocytotropic" for example.[22,83] Variability in transmission
may occur, which is associated with greater heterosexual transmission, aided by its propensity to
infect dendritic cells that can be found in mucosal epithelium.[92] However, the role of HIV-1
subtypes in transmission and pathogenesis of HIV remains, for the most part, unclear.[93]
There are four major groups of HIV-1, based upon phylogenetic analysis, which likely
arose from different transmission events in history among chimpanzee and gorilla primates and
humans. These groups are defined as M (major), N (nonmajor and nonoutlier), O (outlier), and
P. These groups are very similar to simian immunodeficiency viruses SIVcpz (M and N) and
SIVgor (O and P).[94]
Within these HIV-1 groups are subtypes. The predominant group M has recognized
subtypes A, B, C, D, F, G, H, J, and K.[95] Group O is distinctly different and genetically more
closely related to simian immunodeficiency virus (SIV) and HIV-2.[98,96] Group N appears to
have arisen from interaction between a group M and a group O virus.[97] The vast majority of
HIV-1 infections have been with group M. In contrast, only about 100,000 infections with group
O have occurred, and group N and P infections are rare.[28]
Even within HIV-1 subtypes, genetic diversity can reach 15 to 20%; between subtypes, it
is 25 to 30%. Different subtypes of HIV-1 that have arisen and will continue to arise in the
course of the AIDS epidemic have been identified with certain geographic distributions, though
movement of individuals among populations creates more variability over time.[95] Variability
of HIV subtypes may also confound testing strategies, because diagnostic sensitivity and
specificity of laboratory tests may not be the same across all subtypes.[98]
There is increasing diversity of HIV-1 in the form of recombination of subtypes.
Recombinants between subtypes are termed circulating recombinant forms (CRFs). Through
2011 there were 48 different CRFs described. The term unique recombinant form (URF) is used
to designate strains of HIV-1 not meeting these criteria. In a study of 65,913 samples from HIV-
infected persons obtained in 109 countries between 2000 and 2007, data from 2004– 2007
showed subtype C accounted for nearly half (48%) of all global infections, followed by subtypes
A (12%) and B (11%), CRF02_AG (8%), CRF01_AE (5%), subtype G (5%) and D (2%).
Subtypes F, H, J and K together accounted for fewer than 1% of all global HIV infections. Other
CRFs and URFs were each responsible for 4% of global infections, bringing the combined total
of worldwide CRFs to 16% and all recombinants (CRFs along with URFs) to 20%. Thus, there
has been a global increase in the proportion of CRFs, a decrease in URFs and an overall increase
in recombinants.[99]
The detection of mosaic HIV-1 sequences suggests that persons can become coinfected
with differing HIV-1 subtypes that can then undergo recombination to new strains that may have
different biologic characteristics from the original strains. Mutations and recombination’s can
confer antiretroviral drug resistance. The major groups and subtypes of HIV-1 as listed above,
with epidemiologic correlates for locations of greatest prevalence. Recombinant forms are
appearing more frequently as the epidemic progresses.[95]
st
At the beginning of the 21 century, over 90% of new HIV infections are emerging in
Asia, Africa, and Eastern Europe. The non-B HIV-1 subtypes A and C are more prevalent in