Bimodal virological response to antiretroviral therapy for HIV infection: an application using a mixture model with left censoring.
OBJECTIVE
To assess whether HIV RNA levels (log(10) scale) in highly active antiretroviral therapy (HAART) treated population have a bimodal distribution, suggesting optimal or suboptimal response to HAART.


METHODS
The study population from two ongoing cohort studies comprised 564 men (4785 person visits) and 1173 women (8675 person visits) with known dates of HAART initiation and with HIV RNA measurements before and after initiation. Values below detection limit of assays were treated in the analysis as left censored. Maximum likelihood methods were used to estimate parameters and to determine possible bimodality of HIV RNA distributions.


RESULTS
A two component mixture model fitted HIV RNA levels significantly better than did a single component distribution at different years from HAART initiation in both therapy experienced and therapy naive patients. In the fifth year after HAART initiation, 32% of men and 44% of women had HIV RNA in the higher component with medians of 5247 and 9253 copies/ml, respectively, suggesting suboptimal virological response to HAART, which was associated with poor adherence and lower frequency of CCR5 heterozygous genotype.


CONCLUSIONS
The bimodal distribution of HIV RNA persisted during the years after HAART initiation. The high occurrence of suboptimal virological response at the fifth year after HAART initiation underscore the needs for careful monitoring and patient education about the importance of treatment adherence. This data analysis overcomes limitations of measurement techniques of observations having values below detection limits and serves to characterise the dynamics of the virological response to therapies.
Li
Xiuhong
X
Room E7648, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Chu
Haitao
H
Gallant
Joel E
JE
Hoover
Donald R
DR
Mack
Wendy J
WJ
Chmiel
Joan S
JS
Muñoz
Alvaro
A
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015331:Cohort Studies; D005260:Female; D006678:HIV / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010349:Patient Compliance; D012367:RNA, Viral / Q000097:blood / Q000187:drug effects*; D013997:Time Factors; D014481:United States; D019562:Viral Load
D019380:Anti-HIV Agents; D012367:RNA, Viral