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as there could be evolutionary and adaptive limits of HIV-1 (Yuste, 1999, Nijhuis, 1999). Diminished fitness underlies the lower pathogenicity of multidrug-resistant strains (Kaufmann, 1998). Fitness cost can also be translated into transmissibility cost. Resistant strains, and in particularly multidrug-resistant viruses are less transmissible in a population (Yerly, 2004), a phenomenon that can be ascribed to adaptive attenuation. Adaptation to immune pressure. Immune selective pressure forces the emergence of viruses with escape mutations that result in infected cells not being recognized by cytotoxic T lymphocytes (CTL) (Lieberman, 2002). Viruses adapt to the host they infect through a process of HLA- associated selection (Moore, 2002). This carries a fitness cost, as prov- en by reversion after viral transmission to a different host, when the CTL pressure exerted on the virus shifts (Leslie, 2004). This process, when brought to the scale of the population, implies that after many cycles of viral replication and passage in human hosts, the viral popu- lation evolves to a consensus virus with mutations in genes that encode dominant immunogenic peptides (Scherer, 2004). MHC-restricted immune responses may shape the viral genetic diversity over time, pro- viding a selective pressure that is a function of the frequency of various alleles as the virus is passed from one host to the next. In this scenario, it may be predicted that the most common viral population (ie the ‘population consensus sequence’) is likely to represent the genotype best adapted to the most frequently encountered disease-modifying MHC alleles (or haplotypes). Trachtenberg et al. (Trachtenberg, 2003) proposed the occurrence of frequency-dependent selection according to HLA supertypes, an attractive hypothesis (Telenti, 2003) that has recently gained support with the identification of a higher capacity to elicit CTL responses by rare HLA supertypes (Scherer, 2004). Eventually, pathogen diversity and discrete strain structure may be determined by different host networks (Buckee, 2004). Adaptation of the human population to HIV-1 While the response of the virus to selective pressures imposed by the host can be readily observed, it is much more difficult to define the evo- 18