Changes in human immunodeficiency virus type 1 fitness and genetic diversity during disease progression.
This study examined the relationship between ex vivo human immunodeficiency virus type 1 (HIV-1) fitness and viral genetic diversity during the course of HIV-1 disease. Primary HIV-1 isolates from 10 patients at different time points were competed against control HIV-1 strains in peripheral blood mononuclear cell (PBMC) cultures to determine relative fitness values. Patient HIV-1 isolates sequentially gained fitness during disease at a significant rate that directly correlated with viral load and HIV-1 env C2V3 diversity. A loss in both fitness and viral diversity was observed upon the initiation of antiretroviral therapy. A possible relationship between genotype and phenotype (virus replication efficiency) is supported by the parallel increases in ex vivo fitness and viral diversity during disease, of which the correlation is largely based on specific V3 sequences. Syncytium-inducing, CXCR4-tropic HIV-1 isolates did have higher relative fitness values than non-syncytium-inducing, CCR5-tropic HIV-1 isolates, as determined by dual virus competitions in PBMC, but increases in fitness during disease were not solely powered by a gradual switch in coreceptor usage. These data provide in vivo evidence that increasing HIV-1 replication efficiency may be related to a concomitant increase in HIV-1 diversity, which in turn may be a determining factor in disease progression.
Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA.
Ryan M
RM
Troyer
Kalonji R
KR
Collins
Awet
A
Abraha
Erika
E
Fraundorf
Dawn M
DM
Moore
Randall W
RW
Krizan
Zahra
Z
Toossi
Robert L
RL
Colebunders
Mark A
MA
Jensen
James I
JI
Mullins
Guido
G
Vanham
Eric J
EJ
Arts
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D014644:Genetic Variation; D015497:HIV-1 / Q000145:classification / Q000235:genetics*; D020180:Heteroduplex Analysis; D006801:Humans; D008875:Middle Aged; D015728:Receptors, HIV / Q000502:physiology; D019562:Viral Load
D019380:Anti-HIV Agents; D015728:Receptors, HIV