Differential rates of disease progression are obviously multifactorial, but the virulence of the actual infecting virus is most frequently ignored as potential source of slow or rapid disease progression. In this review, the argument will be made that nearly all elite suppressors are infected by weak HIV-1 strain (in terms of replicative capacity). Whether this poor virus replication is the cause of elite suppression or the consequence of a strong immune response remains a leading question in the field.
Although numerous research studies have related HIV-1 replicative capacity/fitness in tissue culture to virulence within patients, this review will focus on several recent and key discoveries on the important role of HIV-1 fitness in elite suppression. First, elite suppressors appear to harbor HIV-1 variants that encode Gag, Pol, and Env proteins that are less efficient than their counterparts of HIV-1 in typical/chronic progressors. Second, the actual HIV-1 clone(s) that establish acute infection may be less fit in patients who become elite controllers as compared with typical progressors. Finally, the fitness costs of cytotoxic T lymphocyte escape in HIV-1 may be easily compensated by secondary mutations if the infecting strain is capable of high replication kinetics and rapid evolution. A strain with weak replicative capacity might not compensate for fitness loss or even generate the initial escape mutations.
A combination of good, anti-HIV-1 host genetics (e.g. HLA-B*57) along with infection by a ‘whimpy’ HIV-1 strain may be necessary for elite suppression, whereas only one of these may lead to slow progression and viremia.
aDepartment of Medicine, Stanford University Hospital and Clinics, Palo Alto, USA
bJ. David Gladstone Institutes of Virology and Immunology, University of California, San Francisco, California, USA
cDivision of Infectious Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
Correspondence to Eric J. Arts, Division of Infectious Diseases, BRB 1029, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA Tel: +1 216 368 8904; fax: +1 216 368 2034; e-mail: firstname.lastname@example.org