The impact of HIV tropism on decreases in CD4 cell count, clinical progression, and subsequent response to a first antiretroviral therapy regimen.
BACKGROUND
Human immunodeficiency virus (HIV) uses 2 distinct chemokine receptors, CCR5 (R5) or CXCR4 (X4), during entry. Viruses may be R5 tropic, X4 tropic, or dual/mixed (D/M) tropic. R5-tropic virus predominates at high CD4 cell counts, with the number of X4-tropic strains increasing as CD4 cell count decreases.


METHODS
We investigated the relationship between tropism and decreases in CD4 cell count before antiretroviral therapy initiation, the frequency of clinical events, and responses to antiretroviral therapy in a cohort of treatment-naive patients.


RESULTS
Four hundred two treatment-naive patients underwent tropism determination; 326 harbored R5-tropic virus, and 76 harbored X4- or D/M-tropic virus. After adjustment for baseline characteristics, the rate of decrease in CD4 cell count was significantly greater in patients infected with X4- or D/M-tropic virus at 12 months (P=.026). Two hundred twenty-nine individuals infected with R5-tropic virus and 60 individuals infected with X4- or D/M-tropic virus commenced antiretroviral therapy between tropism testing and the time of data analysis. Time to viral suppression and the proportion of patients achieving viral suppression were similar at 6, 12, and 24 months. CD4 cell count increases were similar. Clinical events were significantly more common in the group infected with X4- or D/M-tropic virus. Multivariate analysis demonstrated a relative risk of experiencing a clinical event of 2.56 (95% confidence interval, 1.37-4.76; P=.003) among patients infected with X4- or D/M-tropic virus.


CONCLUSIONS
The presence of D/M- or X4-tropic virus has a deleterious effect on CD4 cell count decrease and risk of clinical disease. Response to standard antiretroviral therapy is not affected by viral tropism.
Waters
Laura
L
St. Stephens AIDS Trust, Department of Genitourinary/HIV Medicine, Chelsea and Westminster Hospital, London, United Kingdom.
Mandalia
Sundhiya
S
Randell
Paul
P
Wildfire
Adrian
A
Gazzard
Brian
B
Moyle
Graeme
G
D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008297:Male; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D016896:Treatment Outcome; D019562:Viral Load
D044966:Anti-Retroviral Agents; D019713:Receptors, CCR5; D019718:Receptors, CXCR4