Immunologic and virologic response to highly active antiretroviral therapy in the Multicenter AIDS Cohort Study.
OBJECTIVE
To evaluate prior antiretroviral therapy experience and host characteristics as determinants of immunologic and virologic response to highly active antiretroviral therapy (HAART).


METHODS
We studied 397 men from the Multicenter AIDS Cohort Study (MACS) who initiated HAART between October 1995 and March 1999. CD4 cell count and HIV-1 RNA responses to HAART were measured at the first visit following HAART (short-term) and extending from the first visit to approximately 33 months after HAART (long-term). Prior antiretroviral experience was classified into three groups based on antiretroviral therapy use during the 5 years prior to HAART. Age, race and host genetic characteristics also were assessed for their effects on treatment response.


RESULTS
Better short- and long-term CD4 cell and HIV-1 RNA responses were observed in the treatment-naive users. Intermittently and consistently experienced users did not significantly differ in response. Whereas race did not independently affect response, among those initiating HAART with > 400 x 10(6) CD4 cells/l, younger age and the Delta32 CCR5 genotype were associated with a better short-term CD4 cell response. There was a suggestion that having the protective CCR5 genotype also was associated with a better long-term CD4 cell response.


CONCLUSIONS
Immunologic and virologic response to HAART was stronger in individuals who had no prior experience with the antiretroviral therapy agents subsequently included in their initial HAART regimen. Age, level of immune competence and immunogenetics appeared to play a role in the subsequent immune reconstitution following use of highly effective HIV therapy.
Yamashita
T E
TE
Johns Hopkins School of Public Health, Baltimore, Maryland 21205, USA.
Phair
J P
JP
Muñoz
A
A
Margolick
J B
JB
Detels
R
R
O'Brien
S J
SJ
Mellors
J W
JW
Wolinsky
S M
SM
Jacobson
L P
LP
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D000328:Adult; D000367:Age Factors; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D003627:Data Interpretation, Statistical; D005838:Genotype; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D044469:Racial Groups; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics; D013997:Time Factors
D019380:Anti-HIV Agents; C515334:CCR2 protein, human; D012367:RNA, Viral; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine